In both cases though, it tends to refer to personal habits or traits that the user considers to be a negative feature of the subject, even when it is a self-reference.  For example, when concerned that a person is being overly methodical they might say 'I know I'm being an old fart', potentially to forestall negative thoughts and opinions in others. When used in an attempt to be offensive, the word is still considered vulgar, but it remains a mild example of such an insult. This usage dates back to the Medieval period, where the phrase 'not worth a fart' would be applied to an item held to be worthless. [ 13 ]


The word  fart  in  Middle English  occurs in " Sumer Is Icumen In ", where one sign of summer is "bucke uerteþ" (the  buck  farts). It appears in several of  Geoffrey Chaucer 's  Canterbury Tales . In " The Miller's Tale ", Absolon has already been tricked into kissing Alison's buttocks when he is expecting to kiss her face. Her boyfriend Nicholas hangs his  buttocks  out of a window, hoping to trick Absolon into kissing his buttocks in turn and then farts in the face of his rival. In " The Summoner's Tale ", the friars in the story are to receive the smell of a fart through a twelve-spoked wheel.


In the early modern period, the word  fart  was not considered especially vulgar; it even surfaced in literary works. For example,  Samuel Johnson 's  A Dictionary of the English Language , published in 1755, included the word.  Johnson defined it  [ vague ]  with two poems, one by  Jonathan Swift , the other by  Sir John Suckling . [ 14 ] [ 15 ]


Benjamin Franklin prepared  an essay on the topic  for the Royal Academy of Brussels in 1781 urging scientific study. In 1607, a group of  Members of Parliament  had written a ribald poem entitled  The Parliament Fart , as a symbolic protest against the conservatism of the  House of Lords  and the king,  James I . [ 16 ] [ 17 ]


While not one of  George Carlin 's original  seven dirty words , he noted in a later routine that the word  fart  ought to be added to "the list" of words that were not acceptable (for broadcast) in any context (which have non-offensive meanings), and described television as (then) a "fart-free zone". [ 18 ] [ 19 ]   Thomas Wolfe  had the phrase "a fizzing and sulphuric fart" cut out of his 1929 work  Look Homeward, Angel  by his publisher.  Ernest Hemingway , who had the same publisher, accepted the principle that "fart" could be cut, on the grounds that  words should not be used purely to shock. [ 20 ]  The  hippie  movement in the 1970s saw a new definition develop, with the use of "fart" as a personal noun, to describe a "detestable person, or someone of small stature or limited mental capacity", gaining wider and more open usage as a result. [ 21 ]


Rhyming slang  developed the alternative form "raspberry tart", later shortened to "raspberry", and occasionally abbreviated further to "razz".  This was associated with the phrase " blowing a raspberry ". [ 22 ]  The word has become more prevalent, and now features in children's literature, such as the  Walter the Farting Dog  series of children's books,  Robert Munsch 's  Good Families Don't  and  The Gas We Pass  by Shinta Cho.


The  fauces ,  isthmus of fauces , or the  oropharyngeal isthmus  is the opening at the back of the  mouth  into the  throat . [ 1 ]  It is a narrow passage between the  velum  and the base of the  tongue . [ 2 ]


The fauces is a part of the  oropharynx  directly behind the  oral cavity  as a subdivision, bounded superiorly by the  soft palate , laterally by the  palatoglossal  and  palatopharyngeal arches , and inferiorly by the  tongue . The arches form the  pillars of the fauces . The anterior pillar is the palatoglossal arch formed of the  palatoglossus muscle . The posterior pillar is the palatopharyngeal arch formed of the  palatopharyngeus muscle . Between these two arches on the lateral walls of the oropharynx is the  tonsillar fossa  which is the location of the  palatine tonsil . [ 3 ]  The arches are also known together as the  palatine arches .


Each arch runs downwards, laterally and forwards, from the soft palate to the side of the tongue. The approximation of the arches due to the contraction of the palatoglossal muscles constricts the fauces, and is essential to  swallowing .


Inflammation of the fauces, known as  faucitis , is seen in animals. In cats, faucitis is usually a secondary disease to  gingivitis  but can be a primary disease. In this species faucitis is usually caused by  bacterial  and  viral infections  although  food allergies  need to be excluded in any diagnosis. Treatment is  symptomatic  and includes  broad-spectrum antibiotics  and in severe cases where cats are inappetant,  corticosteroids  (often given as  depot forms , e.g.  depomedrol ) or  chemotherapy  (e.g.  chlorambucil ).


A  fecal plug  (sometimes referred to as a  tappen ) is a significant biological phenomenon observed in  bears  and other animals during  hibernation . It is a dense mass of hardened  feces  that forms in the  colon  due to having remained in the intestine so long that the intestinal walls have absorbed the fluids out of it, leaving it dry and hard. [ 1 ]  An erroneous speculation still repeated in popular literature today is that bears prepare for hibernation by eating indigestible plant material to purge their digestive tracts and form a rectal plug that prevents further eating. [ 1 ]


The fecal plug forms as the bear enters hibernation, a period characterized by a significant decrease in the animal's metabolic rate. During this time, bears do not eat, drink, urinate, or defecate. The plug consists of various materials ingested in the period leading up to hibernation, including undigested food, shed intestinal cells, ingested bedding materials, and even small rocks or soil particles consumed during grooming. A notable component of the plug is bits of dried,  callused  skin from the bear's  footpads , which the bear may chew or lick during the later stages of hibernation.


The primary function of the fecal plug is to prevent defecation during the months of hibernation, aiding in maintaining the bear's energy conservation. It acts as a physical blockage, ensuring that the bear remains in a state of minimal digestive activity. [ citation needed ]  This adaptation is crucial for the bear's survival, as it allows for the conservation of energy and resources in an environment where food is scarce.


Upon the conclusion of hibernation in spring, the bear expels the fecal plug. This typically occurs near the entrance of the den and signifies the bear's return to its regular physiological functions. The expulsion of the plug is often one of the first activities a bear undertakes after emerging from its den, marking the end of its hibernation period.


The study of fecal plugs provides valuable insights into bear biology, particularly their hibernation habits and digestive processes. Researchers analyze the composition of the plugs to understand more about bear diet and health before hibernation. This research also contributes to broader ecological studies, as it helps in understanding the role of bears in their natural habitats.


While the fecal plug is most notably associated with bears, similar phenomena have been observed in other hibernating animals. Understanding these similarities and differences can provide deeper insights into the evolutionary adaptations for hibernation across different species.


Bears play a significant role in their ecosystems, and the process of hibernation, including the formation and expulsion of fecal plugs, is part of this role. The nutrients and materials contained in expelled plugs can have an impact on the local flora and fauna, contributing to the  nutrient cycle  in bear habitats.


The fecal plug of bears has also found a place in human culture and history. Indigenous peoples and early naturalists have observed and documented this phenomenon, contributing to our understanding and the mythology surrounding bears and hibernation.


Hibernation


Flatulence  is the expulsion of gas from the  intestines  via the anus, commonly referred to as  farting . "Flatus" is the medical word for gas generated in the  stomach  or bowels. [ 1 ]  A proportion of intestinal gas may be swallowed environmental air, and hence flatus is not entirely generated in the stomach or bowels. The scientific study of this area of medicine is termed  flatology . [ 2 ]


Flatus is brought to the  rectum  and pressurized by  muscles  in the intestines. It is normal to pass flatus ("to fart"), though volume and frequency vary greatly among individuals. It is also normal for intestinal gas to have a  feculent  or unpleasant odor, which may be intense. The noise commonly associated with flatulence is produced by the  anus  and  buttocks , which act together in a manner similar to that of an  embouchure . Both the sound and odor are sources of  embarrassment , annoyance or amusement ( flatulence humor ). In many societies, flatus is a  taboo . Thus, many people either let their flatus out quietly or even hold it completely. [ 3 ] [ 4 ]  However, holding the gases inside is not healthy. [ 5 ] [ 6 ]


There are several general symptoms related to intestinal gas: pain,  bloating  and abdominal distension, excessive flatus volume, excessive flatus odor, and gas incontinence. Furthermore,  eructation  (colloquially known as "burping") is sometimes included under the topic of flatulence. [ 7 ]  When excessive or malodorous, flatus can be a sign of a health disorder, such as  irritable bowel syndrome ,  celiac disease  or  lactose intolerance . [ 8 ]


Non-medical definitions of the term include "the uncomfortable condition of having gas in the stomach and bowels", or "a state of excessive gas in the alimentary canal". These definitions highlight that many people consider "bloating",  abdominal distension  or increased volume of intestinal gas, to be synonymous with the term flatulence (although this is technically inaccurate).


Colloquially, flatulence may be referred to as "farting", "pumping", "trumping", [ 9 ]  "blowing off", "pooting", "passing gas", "breaking wind", "backfiring", "tooting", "beefing", or simply (in  American English ) "gas" or ( British English ) "wind". Derived terms include  vaginal flatulence , otherwise known as a  queef .


Generally speaking, there are four different types of complaints that relate to intestinal gas, which may present individually or in combination.


Patients may complain of bloating as  abdominal distension , discomfort and pain from "trapped wind". In the past, functional bowel disorders such as  irritable bowel syndrome  that produced symptoms of bloating were attributed to increased production of intestinal gas.


However, three significant pieces of evidence refute this theory. First, in normal subjects, even very high rates of gas infusion into the small intestine (30   mL/min) is tolerated without complaints of pain or bloating and harmlessly passed as flatus per rectum. [ 10 ]  Secondly, studies aiming to quantify the total volume of gas produced by patients with irritable bowel syndrome (some including gas emitted from the mouth by eructation) have consistently failed to demonstrate increased volumes compared to healthy subjects. The proportion of hydrogen produced may be increased in some patients with irritable bowel syndrome, but this does not affect the total volume. [ 11 ]  Thirdly, the volume of flatus produced by patients with irritable bowel syndrome who have pain and abdominal distension would be tolerated in normal subjects without any complaints of pain.


Patients who complain of bloating frequently can be shown to have objective increases in abdominal girth, often increased throughout the day and then resolving during  sleep . The increase in girth combined with the fact that the total volume of flatus is not increased led to studies aiming to image the distribution of intestinal gas in patients with bloating. They found that gas was not distributed normally in these patients: there was segmental gas pooling and focal distension. [ 10 ]  In conclusion, abdominal distension, pain and bloating symptoms are the result of abnormal intestinal gas dynamics rather than increased flatus production.


The range of volumes of flatus in normal individuals varies hugely (476–1,491 mL/24 h). [ 2 ]  All intestinal gas is either swallowed environmental air, present intrinsically in foods and beverages, or the result of gut fermentation.


Swallowing small amounts of air occurs while eating and drinking. This is emitted from the mouth by eructation (burping) and is normal. Excessive swallowing of environmental air is called  aerophagia , and has been shown in a few case reports to be responsible for increased flatus volume. This is, however, considered a rare cause of increased flatus volume. Gases contained in food and beverages are likewise emitted largely through eructation, e.g., carbonated beverages.


