The international Synthetic Yeast Genome Project (Sc2.0 or  Saccharomyces cerevisiae version 2.0 ) aims to build an entirely designer, customizable, synthetic  S. cerevisiae  genome from scratch that is more stable than the wild type. In the synthetic genome all  transposons ,  repetitive elements  and many  introns  are removed, all UAG  stop codons  are replaced with UAA, and  transfer RNA  genes are moved to a novel  neochromosome . As of March 2017 [update] , 6 of the 16 chromosomes have been synthesized and tested. No significant fitness defects have been found. [ 63 ]


All 16 chromosomes can be fused into one single chromosome by successive end-to-end chromosome fusions and  centromere  deletions. The single-chromosome and wild-type yeast cells have nearly identical  transcriptomes  and similar phenotypes. The giant single chromosome can support cell life, although this strain shows reduced growth across environments, competitiveness,  gamete  production and viability. [ 64 ]


Among other microorganisms, a sample of living  S. cerevisiae  was included in the  Living Interplanetary Flight Experiment , which would have completed a three-year interplanetary round-trip in a small capsule aboard the Russian  Fobos-Grunt  spacecraft, launched in late 2011. [ 65 ] [ 66 ]  The goal was to test whether selected  organisms  could survive a few years in  deep space  by flying them through interplanetary space. The experiment would have tested one aspect of  transpermia , the hypothesis that  life  could survive space travel, if protected inside rocks blasted by impact off one planet to land on another. [ 65 ] [ 66 ] [ 67 ]  Fobos-Grunt's mission ended unsuccessfully, however, when it failed to escape low Earth orbit. The spacecraft along with its instruments fell into the Pacific Ocean in an uncontrolled re-entry on January 15, 2012. The next planned exposure mission in deep space using  S. cerevisiae  is  BioSentinel . (see:  List of microorganisms tested in outer space )


Saccharomyces cerevisiae  is used in brewing beer, when it is sometimes called a  top-fermenting  or top-cropping yeast. It is so called because during the fermentation process its hydrophobic surface causes the  flocs  to adhere to CO 2  and rise to the top of the fermentation vessel. Top-fermenting yeasts are fermented at higher temperatures than the lager yeast  Saccharomyces pastorianus , and the resulting beers have a different flavor from the same beverage fermented with a lager yeast. "Fruity esters" may be formed if the yeast undergoes temperatures near 21 °C (70 °F), or if the fermentation temperature of the beverage fluctuates during the process. Lager yeast normally ferments at a temperature of approximately 5 °C (41 °F) or 278 k, where  Saccharomyces cerevisiae  becomes dormant. A variant yeast known as  Saccharomyces cerevisiae  var.  diastaticus  is a beer spoiler which can cause secondary fermentations in packaged products. [ 68 ]


In May 2013, the  Oregon  legislature made  S. cerevisiae  the  official state microbe  in recognition of the impact craft beer brewing has had on the state economy and the state's identity. [ 69 ]


S. cerevisiae  is used in baking; the carbon dioxide generated by the fermentation is used as a  leavening agent  in bread and other baked goods. Historically, this use was closely linked to the brewing industry's use of yeast, as bakers took or bought the  barm  or yeast-filled foam from brewing  ale  from the brewers (producing the  barm cake ); today, brewing and baking yeast strains are somewhat different. [ citation needed ]


Saccharomyces cerevisiae  is the main source of nutritional yeast, which is sold commercially as a food product. It is popular with vegans and vegetarians as an ingredient in cheese substitutes, or as a general food additive as a source of vitamins and minerals, especially amino acids and B-complex vitamins.


Owing to the high cost of commercial CO 2  cylinder systems,  CO 2  injection  by yeast is one of the most popular  DIY  approaches followed by aquaculturists for providing CO 2  to underwater aquatic plants. The yeast culture is, in general, maintained in plastic bottles, and typical systems provide one bubble every 3–7 seconds. Various approaches have been devised to allow proper absorption of the gas into the water. [ 70 ]


Saccharomyces cerevisiae  is used as a  probiotic  in humans and animals. The strain  Saccharomyces cerevisiae var. boulardii  is industrially manufactured and used clinically as a medication.


Several clinical and experimental studies have shown that  S. cerevisiae var. boulardii  is, to lesser or greater extent, useful for prevention or treatment of several gastrointestinal diseases. [ 71 ]  Moderate quality evidence has shown  S. cerevisiae var. boulardii  reduces risk of antibiotic-associated diarrhoea both in adults [ 72 ] [ 71 ] [ 73 ]  and in children [ 72 ] [ 71 ]  and to reduce risk of adverse effects of  Helicobacter pylori  eradication therapy. [ 74 ] [ 71 ] [ 73 ]  There is some evidence to support efficacy of  S. cerevisiae var. boulardii  in prevention (but not treatment) of traveler's diarrhoea [ 71 ] [ 73 ]  and, at least as an adjunct medication, in treatment of acute diarrhoea in adults and children and of persistent diarrhoea in children. [ 71 ]  It may also reduce symptoms of  allergic rhinitis. [ 75 ]


Administration of  S. cerevisiae var. boulardii  is considered generally safe. [ 73 ]  In clinical trials it was well tolerated by patients, and adverse effects rate was similar to that in control groups (i. e. groups with  placebo  or no treatment). [ 72 ]  No case of  S. cerevisiae var. boulardii  fungemia has been reported during clinical trials. [ 73 ]


In clinical practice, however, cases of  fungemia , caused by  S. cerevisiae var. boulardii  are reported. [ 73 ] [ 71 ]  Patients with  compromised immunity  or those with central vascular catheters are at special risk. Some researchers have recommended avoiding use of  S. cerevisiae var. boulardii  as treatment in such patients. [ 73 ]  Others suggest only that caution must be exercised with its use in risk group patients. [ 71 ]


Saccharomyces cerevisiae  is proven to be an  opportunistic human pathogen , though of relatively low  virulence . [ 76 ]  Despite widespread use of this microorganism at home and in industry, contact with it very rarely leads to infection. [ 77 ]
 Saccharomyces cerevisiae  was found in the skin, oral cavity, oropharinx, duodenal mucosa, digestive tract, and vagina of healthy humans [ 78 ]  (one review found it to be reported for 6% of samples from human intestine [ 79 ] ). Some specialists consider  S. cerevisiae  to be a part of the  normal microbiota  of the gastrointestinal tract, the respiratory tract, and the vagina of humans, [ 80 ]  while others believe that the species cannot be called a true  commensal  because it originates in food. [ 79 ] [ 81 ]  Presence of  S. cerevisiae  in the human digestive system may be rather transient; [ 81 ]  for example, experiments show that in the case of oral administration to healthy individuals it is eliminated from the intestine within 5 days after the end of administration. [ 79 ] [ 77 ]


Under certain circumstances, such as  degraded immunity ,  Saccharomyces cerevisiae  can cause infection in humans. [ 77 ] [ 76 ]  Studies show that it causes 0.45–1.06% of the cases of  yeast-induced vaginitis . In some cases, women suffering from  S. cerevisiae -induced vaginal infection were intimate partners of bakers, and the strain was found to be the same that their partners  used for baking . As of 1999, no cases of  S. cerevisiae -induced vaginitis in women, who worked in bakeries themselves, were reported in scientific literature. Some cases were linked by researchers to the use of the yeast in home baking. [ 76 ]  Cases of infection of  oral cavity  and  pharynx  caused by  S. cerevisiae  are also known. [ 76 ]


Occasionally   Saccharomyces cerevisiae  causes  invasive infections  (i. e. gets into the bloodstream or other normally sterile body fluid or into a deep site tissue, such as  lungs ,  liver  or  spleen ) that can go  systemic  (involve multiple organs). Such conditions are life-threatening. [ 76 ] [ 81 ]  More than 30% cases of  S. cerevisiae  invasive infections lead to death even if treated. [ 81 ]   S. cerevisiae  invasive infections, however, are much rarer than invasive infections caused by  Candida albicans [ 76 ] [ 82 ]  even in patients weakened by cancer. [ 82 ]   S. cerevisiae  causes 1% to 3.6%  nosocomial  cases of  fungemia . [ 81 ]  A comprehensive review of  S. cerevisiae  invasive infection cases found all patients to have at least one predisposing condition. [ 81 ]


Saccharomyces cerevisiae  may enter the bloodstream or get to other deep sites of the body by translocation from  oral  or  enteral   mucosa  or through contamination of intravascular catheters (e. g.  central venous catheters ). [ 80 ]  Intravascular catheters, antibiotic therapy and compromised immunity are major predisposing factors for  S. cerevisiae  invasive infection. [ 81 ]


A number of cases of  fungemia  were caused by intentional ingestion of living  S. cerevisiae  cultures for dietary or therapeutic reasons, including use of  Saccharomyces boulardii  (a strain of  S. cerevisiae   which is used as a  probiotic  for treatment of certain forms of  diarrhea ). [ 76 ] [ 81 ]   Saccharomyces boulardii  causes about 40% cases of invasive  Saccharomyces  infections [ 81 ]  and is more likely (in comparison to other  S. cerevisiae  strains) to cause invasive infection in humans without general problems with immunity, [ 81 ]  though such adverse effect is very rare relative to  Saccharomyces boulardii  therapeutic administration. [ 83 ]


S. boulardii  may contaminate intravascular catheters through hands of medical personnel involved in administering probiotic preparations of  S. boulardii  to patients. [ 81 ]


Systemic infection usually occurs in patients who have their  immunity compromised  due to severe illness ( HIV/AIDS ,  leukemia , other forms of  cancer ) or certain medical procedures ( bone marrow transplantation ,  abdominal surgery ). [ 76 ]


A case was reported when a  nodule  was  surgically excised  from a lung of a man employed in baking business, and examination of the tissue revealed presence of  Saccharomyces cerevisiae . Inhalation of  dry baking yeast powder  is supposed to be the source of infection in this case. [ 84 ] [ 81 ]


Not all strains of  Saccharomyces cerevisiae  are equally virulent towards humans. Most environmental strains are not capable of growing at temperatures above 35 °C (i. e. at temperatures of living body of humans and other  mammalian ). Virulent strains, however, are capable of growing at least above 37 °C  and often up to 39 °C (rarely up to 42 °C). [ 78 ]  Some industrial strains are also capable of growing above 37 °C. [ 76 ]   European Food Safety Authority  (as of 2017) requires that all  S. cerevisiae  strains capable of growth above 37 °C that are added to the food or feed chain in viable form must, as to be qualified presumably safe, show no resistance to antimycotic drugs used for treatment of yeast infections. [ 85 ]


The ability to grow at elevated temperatures is an important factor for strain's virulence but not the sole one. [ 78 ]


Other traits that are usually believed to be associated with virulence are: ability to produce certain enzymes such as  proteinase [ 76 ]  and  phospholipase , [ 78 ]  invasive growth [ 78 ]  (i.e. growth with intrusion into the nutrient medium), ability to adhere to mammalian cells, [ 78 ]  ability to survive in the presence of  hydrogen peroxide [ 78 ]  (that is used by  macrophages  to kill foreign microorganisms in the body) and other abilities allowing the yeast to resist or influence immune response of the host body. [ 78 ]  Ability to form branching chains of cells, known as  pseudohyphae  is also sometimes said to be associated with virulence, [ 76 ] [ 78 ]  though some research suggests that this trait may be common to both virulent and non-virulent strains of  Saccharomyces cerevisiae . [ 78 ]


Footnotes


Citations


Satiety  ( /səˈtaɪ.ə.ti/   sə-TYE-ə-tee ) is a state or condition of fullness gratified beyond the point of satisfaction, the opposite of  hunger . Following satiation (meal termination), satiety is a feeling of fullness lasting until the next meal. [ 1 ]  When food is present in the  GI tract  after a meal, satiety signals overrule hunger signals, but satiety slowly fades as hunger increases.


