In the 19th century many new types of enema administration equipment were devised. Devices allowing gravity to infuse the solution, like those mentioned above used by South American indigenous people and like the enema bag described by Johann Jacob Woyts, came into common use. These consist of a nozzle at the end of a hose which connects a reservoir, either a bucket or a rubber bag, which is filled with liquid and held or hung above the recipient. [ 93 ]


In the early 20th century the disposable  microenema , a squeeze bottle, was invented by  Charles Browne Fleet . [ 99 ]


The term "colonic irrigation" is commonly used in  gastroenterology  to refer to the practice of introducing water through a colostomy or a surgically constructed conduit as a treatment for constipation. [ 100 ]  The  Food and Drug Administration  has ruled that colonic irrigation equipment is not approved for sale for the purpose of general well-being [ 101 ]  and has taken action against many distributors of this equipment, including a  Warning Letter . [ 102 ]


The same term is also used in  alternative medicine  where it may involve the use of substances mixed with water in order to  detoxify  the body. Practitioners believe the accumulation of fecal matter in the large intestine leads to ill health. [ 103 ]   This resurrects the old medical concept of  autointoxication  which was orthodox doctrine up to the end of the 19th century but which has now been discredited. [ 104 ] [ 105 ] [ 106 ]


In the late 19th century Dr.  John Harvey Kellogg  made sure that the bowel of each and every patient was plied with water, from above and below. His favorite device was an enema machine ("just like one I saw in Germany") that could run fifteen gallons of water through a person's bowel in a matter of seconds. Every water enema was followed by a pint of yogurt—half was eaten, the other half was administered by enema "thus planting the protective germs where they are most needed and may render most effective service." The yogurt served to replace "the intestinal flora" of the bowel, creating what Kellogg claimed was a completely clean intestine. [ 107 ]


Chlorine dioxide  enemas have been fraudulently marketed as a medical treatment, primarily for  autism . This has resulted, for example, in a six-year-old boy needing to have his colon removed and a colostomy bag fitted, [ 108 ] [ 109 ]  complaints to the FDA reporting life-threatening reactions, [ 110 ]  and even death. [ 111 ]


Proponents falsely claim that administering autistic children these enemas results in the expulsion of parasitic worms (" rope worms "), which actually are fragments of damaged intestinal  epithelium  that are misinterpreted as being human pathogens. [ 112 ] [ 113 ]  Oral and rectal use of the solution has also been promoted as a cure for  HIV ,  malaria ,  viral hepatitis ,  influenza ,  common colds ,  acne ,  cancer ,  Parkinson's , and much more.


Chlorine dioxide is a potent and toxic bleach [ 114 ]  that is relabeled for "medicinal purposes" to a variety of brand names including, but not limited, to MMS,  Miracle Mineral Supplement , and CD protocol. [ 115 ]  For oral use, the doses recommended on the labeling can cause nausea, vomiting, diarrhea, and potentially life-threatening dehydration. [ 116 ]


No clinical trials have been performed to test the health claims made for chlorine dioxide, which originate from former  Scientologist  Jim Humble [ 117 ]  in his 2006  self-published  book,  The Miracle Mineral Solution of the 21st Century [ 118 ]  and from anecdotal reports. The name MMS was coined by Humble. Sellers sometimes describe MMS as a  water purifier  so as to circumvent medical regulations. [ 119 ]  The  International Federation of Red Cross and Red Crescent Societies  rejected "in the strongest terms" reports by promoters of MMS that they had used the product to fight malaria. [ 120 ]


Well documented as having no proven benefits and considered by medical authorities as rash and potentially dangerous is an enema of  coffee . [ 104 ] [ 121 ]


A coffee enema can cause numerous maladies including  infections ,  sepsis  (including  campylobacter  sepsis), severe  electrolyte imbalance ,  colitis , polymicrobial enteric sepsis,  proctocolitis ,  salmonella ,  brain abscess , and heart failure, [ 122 ] [ 123 ] [ 124 ] [ 125 ] [ 126 ] [ 127 ] [ 128 ] [ 129 ] [ 130 ] [ excessive citations ]


and deaths related to coffee enemas have been documented. [ 131 ]


Gerson therapy  includes administering enemas of coffee, [ 132 ]  as well as of  castor oil  and sometimes of  hydrogen peroxide  or of  ozone . [ 133 ]


Some proponents of alternative medicine have claimed that coffee enemas have an anti- cancer  effect by "detoxifying" metabolic products of tumors [ 122 ]  but there is no medical scientific evidence to support this. [ 121 ] [ 123 ] [ 134 ]


Enjoyment of enemas is known as  klismaphilia , which medically is classified as a  paraphilia . [ 135 ] [ 136 ]  A person with klismaphilia is a  klismaphile .


Both women and men may enjoy sexual enema play, heterosexually and homosexually, experiencing  sexual arousal  from enemas which they find gratifying or sensual [ 137 ] [ 138 ]  and which can be an auxiliary to, or even a substitute for, genital  sexual activity . [ 137 ] [ 138 ]


Klismaphiles may perceive pleasure from a large, water-distended belly, or the feeling of internal pressure. An enema fetish may include sexual attraction to the involved equipment, processes, environments, situations, or scenarios, [ 139 ]  Klismaphiles can gain satisfaction of enemas through fantasies, by actually receiving or giving one, or through the process of eliminating steps to being administered one (e.g., under the pretence of being constipated). [ 138 ]


That some women use enemas while masturbating was documented by  Alfred Kinsey  in  Sexual Behavior in the Human Female : "There were still other masturbatory techniques which were regularly or occasionally employed by some 11 percent of the females in the sample... Douches, streams of running water, vibrators, urethral insertions, enemas, other anal insertions, sado-masochistic activity, and still other methods were occasionally employed, but none of them in any appreciable number of cases." [ 140 ]


Besides klismaphilia, the intrinsic enjoyment of enemas, there are other uses of enemas in sexual play. [ 141 ]


Enemas are sometimes used in  sadomasochistic  activities [ 142 ] [ 143 ]  for  erotic humiliation [ 144 ]  or for physical discomfort. [ 145 ]


Another sexual use for enemas is to empty the rectum as a prelude to other anal sexual activities such as  anal sex , [ 146 ]  possibly reducing risk of infection.


This is different from klismaphilia, in which the enema is enjoyed for itself and as a part of sexual arousal and gratification. [ 146 ]


Rectal douching is a common practice among people who take a receptive role in anal sex [ 147 ]  although rectal douching before anal sex may increase the risk of transferring  HIV , [ 148 ]   hepatitis B , [ 149 ]  and other diseases. [ 150 ]


Noting that deaths have been reported from  alcohol poisoning  via enemas, [ 151 ]  an  alcohol enema  can be used to very quickly instill alcohol into the bloodstream, absorbed through the membranes of the colon. However, great care must be taken as to the amount of alcohol used. Only a small amount is needed as the intestine absorbs the alcohol far more quickly than the stomach.


Preceding an enema for administration of drugs or alcohol, a cleansing enema may first be used for cleaning the colon to help increase the rate of absorption. [ 152 ]


All across  Mesoamerica  ritual enemas were employed to consume psychoactive substances, e.g.,  balché ,  alcohol ,  tobacco ,  peyote , and other  hallucinogenic drugs  and  entheogens , most notably by the  Maya , thus attaining more intense trance states more quickly, and Mayan classic-period sculpture and ceramics depict hallucinogenic enemas used in rituals. [ 79 ]  Some tribes continue the practice in the present day. [ 153 ]


With historical roots in the  Indian subcontinent , enemas in  Ayurveda , called  Basti  or Vasti, form part of  Panchakarma  procedure in which  herbal medicines  are introduced rectally. [ 154 ]


Enemas have also been forcibly applied as a means of punishment.