Endogenously produced intestinal gases make up 74 percent of flatus in normal subjects. The volume of gas produced is partially dependent upon the composition of the intestinal microbiota, which is normally very resistant to change, but is also very different in different individuals. Some patients are predisposed to increased endogenous gas production by virtue of their gut microbiota composition. [ 10 ]  The greatest concentration of gut bacteria is in the colon, while the small intestine is normally nearly sterile. Fermentation occurs when unabsorbed food residues arrive in the colon.


Therefore, even more than the composition of the microbiota, diet is the primary factor that dictates the volume of flatus produced. [ 10 ]  Diets that aim to reduce the amount of undigested fermentable food residues arriving in the colon have been shown to significantly reduce the volume of flatus produced. Again, increased volume of intestinal gas will not cause bloating and pain in normal subjects. Abnormal intestinal gas dynamics will create pain, distension, and bloating, regardless of whether there is high or low total flatus volume.


Although flatus possesses an odor, this may be abnormally increased in some patients and cause social distress to the patient. Increased odor of flatus presents a distinct clinical issue from other complaints related to intestinal gas. [ 12 ]  Some patients may exhibit over-sensitivity to bad flatus odor, and in extreme forms,  olfactory reference syndrome  may be diagnosed. Recent informal research found a correlation between flatus odor and both loudness and humidity content. [ 13 ]


"Gas incontinence" could be defined as loss of voluntary control over the passage of flatus. It is a recognised subtype of  faecal incontinence , and is usually related to minor disruptions of the continence mechanisms. Some consider gas incontinence to be the first, sometimes only, symptom of faecal incontinence. [ 14 ]


Intestinal gas is composed of varying quantities of exogenous sources and endogenous sources. [ 15 ]  The exogenous gases are swallowed ( aerophagia ) when eating or drinking or increased swallowing during times of excessive salivation (as might occur when nauseated or as the result of  gastroesophageal reflux  disease). The  endogenous  gases are produced either as a by-product of digesting certain types of food, or of incomplete  digestion , as is the case during  steatorrhea . Anything that causes food to be incompletely digested by the  stomach  or  small intestine  may cause flatulence when the material arrives in the large intestine, due to  fermentation  by  yeast  or  prokaryotes  normally or abnormally present in the  gastrointestinal tract .


Flatulence-producing foods are typically high in certain  polysaccharides , especially  oligosaccharides  such as  inulin . Those foods include  beans ,  lentils ,  dairy products ,  onions ,  garlic ,  spring onions ,  leeks ,  turnips ,  swedes ,  radishes ,  sweet potatoes ,  potatoes ,  cashews ,  Jerusalem artichokes ,  oats ,  wheat , and  yeast  in  breads .  Cauliflower ,  broccoli ,  cabbage ,  Brussels sprouts  and other  cruciferous vegetables  that belong to the genus  Brassica  are commonly reputed to not only increase flatulence, but to increase the pungency of the flatus. [ 16 ] [ 17 ]


In beans, endogenous gases seem to arise from complex oligosaccharides ( carbohydrates ) that are particularly resistant to digestion by mammals, but are readily digestible by  microorganisms  ( methane-producing  archaea;  Methanobrevibacter smithii ) that inhabit the  digestive tract . These oligosaccharides pass through the small intestine largely unchanged, and when they reach the large intestine,  bacteria  ferment them, producing copious amounts of flatus. [ 18 ]


When excessive or malodorous, flatus can be a sign of a health disorder, such as  irritable bowel syndrome ,  celiac disease ,  non-celiac gluten sensitivity  or  lactose intolerance . It can also be caused by certain medicines, such as  ibuprofen ,  laxatives ,  antifungal  medicines or  statins . [ 8 ] [ 19 ]  Some infections, such as  giardiasis , are also associated with flatulence. [ 20 ]


Interest in the causes of flatulence was spurred by high-altitude  flight  and  human spaceflight ; the low  atmospheric pressure , confined conditions, and stresses peculiar to those endeavours were cause for concern. [ 18 ]  In the field of mountaineering, the phenomenon of  high altitude flatus expulsion  was first recorded over two hundred years ago.


Flatus (intestinal gas) is mostly produced as a byproduct of bacterial fermentation in the gastrointestinal (GI) tract, especially the  colon . [ 21 ]  There are reports of  aerophagia  (excessive air swallowing) causing excessive intestinal gas, but this is considered rare. [ 22 ]


Over 99% of the volume of flatus is composed of odorless gases. [ 2 ]  These include  oxygen ,  nitrogen ,  carbon dioxide ,  hydrogen  and  methane . Nitrogen is not produced in the gut, but a component of environmental air. Patients who have excessive intestinal gas that is mostly composed of nitrogen have aerophagia. [ 23 ]  Hydrogen, carbon dioxide and methane are all produced in the gut and contribute 74% of the volume of flatus in normal subjects. [ 24 ]  Methane and hydrogen are  flammable , and so  flatus can be ignited  if it contains adequate amounts of these components. [ 25 ]


Not all humans produce flatus that contains methane. For example, in one study of the  faeces  of nine adults, only five of the samples contained  archaea  capable of producing methane. [ 26 ]  The prevalence of methane over hydrogen in human flatus may correlate with obesity, constipation and irritable bowel syndrome, as archaea that oxidise hydrogen into methane promote the metabolism's ability to absorb fatty acids from food. [ 27 ]


The remaining trace (<1% volume) compounds contribute to the odor of flatus. Historically, compounds such as  indole ,  skatole ,  ammonia  and  short chain fatty acids  were thought to cause the odor of flatus. More recent evidence proves that the major contribution to the odor of flatus comes from a combination of volatile  sulfur  compounds. [ 2 ] [ 28 ]   Hydrogen sulfide ,  methyl mercaptan  (also known as  methanethiol ),  dimethyl sulfide ,  dimethyl disulfide  and  dimethyl trisulfide  are present in flatus. The benzopyrrole volatiles  indole  and  skatole  have an odor of mothballs,  and therefore probably do not contribute greatly to the characteristic odor of flatus.


In one study, hydrogen sulfide concentration was shown to correlate convincingly with perceived bad odor of flatus, followed by methyl mercaptan and dimethyl sulfide. [ 23 ]  This is supported by the fact that hydrogen sulfide may be the most abundant volatile sulfur compound present. These results were generated from subjects who were eating a diet high in  pinto beans  to stimulate flatus production.


Others report that methyl mercaptan was the greatest contributor to the odor of flatus in patients not under any specific dietary alterations. [ 2 ]  It has now been demonstrated that methyl mercaptan, dimethyl sulfide, and hydrogen sulfide (described as decomposing vegetables, unpleasantly sweet/wild radish and rotten eggs respectively) are all present in human flatus in concentrations above their smell perception thresholds. [ 2 ]


It is recognized that increased dietary sulfur-containing amino acids significantly increases the odor of flatus. It is therefore likely that the odor of flatus is created by a combination of volatile sulfur compounds, with minimal contribution from non-sulfur volatiles. [ 23 ]  This odor can also be caused by the presence of large numbers of microflora  bacteria  or the presence of faeces in the rectum. Diets high in protein, especially sulfur-containing amino acids, have been demonstrated to significantly increase the odor of flatus.


Normal flatus volume is 476 to 1491 mL per 24 hours. [ 2 ] [ 21 ]  This variability between individuals is greatly dependent upon diet. Similarly, the number of flatus episodes per day is variable; the normal range is given as 8–20 per day. [ 23 ]  The volume of flatus associated with each flatulence event again varies (5–375 mL). [ 2 ] [ 21 ] [ 24 ]  The volume of the first flatulence upon waking in the morning is significantly larger than those during the day. [ 2 ]  This may be due to buildup of intestinal gas in the colon during sleep, the peak in peristaltic activity in the first few hours after waking or the strong prokinetic effect of rectal distension on the rate of transit of intestinal gas. [ 10 ]  It is now known that gas is moved along the gut independently of solids and liquids, and this transit is more efficient in the erect position compared to when supine. [ 10 ]  It is thought that large volumes of intestinal gas present low resistance, and can be propelled by subtle changes in gut tone, capacitance and proximal contraction and distal relaxation. This process is thought not to affect solid and liquid intra-lumenal contents. [ 10 ]


Researchers investigating the role of sensory nerve endings in the anal canal did not find them to be essential for retaining fluids in the anus, and instead speculate that their role may be to distinguish between flatus and faeces, thereby helping detect a need to defecate or to signal the end of defecation. [ 29 ]


The sound varies depending on the volume of gas, the size of the opening that the air is being pushed through, which is affected by the state of tension in the  sphincter muscle , and the  force  or  velocity  of the  gas  being propelled, as well as other factors, such as whether the gas was caused by swallowed air. [ 30 ] [ 31 ]  Among humans, flatulence occasionally happens accidentally, such as incidentally to  coughing [ 32 ]  or  sneezing  or during  orgasm ; on other occasions, flatulence can be voluntarily elicited by tensing the rectum or "bearing down" on stomach or bowel muscles and subsequently relaxing the anal sphincter, resulting in the expulsion of flatus. [ citation needed ]


Since problems involving intestinal gas present as different (but sometimes combined) complaints, the management is cause-related.


While not affecting the production of the gases themselves,  surfactants  (agents that lower  surface tension ) can reduce the disagreeable sensations associated with flatulence, by aiding the dissolution of the gases into liquid and solid faecal matter. [ 33 ]  Preparations containing  simethicone  reportedly operate by promoting the coalescence of smaller bubbles into larger ones more easily passed from the body, either by  burping  or flatulence. Such preparations do not decrease the total amount of gas generated in or passed from the colon, but make the bubbles larger and thereby allowing them to be passed more easily. [ 33 ]


Other drugs including  prokinetics ,  lubiprostone , antibiotics and probiotics are also used to treat bloating in patients with functional bowel disorders such as irritable bowel syndrome, and there is some evidence that these measures may reduce symptoms. [ 34 ]


A flexible tube, inserted into the  rectum , can be used to collect intestinal gas in a flatus bag. This method is occasionally needed in a hospital setting, when the patient is unable to pass gas normally. [ 35 ]


One method of reducing the volume of flatus produced is dietary modification, reducing the amount of fermentable carbohydrates. This is the theory behind diets such as the  low-FODMAP diet  (a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, alcohols, and polyols). [ 36 ]


Most starches, including potatoes, corn, noodles, and wheat, produce gas as they are broken down in the large intestine. [ 15 ]  Intestinal gas can be reduced by fermenting the beans, and making them less gas-inducing, or by cooking them in the liquor from a previous batch. For example, the fermented bean product  miso  is less likely to produce as much intestinal gas. Some  legumes  also stand up to prolonged cooking, which can help break down the oligosaccharides into simple sugars. Fermentative lactic acid bacteria such as  Lactobacillus casei  and  Lactobacillus plantarum  reduce flatulence in the human intestinal tract. [ 37 ]


Probiotics  ( live yogurt ,  kefir , etc.) are reputed to reduce flatulence when used to restore balance to the normal  intestinal flora . [ 38 ]  Live (bioactive) yogurt contains, among other lactic bacteria,  Lactobacillus acidophilus , which may be useful in reducing flatulence.  L. acidophilus  may make the intestinal environment more acidic, supporting a natural balance of the fermentative processes.  L. acidophilus  is available in supplements.  Prebiotics , which generally are non-digestible oligosaccharides, such as  fructooligosaccharide , generally increase flatulence in a similar way as described for lactose intolerance.