The satiety center in animals is located in  ventromedial nucleus  of the  hypothalamus . [ 2 ]


Satiety is signaled through the vagus nerve as well as circulating hormones. During intake of a meal, the stomach must stretch to accommodate this increased volume. This gastric accommodation activates stretch receptors in the proximal (upper) portion of the stomach. These receptors then signal through  afferent  vagus nerve fibers to the hypothalamus, increasing satiety. [ 3 ]


In addition, as the food moves into the duodenum, duodenal cells release multiple substances that affect digestion and satiety.  Glucagon-like peptide-1  (GLP-1) is an  incretin  released by the duodenum that inhibits relaxation of the stomach. This inhibition causes increased stretch of the stomach, increasing activation of proximal gastric stretch receptors. It also slows overall gut motility, increasing the duration of satiety. [ 3 ]  This effect is used to increase weight loss and treat obesity through GLP-1 agonists. [ 4 ]   Cholecystokinin  (CCK) is gut peptide produced by the duodenum in response to fat and proteins. CCK has the effect of slowing gut motility and increasing satiety as well as activating release of pancreatic digestive enzymes and bile from the gallbladder. [ citation needed ]


ENSG00000070031 ENSG00000274473


NM_011328 NM_001287171 NM_001309439


NP_001274100 NP_001296368 NP_035458


Secretin  is a  hormone  that regulates  water homeostasis  throughout the body and influences the environment of the  duodenum  by regulating secretions in the  stomach ,  pancreas , and  liver . It is a  peptide hormone  produced in the  S cells  of the duodenum, which are located in the  intestinal glands . [ 5 ]  In humans, the secretin peptide is encoded by the  SCT   gene . [ 6 ]


Secretin helps regulate the  pH  of the duodenum by inhibiting the secretion of  gastric acid  from the  parietal cells  of the stomach and stimulating the production of  bicarbonate  from the  ductal cells  of the pancreas. [ 7 ] [ 8 ]  It also stimulates the secretion of bicarbonate and water by  cholangiocytes  in the bile duct, protecting it from  bile acids  by controlling the pH and promoting the flow in the duct. [ 9 ]  Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum,  cholecystokinin  (CCK), stimulates the  gallbladder  to contract, delivering its stored bile.


Prosecretin  is a precursor to secretin, which is present in digestion. Secretin is stored in this unusable form, and is activated by  gastric acid . This indirectly results in the neutralisation of duodenal pH, thus ensuring no damage is done to the small intestine by the aforementioned acid. [ 10 ]


In 2007, secretin was discovered to play a role in  osmoregulation  by acting on the  hypothalamus ,  pituitary gland , and  kidney . [ 11 ] [ 12 ]


In 1902,  William Bayliss  and  Ernest Starling  were studying how the nervous system controls the process of digestion. [ 13 ]  It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion  secretin . This type of 'chemical messenger' substance is now called a  hormone , a term coined by Starling in 1905. [ 14 ]


Secretin is frequently erroneously stated to have been the first hormone identified. [ 15 ]  However, British researchers  George Oliver  and  Edward Albert Schäfer  had already published their findings of an adrenal extract increasing blood pressure and heart rate in brief reports in 1894 and a full publication in 1895, making  adrenaline  the first discovered hormone. [ 16 ] [ 17 ]


Secretin is initially synthesized as a 120 amino acid precursor protein known as  prosecretin . This precursor contains an  N-terminal  signal peptide, spacer, secretin itself (residues 28–54), and a 72-amino acid  C-terminal  peptide. [ 6 ]


The mature secretin peptide is a linear  peptide hormone , which is composed of 27  amino acids  and has a  molecular weight  of 3055. A helix is formed in the amino acids between positions 5 and 13. The amino acids sequences of secretin have some similarities to that of  glucagon ,  vasoactive intestinal peptide  (VIP), and  gastric inhibitory peptide  (GIP). Fourteen of 27 amino acids of secretin reside in the same positions as in glucagon, 7 the same as in VIP, and 10 the same as in GIP. [ 18 ]


Secretin also has an amidated  carboxyl-terminal  amino acid which is valine. [ 19 ]  The sequence of amino acids in secretin is H– His - Ser - Asp - Gly - Thr - Phe - Thr - Ser - Glu - Leu - Ser - Arg - Leu - Arg - Asp - Ser - Ala - Arg - Leu - Gln - Arg - Leu - Leu - Gln - Gly - Leu - Val –NH 2 . [ 19 ]


Secretin is synthesized in cytoplasmic secretory granules of S-cells, which are found mainly in the  mucosa  of the  duodenum , and in smaller numbers in the  jejunum  of the  small intestine . [ 20 ]


Secretin is released into circulation and/or intestinal lumen in response to low duodenal pH that ranges between 2 and 4.5 depending on species; the acidity is due to  hydrochloric acid  in the  chyme  that enters the duodenum from the stomach via the  pyloric sphincter . [ 21 ]  Also, the secretion of secretin is increased by the products of protein digestion bathing the mucosa of the upper small intestine. [ 22 ]


Secretin release is inhibited by  H 2  antagonists , which reduce gastric acid secretion. As a result, if the pH in the duodenum increases above 4.5, secretin cannot be released. [ 23 ]


Secretin primarily functions to neutralize the pH in the  duodenum , allowing digestive  enzymes  from the pancreas (e.g.,  pancreatic amylase  and  pancreatic lipase ) to function optimally. [ 24 ]


Secretin targets the  pancreas ; pancreatic centroacinar cells have  secretin receptors  in their plasma membrane. As secretin binds to these receptors, it stimulates adenylate cyclase activity and converts  ATP  to  cyclic AMP . [ 25 ]  Cyclic AMP acts as second messenger in intracellular signal transduction and causes the organ to secrete a  bicarbonate -rich fluid that flows into the  intestine . Bicarbonate is a base that neutralizes the acid, thus establishing a pH favorable to the action of other digestive enzymes in the small intestine. [ 26 ]


Secretin also increases water and bicarbonate secretion from duodenal  Brunner's glands  to buffer the incoming  protons  of the acidic chyme, [ 24 ]  and also reduces acid secretion by  parietal cells  of the  stomach . [ 27 ]  It does this through at least three mechanisms: 1) By stimulating release of  somatostatin , 2) By inhibiting release of  gastrin  in the  pyloric antrum , and 3) By direct  downregulation  of the parietal cell acid secretory mechanics. [ 28 ] [ 21 ]


It counteracts  blood glucose  concentration spikes by triggering increased  insulin  release from pancreas, following oral  glucose  intake. [ 29 ]


Secretin modulates  water  and  electrolyte  transport in  pancreatic duct  cells, [ 30 ]  liver  cholangiocytes , [ 31 ]  and  epididymis  epithelial cells. [ 32 ]  It is found [ 33 ]  to play a role in the  vasopressin -independent regulation of  renal water reabsorption . [ 11 ]


Secretin is found in the magnocellular neurons of the paraventricular and supraoptic nuclei of the  hypothalamus  and along the neurohypophysial tract to  neurohypophysis . During increased osmolality, it is released from the  posterior pituitary . In the hypothalamus, it activates  vasopressin  release. [ 12 ]  It is also needed to carry out the central effects of angiotensin II. In the absence of secretin or its receptor in the gene knockout animals, central injection of angiotensin II was unable to stimulate water intake and vasopressin release. [ 34 ]


It has been suggested that abnormalities in such secretin release could explain the abnormalities underlying type D  syndrome of inappropriate antidiuretic hormone hypersecretion  (SIADH). [ 12 ]  In these individuals, vasopressin release and response are normal, although abnormal renal expression, translocation of  aquaporin 2 , or both are found. [ 12 ]  It has been suggested that "Secretin as a neurosecretory hormone from the posterior pituitary, therefore, could be the long-sought vasopressin independent mechanism to solve the riddle that has puzzled clinicians and physiologists for decades." [ 12 ]


Secretin and its receptor are found in discrete nuclei of the hypothalamus, including the  paraventricular nucleus  and the  arcuate nucleus , which are the primary brain sites for regulating body energy homeostasis. It was found that both central and peripheral injection of Sct reduce food intake in mouse, indicating an anorectic role of the peptide. This function of the peptide is mediated by the  central melanocortin system . [ 35 ]


Secretin is used in diagnostic tests for pancreatic function; secretin is injected and the pancreatic output can then be imaged with  magnetic resonance imaging , a noninvasive procedure, or secretions generated as a result can gathered either through an endoscope or through tubes inserted through the mouth, down into the duodenum. [ 36 ] [ 37 ] [ 38 ]


A recombinant human secretin has been available since 2004 for these diagnostic purposes. [ 39 ]   There were problems with the availability of this agent from 2012 to 2015. [ 40 ]


A wave of enthusiasm for secretin as a possible treatment for  autism  arose in the 1990s based on a hypothetical gut-brain connection; as a result the NIH ran a series of clinical trials that showed that secretin was not effective, which brought an end to popular interest. [ 41 ] [ 42 ] [ 43 ]


A high-affinity and optimized secretin receptor antagonist (Y10,c[E16,K20],I17,Cha22,R25)sec(6-27) has been designed and developed which has allowed the structural characterization of secreting inactive conformation. [ 44 ]


Segmentation contractions  (or  movements ) are a type of  intestinal motility .


Unlike  peristalsis , which predominates in the  esophagus ,  segmentation contractions  occur in the  large intestine  and  small intestine , while predominating in the latter. While peristalsis involves one-way motion in the caudal direction, segmentation contractions move  chyme  in both directions, which allows greater mixing with the secretions of the intestines.  Segmentation involves contractions of the circular muscles in the digestive tract, while peristalsis involves rhythmic contractions of the longitudinal muscles in the  gastrointestinal tract .  Unlike peristalsis, segmentation actually can slow progression of chyme through the system.


The  septum transversum  is a thick mass of cranial  mesenchyme , formed in the  embryo , that gives rise to parts of the  thoracic diaphragm  and the  ventral mesentery  of the foregut in the developed human being and other mammals.