Political dissenters in post-independence Argentina were given enemas of  chili pepper  and  turpentine . [ 155 ]  Turpentine enemas are very harsh purgatives. [ 156 ]


In the  Guantanamo Bay Detention Camp , the  Senate Intelligence Committee report on CIA torture  documented instances of enemas being used by the  Central Intelligence Agency  in order to ensure "total control" over detainees. [ 157 ]  Enemas, officials said, are uncomfortable and degrading, [ 158 ]  The CIA forced nutrient enema on detainees who attempted hunger strikes, documenting "With head lower than torso … sloshing up the large intestines … [what] I infer is that you get a tube up as you can … We used the largest Ewal  [ sic ] tube we had" wrote an officer, [ 159 ]  and "violent enemas" is how a detainee described what he received. [ 160 ]


In the  Dionysus '  satyr play   Limos ,  Silenus  attempts to give an enema to  Heracles . [ 161 ]


In  Cervantes '  Don Quixote , a narrative to Sancho includes “The Knight of the Sun ... bound hand and foot ... was administered a clyster of snow water and sand that almost disracted him" [ 162 ]


In the 17th century, satirists made physicians a favorite target, resembling  Molière 's caricature whose prescription for anything was "clyster, bleed, purge," or "purge, bleed, clyster". [ 163 ]


In Molière's play  The Imaginary Invalid , Argan, a severe  hypochondriac , is addicted to enemas as indicated by such lines as when Bĕralde asks, "Can't you be one moment without a purge?" [ 164 ]


In  Grace Metalious 's novel  Peyton Place , the town doctor tells of "a young boy with the worst case of dehydration I ever saw. It came from getting too many enemas that he didn't need. Sex, with a capital S-E-X.". [ 165 ]  As a teenager, the boy enjoys receiving enemas from his mother. [ 166 ]


In  Flora Rheta Schreiber 's book  Sybil , Sybil's psychiatrist asks her "What's Mama been doing to you, dear?...I know she gave you the enemas." [ 167 ]


In  The Right Stuff , during flight training astronaut  Alan Shepard  retains a barium enema, [ 168 ]  given two floors away from a toilet, embarrassedly riding a public elevator wearing a  hospital gown  and holding the enema bag with its tip still inserted in him. [ 169 ] [ 170 ]


Water Power  is a film loosely based on the real-life exploits of  Michael H. Kenyon , an American criminal who pleaded guilty to a decade-long series of armed robberies of female victims, some of which involved sexual assaults in which he would give them enemas. [ 171 ]


The lyrics of  Frank Zappa 's song  The Illinois Enema Bandit  are concerned with  Michael H. Kenyon 's  sexual assaults  which included administering involuntary enemas. [ 172 ]


A 365-kilogram (805-pound) brass statue of a syringe enema bulb held aloft by three cherubs stands in front of the "Mashuk" spa in the settlement of  Zheleznovodsk  in Russia. Inspired by the 15th century Renaissance painter Botticelli, it was created by a local artist who commented that "An enema is an unpleasant procedure as many of us may know. But when cherubs do it, it's all right." When unveiled on 19 June 2008, posted on one of the spa's wall was a banner declaring "Let's beat constipation and sloppiness with enemas."  The spa lying in the Caucasus Mountains region, known for dozens of spas that routinely treat digestive and other complaints with enemas of mineral spring water, the director commented "An enema is almost a symbol of our region." [ 173 ] [ 174 ]  It is the only known monument to the enema. [ 175 ]


Sources


"A professional nursing instructional video demonstrating administering a cleansing enema" .  Taber's Medical Dictionary . K. A. Davis Company . Retrieved  17 July  2014 .


In medicine  Enteroenteric circulation  is the secretion back into the  intestines  of substances previously taken up from it. It occurs when there is a negative relative concentration of substance in the
intestines, making it passively diffuse from the  mesenteric circulation  into the  intestinal lumen  and is trapped. [ 1 ]


Examples of toxins that exhibit enteroenteric circulation include  theophylline ,  phenobarbital , and  phenytoin . [ 1 ]  Administration of  activated charcoal  inhibits the enteroenteric circulation of such substances, and is therefore useful in overdose or intoxication. [ 2 ]


The  enterogastric reflex  is one of the three extrinsic reflexes of the  gastrointestinal tract , the other two being the  gastroileal reflex  and the  gastrocolic reflex . [ 1 ]   The enterogastric reflex is stimulated by  duodenal  distension. [ 2 ]  It can also be stimulated by a pH of 3-4 in the  duodenum  and by a pH of 1.5 in the stomach.  Upon initiation of the reflex, the release of  gastrin  by G-cells in the antrum of the  stomach  is shut off.  This in turn inhibits  gastric motility  and the secretion of  gastric acid  ( HCl ). [ 1 ]


The stomach's contents are inhibited from emptying into the small intestine by:


The stomach's contents empty through the pylorus, allowing digestion to proceed, when there is:


In  medicine , the  fecal fat test  is a diagnostic test for  fat   malabsorption  conditions, which lead to excess fat in the feces ( steatorrhea ).


In the  duodenum , dietary fat (primarily  triglycerides ) is digested by  enzymes  such as  pancreatic lipase  into smaller molecules of 1,2-Diacylglycerols and free fatty acids, which can be absorbed through the wall of the  jejenum  of the small intestine  [ 1 ]  and enter  circulation  for  metabolism  and storage. Since  fat  is a valuable nutrient,  human feces  normally contains very little undigested fat. However, a number of diseases of the pancreas and gastrointestinal tract are characterized by fat malabsorption.


Examples of such diseases are:


In the simplest form of the fecal fat test, a random fecal specimen is submitted to the  hospital laboratory  and examined under a  microscope  after  staining  with a  Sudan III  or  Sudan IV  dye (" Sudan staining "). Visible amounts of fat indicate some degree of fat malabsorption.


Quantitative fecal fat tests measure and report an amount of fat. This is usually done over a period of three days, the patient collecting all of their feces into a container.


The container is thoroughly mixed to homogenize the feces, without using specific mixer equipment. A small sample from the feces is collected. The fat content is extracted with  solvents  and measured by  saponification  (turning the fat into  soap ).


Normally, up to 7  grams  of fat can be malabsorbed in people consuming 100 grams of fat per day. In patients with  diarrhea , up to 12 grams of fat may be malabsorbed since the presence of diarrhea interferes with fat absorption, even when the diarrhea is not due to fat malabsorption.


Fish oil , sold under the brand name  Omegaven , is a  fatty acid  emulsion. [ 2 ]  It is used for  total parenteral nutrition  (feeding directly into a  venous  catheter), e.g. in  short bowel syndrome . [ 2 ]  It is rich in  omega-3 fatty acids . [ 2 ]


Fish oil triglycerides was approved for use in the United States in July 2018, [ 3 ]  and is available to people on the US market by prescription effective November 2018. [ 4 ]


In 2021, it was the 283rd most commonly prescribed medication in the United States, with more than 700,000 prescriptions. [ 5 ] [ 6 ]


It has gained popularity in children in preference to the more commonly used  intralipid  after case reports that it reduced the risk of liver damage. [ 7 ]


A 2007, study indicated that the use of Omegaven may be an appropriate intervention strategy for newborns with a very  low birth weight ,  gastroschisis , and  intestinal atresia . [ 8 ]


A  clinical trial  exploring the use of fish oil as an adjunct to parenteral nutrition in surgical  intensive care units  at  National Taiwan University Hospital  completed in March 2007. [ 9 ]


Although the use of fish oil triglycerides in children in the United States is experimental, the use of it in adults in Europe is less controversial. [ 10 ]  In European studies, fish oil triglycerides have been associated with a reduction in  psoriasis , when contrasted to administration of  omega-6 fatty acid   Lipoven . [ 11 ]  Fish oil triglycerides have also been associated with reduced mortality and antibiotic use during hospital stays. [ 12 ]


FODMAPs  or  fermentable  oligosaccharides ,  disaccharides ,  monosaccharides , and  polyols [ 1 ]  are short-chain  carbohydrates  that are poorly absorbed in the  small intestine  and ferment in the colon. They include short-chain  oligosaccharide  polymers of  fructose  ( fructans ) and  galactooligosaccharides  (GOS,  stachyose ,  raffinose ),  disaccharides  ( lactose ),  monosaccharides  ( fructose ), and  sugar alcohols  ( polyols ), such as  sorbitol ,  mannitol ,  xylitol , and  maltitol . [ 1 ] [ 2 ]  Most FODMAPs are naturally present in food and the human diet, but the polyols may be added artificially in commercially prepared foods and beverages.