Digestive enzyme  supplements may significantly reduce the amount of flatulence caused by some components of foods not being digested by the body and thereby promoting the action of microbes in the small and large  intestines . It has been suggested that  alpha-galactosidase   enzymes , which can digest certain complex sugars, are effective in reducing the volume and frequency of flatus. [ 39 ]  The  enzymes   alpha-galactosidase ,  lactase ,  amylase ,  lipase ,  protease ,  cellulase ,  glucoamylase ,  invertase , malt  diastase ,  pectinase , and  bromelain  are available, either individually or in combination blends, in commercial products.


The  antibiotic   rifaximin , often used to treat  diarrhea  caused by the  microorganism   E. coli , may reduce both the production of intestinal gas and the frequency of flatus events. [ 40 ]


Bismuth


The  odor  created by flatulence is commonly treated with  bismuth subgallate , available under the name Devrom. Bismuth subgallate is commonly used by individuals who have had  ostomy  surgery,  bariatric surgery ,  faecal incontinence  and  irritable bowel syndrome . [ 41 ] [ 42 ]   Bismuth subsalicylate  is a compound that binds hydrogen sulfide, and one study reported a dose of 524 mg four times a day for 3–7 days bismuth subsalicylate yielded a >95% reduction in faecal hydrogen sulfide release in both humans and rats. [ 43 ]
Another bismuth compound, bismuth subnitrate was also shown to bind to hydrogen sulfide. [ 44 ]  Another study showed that bismuth acted synergistically with various antibiotics to inhibit sulfate-reducing gut bacteria and sulfide production. [ 45 ]  Some authors proposed a theory that hydrogen sulfide was involved in the development of  ulcerative colitis  and that bismuth might be helpful in the management of this condition. [ 46 ]  However, bismuth administration in rats did not prevent them from developing ulcerative colitis despite reduced hydrogen sulfide production. [ 46 ]  Also, evidence suggests that colonic hydrogen sulfide is largely present in bound forms, probably sulfides of iron and other metals. [ 2 ]  Rarely, serious bismuth toxicity may occur with higher doses. [ 47 ]


Activated charcoal


Despite being an ancient treatment for various digestive complaints,  activated charcoal  did not produce reduction in both the total flatus volume nor the release of sulfur-containing gasses, and there was no reduction in abdominal symptoms (after 0.52   g activated charcoal four times a day for one week). [ 48 ]  The authors suggested that saturation of charcoal binding sites during its passage through the gut was the reason for this. A further study concluded that activated charcoal (4   g) does not influence gas formation in vitro or in vivo. [ 49 ]  Other authors reported that activated charcoal was effective. A study in 8 dogs concluded activated charcoal (unknown oral dose) reduced hydrogen sulfide levels by 71%. In combination with yucca schidigera, and zinc acetate, this was increased to an 86% reduction in hydrogen sulfide, although flatus volume and number was unchanged. [ 50 ]  An early study reported activated charcoal (unknown oral dose) prevented a large increase in the number of flatus events and increased breath hydrogen concentrations that normally occur following a gas-producing meal. [ 51 ]


Garments and external devices


In 1998, Chester "Buck" Weimer of  Pueblo, Colorado , received a patent for the first  undergarment  that contained a replaceable  charcoal filter . The undergarments are  air-tight  and provide a pocketed  escape hole  in which a charcoal filter can be inserted. [ 52 ]  In 2001 Weimer received the  Ig Nobel Prize  for Biology for his invention. [ 53 ]


A similar product was released in 2002, but rather than an entire undergarment, consumers are able to purchase an insert similar to a  pantiliner  that contains activated charcoal. [ 54 ]  The inventors, Myra and Brian Conant of  Mililani, Hawaii , still claim on their website to have discovered the undergarment product in 2002 (four years after Chester Weimer filed for a patent for his product), but state that their tests "concluded" that they should release an insert instead. [ 55 ]


Flatus incontinence where there is involuntary passage of gas, is a type of  faecal incontinence , and is managed similarly.


In many  cultures , flatulence in public is regarded as embarrassing, but, depending on context, may also be considered humorous. [ 56 ]  People will often strain to hold in the passing of gas when in polite company, or position themselves to silence or conceal the passing of gas. In other cultures, [ example needed ]  it may be no more embarrassing than  coughing .


While the act of passing flatus in some cultures is generally considered to be an unfortunate occurrence in public settings, flatulence may, in casual circumstances and especially among children, be used as either a humorous supplement to a joke ("pull my finger"), or as a comic activity in and of itself. The social acceptability of flatulence-based humour in entertainment and the mass media varies over the course of time and between cultures. A sufficient number of entertainers have performed using their flatus to lead to the coining of the term  flatulist . The  whoopee cushion  is a joking device invented in the early 20th century for simulating a fart. In 2008, a farting application for the  iPhone  earned nearly $10,000 in one day. [ 57 ]


A  farting  game named  Touch Wood  was documented by  John Gregory Bourke  in the 1890s. [ 58 ]  It was known as  Safety  in the 20th century in the U.S., and is still played by children as of 2011. [ 58 ]


In January 2011, the  Malawi   Minister of Justice ,  George Chaponda , said that  Air Fouling Legislation  would make public "farting" illegal in his country. When reporting the story, the media satirised Chaponda's statement with punning headlines. Later, the minister withdrew his statement. [ 59 ]


Flatulence is often blamed as a significant source of  greenhouse gases , owing to the erroneous belief that the methane released by  livestock  is in the flatus. [ 61 ]  While livestock account for around 20% of global  methane emissions , [ 62 ]  90–95% of that is released by  exhaling  or  burping . [ 63 ]  In cows, gas and burps are produced by methane-generating microbes called  methanogens , which live inside the cow's digestive system. Proposals for reducing methane production in cows include the feeding of supplements such as  oregano  and  seaweed , and the genetic engineering of gut biome microbes to produce less methane. [ 60 ]


Since New Zealand produces large amounts of agricultural products, it has the unique position of having higher methane emissions from livestock compared to other greenhouse gas sources. The New Zealand government is a signatory to the  Kyoto Protocol  and therefore attempts to reduce  greenhouse emissions . To achieve this, an  agricultural emissions research levy  was proposed, which promptly became known as a " fart tax " or "flatulence tax". It encountered opposition from farmers, farming lobby groups and opposition politicians.


Historical comment on the ability to fart at will is observed as early as  Saint Augustine 's  The City of God  (5th century A.D.). Augustine mentions "people who produce at will without any stench such rhythmical sounds from their fundament that they appear to be making music even from that quarter." [ 64 ]  Intentional passing of gas and its use as entertainment for others appear to have been somewhat well known in pre-modern Europe, according to mentions of it in medieval and later literature, including  Rabelais . [ citation needed ]


Le Pétomane  ("the Fartomaniac") was a famous French performer in the 19th century who, as well as many  professional farters  before him, did flatulence impressions and held shows. The performer  Mr. Methane  carries on le Pétomane's tradition today. Also, a 2002 fiction film  Thunderpants  revolves around a boy named Patrick Smash who has an ongoing flatulence problem from the time of his birth. [ 65 ]


Since the 1970s, farting has increasingly been featured in film, especially comedies such as  Blazing Saddles  and  Scooby-Doo . [ 66 ]


In the popular vulgar cartoon series " South Park ," characters sometimes watch a  show-within-a-show  called "The  Terrance and Phillip  Show" whose humor primarily revolves around flatulence.


People find other peoples' flatus unpleasant, but are unfazed by, and may even enjoy, the scent of their own. [ 67 ]  While there has been little research carried out upon the subject, some speculative guesses have been made as to why this might be so. For example, one explanation for this phenomenon is that people are very familiar with the scent of their own flatus, and that survival in nature may depend on the detection of and reaction to foreign scents. [ 68 ]


Some people have Eproctophilla, the  fetish  of flatulence, finding  sexual gratification  and  pleasure  from either the sound of the gas, smells from the gas, feeling of the gas, some combination of the three, or all three.


Foregut fermentation  is a form of  digestion  that occurs in the  foregut  of some animals such as the  hamster rat ,  langur monkey , and the  hippopotamus . [ 1 ]  It has  evolved independently  in several groups of mammals, and also in the  hoatzin , a bird species.


Foregut fermentation is employed by  ruminants  and  pseudoruminants , some  rodents  and some  marsupials . [ 2 ]  It has also evolved in  colobine  monkeys and in  sloths . [ 3 ]


This  vertebrate anatomy –related article is a  stub . You can help Wikipedia by  expanding it .


The  Gal4 transcription factor  is a positive regulator of gene expression of galactose-induced genes. [ 1 ]  This protein represents a large fungal family of transcription factors, Gal4 family, which includes over 50 members in the yeast  Saccharomyces cerevisiae  e.g. Oaf1, Pip2, Pdr1, Pdr3, Leu3. [ 2 ]


Gal4 recognizes genes with UAS G , an  upstream activating sequence , and activates them. In yeast cells, the principal targets are GAL1 ( galactokinase ), GAL10 ( UDP-glucose 4-epimerase ), and GAL7 ( galactose-1-phosphate uridylyltransferase ), three enzymes required for galactose metabolism. This binding has also proven useful in constructing the  GAL4/UAS system , a technique for controlling expression in insects. [ 3 ]  In yeast, Gal4 is by default repressed by Gal80, and activated in the presence of  galactose  as Gal3 binds away Gal80. [ 4 ]


Two executive domains, DNA binding and activation domains, provide key function of the Gal4 protein conforming to most of the transcription factors.


Gal4 N-terminus is a zinc finger and belongs to the  Zn(2)-C6  fungal family. It forms a Zn – cysteines thiolate cluster, [ 5 ] [ 6 ]  and specifically recognizes UAS G  in GAL1 promoter.  [ 7 ] [ 8 ]


Localised to the C-terminus, belongs to the nine amino acids  transactivation domain  family, 9aaTAD, together with Oaf1, Pip2, Pdr1, Pdr3, but also  p53 ,  E2A ,  MLL . [ 9 ] [ 10 ]


Galactose  induces Gal4 mediated transcription albeit Glucose causes severe repression. [ 11 ] [ 12 ]


As a part of the Gal4 regulation, inhibitory protein Gal80 recognises and binds to the Gal4 region (853-874 aa). [ 13 ] [ 14 ] [ 15 ]


The inhibitory protein Gal80 is sequestered by regulatory protein Gal3 in Galactose dependent manner. This allows for Gal4 to work when there is galactose. [ 16 ] [ 4 ] [ 17 ] [ 18 ]


The Gal4 loss-of-function mutant gal4-64 (1-852 aa, deletion of the Gal4 C-terminal 29 aa) lost both interaction with Gal80 and activation function. [ 19 ] [ 20 ] [ 21 ]


In the Gal4 reverted mutant Gal4C-62 mutant, [ 22 ]  a sequence (QTAY N AFMN) with the 9aaTAD pattern emerged and restored activation function of the Gal4 protein.