The septum transversum originally arises as the most cranial part of the  mesenchyme  on day 22. [ 1 ]  During craniocaudal folding, it assumes a position cranial to the developing heart at the level of the cervical vertebrae. [ 1 ]  During subsequent weeks the dorsal end of the embryo grows much faster than its ventral counterpart resulting in an  apparent descent  of the ventrally located septum transversum. At week 8, it can be found at the level of the thoracic vertebrae. [ 1 ] [ 2 ]


After successful craniocaudal folding the septum transversum picks up innervation from the adjacent  ventral rami  of spinal nerves C3, C4 and C5, thus forming the precursor of the  phrenic nerve . During the descent of the septum, the  phrenic nerve  is carried along and assumes its descending pathway.


During embryonic development of the  thoracic diaphragm ,  myoblast  cells from the septum invade the other components of the diaphragm. They thus give rise to the motor and sensory innervation of the muscular diaphragm by the  phrenic nerve .


The  cranial  part of the septum transversum gives rise to the  central tendon  of the diaphragm, [ 1 ]  and is the origin of the  myoblasts  that invade the  pleuroperitoneal  folds resulting in the formation of the muscular diaphragm. [ 3 ]


The  caudal  part of the septum transversum is invaded by the  hepatic diverticulum  which divides within it to form the liver and thus gives rise to the  ventral mesentery  of the foregut, which in turn is the precursor of the  lesser omentum , the  visceral peritoneum  of the  liver  and the  falciform ligament .


Though not derived from the septum transversum, development of the liver is highly dependent upon signals originating here.   Bone morphogenetic protein 2  (BMP-2),  BMP-4  and  BMP-7  produced from the septum transversum join  fibroblast growth factor  (FGF) signals from the cardiac  mesoderm  induce part of the foregut to differentiate towards a hepatic fate. [ 4 ]


The  sigmoid colon  (or  pelvic colon ) is the part of the  large intestine  that is closest to the  rectum  and  anus . It forms a loop that averages about 35–40 centimetres (14–16 in) in length. The loop is typically shaped like a Greek letter sigma (ς) or Latin letter S (thus  sigma  +  -oid ). This part of the colon normally lies within the  pelvis , but due to its freedom of movement it is liable to be displaced into the  abdominal cavity . [ 2 ]


The sigmoid colon begins at the  superior aperture  of the  lesser pelvis , where it is continuous with the  iliac colon , and passes transversely across the front of the  sacrum  to the right side of the pelvis.


It then curves on itself and turns toward the left to reach the middle line at the level of the third piece of the  sacrum , where it bends downward and ends in the  rectum .


Its function is to expel solid and gaseous waste from the gastrointestinal tract. The curving path it takes toward the anus allows it to store gas in the superior arched portion, enabling the colon to expel gas without excreting faeces simultaneously.


The sigmoid colon is completely surrounded by  peritoneum  (and thus is not  retroperitoneal ), which forms a  mesentery  ( sigmoid mesocolon ), which diminishes in length from the center toward the ends of the loop, where it disappears, so that the loop is fixed at its junctions with the  iliac colon  and rectum, but enjoys a considerable range of movement in its central portion.


Pelvic splanchnic nerves  are the primary source for  parasympathetic  innervation.   Lumbar splanchnic nerves  provide  sympathetic  innervation via the  inferior mesenteric ganglion .


Behind the sigmoid colon are the  external iliac vessels , ovary, obturator nerve, the left  piriformis , and left  sacral plexus  of nerves.


In front, it is separated from the  bladder  in the  male , and the  uterus  in the  female , by some coils of the  small intestine .


Diverticulosis  often occurs in the sigmoid colon in association with increased intraluminal pressure and focal weakness in the colonic wall. It is a common cause of  hematochezia .


Volvulus  occurs when a portion of the bowel twists around its mesentery, which can lead to obstruction and  infarction . Volvulus in the elderly commonly occurs in the sigmoid colon, whereas in infants and children it is more likely to occur in the midgut. This may correct itself spontaneously or the rotation may continue until the blood supply of the gut is cut off completely.


This article incorporates text in the  public domain  from  page 1182  of the 20th edition of   Gray's Anatomy   (1918)


Simeticone  ( INN ), also known as  simethicone  ( USAN ), is an  anti-foaming agent  used to reduce  bloating , discomfort or pain caused by excessive gas.


Simeticone is used to relieve the symptoms of excessive gas in the  gastrointestinal tract , namely bloating, burping, and flatulence. [ 2 ] [ 3 ]  While there is a lack of conclusive evidence that simeticone is effective for this use, [ 4 ] [ 5 ] [ failed verification ]  studies have shown that it can relieve symptoms of  functional dyspepsia [ 6 ]  and  functional bloating . [ 7 ]


It has not been fully established that simeticone is useful to treat  colic  in babies, [ 8 ]  and it is not recommended for this purpose. [ 5 ]  A study in the United Kingdom reported that according to parental perception simeticone helped infant colic in some cases. [ 9 ]


Simeticone can also be used for suspected  postoperative   abdominal discomfort  in infants. [ 10 ]


Simeticone does not have any serious side effects. [ 11 ]  Two uncommon side effects (occurring in 1 in 100 to 1 in 1,000 patients) are constipation and nausea. [ 12 ]


Simeticone is a non-systemic  surfactant  which decreases the surface tension of gas bubbles in the GI tract. [ 11 ]  This allows gas bubbles to leave the GI tract as  flatulence  or  belching . [ 11 ]  Simeticone does not reduce or prevent the formation of gas. [ 13 ]  Its effectiveness has been shown in several  in vitro  studies. [ 14 ] [ 15 ]


Simeticone is a mixture of  dimethicone  and  silicon dioxide . [ 16 ]


The INN name is "simeticone", which was added to the INN recommended list in 1999. [ 17 ]


Simeticone is marketed under many brand names and in many  combination drugs ; it is also marketed as a veterinary drug. [ 18 ]


Brand names include A.F., Acid Off, Aero Red, Aero-OM, Aero-Sim, Aerocol, Aerox, Aesim, Aflat, Air-X, Anaflat, Antiflat, Baby Rest, Bicarsim, Bicarsim Forte, Blow-X, Bobotic, Bobotik, Carbogasol, Colic E, Colin, Cuplaton, Degas, Dentinox, Dermatix, Digesta, Dimetikon Meda, Disflatyl, Disolgas, Elugan N, Elzym, Endo-Paractol, Enterosilicona, Espaven Antigas, Espumisan, Espumisan L, Flacol, Flapex, Flatidyl, Flatoril, Flatulex, Flucolic, Gas X, Gas-X, Gaselab, Gaseoflat, Gaseoflatex, Gaseophar, Gaseoplus, Gaseovet, Gaservol, Gasimetin, Gasnil, Gasofilm, Gastrex, Gastrosen, Gazim X, Gazix, Geludrox-HS, Genasyme, Ilio-Funkton, Imogas, Imogaze, Imonogas, Infacalm, Infacol, Infacolic, Lefax, Lefaxin, Lefoam, Logastin, Luftal, Maxi Flat, Meteosim, Metiorisan, Metsil, Mylanta, Mylicon, Mylicongas, Mylom, Mymus, Nanog, Neodrop, Neogasol, Neolanta, Orocure, Ovol, Pedicon, Phazin, Phazyme, Polysilane Junior, Restime, Rugby Gas Relief, Sab Simplex, Salinal, Semecon, Semeth, Sicongast, Siflat, Silbione, Siligas, Silipin, Sim, Simcone, Simecon, Simecrin, Simedill, Simegut, Simet, Simethicon, Simethicone, Simetic, Simeticon, Simeticona, Simeticone, Siméticone, Simeticonum, Simetigast, Simflat, Simicol, Simicon, Wilcon, Wind-eze and WindSetlers. [ 18 ]


It is also marketed as a  combination drug : [ 18 ]


It is also marketed as a veterinary drug under the brands Birp and Methysilox.


The  small intestine  or  small bowel  is an  organ  in the  gastrointestinal tract  where most of the  absorption  of  nutrients  from food takes place.  It lies between the  stomach  and  large intestine , and receives  bile  and  pancreatic juice  through the  pancreatic duct  to aid in  digestion . The small intestine is about 5.5 metres (18 feet) long and folds many times to fit in the abdomen. Although it is longer than the large intestine, it is called the small intestine because it is narrower in diameter.


The small intestine has three distinct regions – the  duodenum ,  jejunum , and  ileum . The duodenum, the shortest, is where preparation for absorption through small finger-like protrusions called  villi  begins. [ 2 ]  The jejunum is specialized for the absorption through its lining by  enterocytes : small nutrient particles which have been previously digested by  enzymes  in the duodenum.  The main function of the ileum is to absorb  vitamin B 12 ,  bile salts , and whatever products of digestion that were not absorbed by the jejunum.


The length of the small intestine can vary greatly, from as short as 3 metres (10 feet) to as long as  10.5 m ( 34 + 1 ⁄ 2  ft), also depending on the measuring technique used. [ 3 ]  The typical length in a living person is  3–5 m (10– 16 + 1 ⁄ 2  ft). [ 4 ] [ 5 ]  The length depends both on how tall the person is and how the length is measured. [ 3 ]  Taller people generally have a longer small intestine and measurements are generally longer after death and when the bowel is empty. [ 3 ]


It is approximately  1.5 centimetres ( 5 ⁄ 8  inch) in diameter in  newborns  after 35 weeks of  gestational age , [ 7 ]  and  2.5–3 cm (1– 1 + 1 ⁄ 8  in) in diameter in adults. On  abdominal X-rays , the small intestine is considered to be abnormally dilated when the diameter exceeds 3 cm. [ 8 ] [ 9 ]  On  CT scans , a diameter of over 2.5 cm is considered abnormally dilated. [ 8 ] [ 10 ]  The surface area of the human  small intestinal mucosa , due to enlargement caused by folds, villi and microvilli, averages 30 square metres (320 sq ft). [ 11 ]


The small intestine is divided into three structural parts.


The jejunum and ileum are suspended in the  abdominal cavity  by  mesentery . The mesentery is part of the  peritoneum . Arteries, veins, lymph vessels and nerves travel within the mesentery. [ 13 ]


The small intestine receives a blood supply from the  celiac trunk  and the  superior mesenteric artery . These are both branches of the  aorta . The duodenum receives blood from the  coeliac trunk  via the  superior pancreaticoduodenal artery  and from the superior mesenteric artery via the  inferior pancreaticoduodenal artery . These two arteries both have  anterior and posterior  branches that meet in the midline and  anastomose .  The jejunum and ileum receive blood from the superior mesenteric artery. [ 14 ]  Branches of the superior mesenteric artery form a series of arches within the mesentery known as  arterial arcades , which may be several layers deep. Straight blood vessels known as  vasa recta  travel from the arcades closest to the ileum and jejunum to the organs themselves. [ 14 ]


The three sections of the small intestine look similar to each other at a microscopic level, but there are some important differences. The parts of the intestine are as follows:


About 20,000 protein coding genes are  expressed  in human cells and 70% of these genes are expressed in the normal duodenum. [ 15 ] [ 16 ]  Some 300 of these genes are more specifically expressed in the duodenum with very few genes expressed only in the small intestine. The corresponding specific proteins are expressed in glandular cells of the mucosa, such as  fatty acid binding protein   FABP6 .  Most of the more specifically expressed genes in the small intestine are also expressed in the duodenum, for example  FABP2  and the  DEFA6  protein expressed in secretory granules of  Paneth cells . [ 17 ]


The small intestine develops from the  midgut  of the  primitive gut tube . [ 18 ]  By the fifth week of  embryological  life, the  ileum  begins to grow longer at a very fast rate, forming a U-shaped fold called the  primary intestinal loop . The loop grows so fast in length that it outgrows the abdomen and protrudes through the  umbilicus . By week 10, the loop retracts back into the abdomen. Between weeks six and ten the small intestine rotates anticlockwise, as viewed from the front of the embryo. It rotates a further 180 degrees after it has moved back into the abdomen. This process creates the twisted shape of the  large intestine . [ 18 ]


Food from the stomach is allowed into the duodenum through the  pylorus  by a muscle called the pyloric sphincter.