FODMAPs cause digestive discomfort in some people. The reasons are hypersensitivity to  luminal  distension or a proclivity to excess water retention and gas production and accumulation, but they do not cause intestinal inflammation. Naturally occurring FODMAPs may help avert digestive discomfort for some people because they produce beneficial alterations in the  gut flora . [ 3 ] [ 4 ] [ 5 ] [ 6 ]  They are not the cause of these disorders, [ 7 ]  but a  low-FODMAP diet , restricting FODMAPs, might help to improve digestive symptoms in adults with  irritable bowel syndrome  (IBS) and other  functional gastrointestinal disorders  (FGID). [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ]  Avoiding all FODMAPs long-term may have a detrimental impact on the  gut microbiota  and  metabolome . [ 2 ] [ 9 ] [ 11 ] [ 12 ]


FODMAPs, especially fructans, are present in small amounts in  gluten-containing grains  and have been identified as a possible cause of symptoms in people with  non-celiac gluten sensitivity . [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 3 ]  They are only minor sources of FODMAPs when eaten in the usual standard quantities in the daily diet. [ 13 ]  As of 2019, reviews conclude that although FODMAPs present in wheat and related grains may play a role in non-celiac gluten sensitivity, they only explain certain gastrointestinal symptoms, such as  bloating , but not the  extra-digestive symptoms  that people with non-celiac gluten sensitivity may develop, such as  neurological disorders ,  fibromyalgia , psychological disturbances, and  dermatitis . [ 3 ] [ 17 ] [ 13 ]  Consuming a low FODMAP diet without a previous medical evaluation could cause health risks because it can ameliorate and mask digestive symptoms of  celiac disease , delaying or avoiding its correct diagnosis and therapy. [ 18 ]


Some FODMAPs, such as fructose, are readily absorbed in the small intestine of humans via  GLUT receptors . [ 19 ]  Absorption thus depends on the appropriate expression and delivery of these receptors in the intestinal  enterocyte  to both the apical surface, contacting the lumen of the intestine (e.g.,  GLUT5 ), and to the basal membrane, contacting the blood (e.g.,  GLUT2 ). [ 19 ]  Improper absorption of these FODMAPS in the small intestine leaves them available for absorption by  gut flora . The resultant metabolism by the gut flora leads to the production of gas and potentially results in bloating and  flatulence . [ 7 ]


Although FODMAPs can cause certain digestive discomfort in some people, not only do they not cause intestinal inflammation, but they help prevent it because they produce beneficial alterations in the intestinal flora that contribute to maintaining good colon health. [ 4 ] [ 5 ] [ 6 ]


FODMAPs are not the cause of  irritable bowel syndrome  or other  functional gastrointestinal disorders , but rather a person develops symptoms when the underlying bowel response is exaggerated or abnormal. [ 7 ]


Fructose malabsorption  and  lactose intolerance  may produce IBS symptoms through the same mechanism, but unlike other FODMAPs, poor absorption of fructose is found in only a minority of people. Lactose intolerance is found in most adults, except for specific geographic populations, notably those of European descent. [ 20 ]  Many who benefit from a low FODMAP diet need not restrict fructose or lactose. It is possible to identify these two conditions with  hydrogen  and  methane   breath testing , thus eliminating the necessity for dietary compliance. [ 7 ]


The significance of sources of FODMAPs varies through differences in dietary groups such as geography, ethnicity, and other factors. [ 7 ]  Commonly used FODMAPs comprise the following: [ 21 ]


Sources of fructans  include  wheat ,  rye ,  barley ,  onion ,  garlic ,  Jerusalem  and  globe artichoke ,  beetroot ,  dandelion leaves , the white part of  leeks , the white part of  spring onion ,  brussels sprouts ,  savoy cabbage , and  prebiotics  such as fructooligosaccharides ( FOS ),  oligofructose  and  inulin . [ 22 ] [ failed verification ] [ 7 ] [ 23 ]   Asparagus ,  fennel ,  red cabbage , and  radicchio  contain moderate amounts but may be eaten if the advised portion size is observed. [ 22 ] [ failed verification ]


Pulses  and  beans  are the main dietary sources (although  green beans , canned  lentils , sprouted  mung beans ,  tofu  (not silken), and  tempeh  contain comparatively low amounts). [ 22 ] [ failed verification ] [ 23 ]  Supplements of the enzyme  alpha-galactosidase  may reduce symptoms, [ 24 ]  assuming the enzyme product does not contain other FODMAPs, such as polyol  artificial sweeteners . [ citation needed ]


Polyols are found naturally in  mushrooms , some fruit (particularly  stone fruits ), including  apples ,  apricots ,  avocados ,  blackberries ,  cherries ,  lychees ,  nectarines ,  peaches ,  pears ,  plums ,  prunes ,  watermelon , and in some vegetables, including  cauliflower ,  snow peas , and mange-tout peas. [ 25 ]   Cabbage ,  chicory , and fennel contain moderate amounts, but may be eaten in a low-FODMAP diet if the advised portion size is observed. [ 26 ] [ better source needed ] [ failed verification ]


Polyols, specifically  sugar alcohols , used as  artificial sweeteners  in commercially prepared food, beverages, and chewing gum, include  isomalt ,  maltitol ,  mannitol ,  sorbitol , and  xylitol . [ 7 ] [ 23 ]


People following a low-FODMAP diet may be able to tolerate moderate amounts of fructose and lactose, particularly if they have  lactase persistence . [ 27 ]


A  low-FODMAP diet  consists of the global restriction of all fermentable carbohydrates (FODMAPs), [ 7 ]  and is recommended only for a short time. A low-FODMAP diet is recommended for managing patients with  irritable bowel syndrome  (IBS) and can reduce digestive symptoms of IBS, including bloating [ 28 ]  and flatulence. [ 29 ]


Several studies have found a low-FODMAP diet to improve digestive symptoms in adults with irritable bowel syndrome, [ 8 ] [ 9 ] [ 10 ] [ 11 ]  but its long-term use can have negative effects, because it has a detrimental impact on the  gut microbiota  and  metabolome . [ 2 ] [ 9 ] [ 11 ] [ 12 ]  It should only be used for short periods and under the advice of a specialist. [ 30 ]  More study is needed to evaluate its effectiveness in children with irritable bowel syndrome. [ 8 ]  Small studies (which are susceptible to bias) show little evidence of its effectiveness in treating functional symptoms of  inflammatory bowel disease  (IBD). [ 31 ] [ 32 ]  More study is needed to assess the true impact of this diet on health. [ 9 ] [ 11 ]


FODMAPs present in  gluten-containing grains  have been identified as a possible cause of gastrointestinal symptoms in people with  non-celiac gluten sensitivity , either by themselves, [ 33 ]  or in combination effect with gluten and other proteins in gluten-containing cereals, such as amylase-trypsin inhibitors (ATIs). [ 14 ] [ 13 ]  The amount of fructans in these cereals is small. In rye, they account for 3.6–6.6% of dry matter, 0.7–2.9% in wheat, and barley contains only trace amounts. [ 3 ]  They are only minor sources of FODMAPs when eaten in common dietary amounts. [ 13 ]  Wheat and rye may comprise a major source of fructans when consumed in large amounts. [ 7 ]


In a 2018 double-blind, crossover research study on 59 persons on a  gluten-free diet  with challenges of  gluten ,  fructans , or  placebo , intestinal symptoms (specifically  bloating ) were (borderline) significantly higher after challenge with fructans, in comparison with gluten proteins (P=0.049). [ 3 ] [ 17 ]  Although the differences between the three interventions were small, the authors concluded that fructans are more likely to cause gastrointestinal symptoms in non-celiac gluten sensitivity than gluten. [ 3 ]  Fructans used in the study were extracted from  chicory  root, and the results may or may not apply to wheat fructans. [ 17 ]


A 2018 review concluded that although fructan intolerance may play a role in non-celiac gluten sensitivity, it only explains some gastrointestinal symptoms. Fructan intolerance does not explain the   extra-digestive symptoms  that people with non-celiac gluten sensitivity may develop, such as  neurological disorders ,  fibromyalgia , psychological disturbances, and  dermatitis . This review also found that FODMAPs may cause digestive symptoms when the person is hypersensitive to  luminal  distension. [ 3 ]