The activation domain Gal4 is inhibited by C-terminal domain in some Gal4 constructs. [ 23 ] [ 24 ]


The Gal4 activation function is mediated by  MED15  (Gal11). [ 25 ] [ 26 ] [ 27 ] [ 28 ] [ 29 ] [ 30 ] [ 31 ]


The Gal4 protein interacts also with other mediators of transcription as are Tra1, [ 32 ] [ 33 ] [ 34 ]  TAF9, [ 35 ]  and SAGA/MED15 complex. [ 36 ] [ 37 ]


A subunit of the 26 S proteasome Sug2 regulatory protein has a molecular and functional interaction with Gal4 function. [ 38 ] [ 39 ]  Proteolytic turnover of the Gal4 transcription factor is not required for function in vivo. [ 40 ]  The native Gal4 monoubiquitination protects from 19S-mediated destabilizing under inducing conditions. [ 41 ]


The broad use of the Gal4 is in yeast  two-hybrid screening  to screen or to assay protein-protein interactions in eukaryotic cells from yeast to human.


In the  GAL4/UAS system , the Gal4 protein and Gal4 upstream activating region (UAS) are used to study the gene expression and function in organisms such as the fruit fly. [ 3 ]


The Gal4 and inhibitory protein Gal80 have found application in a genetics technique for creating individually labeled homozygous cells called  MARCM  (Mosaic analysis with a repressible cell marker).


In  vertebrates , the  gallbladder , also known as the  cholecyst , is a small hollow  organ  where  bile  is stored and concentrated before it is released into the  small intestine . In humans, the pear-shaped gallbladder lies beneath the  liver , although the structure and position of the gallbladder can vary significantly among animal species. It receives bile, produced by the liver, via the  common hepatic duct , and stores it. The bile is then released via the  common bile duct  into the  duodenum , where the bile helps in the digestion of  fats .


The gallbladder can be affected by  gallstones , formed by material that cannot be dissolved – usually  cholesterol  or  bilirubin , a product of  hemoglobin  breakdown. These may cause significant pain, particularly in the upper-right corner of the abdomen, and are often treated with removal of the gallbladder (called a  cholecystectomy ).  Cholecystitis , inflammation of the gallbladder, has a wide range of causes, including result from the impaction of gallstones, infection, and autoimmune disease.


The human gallbladder is a hollow grey-blue  organ  that sits in a shallow depression below the right lobe of the  liver . [ 2 ]  In adults, the gallbladder measures approximately 7 to 10 centimetres (2.8 to 3.9 inches) in length and 4 centimetres (1.6 in) in diameter when fully distended. [ 3 ]  The gallbladder has a capacity of about 50 millilitres (1.8 imperial fluid ounces). [ 2 ]


The gallbladder is shaped like a pear, with its tip opening into the  cystic duct . [ 4 ]  The gallbladder is divided into three sections: the  fundus ,  body , and  neck . The  fundus  is the rounded base, angled so that it faces the  abdominal wall . The  body  lies in a depression in the surface of the lower liver. The  neck  tapers and is continuous with the  cystic duct , part of the  biliary tree . [ 2 ]  The gallbladder fossa, against which the fundus and body of the gallbladder lie, is found beneath the junction of  hepatic segments  IVB and V. [ 5 ]  The cystic duct unites with the  common hepatic duct  to become the  common bile duct . At the junction of the neck of the gallbladder and the cystic duct, there is an out-pouching of the gallbladder wall forming a mucosal fold known as " Hartmann 's pouch". [ 2 ]


Lymphatic drainage of the gallbladder follows the cystic node, which is located between the cystic duct and the common hepatic duct. Lymphatics from the lower part of the organ drain into lower  hepatic lymph nodes . All the lymph finally drains into  celiac lymph nodes .


The gallbladder wall is composed of a number of layers. The innermost surface of the gallbladder wall is lined by a single layer of  columnar cells  with a  brush border  of  microvilli , very similar to intestinal absorptive cells. [ 2 ]  Underneath the epithelium is an underlying  lamina propria , a  muscular layer , an outer perimuscular layer and  serosa . Unlike elsewhere in the intestinal tract, the gallbladder does not have a  muscularis mucosae , and the muscular fibres are not arranged in distinct layers. [ 6 ]


The  mucosa , the inner portion of the gallbladder wall, consists of a  lining  of a  single layer of columnar  cells, with cells possessing small hair-like attachments called  microvilli . [ 2 ]  This sits on a thin layer of connective tissue, the  lamina propria . [ 6 ]  The mucosa is curved and collected into tiny outpouchings called  rugae . [ 2 ]


A muscular layer sits beneath the mucosa. This is formed by  smooth muscle , with fibres that lie in longitudinal, oblique and transverse directions, and are not arranged in separate layers. The muscle fibres here contract to expel bile from the gallbladder. [ 6 ]  A distinctive feature of the gallbladder is the presence of  Rokitansky–Aschoff sinuses , deep outpouchings of the mucosa that can extend through the muscular layer, and which indicate  adenomyomatosis . [ 7 ]  The muscular layer is surrounded by a layer of connective and  fat  tissue. [ 2 ]


The outer layer of the fundus of gallbladder, and the surfaces not in contact with the liver, are covered by a thick  serosa , which is exposed to the  peritoneum . [ 2 ]  The serosa contains blood vessels and lymphatics. [ 6 ]  The surfaces in contact with the liver are covered in  connective tissue . [ 2 ]


The gallbladder varies in size, shape, and position among different people. [ 2 ]  Rarely, two or even three gallbladders may coexist, either as separate bladders draining into the cystic duct, or sharing a common branch that drains into the cystic duct. Additionally, the gallbladder may fail to form at all. Gallbladders with two lobes separated by a  septum  may also exist. These abnormalities are not likely to affect function and are generally asymptomatic. [ 8 ]


The location of the gallbladder in relation to the liver may also vary, with documented variants including gallbladders found within, [ 9 ]  above, on the left side of, behind, and detached or suspended from the liver. Such variants are very rare: from 1886 to 1998, only 110 cases of left-lying liver, or less than one per year, were reported in scientific literature. [ 10 ] [ 11 ] [ 2 ]


An  anatomical variation  can occur, known as a  Phrygian cap , which is an innocuous fold in the fundus, named after its resemblance to the  Phrygian cap . [ 12 ]


The gallbladder develops from an  endodermal  outpouching of the embryonic gut tube. [ 13 ]  Early in development, the human embryo has three  germ layers  and abuts an embryonic  yolk sac . During the second week of  embryogenesis , as the embryo grows, it begins to surround and envelop portions of this sac. The enveloped portions form the basis for the adult gastrointestinal tract. Sections of this  foregut  begin to differentiate into the organs of the gastrointestinal tract, such as the  esophagus ,  stomach , and  intestines . [ 13 ]


During the fourth week of embryological development, the stomach rotates. The stomach, originally lying in the midline of the embryo, rotates so that its body is on the left. This rotation also affects the part of the gastrointestinal tube immediately below the stomach, which will go on to become the  duodenum . By the end of the fourth week, the developing duodenum begins to spout a small outpouching on its right side, the  hepatic diverticulum , which will go on to become the  biliary tree . Just below this is a second outpouching, known as the  cystic diverticulum , that will eventually develop into the gallbladder. [ 13 ]


The main functions of the gallbladder are to store and concentrate  bile , also called gall, needed for the digestion of fats in food. Produced by the liver, bile flows through small vessels into the larger  hepatic ducts  and ultimately through the  cystic duct  (parts of the  biliary tree ) into the gallbladder, where it is stored. At any one time, 30 to 60 millilitres (1.0 to 2.0 US fl oz) of bile is stored within the gallbladder. [ 15 ]


When food containing fat enters the  digestive tract , it stimulates the  secretion  of  cholecystokinin  (CCK) from  I cells  of the duodenum and jejunum. In response to cholecystokinin, the gallbladder rhythmically contracts and releases its contents into the  common bile duct , eventually draining into the  duodenum . The bile  emulsifies  fats in partly digested food, thereby assisting their absorption. Bile consists primarily of water and  bile salts , and also acts as a means of eliminating  bilirubin , a product of  hemoglobin  metabolism, from the body. [ 15 ]


The bile that is secreted by the liver and stored in the gallbladder is not the same as the bile that is secreted by the gallbladder. During gallbladder storage of bile, it is concentrated 3–10 fold [ 16 ]  by removal of some water and electrolytes. This is through the  active transport  of sodium and chloride ions [ 17 ]  across the epithelium of the gallbladder, which creates an  osmotic pressure  that also causes water and other electrolytes to be reabsorbed. [ 15 ]


A function of the gallbladder appears to be protection against  carcinogenesis  as indicated by  observations that removal of the gallbladder ( cholecystectomy ) increases subsequent cancer risk.  For instance, a systematic review and meta analysis of eighteen studies concluded that cholecystectomy has a harmful effect on the risk of right-sided colon cancer. [ 18 ]   Another recent study reported a significantly increased total cancer risk, including increased risk of several different types of cancer, after cholecystectomy. [ 19 ]


Gallstones  form when the bile is  saturated , usually with either  cholesterol  or  bilirubin . [ 20 ]  Most gallstones do not cause symptoms, with stones either remaining in the gallbladder or passed along the  biliary system . [ 21 ]  When symptoms occur, severe "colicky" pain in the upper right  quadrant  of the abdomen is often felt. [ 20 ]  If the  stone blocks the gallbladder , inflammation known as  cholecystitis  may result. If the stone lodges in the biliary system,  jaundice  may occur; if the stone blocks the  pancreatic duct ,  pancreatitis  may occur. [ 21 ]  Gallstones are diagnosed using  ultrasound . [ 20 ]  When a symptomatic gallstone occurs, it is often managed by waiting for it to be passed naturally. [ 21 ]  Given the likelihood of recurrent gallstones, surgery to remove the gallbladder is often considered. [ 21 ]  Some medication, such as  ursodeoxycholic acid , may be used;  lithotripsy , a non-invasive mechanical procedure used to break down the stones, may also be used. [ 21 ]


Known as  cholecystitis , inflammation of the gallbladder is commonly caused by obstruction of the duct with gallstones, which is known as  cholelithiasis . Blocked bile accumulates, and pressure on the gallbladder wall may lead to the release of substances that cause inflammation, such as  phospholipase . There is also the risk of bacterial infection. An inflamed gallbladder is likely to cause sharp and localised pain, fever, and tenderness in the upper, right corner of the abdomen, and may have a positive  Murphy's sign . Cholecystitis is often managed with rest and antibiotics, particularly  cephalosporins  and, in severe cases,  metronidazole . Additionally the gallbladder may need to be removed surgically if inflammation has progressed far enough. [ 21 ]


A  cholecystectomy  is a procedure in which the gallbladder is removed. It may be removed because of recurrent gallstones and is considered an  elective procedure . A cholecystectomy may be an  open  procedure, or a  laparoscopic  one. In the surgery, the gallbladder is removed from the neck to the fundus, [ 22 ]  and so bile will drain directly from the liver into the  biliary tree . About 30 percent of patients may experience some degree of  indigestion  following the procedure, although severe complications are much rarer. [ 21 ]  About 10 percent of surgeries lead to a chronic condition of  postcholecystectomy syndrome . [ 23 ]