The small intestine is where most chemical digestion takes place. Many of the  digestive enzymes  that act in the small intestine are secreted by the  pancreas  and  liver  and enter the small intestine via the  pancreatic duct . Pancreatic enzymes and  bile  from the gallbladder enter the small intestine in response to the hormone  cholecystokinin , which is produced in the response to the presence of nutrients.  Secretin , another hormone produced in the small intestine, causes additional effects on the pancreas, where it promotes the release of  bicarbonate  into the duodenum in order to neutralize the potentially harmful acid coming from the stomach.


The three major classes of nutrients that undergo digestion are  proteins ,  lipids  (fats) and  carbohydrates :


Digested food is now able to pass into the blood vessels in the wall of the intestine through either  diffusion  or  active transport . The small intestine is the site where most of the nutrients from ingested food are absorbed. The inner wall, or mucosa, of the small intestine, is lined with  intestinal epithelium , a  simple columnar epithelium . Structurally, the mucosa is covered in wrinkles or flaps called  circular folds , which are considered permanent features in the mucosa. They are distinct from  rugae  which are considered non-permanent or temporary allowing for distention and contraction. From the circular folds project microscopic finger-like pieces of tissue called  villi  ( Latin  for "shaggy hair"). The individual epithelial cells also have finger-like projections known as  microvilli . The functions of the circular folds, the villi, and the microvilli are to increase the amount of surface area available for the absorption of  nutrients , and to limit the loss of said nutrients to intestinal fauna.


Each villus has a network of  capillaries  and fine lymphatic vessels called  lacteals  close to its surface. The epithelial cells of the villi transport nutrients from the lumen of the intestine into these capillaries (amino acids and carbohydrates) and lacteals (lipids). The absorbed substances are transported via the blood vessels to different organs of the body where they are used to build complex substances such as the proteins required by our body. The material that remains undigested and unabsorbed passes into the large intestine.


Absorption of the majority of nutrients takes place in the  jejunum , with the following notable exceptions:


The small intestine supports the body's  immune system . [ 20 ]   The presence of  gut flora  appears to contribute positively to the host's immune system.
 Peyer's patches , located within the ileum of the small intestine, are an important part of the digestive tract's local immune system. They are part of the lymphatic system, and provide a site for antigens from potentially harmful bacteria or other microorganisms in the digestive tract to be sampled, and subsequently presented to the immune system. [ 21 ]


The small intestine is a complex organ, and as such, there are a very large number of possible conditions that may affect the function of the small bowel. A few of them are listed below, some of which are common, with up to 10% of people being affected at some time in their lives, while others are vanishingly rare.


The small intestine is found in all  tetrapods  and also in  teleosts , although its form and length vary enormously between species. In teleosts, it is relatively short, typically around one and a half times the length of the fish's body. It commonly has a number of  pyloric caeca , small pouch-like structures along its length that help to increase the overall surface area of the organ for digesting food. There is no ileocaecal valve in teleosts, with the boundary between the small intestine and the  rectum  being marked only by the end of the digestive epithelium. [ 22 ]


In tetrapods, the  ileocaecal valve  is always present, opening into the colon. The length of the small intestine is typically longer in tetrapods than in teleosts, but is especially so in  herbivores , as well as in mammals and  birds , which have a higher  metabolic rate  than  amphibians  or  reptiles . The lining of the small intestine includes microscopic folds to increase its surface area in all vertebrates, but only in mammals do these develop into true villi. [ 22 ]


The boundaries between the duodenum, jejunum, and ileum are somewhat vague even in humans, and such distinctions are either ignored when discussing the anatomy of other animals, or are essentially arbitrary. [ 22 ]


There is no small intestine as such in non-teleost fish, such as  sharks ,  sturgeons , and  lungfish . Instead, the digestive part of the gut forms a  spiral intestine , connecting the stomach to the rectum. In this type of gut, the intestine itself is relatively straight but has a long fold running along the inner surface in a spiral fashion, sometimes for dozens of turns. This valve greatly increases both the surface area and the effective length of the intestine. The lining of the spiral intestine is similar to that of the small intestine in teleosts and non-mammalian tetrapods. [ 22 ]


In  lampreys , the spiral valve is extremely small, possibly because their diet requires little digestion.  Hagfish  have no spiral valve at all, with digestion occurring for almost the entire length of the intestine, which is not subdivided into different regions. [ 22 ]


In  traditional Chinese medicine , the  small intestine  is a  yang  organ. [ 23 ]


The  Solitary lymphatic nodules  (or  solitary follicles ) are structures found in the  small intestine  and  large intestine .


The solitary lymphatic nodules are found scattered throughout the  mucous membrane  of the small intestine, but are most numerous in the lower part of the  ileum .


Their free surfaces are covered with rudimentary  villi , except at the summits, and each gland is surrounded by the openings of the intestinal glands.


Each consists of a dense interlacing  retiform  tissue closely packed with  lymph -corpuscles, and permeated with an abundant capillary network.


The interspaces of the retiform tissue are continuous with larger lymph spaces which surround the gland, through which they communicate with the  lacteal  system.


They are situated partly in the submucous tissue, partly in the mucous membrane, where they form slight projections of its  epithelial  layer.


The solitary lymphatic nodules of the large intestine are most abundant in the  cecum  and  vermiform process , but are irregularly scattered also over the rest of the intestine.


They are similar to those of the small intestine.


This article incorporates text in the  public domain  from  page 1176  of the 20th edition of   Gray's Anatomy   (1918)


The  sphincter of Boyden  (also known as the  choledochal sphincter ) is a  sphincter  located in the  common bile duct  before it joins with the  pancreatic duct  to form the  ampulla of vater . This sphincter controls the flow of  bile  into the pancreatic duct and it helps in filling up of the  gallbladder  with  bile .


The sphincter of Boyden is a smooth muscle sphincter surrounding the  common bile duct  (ductus choledocus). [ 1 ] [ 2 ]  It occurs just before the junction with the  pancreatic duct , where the  ampulla of Vater  is formed. [ 1 ]  Occasionally, some fibres also surround the pancreatic duct. [ 2 ]


It is subdivided into two parts - pars superior and pars inferior. The pars inferior is the strongest component of the  sphincter of Oddi complex . [ 3 ] [ 4 ]


The sphincter of Boyden controls the flow of  bile  from the  common bile duct  into the  pancreatic duct . [ 1 ]  This helps with filling of the  gallbladder  with  bile .


Its contractions regulate the passage of bile into the  gall bladder  or the  duodenum . [ 4 ] [ 3 ]


This is named after the American anatomist  Edward Allen Boyden  (1886-1976).


The  sphincter of Oddi  (also  hepatopancreatic sphincter  or  Glisson's sphincter ), abbreviated as  SO , [ 1 ]  is a muscular valve that in some animals, including humans, controls the flow of  bile  and  pancreatic juice  out of the gallbladder and pancreas respectively through the  ampulla of Vater  into the second part of the  duodenum . It is named after  Ruggero Oddi .


The sphincter of Oddi is a circular muscle band ( sphincter ) that surrounds the  major duodenal papilla . [ 2 ]


The sphincter regulates the secretion of pancreatic juice and bile into the duodenum. [ 3 ]  It also prevents reflux of duodenal contents into the ampulla of Vater. [ 4 ]  By preventing reflux of the contents of the duodenum, the sphincter of Oddi prevents the accumulation of particulate matter and sludge in the bile ducts, reducing the risk of  cholangitis . The sphincter of Oddi also allows retrograde filling of the gallbladder. [ 5 ]


The sphincter of Oddi is relaxed by the hormone  cholecystokinin [ 6 ] [ 7 ]  via  vasoactive intestinal peptide . [ 8 ]


Pancreatitis  can result from a failure of pancreatic secretions to drain properly. One possible cause of impaired drainage of pancreatic juice is blockage of the sphincter of Oddi. A common cause of blockage is a  gallstone  in the  common bile duct . [ citation needed ]


Opiates may cause spasms of the sphincter of Oddi, leading to increased serum amylase levels. [ 9 ]


The sphincter was described for the first time by  Ruggero Oddi  when he was a young student in 1887. [ 10 ]  This description followed extensive research into the physiology of dogs and detailed  histological  examinations of humans and many other species. [ 1 ]


In many mammals (including  mice ,  guinea pigs ,  dogs , and  opossums ), the  smooth muscle  around the  ampulla of Vater  does not form a sphincter. [ 11 ]


Spiral folds of cystic duct [ 2 ] [ 1 ]  (also known as the  spiral mucosal folds , [ 3 ]   spiral valves of Cina , [ citation needed ]   Amussat valve , or  Cina valves ) are a series of crescenteric, spirally arranged  mucosal  folds [ 4 ] [ 2 ]  in the proximal part of [ 2 ]  the  cystic duct . [ 4 ] [ 2 ]


The folds are 2-10 in number. They project into the lumen of the duct. They are continuous with the folds of the neck of the gallbladder. [ 4 ]  They are arranged in a somewhat spiral manner. [ 2 ]


The spiral valves are supported by underlying smooth  muscle  fibers. [ 3 ]


The function of the valves is not known. [ 4 ]  Since the structures' discovery, various functions have been proposed, including the structural support to the cystic duct, and moderation of the speed of passage of bile through the duct in either direction [ 3 ]  Their role has been commonly ascribed to the regulation of bile flow, however, [ 4 ] [ 3 ]  they may instead maintain patency of the duct (i.e. keep the duct open) [ 4 ] [ 5 ] [ 3 ]  as the duct is thin and tortuous and thus prone to kinking; the observation that the folds are more prominent in younger individuals in whom the duct is also thinner supports this hypothesis. [ 3 ]


The presence of the spiral folds, in combination with the tortuosity of the cystic duct, makes  endoscopic   cannulation  and  catheterization  of the cystic duct extremely difficult. The valves of Cina are susceptible to  lacerations  and were once a serious obstacle to the surgical canalization, which has since been overcome by newer technologies. [ 6 ]


On ultrasound, valves of Cina are echogenic. [ 7 ]


Stercobilin  is a  tetrapyrrolic   bile pigment  and is one end-product of  heme   catabolism . [ 1 ] [ 2 ]  It is the chemical responsible for the brown color of  human feces  and was originally isolated from feces in 1932. Stercobilin (and related  urobilin ) can be used as a marker for biochemical identification of fecal pollution levels in rivers. [ 3 ]