A 2019 review concluded that wheat fructans could cause certain IBS-like symptoms, such as  bloating , but that they are not likely to cause immune activation or extra-digestive symptoms, as many people with non-celiac gluten sensitivity reported resolution of their symptoms after removing gluten-containing cereals. These same participants continued to eat fruits and vegetables with high FODMAP content without issue. [ 17 ]


In  medicine ,  fragmentation  is an operation that breaks of solid matter in a body part into pieces. [ 1 ]   Physical force  (e.g.,  manual force ,  ultrasonic force ), applied directly or indirectly through intervening body parts, are used to break down the solid matter into pieces. The solid matter may be an abnormal  by-product of a biological function, or a  foreign body . The pieces of solid matter are not taken out, but are eliminated or absorbed through normal biological functions. Examples would be the fragmentation of  kidney  and  urinary bladder  stones ( nephrolithiasis  and  urolithiasis , respectively) by  shock-wave lithotripsy ,  laser   lithotripsy , or  transurethral lithotripsy . [ citation needed ]


The code for fragmentation in  ICD-10-PCS  is 0FF. [ 1 ] [ unreliable source? ]


This  medical treatment –related article is a  stub . You can help Wikipedia by  expanding it .


2L71 ,  2B4N ,  2OBU ,  2QKH ,  2L70 ,  1T5Q


Gastric inhibitory polypeptide   (GIP ), also known as  glucose-dependent insulinotropic polypeptide , is an  inhibiting hormone  of the  secretin family  of  hormones . [ 5 ]   While it is a weak inhibitor of  gastric acid  secretion, its main role, being an  incretin , is to stimulate  insulin  secretion. [ 6 ]


GIP, along with  glucagon-like peptide-1  (GLP-1), belongs to a class of molecules referred to as  incretins , [ 7 ]  which stimulate insulin release on oral food intake.


GIP is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesized by K cells, which are found in the  mucosa  of the  duodenum  and the  jejunum  of the  gastrointestinal tract . [ 8 ]


Like all  endocrine   hormones , it is transported by blood.


Gastric inhibitory polypeptide receptors  are seven-transmembrane proteins ( GPCRs ) found on  beta-cells  in the  pancreas .


It has traditionally been named  gastrointestinal inhibitory peptide  or  gastric inhibitory peptide  and was found to decrease the secretion of  stomach acid [ 9 ]   to protect the  small intestine  from acid damage, reduce the rate at which  food  is transferred through the  stomach , and inhibit the GI motility and secretion of acid. However, this is incorrect, as it was discovered that these effects are achieved only with higher-than-normal physiological level, and that these results naturally occur in the body through a similar  hormone ,  secretin . [ 10 ]


It is now believed that the function of GIP is to induce  insulin  secretion, which is stimulated primarily by  hyperosmolarity  of  glucose  in the duodenum. [ 11 ]  After this discovery, some researchers prefer the new name of  glucose-dependent insulinotropic peptide , while retaining the  acronym  "GIP."  The amount of insulin secreted is greater when glucose is administered orally than intravenously. [ 12 ]


In addition to its role as an incretin, GIP is known to inhibit  apoptosis  of the pancreatic beta cells and to promote their proliferation. It also stimulates  glucagon  secretion and fat accumulation. GIP receptors are expressed in many organs and tissues including the  central nervous system  enabling GIP to influence  hippocampal  memory formation and regulation of appetite and satiety. [ 13 ]


GIP recently appeared as a major player in  bone remodeling . Researchers at Universities of Angers and Ulster evidenced that genetic ablation of the GIP receptor in mice resulted in profound alterations of bone microarchitecture through modification of the adipokine network. [ 14 ]  Furthermore, the deficiency in GIP receptors has also been associated in mice with a dramatic decrease in bone quality and a subsequent increase in fracture risk. [ 15 ]  However, the results obtained by these groups are far from conclusive because their animal models give discordant answers and  these works should be analysed very carefully. [ citation needed ]


It has been found that  type 2 diabetics  are not responsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. [ 16 ]  In research involving  knockout mice , it was found that absence of the GIP receptors correlates with resistance to  obesity . [ 17 ]


Gelesis100 , sold under the brand name  Plenity , is an oral  hydrogel  used to treat  overweight  and  obesity . [ 1 ]  It absorbs water and expands in the  stomach  and  small bowel  thereby increasing feelings of fullness. Possible side effects include primarily gastrointestinal symptoms, [ 2 ]  such as  diarrhea ,  abdominal distention , infrequent bowel movements,  constipation ,  abdominal pain , and  flatulence . [ 3 ]  It is contraindicated in  pregnancy ,  chronic malabsorption syndromes , and  cholestasis . [ 1 ]  The  US Food and Drug Administration  approved it in 2019 as a medical device. Gelesis100 was developed by the company  Gelesis .


The US Food and Drug Administration approved the use of Gelesis100 in April 2019 as a  medical device . [ 4 ]  Gelesis100 is the first treatment of its kind for overweight and obesity. [ 2 ]  In 2022, the American Gastroenterology Association published a guideline for the management of obesity, which recommended the use of Gelesis100 be limited to clinical trials due to limited evidence. [ 5 ]


Gelesis100 is used to treat obesity and overweight as an  anti-obesity medication . [ 1 ]  Gelesis100 is taken as a pill before meals with water. [ 6 ] [ 7 ]


Gelesis100 has been criticized for its small impact on weight loss relative to side effects. [ 8 ]


Gelesis100 is an oral superabsorbent hydrogel, which is produced from  carboxymethylcellulose  and  citric acid . [ 1 ] [ 9 ]  The cross-linked product forms a hydrophilic matrix, which absorbs water. [ 1 ]  Taken in capsule form by mouth, [ 10 ]  as Gelesis100 absorbs water, it expands in the stomach and small intestine. [ 3 ] [ 6 ]  After absorbing water, a semisolid gel structure forms, which may promote satiety and result in weight loss [ 1 ]  via reduced caloric intake. [ 5 ]


Gelesis100 is contraindicated in pregnancy, chronic malabsorption syndromes, and cholestasis. [ 1 ]


Side effects consist of minor gastrointestinal symptoms, [ 2 ]  including diarrhea, abdominal distention, infrequent bowel movements, constipation, abdominal pain, and flatulence. [ 3 ]  Gelesis100 is not associated with any severe adverse events. [ 11 ]  However, long-term safety data beyond 24 weeks is not available. [ 11 ]


Glycogen storage disease type 0  is a disease characterized by a deficiency in the  glycogen synthase  enzyme (GSY). Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified as a  glycogen storage disease  because it is another defect of glycogen storage and can cause similar problems. There are two  isoforms  (types) of glycogen synthase enzyme; GSY1 in muscle and GSY2 in liver, each with a corresponding form of the disease. [ 1 ]  Mutations in the liver  isoform  (GSY2), causes  fasting   hypoglycemia , high blood  ketones , increased free fatty acids and low levels of  alanine  and  lactate .  Conversely, feeding in these patients results in  hyperglycemia  and  hyperlactatemia .