Biliary injury (bile duct injury) is the traumatic damage of the  bile ducts . It is most commonly an  iatrogenic  complication of  cholecystectomy  — surgical removal of  gall bladder , but can also be caused by other operations or by  major trauma . The risk of biliary injury is more during laparoscopic cholecystectomy than during open cholecystectomy. Biliary injury may lead to several complications and may even cause death if not diagnosed in time and managed properly. Ideally biliary injury should be managed at a center with facilities and expertise in  endoscopy ,  radiology  and surgery. [ 24 ]


Biloma is collection of  bile  within the  abdominal cavity . It happens when there is a bile leak, for example after surgery for removing the gallbladder ( laparoscopic cholecystectomy ), with an incidence of 0.3–2%. Other causes are biliary surgery,  liver biopsy ,  abdominal trauma , and, rarely, spontaneous perforation. [ 25 ]


Cancer of the gallbladder is uncommon and mostly occurs in later life. When cancer occurs, it is mostly of the glands lining the surface of the gallbladder ( adenocarcinoma ). [ 21 ]  Gallstones are thought to be linked to the formation of cancer. Other risk factors include large (>1 cm)  gallbladder polyps  and having a highly calcified  "porcelain" gallbladder . [ 21 ]


Cancer of the gallbladder can cause attacks of biliary pain, yellowing of the skin ( jaundice ), and weight loss. A large gallbladder may be able to be felt in the abdomen.  Liver function tests  may be elevated, particularly involving  GGT  and  ALP , with ultrasound and CT scans being considered  medical imaging  investigations of choice. [ 21 ]  Cancer of the gallbladder is managed by removing the gallbladder, however, as of 2010, [update]  the prognosis remains poor. [ 21 ]


Cancer of the gallbladder may also be found incidentally after surgical removal of the gallbladder, with 1–3% of cancers identified in this way.  Gallbladder polyps  are mostly benign growths or lesions resembling growths that form in the gallbladder wall, [ 26 ]  and are only associated with cancer when they are larger in size (>1 cm). [ 21 ]  Cholesterol polyps, often associated with  cholesterolosis  ("strawberry gallbladder", a change in the gallbladder wall due to excess  cholesterol [ 27 ] ), often cause no symptoms and are thus often detected in this way. [ 21 ]


Tests used to investigate for gallbladder disease include  blood tests  and  medical imaging . A  full blood count  may reveal an increased white cell count suggestive of inflammation or infection. Tests such as  bilirubin  and  liver function tests  may reveal if there is inflammation linked to the biliary tree or gallbladder, and whether this is associated with inflammation of the liver, and a  lipase  or  amylase  may be elevated if there is  pancreatitis . Bilirubin may rise when there is obstruction of the flow of bile. A  CA 19-9  level may be taken to investigate for cholangiocarcinoma. [ 21 ]


An  ultrasound  is often the first  medical imaging  test performed when gallbladder disease such as gallstones are suspected. [ 21 ]  An  abdominal X-ray  or  CT scan  is another form of imaging that may be used to examine the gallbladder and surrounding organs. [ 21 ]  Other imaging options include MRCP ( magnetic resonance cholangiopancreatography ),  ERCP  and percutaneous or intraoperative  cholangiography . [ 21 ]  A  cholescintigraphy  scan is a  nuclear imaging  procedure used to assess the condition of the gallbladder. [ 28 ]


Most  vertebrates  have gallbladders, but the form and arrangement of the bile ducts may vary considerably. In many species, for example, there are several separate ducts running to the intestine, rather than the single common bile duct found in humans. Several species of  mammals  (including  horses ,  deer ,  rats , and  laminoids ), [ 29 ] [ 30 ]  several species of  birds  (such as pigeons and some  psittacine  species),  lampreys  and all  invertebrates  do not have a gallbladder. [ 31 ] [ 32 ]


The bile from several species of bears is used in  traditional Chinese medicine ;  bile bears  are kept alive in captivity while their bile is extracted, in an industry characterized by  animal cruelty . [ 33 ] [ 34 ]


Depictions of the gallbladder and biliary tree are found in  Babylonian  models found from 2000 BCE, and in ancient  Etruscan  model from 200 BCE, with models associated with divine worship. [ 35 ]


Diseases of the gallbladder are known to have existed in humans since antiquity, with gallstones found in the mummy of Princess Amenen of  Thebes  dating to 1500 BCE. [ 35 ] [ 36 ]  Some historians believe the death of  Alexander the Great  may have been associated with an acute episode of cholecystitis. [ 35 ]  The existence of the gallbladder has been noted since the 5th century, but it is only relatively recently that the function and the diseases of the gallbladder has been documented, [ 36 ]  particularly in the last two centuries. [ 35 ]


The first descriptions of gallstones appear to have been in the  Renaissance , perhaps because of the low incidence of gallstones in earlier times owing to a diet with more cereals and vegetables and less meat. [ 37 ]  Anthonius Benevinius in 1506 was the first to draw a connection between symptoms and the presence of gallstones. [ 37 ]   Ludwig Georg Courvoisier , after examining a number of cases in 1890 that gave rise to the  eponymous   Courvoisier's law , stated that in an enlarged, nontender gallbladder, the cause of  jaundice  is unlikely to be gallstones. [ 35 ]


The first surgical removal of a gallstone (cholecystolithotomy) was in 1676 by physician Joenisius, who removed the stones from a spontaneously occurring  biliary fistula . [ 35 ]  Stough Hobbs in 1867 performed the first recorded  cholecystotomy , [ 37 ]  although such an operation was in fact described earlier by French surgeon  Jean Louis Petit  in the mid eighteenth century. [ 35 ]  German surgeon  Carl Langenbuch  performed the first cholecystectomy in 1882 for a sufferer of cholelithiasis. [ 36 ]  Before this, surgery had focused on creating a  fistula  for drainage of gallstones. [ 35 ]  Langenbuch reasoned that given several other species of mammal have no gallbladder, humans could survive without one. [ 35 ]


The debate whether surgical removal of the gallbladder or simply gallstones was preferred was settled in the 1920s, with the consensus that removal of the gallbladder was preferred. [ 36 ]  It was only in the mid and late parts of the twentieth century that medical imaging techniques such as use of  contrast medium  and  CT scans  were used to view the gallbladder. [ 35 ]  The first  laparoscopic  cholecystectomy performed by  Erich Mühe  of Germany in 1985, although French surgeons Phillipe Mouret and Francois Dubois are often credited for their operations in 1987 and 1988 respectively. [ 38 ]


To have "gall" is associated with bold, belligerent behaviour, whereas to have "bile" is associated with sourness. [ 39 ]


In the  Chinese medicine , the gallbladder ( 膽 ) is associated with the  Wuxing  element of wood, in excess its emotion is belligerence and in deficiency cowardice and judgement, in the Chinese language it is related to a myriad of  idioms , including using terms such as "a body completely [of] gall" ( 渾身是膽 ) to describe a forward person, and "single, alone gallbladder hero" ( 孤膽英雄 ) to describe a lone hero, or "they have a lot of gall to talk like that". [ 40 ]


In the  Zangfu  theory of  Chinese medicine  it is an extraordinary Fu or  yang  organ, as it holds bile. The gallbladder not only has a digestive role, but is seen as the seat of decision-making and judgement. [ 40 ]


Ganeden, Inc.  is a privately held United States  probiotic  ingredient manufacturer that sells its products to makers of foods and  dietary supplements . It is based in  Mayfield Heights, Ohio  and was founded in 1997 in  San Diego, California  by Sean Farmer. The company's name, Ganeden, was derived from the Hebrew " Gan Eden ", meaning  Garden of Eden . [ 1 ]  The company moved to Ohio in 2000. [ 1 ]


In 2011, Ganeden sold two of its probiotic brands, Sustenex and Digestive Advantage, to  Schiff Nutrition International . [ 2 ]


In 2017, the Irish-based  Kerry Group  acquired Ganeden for an undisclosed amount. [ 3 ]


Gastric glands  are  glands  in the lining of the  stomach  that play an essential role in the  process of digestion . Their secretions make up the  digestive gastric juice . The gastric glands open into  gastric pits  in the  mucosa . The gastric mucosa is covered in  surface mucous cells  that produce the  mucus  necessary to protect the stomach's  epithelial lining  from  gastric acid  secreted by  parietal cells  in the glands, and from  pepsin , a secreted  digestive enzyme . Surface mucous cells follow the indentations and partly line the gastric pits. Other mucus secreting cells are found in the necks of the glands. These are  mucous neck cells  that produce a different kind of mucus.


There are two types of gastric gland, the  exocrine   oxyntic gland , and the  endocrine   pyloric gland . The major type of gastric gland is the oxyntic gland that is present in the fundus and the body of the stomach making up about 80 per cent of the stomach area. These glands are often referred to simply as the  gastric glands .  The oxyntic gland contains the  parietal cells  that produce  hydrochloric acid  and  intrinsic factor , and  chief cells  that produce  pepsinogen  and  gastric lipase .


The pyloric gland is found in the  pyloric region , the remaining 20 per cent of the stomach. The pyloric glands are mainly in the  pyloric antrum . The pyloric gland secretes  gastrin  from its  G cells . Pyloric glands are similar in structure to the oxyntic glands but have hardly any parietal cells.


The gastric glands are glands in the lining of the stomach that play an essential role in the process of  digestion . All of the glands have mucus-secreting  foveolar cells  (also known as surface mucous cells) that line the stomach and partly line the  gastric pits , and mucus-secreting  mucous neck cells  in the necks of the gastric glands. [ 1 ]   Mucus  lines the entire stomach as  gastric mucosa  protecting the stomach lining from the effects of  hydrochloric acid  produced by the parietal cells and released from the oxyntic glands.


Gastric glands are mostly  exocrine glands [ 2 ]  and are all located beneath the gastric pits within the gastric mucosa. [ 3 ]  The gastric mucosa is pitted with innumerable gastric pits which each house 3-5 gastric glands. [ 4 ]  The cells of the exocrine glands (oxyntic glands) are mucous neck cells,  chief cells , and  parietal cells . [ 4 ]  Mucous neck cells produce mucus, parietal cells secrete  hydrochloric acid  and  intrinsic factor , chief cells secrete  pepsinogen  and  gastric lipase . [ 4 ]


The other type of gastric gland is the  pyloric gland  which is an  endocrine gland  that secretes the hormone  gastrin  produced by its  G cells .


The secretions of the different exocrine gastric gland cells produce a watery, acidic fluid into the stomach lumen called gastric juice. [ 5 ] [ 6 ]  Gastric juice contains water, hydrochloric acid, intrinsic factor, pepsinogen, and salts. Adults produce around two to three litres of gastric juice per day. [ 5 ]  The composition of the fluid varies according to the time of eating, and the rates of activity of the various cells. The cells are more active after eating. The composition of the gastric juice electrolytes is related to its rate of secretion: when secretion increases, the concentration of sodium decreases, and the concentration of hydrogen increases. There is always a higher level of potassium ions in the fluid than in the plasma. [ 5 ]


The glands are named for the region of the stomach that they occupy.