Stercobilin results from breakdown of the heme  moiety  of hemoglobin found in  erythrocytes  (red blood cells).  Macrophages  break down senescent erythrocytes and break the heme down into  biliverdin , which rapidly reduces to free  bilirubin . Bilirubin binds tightly to  plasma  proteins (especially  albumin ) in the blood stream and is transported to the liver, where it is conjugated with one or two  glucuronic acid  residues into  bilirubin diglucuronide , and secreted into the small intestine as  bile . In the small intestine, some bilirubin glucuronide is converted back to bilirubin via bacterial enzymes in the terminal ileum.  This bilirubin is further converted to colorless  urobilinogen  by the bacterial enzyme bilirubin reductase. [ 4 ]  Urobilinogen that remains in the colon can either be reduced to  stercobilinogen  and finally oxidized to stercobilin, or it can be directly reduced to stercobilin. Stercobilin is responsible for the brown color of human feces. Stercobilin is then excreted in the feces. [ 5 ]


In  obstructive jaundice , no bilirubin reaches the small intestine, meaning that there is no formation of stercobilinogen. The lack of stercobilin and other bile pigments causes feces to become clay-colored. [ 5 ]


An analysis of two infants suffering from  cholelithiasis  observed that a substantial amount of stercobilin was present in brown pigment gallstones. This study suggested that brown pigment gallstones could form spontaneously in infants suffering from bacterial infections of the biliary tract. [ 6 ]


A 1996 study by McPhee et al. suggested that stercobilin and other related pyrrolic pigments — including urobilin, biliverdin, and xanthobilirubic acid — has potential to function as a new class of HIV-1  protease inhibitors  when delivered at low micromolar concentrations. These pigments were selected due to a similarity in shape to the successful HIV-1 protease inhibitor  Merck  L-700,417 ( N , N -bis(2-hydroxy-1-indanyl)-2,6-diphenylmethyl-4-hydroxy-1,7-heptandiamide). Further research is suggested to study the pharmacological efficacy of these pigments. [ 7 ]


The  stomach  is a muscular,  hollow organ  in the  upper gastrointestinal tract  of  humans  and many other animals, including several  invertebrates . The stomach has a dilated structure and functions as a vital organ in the  digestive system . The stomach is involved in the  gastric phase of digestion , following the  cephalic phase  in which the sight and smell of food and the act of  chewing  are stimuli.  In the stomach a chemical breakdown of food takes place by means of secreted   digestive enzymes  and  gastric acid .


The stomach is located between the  esophagus  and the  small intestine .  The  pyloric sphincter  controls the passage of partially digested food ( chyme ) from the stomach into the  duodenum , the first and shortest part of the small intestine, where  peristalsis  takes over to move this through the rest of the intestines.


In the  human digestive system , the stomach lies between the  esophagus  and the  duodenum  (the first part of the  small intestine ). It is in the  left upper quadrant  of the  abdominal cavity . The top of the stomach lies against the  diaphragm . Lying behind the stomach is the  pancreas . A large double fold of visceral  peritoneum  called the  greater omentum  hangs down from the  greater curvature  of the stomach. Two  sphincters  keep the contents of the stomach contained; the  lower esophageal sphincter   (found in the cardiac region), at the junction of the esophagus and stomach, and the  pyloric sphincter  at the junction of the stomach with the duodenum.


The stomach is surrounded by  parasympathetic  (inhibitor) and  sympathetic  (stimulant)  plexuses  (networks of  blood vessels  and  nerves  in the  anterior  gastric,  posterior ,  superior  and  inferior , celiac and myenteric), which regulate both the secretory activity of the stomach and the motor (motion) activity of its muscles.


The stomach is  distensible , and can normally expand to hold about one litre of food. [ 3 ]  In a newborn human baby the stomach will only be able to hold about 30 millilitres. The maximum stomach volume in adults is between 2 and 4 litres, [ 4 ] [ 5 ]  although volumes of up to 15 litres have been observed in extreme circumstances. [ 6 ]


The human stomach can be divided into four sections, beginning at the cardia followed by the fundus, the body and the pylorus. [ 7 ] [ 8 ]


The cardia is defined as the region following the "z-line" of the  gastroesophageal junction , the point at which the  epithelium  changes from  stratified squamous  to  columnar . Near the cardia is the lower esophageal sphincter. [ 9 ]


The  stomach bed  refers to the structures upon which the  stomach rests in mammals. [ 10 ] [ 11 ]  These include the  tail of the pancreas ,  splenic artery , left  kidney , left  suprarenal gland ,  transverse colon  and its  mesocolon , and the  left crus of diaphragm , and the  left colic flexure . The term was introduced around 1896 by Philip Polson of the Catholic University School of Medicine, Dublin. However this was brought into disrepute by surgeon anatomist J Massey. [ 12 ] [ 13 ] [ 14 ]


The lesser curvature of the human stomach is supplied by the  right gastric artery  inferiorly and the  left gastric artery  superiorly, which also supplies the cardiac region. The greater curvature is supplied by the  right gastroepiploic artery  inferiorly and the  left gastroepiploic artery  superiorly. The fundus of the stomach, and also the upper portion of the greater curvature, is supplied by the  short gastric arteries , which arise from the splenic artery.


The two sets of  gastric lymph nodes  drain the stomach's tissue fluid into the lymphatic system.


Like the other parts of the  gastrointestinal wall , the human stomach wall from inner to outer, consists of a  mucosa ,  submucosa ,  muscular layer ,  subserosa  and  serosa . [ 16 ]


The inner part of the stomach wall is the  gastric mucosa  a mucous membrane that forms the lining of the stomach. the membrane consists of an outer layer of  columnar epithelium , a  lamina propria , and a thin layer of  smooth muscle  called the  muscularis mucosa . Beneath the mucosa lies the  submucosa , consisting of  fibrous connective tissue . [ 17 ]   Meissner's plexus  is in this layer interior to the oblique muscle layer. [ 18 ]


Outside of the submucosa lies the muscular layer. It consists of three layers of muscular fibres, with fibres lying at angles to each other. These are the inner oblique, middle circular, and outer longitudinal layers. [ 19 ]  The presence of the inner oblique layer is distinct from other parts of the gastrointestinal tract, which do not possess this layer. [ 20 ]  The stomach contains the thickest muscular layer consisting of three layers, thus maximum peristalsis occurs here.


The  outer longitudinal layer  is responsible for moving the semi-digested food towards the pylorus of the stomach through muscular shortening.


To the outside of the muscular layer lies a  serosa , consisting of layers of connective tissue continuous with the  peritoneum .


Smooth mucosa along the inside of the lesser curvature forms a passageway - the  gastric canal   that fast-tracks liquids entering the stomach, to the pylorus. [ 8 ]


The mucosa lining the stomach is lined with  gastric pits , which receive  gastric juice , secreted by between 2 and 7  gastric glands . [ citation needed ]  Gastric juice is an acidic fluid containing  hydrochloric acid  and digestive enzymes. [ 21 ]  The glands contains a number of cells, with the function of the glands changing depending on their position within the stomach. [ citation needed ]


Within the body and fundus of the stomach lie the  fundic glands . In general, these glands are lined by column-shaped cells that secrete a protective layer of  mucus  and  bicarbonate . Additional cells present include  parietal cells  that secrete hydrochloric acid and  intrinsic factor ,  chief cells  that secrete  pepsinogen  (this is a precursor to pepsin- the highly acidic environment converts the pepsinogen to pepsin), and neuroendocrine cells that secrete  serotonin . [ 22 ] [ citation needed ]


Glands differ where the stomach meets the esophagus and near the pylorus. [ 23 ]  Near the  gastroesophageal junction  lie  cardiac glands , which primarily secrete mucus. [ 22 ]  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 glands  with short ducts  or  compound racemose  resembling the  duodenal   Brunner's glands . [ citation needed ]  Near the pylorus lie  pyloric glands  located in the antrum of the pylorus. They secrete mucus, as well as  gastrin  produced by their  G cells . [ 24 ] [ citation needed ]


About 20,000  protein-coding genes  are expressed in human cells and nearly 70% of these genes are expressed in the normal stomach. [ 25 ] [ 26 ]  Just over 150 of these genes are more specifically expressed in the stomach compared to other organs, with only some 20 genes being highly specific. The corresponding specific proteins expressed in stomach are mainly involved in creating a suitable environment for handling the digestion of food for uptake of nutrients. Highly stomach-specific proteins include  gastrokine-1  expressed in the mucosa;  pepsinogen  and  gastric lipase , expressed in  gastric chief cells ; and a gastric  ATPase  and  gastric intrinsic factor , expressed in  parietal cells . [ 27 ]


In the early part of the  development of the human embryo , the ventral part of the embryo abuts the  yolk sac . During the third week of development, as the embryo grows, it begins to surround parts of the yolk sac. The enveloped portions form the basis for the adult gastrointestinal tract. [ 28 ]  The sac is surrounded by a network of  vitelline arteries and veins . Over time, these arteries consolidate into the three main arteries that supply the developing gastrointestinal tract: the  celiac artery ,  superior mesenteric artery , and  inferior mesenteric artery . The areas supplied by these arteries are used to define the  foregut ,  midgut , and  hindgut . [ 28 ]  The surrounded sac becomes the primitive gut. Sections of this gut begin to differentiate into the organs of the gastrointestinal tract, and the esophagus, and stomach form from the foregut. [ 28 ]


As the stomach rotates during early development, the dorsal and ventral mesentery rotate with it; this rotation produces a space anterior to the expanding stomach called the greater sac, and a space posterior to the stomach called the lesser sac. After this rotation the dorsal mesentery thins and forms the greater  omentum , which is attached to the greater curvature of the stomach. The ventral mesentery forms the lesser omentum, and is attached to the developing  liver . In the adult, these connective structures of omentum and mesentery form the  peritoneum , and act as an insulating and protective layer while also supplying organs with  blood  and lymph vessels as well as nerves. [ 29 ]  Arterial supply to all these structures is from the  celiac trunk , and venous drainage is by the  portal venous system . Lymph from these organs is drained to the prevertebral celiac nodes at the origin of the celiac artery from the  aorta .


In the  human digestive system , a  bolus  (a small rounded mass of  chewed up  food) enters the stomach through the  esophagus  via the  lower esophageal sphincter . The stomach releases  proteases  (protein-digesting  enzymes  such as  pepsin ), and  hydrochloric acid , which kills or inhibits  bacteria  and provides the acidic  pH  of 2 for the  proteases  to work. Food is churned by the stomach through  peristaltic  muscular contractions of the wall – reducing the volume of the bolus, before looping around the fundus [ 30 ]  and the  body of stomach  as the boluses are converted into  chyme  (partially digested food). Chyme slowly passes through the  pyloric sphincter  and into the  duodenum  of the  small intestine , where the extraction of nutrients begins.


Gastric juice  in the stomach also contains  pepsinogen .  Hydrochloric acid  activates this inactive form of enzyme into the active form, pepsin. Pepsin breaks down proteins into  polypeptides .