The most common clinical history in patients with glycogen-storage disease type 0 (GSD-0) is that of an infant or child with symptomatic hypoglycemia or seizures that occur before breakfast or after an inadvertent fast. In affected infants, this event typically begins after they outgrow their nighttime feeds. In children, this event may occur during acute GI illness or periods of poor enteral intake. [ citation needed ]


Mild hypoglycemic episodes may be clinically unrecognized, or they may cause symptoms such as drowsiness, sweating, lack of attention, or pallor. Uncoordinated eye movements, disorientation, seizures, and coma may accompany severe episodes. [ 2 ]


Glycogen-storage disease type 0 affects only the liver. Growth delay may be evident with height and weight percentiles below average. Abdominal examination findings may be normal or reveal only mild hepatomegaly. [ citation needed ]  Signs of acute hypoglycemia may be present, including the following: [ 2 ]


Glycogen-storage disease type 0 is caused by genetic defects in the gene that codes for liver glycogen synthetase (GYS2), which is located on chromosome band 12p12.2. [ citation needed ]


Glycogen synthetase catalyzes the rate-limiting reaction for glycogen synthesis in the liver by transferring glucose units from uridine 5'-diphosphate (UDP)-glucose to a glycogen primer. Its action is highly regulated by a mechanism of  phosphorylation  and dephosphorylation and modulated by counter-regulatory hormones including  insulin ,  epinephrine , and glucagon. [ citation needed ]


Mutations in the gene for liver glycogen synthetase (GYS2, 138571) result in decreased or absent activity of liver glycogen synthetase and moderately decreased amounts of structurally normal glycogen in the liver. Mutational studies of patients with glycogen-storage disease type 0 do not demonstrate correlations between genotype and phenotype. [3] A different gene (GYS1, 138570) encodes muscle glycogen synthetase, which has normal activity in patients with glycogen-storage disease type 0A. [ 2 ]


In the early stages of fasting, the liver provides a steady source of glucose from glycogen breakdown (or glycogenolysis). With prolonged fasting, glucose is generated in the liver from noncarbohydrate precursors through gluconeogenesis. Such precursors include alanine (derived from the breakdown of proteins in skeletal muscle) and glycerol (derived from the breakdown of triacylglycerols in fat cells). In patients with glycogen-storage disease type 0, fasting hypoglycemia occurs within a few hours after a meal because of the limited stores of hepatic glycogen and inadequate  gluconeogenesis  to maintain normoglycemia. Feeding characteristically results in postprandial hyperglycemia and  glucosuria , in addition to increased blood lactate levels, because glycogen synthesis is limited, and excess glucose is preferentially converted to lactate by means of the  glycolytic pathway . [ 2 ]


Important clinical criteria to consider in the evaluation of a child with hypoglycemia and suspected glycogen-storage disease type 0 (GSD-0) include (1) the presence or absence of hepatomegaly; (2) the characteristic schedule of hypoglycemia, including unpredictable, postprandial, short fast, long fast, or precipitating factors; (3) the presence or absence of lactic acidosis; (4) any associated  hyperketosis  or hypoketosis; and (5) any associated liver failure or cirrhosis. The differential diagnosis also includes ketotic hypoglycemia. Patients with ketotic hypoglycemia have a normal response to glucagon in the fed state. Patients with glycogen-storage disease type 0 have normal-to-increased response to glucagon in the fed state, with hyperglycemia and lactic acidemia. [ 2 ]


Serum glucose levels are measured to document the degree of hypoglycemia. Serum electrolytes calculate the  anion gap  to determine presence of  metabolic acidosis ; typically, patients with glycogen-storage disease type 0 (GSD-0) have an  anion gap  in the reference range and no acidosis. See the Anion Gap calculator. [ citation needed ]


Serum lipids (including triglyceride and total cholesterol) may be measured. In patients with glycogen-storage disease type 0,  hyperlipidemia  is absent or mild and proportional to the degree of fasting. [ citation needed ]


Urine (first voided specimen with dipstick test for ketones and reducing substances) may be analyzed. In patients with glycogen-storage disease type 0, urine ketones findings are positive, and urine-reducing substance findings are negative. However, urine-reducing substance findings are positive (fructosuria) in those with fructose 1-phosphate aldolase deficiency (fructose intolerance). [ citation needed ]


Serum lactate is in reference ranges in fasting patients with glycogen-storage disease type 0. [ citation needed ]


Liver function studies  provide evidence of mild hepatocellular damage in patients with mild elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. [ citation needed ] Plasma amino-acid analysis shows plasma alanine levels as in reference ranges during a fast.


Skeletal radiography may reveal  osteopenia .


Evaluation of a patient with suspected glycogen-storage disease type 0 requires monitored assessment of fasting adaptation in an inpatient setting. [ citation needed ]


Patients typically have hypoglycemia and  ketosis , with lactate and alanine levels in the low or normal part of the reference range approximately 5–7 hours after fasting. [ citation needed ]


A  glucagon tolerance test  may be needed if the fast fails to elicit the expected rise in plasma glucose. Lactate and alanine levels are in the reference range. [ citation needed ]


By contrast, a glucagon challenge test after a meal causes hyperglycemia, with increased levels of plasma lactate and alanine. [ citation needed ]


Oral loading of glucose,  galactose , or  fructose  results in a marked rise in blood lactate levels. [ citation needed ]


Liver biopsy for microscopic analysis and enzyme assay is required for definitive diagnosis. Diagnosis may include linkage analysis in families with affected members and sequencing of the entire coding region of the GSY2 gene for mutations. [ citation needed ]


Histologic  analysis of liver tissue demonstrates moderately decreased amounts of periodic acid-Schiff (PAS)–positive, diastase-sensitive glycogen stores. [ citation needed ]


Evidence of increased fat accumulation in the liver may be observed, as in other glycogen-storage diseases. [ citation needed ]


Electron microscopic analysis of liver sections shows normal glycogen structure. [ citation needed ]


Muscle glycogen stores are normal. [ 2 ]


There are two types of glycogen storage disease type 0 to be considered, they are: [ 3 ] [ 4 ]


The goal for treatment of Glycogen-storage disease type 0 is to avoid hypoglycemia. This is accomplished by avoiding fasting by eating every 1–2 hours during the day. At night, uncooked  corn starch  can be given because it is a complex glucose polymer. This will be acted on slowly by pancreatic amylase and glucose will be absorbed over a 6-hour period. [ citation needed ]


The overall frequency of glycogen-storage disease is approximately 1 case per 20,000–25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. The identification of asymptomatic and oligosymptomatic siblings in several glycogen-storage disease type 0 families has suggested that glycogen-storage disease type 0 is underdiagnosed. [ 2 ]


The major morbidity is a risk of fasting hypoglycemia, which can vary in severity and frequency. Major long-term concerns include growth delay, osteopenia, and neurologic damage resulting in developmental delay, intellectual deficits, and personality changes. [ 2 ]


No sexual predilection is observed because the deficiency of glycogen synthetase activity is inherited as an autosomal recessive trait. [ 2 ]


Glycogen-storage disease type 0 is most commonly diagnosed during infancy and early childhood. [ 2 ]


The  gut–memory connection  is the relation between the  gastrointestinal tract  and  memory  performance. The phenomenon of the gut–memory connection is based on and part of the idea of the  gut-brain axis , a complex communication network, linking the  central nervous system  to the gut. The  gut-brain axis  first gained significant momentum in research and formal recognition in the 20th century with advancements in  neuroscience  and  gastroenterology . The idea of a connection between the gut and emotion has been hinted at in various ancient traditions and medical practices for centuries. [ 1 ] [ 2 ]


As a vital conduit for the communication between  gastrointestinal tract  and the brain, the gut-brain axis influences a variety of  physiological  processes. A prominent example of the gut–memory connection is the effects that alterations in the gut microbiome can have on the  pathogenesis  of  neural diseases  like  Alzheimer's . [ 3 ]


Understanding the connections between the gut microbiome and cognitive health could aid researchers in developing novel strategies for slowing down cognitive decline in  neurodegenerative diseases . [ 4 ]


The  gut-brain axis  is a two-way communication network within human systems that correlates the  gut microbiome  and the brain, encompassing immune, endocrine and neural connections. There is an evident association between the  gastrointestinal tract  and enteric microbiota with functional changes highlighted in the nervous system evidenced in vivo and vitro studies. [ 5 ]  This relationship plays a role in maintaining brain health as a result of resident microbes in the GI tract, influencing pathophysiology and mental behaviours. [ 6 ]   [ 7 ]  This can be accomplished through neuronal function directly or indirectly via vitamins,  neurotransmitters  and  metabolites . [ 8 ]   [ 9 ]  The exact biochemical pathway for this has yet to be determined, while some experimental data may suggest afferent sensory neurons travel via neuroimmune and  endocrine systems  traveling over the  vagus nerve . [ 10 ]  This demonstrates a commensalistic relationship between bacteria that exist in the human GI tract reaping from a diverse source of nutrients while providing indigestible nutrients available to the host. [ 5 ]