The  cardiac glands  are found in the  cardia  of the stomach which is the part nearest to the heart, enclosing the opening where the esophagus joins to the stomach. Cardiac glands primarily secrete mucus. [ 7 ]  They are fewer in number than the other gastric glands and are more shallowly positioned in the mucosa. There are two kinds - either  simple tubular  with short ducts  or   compound racemose  resembling the  duodenal   Brunner's glands . [ citation needed ]


The  fundic glands  (or  oxyntic glands ), are found in the  fundus  and body of the stomach. They are simple almost straight tubes, two or more of which open into a single duct.  Oxyntic  means acid-secreting and they secrete  hydrochloric acid  (HCl) and  intrinsic factor . [ 7 ]


The  pyloric glands  are located in the  antrum  of the  pylorus . They secrete  gastrin  produced by their  G cells . [ 8 ]


There are millions of  gastric pits  (also known as  foveolae )  in the gastric mucosa and their necessary narrowness determines the tubular form of the gastric gland. More than one tube allows for the accommodation of more than one cell type. The form of each gastric gland is similar; they are all described as having a neck region that is closest to the pit entrance, and basal regions on the lower parts of the tubes. [ 9 ]  The epithelium from the gastric mucosa travels into the pit and at the neck the epithelial cells change to short columnar granular cells. These cells almost fill the tube and the remaining lumen is continued as a very fine channel.


Cells found in the gastric glands include mucous neck cells,  chief cells ,  parietal cells ,  G cells , and  enterochromaffin-like cells  (ECLs). The first cells of all of the glands are mucus-secreting  foveolar cells that line the gastric pits. The mucus produced here is less acidic than that produced by the mucous neck cells.


Fundic glands found in the fundus and also in the body have another two cell types–gastric  chief cells  and  parietal cells  (oxyntic cells).


Fundic gland polyposis  is a medical syndrome where the  fundus  and the body of the  stomach  develop many  fundic gland   polyps .


Pernicious anemia  is caused when damaged parietal cells fail to produce the intrinsic factor necessary for the absorption of vitamin B12. This is the most common cause of  vitamin B12 deficiency .


List of distinct cell types in the adult human body


This article incorporates text in the  public domain  from the 20th edition of   Gray's Anatomy   (1918)


A  gastric shield  is an organ in the digestive tract of  bivalves ,  tusk shells , and some  gastropods  against which a  crystalline style  typically rotates, in an action resembling that of a  mortar and pestle . The gastric shield is permeated by microcanals which transmit digestive enzymes from the stomach, and serves to protect the cells of the stomach lining from the abrasive effects of the style. [ 1 ]


Gastrin  is a  peptide hormone  that stimulates secretion of  gastric acid  (HCl) by the  parietal cells  of the  stomach  and aids in gastric motility. It is released by  G cells  in the  pyloric antrum  of the stomach,  duodenum , and the  pancreas .


Gastrin binds to  cholecystokinin B receptors  to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K + /H +  ATPase pumps into the apical membrane of parietal cells (which in turn increases H +  release into the stomach cavity). Its release is stimulated by  peptides  in the  lumen  of the stomach.


In humans, the  GAS  gene is located on the long arm of the  seventeenth chromosome  (17q21). [ 5 ]


Gastrin is a linear  peptide hormone  produced by  G cells  of the duodenum and in the  pyloric antrum  of the  stomach . It is secreted into the bloodstream. The encoded polypeptide is preprogastrin, which is cleaved by enzymes in  posttranslational modification  to produce progastrin (an intermediate, inactive precursor) and then gastrin in various forms, primarily the following three:


Also,  pentagastrin  is an artificially synthesized, five amino acid sequence identical to the last five amino acid sequence at the  C-terminus  end of gastrin.
The numbers refer to the  amino acid  count.


Gastrin is released in response to certain stimuli.  These include:


Gastrin release is inhibited by: [ 8 ] [ 9 ]


The presence of gastrin stimulates  parietal cells  of the stomach to  secrete   hydrochloric acid  (HCl)/gastric acid.  This is done both directly on the parietal cell and indirectly via binding onto  CCK2/gastrin receptors  on  ECL cells  in the stomach, which respond by releasing  histamine , which in turn acts in a paracrine manner on parietal cells stimulating them to secrete  H+ ions . This is the major stimulus for acid secretion by parietal cells. [ 10 ]


Along with the above-mentioned function, gastrin has been shown to have additional functions as well:


Factors influencing secretion of gastrin can be divided into 2 categories: [ 16 ]


In the  Zollinger–Ellison syndrome , gastrin is produced at excessive levels, often by a  gastrinoma  gastrin-producing tumor, mostly benign of the  duodenum  or the  pancreas . To investigate for hypergastrinemia high blood levels of gastrin, a " pentagastrin  test" can be performed. [ 17 ]


In autoimmune  gastritis , the immune system attacks the  parietal cells  leading to  hypochlorhydria  low stomach acid secretion.  This results in an elevated gastrin level in an attempt to compensate for increased pH in the stomach.  Eventually, all the parietal cells are lost and  achlorhydria  results leading to a loss of  negative feedback  on gastrin secretion. Plasma gastrin concentration is elevated in virtually all individuals with  mucolipidosis type IV  (mean 1507 pg/mL; range 400-4100 pg/mL) (normal 0-200 pg/mL) secondary to a constitutive achlorhydria. This finding facilitates the diagnosis of patients with this neurogenetic disorder. [ 18 ]  Additionally, elevated gastrin levels may be present in chronic gastritis resulting from  H. pylori  infection. [ 19 ]


Its existence was first suggested in 1905 by the British physiologist John Sydney Edkins, [ 20 ] [ 21 ]  and gastrins were isolated in 1964 by  Hilda Tracy  and  Roderic Alfred Gregory  at the  University of Liverpool . [ 22 ]  In 1964 the structure of gastrin was determined. [ 23 ]


The  gastrointestinal tract  ( GI tract ,  digestive tract ,  alimentary canal ) is the tract or passageway of the  digestive system  that leads from the  mouth  to the  anus . The GI tract contains all the major  organs  of the digestive system, in humans and other animals, including the  esophagus ,  stomach , and  intestines . Food taken in through the mouth is  digested  to extract  nutrients  and absorb  energy , and the waste expelled at the anus as  feces .  Gastrointestinal  is an adjective meaning of or pertaining to the stomach and intestines.


Most animals  have a "through-gut" or complete digestive tract. Exceptions are more primitive ones:  sponges  have small pores ( ostia ) throughout their body for digestion and a larger dorsal pore ( osculum ) for excretion,  comb jellies  have both a ventral mouth and dorsal anal pores, while  cnidarians  and  acoels  have a single pore for both digestion and excretion. [ 1 ] [ 2 ]


The human gastrointestinal tract consists of the  esophagus ,  stomach, and intestines, and is divided into the upper and lower gastrointestinal tracts. [ 3 ]  The GI tract includes all structures between the  mouth  and the  anus , [ 4 ]  forming a continuous passageway that includes the main organs of digestion, namely, the  stomach ,  small intestine , and  large intestine . The complete  human digestive system  is made up of the gastrointestinal tract plus the accessory organs of digestion (the  tongue ,  salivary glands ,  pancreas ,  liver  and  gallbladder ). [ 5 ]  The tract may also be divided into  foregut ,  midgut , and  hindgut , reflecting the  embryological  origin of each segment. The whole human GI tract is about nine meters (30 feet) long at  autopsy . It is considerably shorter in the living body because the intestines, which are tubes of  smooth muscle tissue , maintain constant  muscle tone  in a halfway-tense state but can relax in spots to allow for local distention and  peristalsis . [ 6 ] [ 7 ]


The gastrointestinal tract contains the  gut microbiota , with some 1,000 different  strains  of  bacteria  having diverse roles in the maintenance of  immune health  and  metabolism , and many other  microorganisms . [ 8 ] [ 9 ] [ 10 ]  Cells of the GI tract release  hormones  to help regulate the digestive process. These  digestive hormones , including  gastrin ,  secretin ,  cholecystokinin , and  ghrelin , are mediated through either  intracrine  or  autocrine  mechanisms, indicating that the cells releasing these hormones are conserved structures throughout  evolution . [ 11 ]


The structure and function can be described both as  gross anatomy  and as  microscopic anatomy  or  histology . The tract itself is divided into upper and lower tracts, and the intestines  small  and  large  parts. [ 12 ]


The upper gastrointestinal tract consists of the  mouth ,  pharynx ,  esophagus ,  stomach , and  duodenum . [ 13 ]
The exact demarcation between the upper and lower tracts is the  suspensory muscle of the duodenum . This differentiates the embryonic borders between the foregut and midgut, and is also the division commonly used by clinicians to describe  gastrointestinal bleeding  as being of either "upper" or "lower" origin. Upon  dissection , the duodenum may appear to be a unified organ, but it is divided into four segments based on function, location, and internal anatomy. The four segments of the duodenum are as follows (starting at the stomach, and moving toward the jejunum):  bulb , descending, horizontal, and ascending. The suspensory muscle attaches the superior border of the ascending duodenum to the  jejunum .


The suspensory muscle is an important anatomical landmark that shows the formal division between the duodenum and the jejunum, the first and second parts of the small intestine, respectively. [ 14 ]  This is a thin muscle which is derived from the  embryonic   mesoderm .


The lower gastrointestinal tract includes most of the  small intestine  and all of the  large intestine . [ 15 ]  In  human anatomy , the  intestine  ( bowel  or  gut ; Greek:  éntera ) is the segment of the gastrointestinal tract extending from the pyloric sphincter of the  stomach  to the  anus  and as in other mammals, consists of two segments: the  small intestine  and the  large intestine . In humans, the small intestine is further subdivided into the  duodenum ,  jejunum , and  ileum  while the large intestine is subdivided into the  cecum , ascending, transverse, descending, and sigmoid  colon ,  rectum , and  anal canal . [ 16 ] [ 17 ]


The  small intestine  begins at the  duodenum  and is a tubular structure, usually between 6 and 7 m long. [ 18 ]  Its  mucosal  area in an adult human is about 30 m 2  (320 sq ft). [ 19 ]  The combination of the  circular folds , the villi, and the microvilli increases the absorptive area of the mucosa about 600-fold, making a total area of about 250 m 2  (2,700 sq ft) for the entire small intestine. [ 20 ]  Its main function is to absorb the products of digestion (including carbohydrates, proteins, lipids, and vitamins) into the bloodstream. There are three major divisions:


The  large intestine , also called the colon, forms an arch starting at the  cecum  and ending at the  rectum  and  anal canal . It also includes the  appendix , which is attached to the  cecum . Its length is about 1.5 m, and the area of the mucosa in an adult human is about 2 m 2  (22 sq ft). [ 19 ]  Its main function is to absorb water and salts. The colon is further divided into:


The gut is an  endoderm -derived structure. At approximately the sixteenth day of human development, the  embryo  begins to fold  ventrally  (with the embryo's ventral surface becoming  concave ) in two directions: the sides of the embryo fold in on each other and the head and tail fold toward one another. The result is that a piece of the  yolk sac , an  endoderm -lined structure in contact with the  ventral  aspect of the embryo, begins to be pinched off to become the primitive gut. The yolk sac remains connected to the gut tube via the  vitelline duct . Usually, this structure regresses during development; in cases where it does not, it is known as  Meckel's diverticulum .