Within a few moments after food enters the stomach, mixing waves begin to occur at intervals of approximately 20 seconds. A mixing wave is a unique type of  peristalsis  that mixes and softens the food with gastric juices to create chyme. The initial mixing waves are relatively gentle, but these are followed by more intense waves, starting at the body of the stomach and increasing in force as they reach the pylorus.


The pylorus, which holds around 30 mL of chyme, acts as a filter, permitting only liquids and small food particles to pass through the mostly, but not fully, closed  pyloric sphincter . In a process called  gastric emptying , rhythmic mixing waves force about 3 mL of chyme at a time through the pyloric sphincter and into the duodenum. Release of a greater amount of chyme at one time would overwhelm the capacity of the small intestine to handle it. The rest of the chyme is pushed back into the body of the stomach, where it continues mixing. This process is repeated when the next mixing waves force more chyme into the duodenum.


Gastric emptying is regulated by both the stomach and the duodenum. The presence of chyme in the duodenum activates receptors that inhibit gastric secretion. This prevents additional chyme from being released by the stomach before the duodenum is ready to process it. [ 31 ]


The fundus stores both undigested food and gases that are released during the process of chemical digestion. Food may sit in the fundus of the stomach for a while before being mixed with the chyme. While the food is in the fundus, the digestive activities of  salivary amylase  continue until the food begins mixing with the acidic chyme. Ultimately, mixing waves incorporate this food with the chyme, the acidity of which inactivates salivary amylase and activates  lingual lipase . Lingual lipase then begins breaking down triglycerides into free fatty acids, and mono- and diglycerides.


The breakdown of protein begins in the stomach through the actions of hydrochloric acid, and the enzyme  pepsin .


The stomach can also produce  gastric lipase , which can help digesting fat.


The contents of the stomach are completely emptied into the duodenum within two to four hours after the meal is eaten. Different types of food take different amounts of time to process. Foods heavy in carbohydrates empty fastest, followed by high-protein foods. Meals with a high triglyceride content remain in the stomach the longest. Since enzymes in the small intestine digest fats slowly, food can stay in the stomach for 6 hours or longer when the duodenum is processing fatty chyme. However, this is still a fraction of the 24 to 72 hours that full digestion typically takes from start to finish. [ 31 ]


Although the absorption in the human digestive system is mainly a function of the small intestine, some absorption of certain small molecules nevertheless does occur in the stomach through its lining. This includes:


The  parietal cells  of the human stomach are responsible for producing  intrinsic factor , which is necessary for the absorption of  vitamin B12 . B12 is used in cellular metabolism and is necessary for the production of  red blood cells , and the functioning of the  nervous system .


Chyme from the stomach is slowly released into the  duodenum  through coordinated  peristalsis  and opening of the pyloric sphincter. The movement and the flow of chemicals into the stomach are controlled by both the  autonomic nervous system  and by the various  digestive hormones  of the digestive system:


Other than gastrin, these hormones all act to turn off the stomach action. This is in response to food products in the  liver  and gall bladder, which have not yet been absorbed. The stomach needs to push food into the small intestine only when the intestine is not busy. While the intestine is full and still digesting food, the stomach acts as storage for food.


Epidermal growth factor  (EGF) results in cellular proliferation, differentiation, and survival. [ 36 ]   EGF is a low-molecular-weight polypeptide first purified from the mouse submandibular gland, but since then found in many human tissues including the  submandibular gland , and the  parotid gland . Salivary EGF, which also seems to be regulated by dietary inorganic  iodine , also plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. The biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis, and mucosal protection from intraluminal injurious factors such as gastric acid, bile acids, pepsin, and trypsin and from physical, chemical, and bacterial agents. [ 37 ]


The human stomach has  receptors responsive to  sodium glutamate [ 38 ]  and this information is passed to the  lateral hypothalamus  and  limbic system  in the  brain  as a  palatability  signal through the  vagus nerve . [ 39 ]  The stomach can also sense, independently of tongue and oral taste receptors,  glucose , [ 40 ]   carbohydrates , [ 41 ]   proteins , [ 41 ]  and  fats . [ 42 ]  This allows the brain to link  nutritional  value of foods to their tastes. [ 40 ]


This syndrome defines the association between thyroid disease and chronic gastritis, which was first described in the 1960s. [ 43 ]  This term was coined also to indicate the presence of thyroid autoantibodies or autoimmune thyroid disease in patients with pernicious anemia, a late clinical stage of atrophic gastritis. [ 44 ]  In 1993, a more complete investigation on the stomach and thyroid was published, [ 45 ]  reporting that the thyroid is, embryogenetically and  phylogenetically, derived from a primitive stomach, and that the thyroid cells, such as primitive gastroenteric cells, migrated and specialized in uptake of iodide and in storage and elaboration of iodine compounds during vertebrate evolution. In fact, the stomach and thyroid share iodine-concentrating ability and many morphological and functional similarities, such as cell polarity and apical microvilli, similar organ-specific antigens and associated autoimmune diseases, secretion of glycoproteins (thyroglobulin and mucin) and peptide hormones, the digesting and readsorbing ability, and lastly, similar ability to form iodotyrosines by peroxidase activity, where iodide acts as an electron donor in the presence of H 2 O 2 . In the following years, many researchers published reviews about this syndrome. [ 46 ]


A  series of radiographs  can be used to examine the stomach for various disorders. This will often include the use of a  barium swallow . Another method of examination of the stomach, is the use of an  endoscope . A  gastric emptying study  is considered the gold standard to assess the gastric emptying rate. [ 47 ]


A large number of studies have indicated that most cases of  peptic ulcers , and  gastritis , in humans are caused by  Helicobacter pylori  infection, and an association has been seen with the development of  stomach cancer . [ 48 ]


A  stomach rumble  is actually noise from the intestines.


In humans, many  bariatric surgery  procedures involve the stomach, in order to lose weight. A  gastric band  may be placed around the cardia area, which can adjust to limit intake. The  anatomy of the stomach may be modified , or the stomach may be  bypassed entirely .


Surgical removal of the stomach is called a  gastrectomy , and removal of the cardia area is a called a  cardiectomy .  "Cardiectomy" is a term that is also used to describe the removal of the  heart . [ 49 ] [ 50 ] [ 51 ]  A gastrectomy may be carried out because of gastric cancer or severe perforation of the stomach wall.


Fundoplication  is stomach surgery in which the fundus is wrapped around the lower esophagus and stitched into place.  It is used to treat  gastroesophageal reflux disease (GERD) . [ 52 ]


The word  stomach  is derived from  Greek   stomachos  ( στόμαχος ), ultimately from  stoma  ( στόμα ) 'mouth'. [ 53 ]   Gastro-  and  gastric  (meaning 'related to the stomach') are both derived from Greek  gaster  ( γαστήρ ) 'belly'. [ 54 ] [ 55 ] [ 56 ]


Although the precise shape and size of the stomach varies widely among different vertebrates, the relative positions of the esophageal and duodenal openings remain relatively constant. As a result, the organ always curves somewhat to the left before curving back to meet the pyloric sphincter. However,  lampreys ,  hagfishes ,  chimaeras ,  lungfishes , and some  teleost  fish have no stomach at all, with the esophagus opening directly into the intestine. These animals all consume diets that require little storage of food, no predigestion with gastric juices, or both. [ 57 ]


The gastric lining is usually divided into two regions, an anterior portion lined by fundic glands and a posterior portion lined with pyloric glands. Cardiac glands are unique to  mammals , and even then are absent in a number of species. The distributions of these glands vary between species, and do not always correspond with the same regions as in humans. Furthermore, in many non-human mammals, a portion of the stomach anterior to the cardiac glands is lined with epithelium essentially identical to that of the esophagus.  Ruminants , in particular, have a complex four-chambered stomach. The first three chambers ( rumen ,  reticulum , and  omasum ) are all lined with esophageal mucosa, [ 57 ]  while the final chamber functions like a  monogastric  stomach, which is called the  abomasum .


In  birds  and  crocodilians , the stomach is divided into two regions. Anteriorly is a narrow tubular region, the  proventriculus , lined by fundic glands, and connecting the true stomach to the  crop . Beyond lies the powerful muscular  gizzard , lined by pyloric glands, and, in some species, containing stones that the animal swallows to help grind up food. [ 57 ]


In  insects , there is also a crop. The insect stomach is called the  midgut .


Information about the stomach in  echinoderms  or  molluscs  can be found under the respective articles.


A  stomach rumble , also known as a  bowel sound ,  peristaltic sound ,  abdominal sound ,  bubble gut  or  borborygmus  (pronounced  / ˌ b ɔːr b ə ˈ r ɪ ɡ m ə s / ; plural  borborygmi ), is a rumbling, growling or gurgling noise produced by movement of the contents of the  gastrointestinal tract  as they are propelled through the  small intestine  by a series of  muscle contractions  called  peristalsis . [ 1 ]  A trained healthcare provider can listen to these intestinal noises with a  stethoscope , but they may be audible enough to be heard with the naked ear as the fluid and gas move forward in the  intestines  (in the vicinity of, but not actually within the  stomach ). The lack of bowel sounds is indicative of  ileus ,  intestinal obstruction , or some other serious pathology.


The scientific name borborygmus is related to the 16th-century French word  borborygme , itself from Latin, ultimately from Ancient Greek βορβορυγμός ( borborygmós ). The Greek term is probably   onomatopoetic  in origin.


Other causes of stomach rumbles:


If symptoms are minimal, treat by:


Avoid foods such as beans and peas along with coarse grains and dried fruits. Limiting consumption of coffee, tea, and alcohol is recommended.


The word  borborygmic  has been used in literature to describe noisy plumbing. In  Ada ,  Vladimir Nabokov  wrote: "All the toilets and waterpipes in the house had been suddenly seized with borborygmic convulsions".
In  A Long Way Down  (New York: Harper, 1959, p. 54), Elizabeth Fenwick wrote: "The room was very quiet, except for its borborygmic old radiator". [ 6 ]
 Graham Greene 's  short story  " Alas, Poor Maling " tells the tale of a luckless individual whose borborygmus takes the form of irritating noises that he has recently heard.


The word  borborygmus  has also been used in journalism to describe political turbulence. In an article in  The Atlantic ,  Graeme Wood [ 7 ]  used the word to describe the effects of mass refugee migration into Europe: "Central Europe had to digest a massive refugee flow from Syria and Afghanistan, and the resulting borborygmus upended European politics and enabled a populist wave that has yet to crest."


The  submucosa  (or  tela submucosa ) is a thin layer of  tissue  in various  organs  of the  gastrointestinal ,  respiratory , and  genitourinary  tracts. It is the layer of  dense irregular connective tissue  that supports the mucosa ( mucous membrane ) and joins it to the  muscular layer , the bulk of overlying  smooth muscle  (fibers running circularly within layer of longitudinal muscle).


The submucosa ( sub-  +  mucosa ) is to a mucous membrane what the  subserosa  ( sub-  +  serosa ) is to a  serous membrane .