It has also been hypothesized that  IBS  can originate as a result of brain-to-gut or gut-to-brain syndrome as well which emphasizes the importance of the gut-brain axis. [ 11 ]   Neurological disorders  could also be a result of microbiota factors explaining why the intestine is known as the second brain as opposed to having neural origin. [ 12 ]  This uncovers the link to discovering mental and neurological disorders such as  depression  and  anxiety  with gut microbiota health. While not much of the ancestral origin of these interactions is not well known, this has a long history based on the coevolution and ecological interactions between vertebrates and bacteria, tightly coupled in animal evolution. [ 13 ]  This can also be evidenced by observing the role of bacteria such as the Hydra holobiont in contractile behaviour necessary for gut motility, demonstrating the product of ancient interaction between bacteria and emerging metazoans. [ 12 ]   [ 13 ]


The ancestral mammalian gut likely harboured a diverse array of microbes that played essential roles in metabolism, digestion and immune response, and as a result, has evolved and adapted in response to selection and dietary pressures. With the development of the vertebrate nervous system, the coordination of digestive processes in the  gastrointestinal tract  with external stimuli would’ve allowed communication. [ 13 ]   [ 14 ]


The anatomical basis of the gut–memory connection includes the  gastrointestinal tract  (GIT), which has its own intrinsic nervous system, called the  enteric nervous system  (ENS). The ENS controls intestinal function and can theoretically operate independently from the  central nervous system  (CNS). [ 15 ]  More than 100 million  efferent neurons  are present in the human ENS. They are connected to the brain through the  vagus nerve , which seems to be the main mediator of  gut-brain communication . [ 16 ]  Around 90% of the vagus nerve fibers connecting the brain and the ENS are afferent, meaning that the brain receives more information from the digestive system than it sends out. [ 17 ]  Afferent vagus nerve fibers have cell bodies in the  nodose ganglia  that synapse with the CNS. The signals are then relayed to the medial  nucleus of the solitary tract  (NTS), which in turn relays them to various  brainstem  and  forebrain  regions, including the  hippocampus  and the  amygdala . [ 18 ]   [ 19 ]


Signals from the GIT can activate the hippocampus, which was shown by directly stimulating the vagus nerve in human participants. [ 20 ]  The connection between the hippocampus and the medial NTS does not appear to be direct. Instead it seems to involve the  locus coeruleus  (LC) and the  medial septum  (MS), making the connection indirect. [ 21 ]  Studies have shown increased memory retention in both humans and rodents, following direct  vagus nerve stimulation . [ 22 ] [ 23 ] [ 24 ]


There are noradrenergic projections from the nucleus of the solitary tract to the amygdala, which is often associated with  emotional learning . [ 19 ]  Direct Vagus nerve stimulation increases the release of  noradrenaline  in the amygdala and has been linked to increased  fear depletion  and positive outcomes of preclinical treatments of  major depressive disorder  (MDD). [ 25 ] [ 26 ] [ 27 ]


Other factors that can indirectly influence memory function, include the  immune system  and  hormonal  processes. The ENS mediates  HPA-axis  function via  gastrointestinal hormones ,  cytokines  and  neuropeptides . Through the same pathways the HPA-axis can influence the ENS. Therefore, the gut can indirectly influence hippocampal functioning and other cortical structures related to memory, via the HPA-axis. [ 28 ]


Probiotics , living bacteria with health benefits, are emerging as a potential tool to influence the  microbiota-gut-brain  axis and improve mental well-being. [ 29 ]  This axis is a complex communication network linking the gut and the brain, primarily mediated by the  vagus nerve  and the production of neuromodulators, which influence nerve activity and brain function. [ 30 ]  Although the exact molecular mechanisms are still unclear, the gut microbiota has been demonstrated to influence behaviour and brain functions, including pain perception, [ 31 ]  stress response, [ 32 ]  prefrontal myelination, [ 33 ]  and brain biochemistry. [ 34 ]


Experimental manipulation of the gut microbial community composition has been shown to modify the host's neural function. For instance, long-term consumption of a probiotic  Lactobacillus  strain by  BALB/c  mice changed gamma-aminobutyric acid ( GABA ) expression in brain regions related to emotional processing. This alteration was associated with reduced anxiety and depression-like behaviour. [ 35 ]  A study found that consuming probiotics for 4–6 weeks altered neural activity in brain regions responsible for the central processing of emotion and sensation in healthy women, even without changes in gut microbial composition. [ 36 ]


Given the evidence that gut microbiota influences emotional processing and the connections between emotion, memory, and decision-making, researchers hypothesized that probiotic ingestion could impact brain mechanisms related to such contexts. Their study demonstrated that administering a multi-strain probiotic significantly impacts behavioural scores and  fMRI  measures in brain regions involved in emotional decision-making and memory. [ 37 ]


Probiotics contribute to the reduction of  oxidative stress , a cellular process that can damage brain cells. Accordingly, probiotics may protect brain cells in the  hippocampus , a region important for memory storage and retrieval while promoting a healthy gut lining. [ 38 ]


A study in middle-aged rats examined the effects of  probiotics ,  prebiotics  and a combination of both,  symbiotics , on memory. The study found that rats given the symbiotic supplement performed significantly better in spatial memory tests than the control groups. Improvement in memory was also accompanied by several positive changes in the brain. The symbiotic group showed lower levels of inflammation, a factor well known to impair memory. They also showed increased levels of  brain-derived neurotrophic factor  (BDNF), a protein important for memory formation, and higher levels of  butyrate , a fatty acid produced by gut bacteria that can improve memory and altered brain cell activity patterns that promote learning and memory. A mixture of probiotics and prebiotics could be a way to improve cognitive abilities, particularly spatial memory. [ 39 ]


Antibiotic medication  can disrupt the natural  gut microbiome , leading to an imbalance in the gut-brain axis. Some studies in mice have shown that probiotic treatment can reverse the negative effects of  antibiotics  on bacteria in the gut, called  dysbiosis  and can also improve memory function. They further found that probiotics not only reduced gut dysbiosis associated with memory loss but also reduced the activity of specific enzymes associated with memory deficits, such as  acetylcholinesterase  and  myeloperoxidase . [ 38 ]


The link between gut bacteria and mental health, particularly  anxiety  and  depression  becomes a stronger focus in research. There exist studies on  germ-free  mice, devoid of any gut bacteria, that show the mice exhibit less anxiety compared to mice with a normal gut microbiome. [ 40 ]   [ 41 ]  Inflammations or infections of the gut tract of mice caused a change in certain behaviour associated with symptoms of anxiety, such as a less drive to explore [ 42 ]  and a stronger inhibition of behavioral responses. [ 43 ] [ 44 ]  This hints at the potential influence specific types of bacteria might have on behaviour and mental health. Studies with rodents have experimentally shown similar results. [ 45 ] [ 46 ] [ 47 ]


Some certain probiotic strains, like  Lactobacillus rhamnosus [ 48 ]  and  Bifidobacterium infantis , [ 49 ]  have shown promise in reducing anxiety-like behaviour in animal models. These probiotics are being explored as potential so-called  psychobiotics  for treating mental health conditions, such as depression and anxiety. [ 50 ]


Further evidence comes from  microbiota  transfer experiments in mice, in which researchers transplanted gut bacteria from one strain of mice to another. It seems to influence their behaviour, suggesting the composition of the gut microbiome plays an important role. Stressful situations can also disrupt the delicate balance of gut bacteria and can lead to maternal separation and social defeat stress alters gut microbiota. [ 51 ]   [ 52 ]


Some other studies of mice exposed to food deprivation or social disruption found changes in their gut bacteria composition. [ 53 ]  The influence seems to go both ways, since research using a depression model in mice revealed alterations in their gut bacteria compared to healthy mice. [ 54 ]  This, in turn, suggests that anxiety and depression might also affect the gut microbiome. [ 55 ]


The  gut-brain axis  acts as a communication network between the gastrointestinal tract and the brain. Due to this communication through neural, endocrine, and immune pathways, the  gut microbiota  and the brain can mutually influence their functions. [ 56 ]  Therefore, changes in the  gut microbiota  can influence the pathogenesis of various neurological diseases. There is rising evidence of a relationship between the  gut microbiome  and the neurodegenerative disease  Alzheimer’s . [ 57 ]