During  fetal  life, the primitive gut is gradually patterned into three segments:  foregut ,  midgut , and  hindgut . Although these terms are often used in reference to segments of the primitive gut, they are also used regularly to describe regions of the definitive gut as well.


Each segment of the gut is further specified and gives rise to specific gut and gut-related structures in later development. Components derived from the gut proper, including the  stomach  and  colon , develop as swellings or dilatations in the cells of the primitive gut. In contrast, gut-related derivatives — that is, those structures that derive from the primitive gut but are not part of the gut proper, in general, develop as out-pouchings of the primitive gut. The blood vessels supplying these structures remain constant throughout development. [ 21 ]


The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. [ 22 ]  The GI tract can be divided into four concentric layers in the following order:


The mucosa is the innermost layer of the gastrointestinal tract. The mucosa surrounds the  lumen , or open space within the tube. This layer comes in direct contact with digested food ( chyme ). The mucosa is made up of:


The mucosae are highly specialized in each organ of the gastrointestinal tract to deal with the different conditions. The most variation is seen in the epithelium.


The submucosa consists of a dense irregular layer of connective tissue with large blood vessels, lymphatics, and nerves branching into the mucosa and  muscularis externa . It contains the  submucosal plexus , an  enteric nervous plexus , situated on the inner surface of the  muscularis externa .


The  muscular layer  consists of an inner circular layer and a  longitudinal  outer layer. The circular layer prevents food from traveling backward and the longitudinal layer shortens the tract. The layers are not truly longitudinal or circular, rather the layers of muscle are helical with different pitches. The inner circular is helical with a steep pitch and the outer longitudinal is helical with a much shallower pitch. [ 23 ]  Whilst the muscularis externa is similar throughout the entire gastrointestinal tract, an exception is the stomach which has an additional inner oblique muscular layer to aid with grinding and mixing of food. The muscularis externa of the stomach is composed of the inner oblique layer, middle circular layer, and the outer longitudinal layer.


Between the circular and longitudinal muscle layers is the  myenteric plexus . This controls peristalsis. Activity is initiated by the pacemaker cells, (myenteric  interstitial cells of Cajal ). The gut has intrinsic peristaltic activity ( basal electrical rhythm ) due to its self-contained enteric nervous system. The rate can be modulated by the rest of the  autonomic nervous system . [ 23 ]


The coordinated contractions of these layers is called  peristalsis  and propels the food through the tract. Food in the GI tract is called a bolus (ball of food) from the mouth down to the stomach. After the stomach, the food is partially digested and semi-liquid, and is referred to as  chyme . In the large intestine, the remaining semi-solid substance is referred to as  faeces . [ 23 ]


The outermost layer of the gastrointestinal tract consists of several layers of  connective tissue .


Intraperitoneal  parts of the GI tract are covered with  serosa . These include most of the  stomach , first part of the  duodenum , all of the  small intestine ,  caecum  and  appendix ,  transverse colon ,  sigmoid colon  and  rectum . In these sections of the gut, there is a clear boundary between the gut and the surrounding tissue. These parts of the tract have a  mesentery .


Retroperitoneal  parts are covered with  adventitia . They blend into the surrounding tissue and are fixed in position. For example, the retroperitoneal section of the duodenum usually passes through the  transpyloric plane . These include the  esophagus ,  pylorus  of the stomach, distal  duodenum ,  ascending colon ,  descending colon  and  anal canal . In addition, the  oral cavity  has adventitia.


Approximately 20,000 protein coding genes are expressed in human cells and 75% of these genes are expressed in at least one of the different parts of the digestive organ system. [ 24 ] [ 25 ]  Over 600 of these genes are more specifically expressed in one or more parts of the GI tract and the corresponding proteins have functions related to digestion of food and uptake of nutrients. Examples of specific proteins with such functions are  pepsinogen PGC  and the  lipase LIPF , expressed in  chief cells , and gastric  ATPase ATP4A  and  gastric intrinsic factor GIF , expressed in  parietal cells  of the stomach mucosa. Specific proteins expressed in the stomach and duodenum involved in defence include  mucin  proteins, such as  mucin 6  and  intelectin-1 . [ 26 ]


The time taken for food to transit through the gastrointestinal tract varies on multiple factors, including age, ethnicity, and gender. [ 27 ] [ 28 ]  Several techniques have been used to measure transit time, including radiography following a  barium -labeled meal, breath  hydrogen  analysis,  scintigraphic  analysis following a  radiolabeled  meal, [ 29 ]  and simple ingestion and spotting of  corn kernels . [ 30 ]  It takes 2.5 to 3 hours for 50% of the contents to leave the stomach. [ medical citation needed ]  The rate of digestion is also dependent of the material being digested, as food composition from the same meal may leave the stomach at different rates. [ 31 ]  Total emptying of the stomach takes around 4–5 hours, and transit through the colon takes 30 to 50 hours. [ 29 ] [ 32 ] [ 33 ]


The gastrointestinal tract forms an important part of the  immune system . [ 34 ]


The surface area of the digestive tract is estimated to be about 32 square meters, or about half a badminton court. [ 19 ]  With such a large exposure (more than three times larger than the  exposed surface of the skin ), these immune components function to prevent pathogens from entering the blood and lymph circulatory systems. [ 35 ]  Fundamental components of this protection are provided by the  intestinal mucosal barrier , which is composed of physical, biochemical, and immune elements elaborated by the intestinal mucosa. [ 36 ]  Microorganisms also are kept at bay by an extensive immune system comprising the  gut-associated lymphoid tissue  (GALT)


There are additional factors contributing to protection from pathogen invasion. For example, low  pH  (ranging from 1 to 4) of the stomach is fatal for many  microorganisms  that enter it. [ 37 ]  Similarly,  mucus  (containing  IgA   antibodies ) neutralizes many pathogenic microorganisms. [ 38 ]  Other factors in the GI tract contribution to immune function include  enzymes  secreted in the  saliva  and  bile .


Beneficial bacteria also can contribute to the homeostasis of the gastrointestinal immune system. For example,  Clostridia , one of the most predominant bacterial groups in the GI tract, play an important role in influencing the dynamics of the gut's immune system. [ 39 ]  It has been demonstrated that the intake of a high fiber diet could be responsible for the induction of  T-regulatory cells  (Tregs). This is due to the production of  short-chain fatty acids  during the fermentation of plant-derived nutrients  such as  butyrate  and  propionate .  Basically, the butyrate induces the differentiation of Treg cells by enhancing  histone H3   acetylation  in the promoter and conserved non-coding sequence regions of the  FOXP3  locus, thus regulating the  T cells , resulting in the reduction of the inflammatory response and allergies.


The large intestine contains multiple types of  bacteria  that can break down molecules the human body cannot process alone, [ 40 ]  demonstrating a  symbiotic  relationship. These bacteria are responsible for gas production at  host–pathogen interface , which is released as  flatulence . Intestinal bacteria can also participate in biosynthesis reactions. For example, certain strains in the large intestine produce vitamin B 12 ; [ 41 ]  an essential compound in humans for things like DNA synthesis and red blood cell production. [ 42 ]  However, the primary function of the large intestine is water absorption from digested material (regulated by the  hypothalamus ) and the reabsorption of  sodium  and nutrients. [ 43 ]


Beneficial  intestinal bacteria  compete with potentially harmful  bacteria  for space and "food", as the intestinal tract has limited resources. A ratio of 80–85% beneficial to 15–20% potentially harmful bacteria is proposed for maintaining  homeostasis . [ citation needed ]  An imbalanced ratio results in  dysbiosis .


Enzymes  such as  CYP3A4 , along with the  antiporter  activities, are also instrumental in the intestine's role of  drug metabolism  in the detoxification of  antigens  and  xenobiotics . [ 44 ]


In most  vertebrates , including  amphibians ,  birds ,  reptiles ,  egg-laying mammals , and some  fish , the gastrointestinal tract ends in a  cloaca  and not an  anus . In the cloaca, the  urinary system  is fused with the genito-anal pore.  Therians  (all mammals that do not lay eggs, including humans) possess separate anal and uro-genital openings. The females of the subgroup  Placentalia  have even separate urinary and genital openings.


During  early development , the asymmetric position of the bowels and inner organs is initiated (see also  axial twist theory ).


Ruminants  show many specializations for digesting and  fermenting  tough plant material, consisting of  additional stomach compartments .


Many birds and other animals have a specialised stomach in the digestive tract called a  gizzard  used for grinding up food.


Another feature found in a range of animals is the  crop . In birds this is found as a pouch alongside the esophagus.


In 2020, the oldest known fossil digestive tract, of an extinct wormlike organism in the  Cloudinidae  was discovered; it lived during the late  Ediacaran   period  about 550 million years ago. [ 45 ] [ 46 ]


A through-gut (one with both mouth and anus) is thought to have evolved within the  nephrozoan  clade of  Bilateria , after their ancestral ventral orifice (single, as in  cnidarians  and  acoels ; re-evolved in nephrozoans like  flatworms ) stretched antero-posteriorly, before the middle part of the stretch would get narrower and closed fully, leaving an anterior orifice (mouth) and a posterior orifice (anus plus  genital opening ). A stretched gut without the middle part closed is present in another branch of bilaterians, the extinct  proarticulates . This and the  amphistomic  development (when both mouth and anus develop from the gut stretch in the embryo) present in some nephrozoans (e.g.  roundworms ) are considered to support this hypothesis. [ 47 ] [ 48 ]


There are many diseases and conditions that can affect the gastrointestinal system, including  infections ,  inflammation  and  cancer .


Various  pathogens , such as  bacteria  that cause  foodborne illnesses , can induce  gastroenteritis  which results from  inflammation  of the stomach and small intestine.  Antibiotics  to treat such bacterial infections can decrease the  microbiome  diversity of the gastrointestinal tract, and further enable inflammatory mediators. [ 49 ]  Gastroenteritis is the most common disease of the GI tract.


Diverticular disease  is a condition that is very common in older people in industrialized countries.  It usually affects the large intestine but has been known to affect the small intestine as well.   Diverticulosis  occurs when pouches form on the intestinal wall.  Once the pouches become inflamed it is known as  diverticulitis .


Inflammatory bowel disease  is an inflammatory condition affecting the bowel walls, and includes the subtypes  Crohn's disease  and  ulcerative colitis . While Crohn's can affect the entire gastrointestinal tract, ulcerative colitis is limited to the large intestine. Crohn's disease is widely regarded as an  autoimmune disease . Although ulcerative colitis is often treated as though it were an autoimmune disease, there is no consensus that it actually is such.