Blood vessels ,  lymphatic vessels , and  nerves  (all supplying the  mucosa ) will run through here. In the intestinal wall, tiny  parasympathetic  ganglia are scattered around forming the  submucous plexus  (or "Meissner's plexus") where  preganglionic  parasympathetic neurons synapse with  postganglionic  nerve fibers that supply the  muscularis mucosae . Histologically, the wall of the alimentary canal shows four distinct layers (from the lumen moving out): mucosa, submucosa, muscularis externa, and either a  serous membrane  or an  adventitia .


In the  gastrointestinal tract  and the  respiratory tract  the submucosa contains the  submucosal glands  that secrete  mucus .


Identification of the submucosa plays an important role in diagnostic and therapeutic  endoscopy , where special  fibre-optic  cameras are used to perform procedures on the  gastrointestinal tract .  Abnormalities of the submucosa, such as  gastrointestinal stromal tumors , usually show integrity of the mucosal surface.


The submucosa is also identified in  endoscopic ultrasound  to identify the depth of tumours and to identify other abnormalities.  An injection of  dye ,  saline , or  epinephrine  into the submucosa is imperative in the safe removal of certain  polyps .


Endoscopic mucosal  resection  involves removal of the mucosal layer, and in order to be done safely, a submucosal injection of dye is performed to ensure integrity at the beginning of the procedure.


Female uterine submucosal layers are liable to develop fibroids during pregnancy and are often excised upon discovery. [ 1 ]


Small intestinal  submucosa (SIS) is submucosal  tissue  in the  small intestines  of  vertebrates .  SIS is harvested (typically from pigs) for  transplanted  structural material in several  clinical  applications, typically  biologic meshes . They have low  immunogenicity .  Some uses under investigation include a  scaffold  for  intervertebral disc  regeneration. [ 2 ] [ 3 ]


Unlike other scaffold materials, the  resorbable  SIS  extracellular matrix  (SIS-ECM) scaffold is replaced by well-organized host tissues, including differentiated  skeletal muscle . [ 4 ]


A scientific article published in March 2018 [ 5 ]  proposed a revision of the anatomical definition of the submucosa. They first saw a non compact tissue which should be submucosa using a technology called  endomicroscopy . They hypothesised that the submucosa was not compact as it was previously seen on histological analysis but form a reticular pattern. To confirm their findings, they performed fixed samples of bile duct into a freezing media in order to conserve the shape of the submucosa. They then performed a histological analysis and with several staining techniques, they described the submucosa as a network of collagenous bands separating open, formerly  fluid-filled spaces. Theses spaces are bordered by fibroblast-like cells  CD34  positive. However, these cells are devoid of ultrastructural features indicative of endothelial differentiation, including pinocytotic vesicles and Weibel-Palade bodies.


The  suspensory muscle of duodenum  (also known as  suspensory ligament of duodenum ,  Treitz's muscle  or  ligament of Treitz [ 1 ] ) is a thin  muscle  connecting the junction between the  duodenum  and  jejunum  (the  small intestine 's first and second parts, respectively), as well as the  duodenojejunal flexure  to  connective tissue  surrounding the  superior mesenteric  and  coeliac arteries . The suspensory muscle most often connects to both the third and fourth parts of the duodenum, as well as the duodenojejunal flexure, although the attachment is quite variable.


The suspensory muscle marks the formal division between the duodenum and the jejunum. This division is used to mark the difference between the  upper and lower gastrointestinal tracts , which is relevant in  clinical medicine  as it may determine the source of gastrointestinal bleeding.


The suspensory muscle is derived from  mesoderm  and plays a role in the  embryological  rotation of the gut, by offering a point of fixation for the rotating gut. It is also thought to help digestion by widening the angle of the duodenojejunal flexure.  Superior mesenteric artery syndrome  is a rare abnormality caused by a congenitally short suspensory muscle.


The  duodenum  and the  jejunum  are the first and second parts of the  small intestine , respectively. The suspensory muscle of the duodenum marks their formal division. [ 2 ]  The suspensory muscle arises from the  right crus  of the  diaphragm  as it passes around the  esophagus , continues as  connective tissue  around the stems of the  celiac trunk  (celiac artery) and  superior mesenteric artery , passes behind the  pancreas , and enters the upper part of the  mesentery , inserting into the junction between the duodenum and jejunum, the duodenojejunal flexure. [ 3 ]  Here, the muscles are continuous with the muscular layers of the duodenum. [ 1 ]


Considerable  anatomic variation  exists, in terms of length and point of attachment. [ 4 ]  Despite the classical description, the muscle only solely attaches to the duodenojejunal flexure in about 8% of people; it is far more common, 40 to 60% of the time to attach additionally to the third and fourth parts of the duodenum; and 20 to 30%  of the time it only attaches to the third and fourth parts. Moreover, separate multiple attachments are not that uncommon. [ 1 ]


According to some authors, who use the original description by Treitz, the muscle may be divided into two sections: a ligamentous portion attaching the  right crus of diaphragm  to the connective tissue surrounding the  coeliac artery  and superior mesenteric artery; and a lower muscular portion from the connective tissue attaching to the duodenum. The superior portion is also described as the  Hilfsmuskel . [ 3 ] [ 4 ]  These two parts are now considered anatomically distinct, with the  suspensory muscle  referring solely to the lower structure attaching at the duodenum. [ 1 ] [ 4 ]


The ligament contains a slender band of skeletal muscle from the diaphragm and a fibromuscular band of smooth muscle from the horizontal and ascending parts of the duodenum. When it contracts, by virtue of connections to the third and fourth parts of the duodenum, the suspensory muscle of the duodenum widens the angle of the duodenojejunal flexure, allowing movement of the intestinal contents. [ 1 ] [ 5 ]


Embryologically , the suspensory muscle of the duodenum is derived from  mesoderm . It plays an important role in the embryological rotation of the small intestine as the superior retention band. [ 1 ] [ 3 ] : 48


This ligament is an important  anatomical  landmark of the duodenojejunal flexure, separating the  upper and lower gastrointestinal tracts . For example,  bloody vomit  or  melena , black tarry stools, usually indicate a gastrointestinal bleed from a location in the upper gastrointestinal tract. In contrast,  hematochezia , bright red blood or clots in the stool, usually indicates gastrointestinal bleeding from the lower part of the gastrointestinal tract. [ 6 ]  It is an especially important landmark to note when looking at the bowel for the presence of  malrotation of the gut , a syndrome often suspected in young children when they have episodes of recurrent vomiting. Visualising a normal location of the ligament of Treitz in radiological images is critical in ruling out malrotation of the gut in a child;  it is abnormally located when malrotation is present. [ 4 ]


During a  Whipple's procedure , commonly used to treat  pancreatic cancer  by removing the  pancreas , duodenum, and part of the jejunum, the ligament of Treitz is separated from the duodenum and preserved. When the remaining jejunum is  anastamosed  with the  pylorus  of the  stomach , it may be passed through the ligament. [ 7 ]


Superior mesenteric artery syndrome  (SMA) is an extremely rare life-threatening condition that can either be congenital and chronic, or induced and acute. SMA Syndrome is characterised by compression of the duodenum between the  abdominal aorta  and the superior mesenteric artery, and may—when congenital—result from a short suspensory muscle. One surgical treatment is  Strong's operation , which involves cutting the suspensory muscle, though this is not often carried out. [ 8 ]


The suspensory muscle of the duodenum was first named in 1853 by  Václav Treitz , as the  musculus suspensorius duodeni  (in Latin), and described as consisting of a lower muscular portion with a broad base, and an upper tendinous portion blending with connective tissue around the origins of the superior mesenteric and coeliac arteries. It is commonly termed the  ligament of Treitz  by  clinicians  and as the  suspensory muscle of the duodenum  by  anatomists . It has also been likened to "a  polar ice cap  ... a structure that many refer to but few have seen." [ 1 ]


Synbiotics  refer to  food ingredients  or  dietary supplements  combining  probiotics  and  prebiotics  in a form of  synergism , hence synbiotics. [ 1 ]  The synbiotic concept was first introduced as "mixtures of probiotics and prebiotics that beneficially affect the host by improving the survival and implantation of live microbial dietary supplements in the  gastrointestinal tract , by selectively stimulating the growth and/or by activating the metabolism of one or a limited number of health-promoting  bacteria , thus improving host welfare". [ 2 ]  As of 2018, the research on this concept is preliminary, with no high-quality evidence from  clinical research  that such benefits exist.


Synbiotics may be complementary synbiotics, where each component is independently chosen for its potential effect on host health, or synergistic synbiotics, where the prebiotic component is chosen to support the activity of the chosen probiotic. [ 3 ]  Research is evaluating if synbiotics can be optimized, (known as 'optibiotics') [ 3 ]  which are purported to enhance the growth and health benefits of existing probiotics. [ 4 ]


Probiotics are live bacteria which are intended to colonize the large intestine, although as of 2018, there is no evidence that adding dietary bacteria to healthy people has any added effect. [ 5 ]  A prebiotic is a food or dietary supplement product that may induce the growth or activity of beneficial microorganisms. A prebiotic may be a  fiber , but a fiber is not necessarily a prebiotic. [ 3 ] [ 6 ]


Using prebiotics and probiotics in combination may be described as synbiotic, but the  United Nations Food & Agriculture Organization   recommends that the term "synbiotic" be used only if the net health benefit is synergistic. [ 7 ]  Synbiotic formulations in combination with pasteurized breast milk are under preliminary clinical research for their potential to ameliorate  necrotizing enterocolitis  in infants, although there was insufficient evidence to warrant recommending synbiotics for this use as of 2016. [ 8 ]


TNO (gastro-) Intestinal Models  (“TIM”) is a system of models mimicking the digestive tract. The system was developed by TNO, the  Netherlands Organisation for Applied Scientific Research . [ 1 ]


The models are dynamic computer controlled multi-compartmental systems with adjustable parameters for the physiological conditions of the stomach and intestine. Temperature, peristalsis, bile secretion, secretion of saliva, stomach and pancreas enzymes are all fully adjustable.
The TIM systems are being used to study the behavior of oral products during transit through the stomach, the small intestine and large intestine. Commonly performed studies concern the digestibility of food and food components, the bioaccessibility for absorption of pharmaceutical compounds, proteins, fat, minerals and (water- and fat-soluble) vitamins.  [ 2 ]
 [ 3 ]
 [ 4 ]
 [ 5 ]
 [ 6 ]
 [ 7 ]
 [ 8 ]


There are different models for the stomach and small intestine ( TIM-1  and  Tiny-TIM ) and a model simulating the physiological conditions of the  colon  ( TIM-2 ).


The  TIM-1  system consists of a stomach compartment and 3 compartments for the  small intestine , the duodenum, jejunum and ileum. The  Tiny-TIM  system consists of a stomach compartment and one single compartment for the small intestine. Samples can be harvested for analysis from these models from any compartment at any time.