The development and progression of  Alzheimer’s disease  are characterised by abnormal brain protein aggregation, inflammation, immune dysregulation, and impaired neuronal and synaptic activity of the brain. [ 56 ]  These abnormalities associated with  Alzheimer’s disease  are also associated with a dysregulation of the gut microbiome. [ 56 ] [ 57 ]  There are different environmental factors such as diet, exercise and exposure to air pollution that have an impact on the  gut microbiome  and therefore could also have an influence on  Alzheimer’s disease . [ 56 ] [ 57 ]  To have positive health outcomes the intestinal bacterial flora should be in an equilibrium. By consuming sufficient  probiotics  such as  Bifidobacteria  and  Lactobacillus  through a diet the achievement of this equilibrium is supported. [ 56 ]   Bifidobacteria  and  Lactobacillus  can be taken as supplements but are also contained in different types of foods. To ensure a variety of microbiota strains in the gut a large and diverse diet is required. [ 56 ]


Further research suggests a correlation between Alzheimer’s disease, low insulin levels (diabetes type 1) and insulin resistance (diabetes type 2), that could be caused by amyloid beta-derived diffusible ligands (ADDLs). These ADDLs are  neurotoxins  that reduce synapse plasticity and provoke  oxidative damage  by altering the shape of insulin receptors. [ 58 ]  This inhibits the learning and memory mechanisms in the brain because Insulin usually supports the necessary regulation of processes like neuronal survival, energy metabolism, and  plasticity . Insulin resistance could therefore explain the memory loss in AD patients. [ 58 ]


There are different theories of the potential mechanisms through which the  gut microbiome  influences the pathogenesis of  Alzheimer’s disease . A viral or bacterial infection can contribute to the development of  Alzheimer's disease . [ 56 ]  The  Heliobacter pylori infection  decreases the MMSE scores of patients with  Alzheimer's disease  through the release of inflammatory mediators. In addition, patients with  Alzheimer's disease  show higher serum levels of Aß40 and Aß42 if they are infected by a bacterial infection. The bacteria can alter the levels of specific neurotransmitters proteins and receptors which are responsible for synaptic plasticity. [ 56 ]  The theory of age-related dysbiosis associates the appearance of  Alzheimer's disease  with the ageing of the immune system. [ 56 ]  Through the process of ageing the levels of  proteobacteria  expand whereas the levels of  probiotics  decrease. These changes alter the composition of the  gut microbiota . [ 56 ] [ 57 ] [ 59 ]  As an alteration of the  gut microbiota  occurs it can lead to differences in the activity of the brain. This connection raises the possibility of a treatment for patients diagnosed with  Alzheimer’s . Therapeutic treatment could manipulate the  gut microbiome  and therefore induce neuronal and synaptic changes in the patient's brain. [ 56 ] [ 57 ]


Irritable bowel syndrome  or  IBS  is a gastrointestinal disorder with the disruption of the  gut-brain axis  as one of its characteristics. There are multiple ways in which this disorder impacts memory performance. IBS is a disorder that can cause  chronic pain ,  stress  and immune activity. [ 60 ] [ 61 ]


Many of the people suffering from IBS have  visceral hypersensitivity . [ 62 ]  Pain disrupts attention which is a crucial factor for  memory  formation. [ 63 ]  The adverse effects of chronic pain also affect  executive functioning ,  working memory ,  episodic memory  and speed of information processing. [ 64 ]   Sleep deprivation  in IBS patients is common and can have adverse effects on memory consolidation, executive functions and mental health, which also impairs memory. [ 65 ] [ 66 ]


IBS patients often show a higher response to stressors, causing dysregulation of the  hypothalamic-pituitary-adrenal ( HPA )  axis and the  autonomic nervous system ( ANS ) . [ 67 ]  The activation of the  HPA axis  leads to the release of  glucocorticoids ,  cortisol  in humans. In people with IBS, the amount of cortisol was found to be higher which is related to a decline in  hippocampus -dependent  episodic memory  performance. [ 68 ]  This also causes  hippocampus  deactivation and morphological changes which have been associated with spatial memory deficits. [ 69 ]  The decrease in blood flow to the  hippocampus  and other brain areas also seems to be involved in the effects of stress on the  hippocampus . [ 70 ]


The  frontal lobes , which are involved in  executive functions  such as  working memory , are more sensitive than the  hippocampus  to  glucocorticoid  levels causing similar disruptive effects of IBS as in the  hippocampus . [ 71 ]  They are also affected by the  ANS . The disruption of the  ANS  in  IBS  causes an increase in  sympathetic nervous system  activation and a decrease in  parasympathetic nervous system  activation, resulting in higher  noradrenaline  levels. This activates  α1 receptors  in the  prefrontal cortex  which impairs  working memory . [ 72 ]   Noradrenaline  and  cortisol  to the  amygdala  have the opposite effect and can enhance emotional memory formation which for  IBS  patients is shown as an enhanced memory for gastrointestinal-related words. [ 73 ]


IBS  patients have an abnormal immune activity which can be seen when measuring  cytokines . They have a higher-than-normal amount of the proinflammatory cytokines  IL6  and  IL8  and some also have elevated  TNF-α  and  IL1-α  levels. [ 74 ] [ 75 ]  (  IL6  is found to be related to cognitive abilities and  Alzheimer's disease  severity. [ 76 ] [ 77 ]  ) Too much of it can affect memory by reducing  neurogenesis  in the  dentate gyrus  and inhibiting  long term potentiation . [ 78 ] [ 79 ]  The high amount of  IL6  and  TNF-α  decreases  episodic memory  performance.  IL1-α  and  TNF-α  have these effects through  LTP  inhibition in the  dentate gyrus  and  TNF-a , through  excitotoxicity  through the modulation of  glutamate  transmission also. [ 80 ]


Obesity  is associated with many adverse effects physically and mentally. These include memory deficits. Obesity causes an increase in inflammation throughout the body. [ 81 ]   Cytokines , the chemicals that regulate this, can cross the  blood-brain barrier  in certain cases and affect the brain, including memory related areas. [ 82 ]


Adipose tissue , which contains the fat, have certain neuroendocrine functions such as the production and release of  adipokines . In  obesity , the body is in a state of adiposopathy in which the secretion of  adipokines  changes. [ 83 ]   leptin , one of the  adipokines , also promotes  axonal  growth and modulates  NMDA  functioning, enhancing  LTP . [ 84 ]  In  obese  states, the body has  leptin  resistance, disrupting these effects of  leptin . [ 85 ]


In adiposopathy, the secretion of  interleukin 6  is increased. [ 86 ]  This leads to reduced  neurogenesis , the inhibition of  LTP  and impaired  working memory  performance as in  irritable bowel syndrome . Some studies also suggest that  cytokines  such as  interleukin 6  may reduce  hippocampal   grey matter  volume. [ 87 ]


In order to analyze the effects  gut microbiota  has on our learning of  spatial memory  and cognition,  animal studies  can be applied to human studies. This implies the use of rats, and mice in experiments in order to study the effects of a sucrose diet on cognitive skills. Experiments on lab animals demonstrated similar results in human experiments whereas sucrose diet has an impact on cognitive abilities.  [ 88 ]


The excessive use of abundant sugar consumption has a significant impact on cognitive performance. Consistent consumption of foods rich in  cholesterol  shows that over a long duration decreases cognitive abilities, specifically spatial memory In order to study spatial learning using  animal models , rodents are placed into an experiment called  radial arm maze  where the  working memory  of  semantic memories  of animals are tested.  [ 89 ]


This experiment uses  operant conditioning  such as rewards and punishments in order to measure working memory in rodents and motivate the animal towards a desired behaviour like figuring out where the food is located in the maze. Findings of high-fat diets include deficits in spatial memory and cognitive impairment. A study including obese mice which encompassed high levels of  palmitic acid  these high concentrations of acid demonstrated a change in the microbiota of the gut which shows deficits in cognition and spatial learning.  [ 90 ]