Functional gastrointestinal disorders  the most common of which is  irritable bowel syndrome . Functional constipation and  chronic functional abdominal pain  are other functional disorders of the intestine that have physiological causes but do not have identifiable structural, chemical, or infectious pathologies.


Several symptoms can indicate problems with the gastrointestinal tract, including:


Gastrointestinal surgery  can often be performed in the outpatient setting.  In the United States in 2012, operations on the digestive system accounted for 3 of the 25 most common ambulatory surgery procedures and constituted 9.1 percent of all outpatient ambulatory surgeries. [ 50 ]


Various methods of imaging the gastrointestinal tract include the  upper  and  lower gastrointestinal series :


Intestines from animals other than humans are used in a number of ways.  From each species of  livestock  that is a source of  milk , a corresponding  rennet  is obtained from the intestines of milk-fed  calves .   Pig  and  calf  intestines are eaten, and pig intestines are used as  sausage  casings. Calf intestines supply  calf-intestinal alkaline phosphatase  (CIP), and are used to make  goldbeater's skin .
Other uses are:


The  gastrointestinal hormones  (or  gut hormones ) constitute a group of  hormones  secreted by  enteroendocrine cells  in the  stomach ,  pancreas , and  small intestine  that control various functions of the digestive organs. Later studies showed that most of the gut peptides, such as  secretin ,  cholecystokinin  or  substance P , were found to play a role of  neurotransmitters  and  neuromodulators  in the central and peripheral nervous systems. [ 1 ]


Enteroendocrine cells do not form glands but are spread throughout the digestive tract. They exert their autocrine and paracrine actions that integrate gastrointestinal function. [ 2 ]


The gastrointestinal hormones [ 3 ]  can be divided into three main groups based upon their  chemical structure .


Ghrelin  is a peptide hormone released from the stomach and liver and is often referred to as the "hunger hormone" since high levels of it are found in individuals that are fasting. Ghrelin agonistic treatments can be used to treat illnesses such as anorexia and loss of appetites in cancer patients. Ghrelin treatments for obesity are still under intense scrutiny and no conclusive evidence has been reached. This hormone stimulates growth hormone release.
 Amylin  controls glucose homeostasis and gastric motility


Glucose-dependent insulinotropic polypeptide  possesses an acute influence on food intake through its effects on adipocytes


Oxyntomodulin  plays a role in controlling acid secretion and satiation


The  gastrointestinal wall  of the  gastrointestinal tract  is made up of four layers of specialised tissue. From the inner cavity of the gut (the  lumen ) outwards, these are the  mucosa , the  submucosa , the  muscular layer  and the  serosa  or  adventitia .


The mucosa is the innermost layer of the gastrointestinal tract. It surrounds the lumen of the tract and comes into direct contact with digested food ( chyme ). The mucosa itself is made up of three layers: [ 1 ]  the  epithelium , where most digestive, absorptive and secretory processes occur; the  lamina propria , a layer of  connective tissue , and the  muscularis mucosae , a thin layer of  smooth muscle .


The submucosa contains nerves including the  submucous plexus  (also called Meissner's plexus), blood vessels and elastic fibres with collagen, that stretches with increased capacity but maintains the shape of the intestine.


The muscular layer surrounds the submucosa. It comprises layers of  smooth muscle  in longitudinal and circular orientation that also helps with continued bowel movements ( peristalsis ) and the movement of digested material out of and along the gut. In between the two layers of muscle lies the  myenteric plexus  (also called plexus).


The  serosa / adventitia  are the final layers. These are made up of loose  connective tissue  and coated in  mucus  so as to prevent any friction damage from the intestine rubbing against other tissue. The serosa is present if the tissue is  within the peritoneum , and the adventitia if the tissue is  retroperitoneal .


When viewed under the  microscope , the gastrointestinal wall has a consistent general form, but with certain parts differing along its course.


The mucosa is the innermost layer of the gastrointestinal tract. It surrounds the cavity ( lumen ) of the tract and comes into direct contact with digested food ( chyme ). The mucosa is made up of three layers: [ 1 ]


The epithelium, the most exposed part of the mucosa, is a  glandular epithelium  with many  goblet cells . Goblet cells secrete  mucus , which lubricates the passage of food along and protects the intestinal wall from digestive enzymes. In the small intestine,  villi  are folds of the mucosa that increase the surface area of the intestine. The villi contain a  lacteal , a vessel connected to the  lymph system  that aids in the removal of  lipids  and tissue fluids.  Microvilli  are present on the epithelium of a villus and further increase the surface area over which absorption can take place. Numerous  intestinal glands  as pocket-like invaginations are present in the underlying tissue. In the large intestines, villi are absent and a flat surface with thousands of glands is observed. Underlying the epithelium is the lamina propria, which contains myofibroblasts, blood vessels, nerves, and several different immune cells, and the  muscularis mucosa  which is a layer of smooth muscle that aids in the action of continued  peristalsis  and  catastalsis  along the gut.


The epithelial lining of the mucosa, differs along the gastrointestinal tract. [ 1 ]  The epithelium is described as stratified if it consists of multiple layers of cells, and simple if it is made up of one layer of cells. Terms used to describe the shape of the cells in it - columnar if column-shaped, and squamous if flat.


Transition between the different types of epithelium occurs at  the junction between the oesophagus and stomach ; between the  stomach and duodenum , between the  ileum and caecum , and at the  pectinate line  of the  anus . [ 1 ]


The submucosa consists of a dense and irregular layer of connective tissue with  blood vessels , lymphatics, and nerves branching into the mucosa and muscular layer. It contains the  submucous plexus , and  enteric nervous plexus , situated on the inner surface of the muscular layer. [ 1 ]


The  muscular layer  consists of two layers of muscle, the inner and outer layer. [ 3 ]  The muscle of the inner layer is arranged in circular rings around the tract, whereas the muscle of the outer layer is arranged longitudinally. The stomach has an extra layer, an inner oblique muscular layer. [ 1 ]  Between the two muscle layers is the  myenteric plexus  (Auerbach's plexus). This controls peristalsis. Activity is initiated by the pacemaker cells ( interstitial cells of Cajal ). The gut has intrinsic peristaltic activity ( basal electrical rhythm ) due to its self-contained enteric nervous system. The rate can, of course, be modulated by the rest of the  autonomic nervous system .


The layers are not truly longitudinal or circular, rather the layers of muscle are helical with different pitches. The inner circular is helical with a steep pitch and the outer longitudinal is helical with a much shallower pitch.


The coordinated contractions of these layers is called  peristalsis  and propels the food through the tract. Food in the GI tract is called a  bolus  (ball of food) from the mouth down to the stomach. After the stomach, the food is partially digested and semi-liquid, and is referred to as  chyme . In the large intestine the remaining semi-solid substance is referred to as faeces. The circular muscle layer prevents food from travelling backward and the longitudinal layer shortens the tract.


The thickness of the muscular layer varies in each part of the tract:


The outermost layer of the gastrointestinal wall consists of several layers of  connective tissue  and is either of  serosa  (below the diaphragm) or  adventitia  above the diaphragm. [ 4 ] [ 1 ] [ 5 ]


Regions of the gastrointestinal tract within the peritoneum (called  Intraperitoneal ) are covered with  serosa . This structure consists of connective tissue covered by a simple squamous epithelium, called the mesothelium, which reduces frictional forces during digestive movements. The intraperitoneal regions include most of the  stomach , first part of the  duodenum , all of the  small intestine ,  caecum  and  appendix ,  transverse colon ,  sigmoid colon  and  rectum . In these sections of the gut there is clear boundary between the gut and the surrounding tissue. These parts of the tract have a  mesentery .


Regions of the gastrointestinal tract behind the peritoneum (called  retroperitoneal ) are covered with  adventitia . They blend into the surrounding tissue and are fixed in position (for example, the retroperitoneal section of the duodenum usually passes through the  transpyloric plane ). The retroperitoneal regions include the  oral cavity ,  esophagus ,  pylorus  of the stomach, distal  duodenum ,  ascending colon ,  descending colon  and  anal canal . [ citation needed ]


The gastrointestinal wall can be affected in a number of conditions.


An  ulcer  is something that's eroded through the epithelium of the wall. Ulcers that affect the tract include  peptic ulcers  and  perforated ulcer  is one that has eroded completely through the layers.


The gastrointestinal wall is inflamed in a number of conditions. This is called  esophagitis ,  gastritis ,  duodenitis ,  ileitis , and  colitis  depending on the parts affected. It can be due to infections or other conditions, including  coeliac disease , and  inflammatory bowel disease  affects the layers of the gastrointestinal tract in different ways.  Ulcerative colitis  involves the colonic mucosa.  Crohn's disease  may produce inflammation in all layers in any part of the gastrointestinal tract and so can result in transmural  fistulae .


Invasion of tumours through the layers of the gastrointestinal wall is used in  staging  of tumour spread. This affects treatment and prognosis.


The normal thickness of the small intestinal wall is 3–5 mm, [ 6 ]  and 1–5 mm in the large intestine. [ 7 ]  Focal, irregular and asymmetrical gastrointestinal wall thickening suggests a malignancy. [ 7 ]  Segmental or diffuse gastrointestinal wall thickening is most often due to ischemic, inflammatory or infectious disease. [ 7 ]


A  gastrolith , also called a  stomach stone  or  gizzard stone , is a  rock  held inside a  gastrointestinal tract . Gastroliths in some species are retained in the muscular  gizzard  and used to grind food in animals lacking suitable grinding  teeth . In other species the rocks are ingested and pass through the digestive system and are frequently replaced. The  grain size  depends upon the size of the animal and the gastrolith's role in digestion. Other species use gastroliths as  ballast . [ 1 ]  Particles ranging in size from  sand  to  cobble  have been documented.


Gastrolith comes from the  Greek  γαστήρ ( gastēr ), meaning "stomach", and λίθος ( lithos ), meaning "stone".


Among living  vertebrates , gastroliths are common among  crocodiles ,  alligators ,  herbivorous   birds ,  seals  and  sea lions . Domestic  fowl  require access to  grit .  Stones swallowed by  ostriches  can exceed a length of 10 centimetres (3.9 in) [ citation needed ] . Apparent microgastroliths have also been found in frog tadpoles. [ 2 ]  Ingestion of silt and gravel by tadpoles of various  anuran  (frog) species has been observed to improve buoyancy control. [ 1 ]


Some  extinct  animals such as  sauropod   dinosaurs  appear to have used stones to grind tough plant matter. A rare example of this is the Early Cretaceous theropod  Caudipteryx  zoui  from northeastern China, which was discovered with a series of small stones, interpreted as gastroliths, in the area of its skeleton that would have corresponded with its abdominal region. Aquatic animals, such as  plesiosaurs , may have used them as ballast, to help balance themselves or to decrease their buoyancy, as  crocodiles  do. [ 3 ]  Research indicates that the presence of gastroliths in  elasmosaurid plesiosaurs  differs from that of the  short-necked plesiosaurs .  While some  fossil  gastroliths are rounded and polished, many stones in living birds are not polished at all. Gastroliths associated with  dinosaur  fossils can weigh several kilograms.