TIM-2  simulates the colon, containing the  microbiota  as found in human colon. This model serves as a tool to study fermentation of non-digestible food components (fibers and prebiotics) and the release of drugs  specifically targeted for the colon. [ 9 ]


The  tongue  is a  muscular   organ  in the  mouth  of a typical  tetrapod . It manipulates food for chewing and swallowing as part of the  digestive process , and is the primary organ of taste. The tongue's upper surface (dorsum) is covered by  taste buds  housed in numerous  lingual papillae . It is sensitive and kept moist by  saliva  and is richly supplied with  nerves  and  blood vessels . The tongue also serves as a natural means of cleaning the teeth. [ 2 ]  A major function of the tongue is to enable speech in humans and  vocalization  in other animals.


The human tongue is divided into two parts, an  oral  part at the front and a  pharyngeal  part at the back. The left and right sides are also separated along most of its length by a vertical section of  fibrous tissue  (the  lingual septum ) that results in a groove, the median sulcus, on the tongue's surface.


There are two groups of glossal muscles. The four intrinsic muscles alter the shape of the tongue and are not attached to bone. The four paired extrinsic muscles change the position of the tongue and are anchored to bone.


The word  tongue  derives from the  Old English   tunge , which comes from  Proto-Germanic  * tungōn . [ 3 ]  It has  cognates  in other  Germanic languages —for example  tonge  in  West Frisian ,  tong  in  Dutch  and  Afrikaans ,  Zunge  in  German ,  tunge  in  Danish  and  Norwegian , and  tunga  in  Icelandic ,  Faroese  and  Swedish . The  ue  ending of the word seems to be a fourteenth-century attempt to show "proper pronunciation", but it is "neither etymological nor phonetic". [ 3 ]  Some used the spelling  tunge  and  tonge  as late as the sixteenth century.


The tongue is a  muscular hydrostat  that forms part of the floor of the  oral cavity . The left and right sides of the tongue are separated by a vertical section of fibrous tissue known as the  lingual septum . This division is along the length of the tongue save for the very back of the pharyngeal part and is visible as a groove called the median sulcus. The human tongue is divided into  anterior and posterior  parts by the terminal sulcus, which is a "V"-shaped groove. The apex of the terminal sulcus is marked by a blind foramen, the foramen cecum, which is a remnant of the median  thyroid diverticulum  in early  embryonic development . The anterior  oral  part is the visible part situated at the front and makes up roughly two-thirds the length of the tongue. The posterior  pharyngeal  part is the part closest to the  throat , roughly one-third of its length. These parts differ in terms of their  embryological development  and  nerve supply .


The anterior tongue is, at its apex, thin and narrow. It is directed forward against the lingual surfaces of the lower  incisor  teeth. The posterior part is, at its root, directed backward, and connected with the  hyoid bone  by the  hyoglossi  and  genioglossi  muscles and the  hyoglossal membrane , with the  epiglottis  by three  glossoepiglottic folds  of mucous membrane, with the  soft palate  by the  glossopalatine arches , and with the  pharynx  by the  superior pharyngeal constrictor muscle  and the  mucous membrane . It also forms the anterior wall of the  oropharynx .


The average length of the human tongue from the  oropharynx  to the tip is 10 cm. [ 4 ]  The average weight of the human tongue from adult males is 99g and for adult females 79g. [ 5 ]


In  phonetics  and  phonology , a distinction is made between the  tip  of the tongue and the  blade  (the portion just behind the tip).  Sounds made with the tongue tip are said to be  apical , while those made with the tongue blade are said to be  laminal .


The upper surface of the tongue is called the dorsum, and is divided by a groove into symmetrical halves by the  median sulcus . The  foramen cecum  marks the end of this division (at about 2.5 cm from the root of the tongue) and the beginning of the  terminal sulcus . The foramen cecum is also the point of attachment of the  thyroglossal duct  and is formed during the descent of the  thyroid diverticulum  in  embryonic development .


The terminal sulcus is a shallow groove that runs forward as a shallow groove in a  V  shape from the foramen cecum, forwards and outwards to the margins (borders) of the tongue. The terminal sulcus divides the tongue into a posterior  pharyngeal  part and an anterior  oral  part. The pharyngeal part is supplied by the  glossopharyngeal nerve  and the oral part is supplied by the  lingual nerve  (a branch of the mandibular branch (V3) of the  trigeminal nerve ) for somatosensory perception and by the  chorda tympani  (a branch of the  facial nerve ) for  taste perception .


Both parts of the tongue develop from different  pharyngeal arches .


On the undersurface of the tongue is a fold of mucous membrane called the  frenulum  that tethers the tongue at the midline to the floor of the mouth. On either side of the frenulum are small prominences called  sublingual caruncles  that the major salivary  submandibular glands  drain into.


The eight muscles of the human tongue are classified as either  intrinsic  or  extrinsic . The four intrinsic muscles act to change the shape of the tongue, and are not attached to any bone. The four extrinsic muscles act to change the position of the tongue, and are anchored to bone.


The four extrinsic muscles originate from bone and extend to the tongue. They are the  genioglossus , the  hyoglossus  (often including the  chondroglossus ) the  styloglossus , and the  palatoglossus . Their main functions are altering the tongue's position allowing for protrusion, retraction, and side-to-side movement. [ 6 ]


The genioglossus arises from the  mandible  and protrudes the tongue. It is also known as the tongue's "safety muscle" since it is the only muscle that propels the tongue forward.


The hyoglossus, arises from the  hyoid bone  and retracts and depresses the tongue. The chondroglossus is often included with this muscle.


The styloglossus arises from the  styloid process  of the  temporal bone  and draws the sides of the tongue up to create a trough for swallowing.


The palatoglossus arises from the  palatine aponeurosis , and depresses the  soft palate , moves the  palatoglossal fold  towards the midline, and elevates the back of the tongue during swallowing.


Four paired intrinsic muscles of the tongue originate and insert within the tongue, running along its length. They are the  superior longitudinal muscle , the  inferior longitudinal muscle , the  vertical muscle , and the  transverse muscle . These muscles alter the shape of the tongue by lengthening and shortening it, curling and uncurling its apex and edges as in  tongue rolling , and flattening and rounding its surface. This provides shape and helps facilitate speech, swallowing, and eating. [ 6 ]


The superior longitudinal muscle runs along the upper surface of the tongue under the mucous membrane, and functions to shorten and curl the tongue upward. It originates near the  epiglottis , at the  hyoid bone , from the median fibrous septum.


The inferior longitudinal muscle lines the sides of the tongue, and is joined to the styloglossus muscle. It functions to shorten and curl the tongue downward.


The vertical muscle is located in the middle of the tongue, and joins the superior and inferior longitudinal muscles. It functions to flatten the tongue.


The transverse muscle divides the tongue at the middle, and is attached to the  mucous membranes  that run along the sides. It functions to lengthen and narrow the tongue.


The tongue receives its  blood  supply primarily from the  lingual artery , a branch of the  external carotid artery . The  lingual veins  drain into the  internal jugular vein . The floor of the mouth also receives its blood supply from the lingual artery. [ 6 ]  There is also a secondary blood supply to the root of tongue from the  tonsillar branch of the facial artery  and the  ascending pharyngeal artery .


An area in the neck sometimes called the  Pirogov triangle  is formed by the intermediate tendon of the  digastric muscle , the posterior border of the  mylohyoid muscle , and the  hypoglossal  nerve. [ 7 ] [ 8 ]  The lingual artery is a good place to stop severe  hemorrhage  from the tongue.


Innervation of the tongue consists of motor fibers,  special sensory  fibers for taste, and  general sensory  fibers for sensation. [ 6 ]


Innervation of taste and sensation is different for the anterior and posterior part of the tongue because they are derived from different embryological structures ( pharyngeal arch  1 and pharyngeal arches 3 and 4, respectively). [ 9 ]


The tip of tongue drains to the submental nodes. The left and right halves of the anterior two-thirds of the tongue drains to  submandibular lymph nodes , while the posterior one-third of the tongue drains to the jugulo-omohyoid nodes.


The upper surface of the tongue is covered in  masticatory mucosa , a type of  oral mucosa , which is of  keratinized stratified squamous epithelium . Embedded in this are numerous  papillae , some of which house the  taste buds  and their  taste receptors . [ 10 ]  The lingual papillae consist of  filiform ,  fungiform ,  vallate  and  foliate papillae , [ 6 ]  and only the filiform papillae are not associated with any taste buds.


The tongue can divide itself in dorsal and ventral surface. The dorsal surface is a stratified squamous keratinized epithelium, which is characterized by numerous mucosal projections called papillae. [ 11 ]  The lingual papillae covers the dorsal side of the tongue towards the front of the terminal groove. The ventral surface is stratified squamous non-keratinized epithelium which is smooth. [ 12 ]


The tongue begins to develop in the fourth week of  embryonic development  from a median swelling – the  median tongue bud  (tuberculum impar) of the  first pharyngeal arch . [ 13 ]


In the fifth week a pair of  lateral lingual swellings , one on the right side and one on the left, form on the first pharyngeal arch. These lingual swellings quickly expand and cover the median tongue bud. They form the anterior part of the tongue that makes up two-thirds of the length of the tongue, and continue to develop through  prenatal development . The line of their fusion is marked by the  median sulcus . [ 13 ]


In the fourth week, a swelling appears from the second  pharyngeal arch , in the midline, called the  copula . During the fifth and sixth weeks, the copula is overgrown by a swelling from the third and fourth arches (mainly from the third arch) called the  hypopharyngeal eminence , and this develops into the posterior part of the tongue (the other third and the posterior most part of the tongue is developed from the fourth pharyngeal arch). The hypopharyngeal eminence develops mainly by the growth of  endoderm  from the third pharyngeal arch. The boundary between the two parts of the tongue, the anterior from the first arch and the posterior from the third arch is marked by the terminal sulcus. [ 13 ]  The terminal sulcus is shaped like a  V  with the tip of the V situated posteriorly. At the tip of the terminal sulcus is the  foramen cecum , which is the point of attachment of the  thyroglossal duct  where the embryonic  thyroid  begins to descend. [ 6 ]


Chemicals that stimulate  taste receptor  cells are known as  tastants . Once a tastant is dissolved in  saliva , it can make contact with the  plasma membrane  of the gustatory hairs, which are the sites of taste  transduction . [ 14 ]


The tongue is equipped with many  taste buds  on its  dorsal  surface, and each taste bud is equipped with taste receptor cells that can sense particular classes of tastes. Distinct types of taste receptor cells respectively detect substances that are sweet, bitter, salty, sour, spicy, or taste of  umami . [ 15 ]  Umami receptor cells are the least understood and accordingly are the type most intensively under research. [ 16 ]  There is a  common misconception  that different sections of the tongue are exclusively responsible for different  basic tastes . Although widely taught in schools in the form of the  tongue map , this is incorrect; all taste sensations come from all regions of the tongue, although certain parts are more sensitive to certain tastes. [ 17 ]


The tongue is an important accessory organ in the digestive system. The tongue is used for crushing food against the hard palate, during mastication and manipulation of food for softening prior to swallowing. The  epithelium  on the tongue's upper, or dorsal surface is  keratinised . Consequently, the tongue can grind against the hard palate without being itself damaged or irritated. [ 18 ]