This type of acid found in an animal study shows similarities with humans, therefore this finding can be applied to humans as well. According to animal studies, high-fat diets contribute to significant alterations in gut microbiota and in decrease of spatial learning.  [ 91 ]


Hampton's line  is a thin,  radiolucent  line seen across the neck of a  gastric ulcer  filled with  barium sulphate  during a  barium meal . It is a sign of  mucosal   edema . [ citation needed ]


It is named after  Aubrey Otis Hampton . [ 1 ]


Healthy digestion , also called  digestive health , results in the absorption of  nutrients  from food without distressing  symptoms . Healthy digestion follows having a  healthy diet , doing appropriate  self-care  including physical activity and exercise, minimizing activities like  smoking  or consuming  alcoholic drinks  which impair digestion, and managing any  medical condition  which disrupts digestion to the best of one's ability. [ 1 ]


A person with healthy digestion will have lower risk of experiencing  diarrhea ,  vomiting ,  constipation ,  heartburn ,  bloating ,  flatulence , and  indigestion . [ 2 ]  Additionally, a person with healthy digestion will have less need of digestive medications than a person who does not have healthy digestion. [ 2 ] [ 1 ]


Some foods like  Banana ,  Avocado ,  Melons ,  Oats ,  Yogurt  quickly or completely digested than others. [ 3 ] [ 4 ]


Many events can disrupt digestion. [ 1 ]  Disrupted digestion can have many symptoms, including diarrhea, constipation, heartburn, bloating, flatulence, and indigestion. [ 1 ]


Some people have chronic medical conditions which disrupt their digestion. [ 1 ]  Other people might be taking a drug which disrupts their digestion. [ 1 ]  In those cases, the person's goals for healthy digestion might be to have their personal best possible digestion since they have other health problems to manage. [ 1 ]


Food intolerance  can disrupt digestion. [ 1 ]


Whenever possible, it is easier for a person to prevent digestive problems from happening rather than to seek to treat them after they begin.


Various drugs can relieve the symptoms of poor digestion.  Laxatives  counter  constipation .  Loperamide  counters  diarrhea .  Antacids  counter heartburn or indigestion.  Simethicone  counters  flatulence . [ citation needed ]


Constipation can also be countered using  enemas  or  suppositories .


Probiotics  have been shown to benefit gastrointestinal disorders and are a popular treatment to promote healthy digestion. [ 5 ]


Many people who seek healthcare for gastrointestinal problems are not satisfied with the treatment options which they find in conventional medicine. [ 6 ]  Because of this, people often use  alternative medicine  to promote healthy digestion. [ 6 ]


Various organizations observe a "World Digestive Health Day" to share information about promoting healthy digestion. [ 7 ]


See text


Helicobacter  is a  genus  of  gram-negative   bacteria  possessing a characteristic  helical  shape. They were initially considered to be members of the genus  Campylobacter , but in 1989, Goodwin  et al.  published sufficient reasons to justify the new genus name  Helicobacter . [ 2 ]  The genus  Helicobacter  contains about 35 species. [ 3 ] [ 4 ] [ 5 ]


Some species have been found living in the lining of the  upper gastrointestinal tract , as well as the  liver  of  mammals  and some  birds . [ 6 ]  The most widely known species of the genus is  H. pylori , which infects up to 50% of the human population. [ 5 ]  It also serves as the  type species  of the genus. Some strains of this bacterium are  pathogenic  to humans, as they are strongly associated with  peptic ulcers , chronic  gastritis ,  duodenitis , and  stomach cancer .


Helicobacter  species are able to thrive in the very  acidic  mammalian  stomach  by producing large quantities of the  enzyme   urease , which locally raises the  pH  from about 2 to a more biocompatible range of 6 to 7. [ 7 ]  Bacteria belonging to this genus are usually susceptible to  antibiotics  such as  penicillin , are  microaerophilic  (optimal  oxygen  concentration between 5 and 14%)  capnophiles , and are fast-moving with their  flagella . [ 8 ] [ 9 ]


Comparative genomic analysis has led to the identification of 11 proteins that are uniquely found in the Helicobacteraceae. Of these proteins, seven are found in all species of the family, while the remaining four are not found in any  Helicobacter  strains and are unique to  Wollinella . Additionally, a rare genetic event has led to the fusion of the  rpoB  and  rpoC  genes in this family, which is characteristic of them. [ 10 ]


Recently, new gastric ( H. suis  and  H. baculiformis ) and enterohepatic ( H. equorum ) species have been reported.  H. pylori  is of primary importance for medicine, but non- H. pylori  species, which naturally inhabit mammals (except humans) and birds, have been detected in human clinical specimens. These encompass two (gastric and enterohepatic) groups, showing different organ specificity. Importantly, some species, such as  H. hepaticus, H. mustelae , and probably  H. bilis , exhibit carcinogenic potential in animals. They harbour many  virulence  genes and may cause diseases not only in animals, but also in humans. Gastric species such as  H. suis  (most often) , H. felis, H. bizzozeronii , and  H. salomonis  have been associated with chronic gastritis and peptic ulcers in humans, and importantly, with higher risk for MALT lymphoma compared to  H. pylori .


Enterohepatic species e.g.,  H. hepaticus,   H. bilis , and  H. ganmani , have been detected by  PCR , but still are not isolated from specimens of patients with hepatobiliary diseases. Moreover, they may be associated with  Crohn's disease  and  ulcerative colitis . The significance of avian helicobacters ( H. pullorum, H. anseris , and  H. brantae)  also has been evaluated extensively.  H. cinaedi  and  H. canis  can cause severe infections, mostly in immunocompromised patients with animal exposure. Briefly, the role of these species in veterinary and human medicine is increasingly recognised. Several other topics such as isolation of still uncultured species,  antibiotic resistance , and treatment regimens for infections and pathogenesis and possible carcinogenesis in humans should be evaluated. [ 3 ]


Helicobacter heilmannii sensu lato  (i.e.  H. heilmanni s.l. ) is a grouping of non- H. pylori   Helicobacter  species that take as part of their definition a similarity to  H. pylori  in being associated with the development of stomach inflammation, stomach ulcers, [ 11 ]  duodenum ulcers, [ 12 ]  stomach cancers that are not lymphomas, and extranodal marginal B cell lymphoma of the stomach in humans and animals. [ 11 ]  Most clinical studies have not identified the exact species of  H. heilmanii  associated with these diseases, so designated these species as  H. heilmanni s.l.  However, investigative studies have identified these species in some patients with the cited  H. heilmanni s.l. -associated  upper gastrointestinal tract  diseases. The  H. heilmani species  identified to date in the stomachs of humans with the cited upper gastrointestinal tract diseases are:  Helicobacter bizzozeronii ,  Helicobacter felis ,  Helicobacter salomonis ,  Helicobacter suis , and  Helicobacter heilmannii s.s. [ 11 ]  It is important to recognize the association of  H. heilmannii sensu lato  with these  upper gastrointestinal tract diseases , particularly extranodal marginal zone lymphoma of the stomach, because some of them have been successfully treated using antibiotic-based drug regimens directed against the instigating  H. heilmannii sensu lato  species. [ 13 ]  The  H. heilmanni s.l. -associated human diseases appear to be acquired from pets and farm animals, so are considered to be  zoonotic diseases . [ 11 ]


The currently accepted taxonomy is based on the  List of Prokaryotic names with Standing in Nomenclature  (LPSN) [ 1 ]  and  National Center for Biotechnology Information  (NCBI) [ 14 ]


Wolinella


H. valdiviensis


H. ganmani


H. mesocricetorum


H. rodentium


H. enhydrae


H. cholecystus


H. brantae


H. pametensis


H. kayseriensis


H. anseris


H. anatolicus


H. mustelae


H. canis


H. bilis


H. canicola   Kawamura et al. 2016


H. cinaedi


H. hepaticus


H. trogontum


H. japonicus


H. muridarum


H. typhlonius


H. mastomyrinus   Shen et al. 2006


H. apri   Zanoni et al. 2016


H. equorum   Moyaert et al. 2007


H. kumamotonensis   Kawamura et al. 2023


H. pullorum


H. canadensis


H. colisuis   Gruntar et al. 2022


H. turcicus


H. marmotae


H. macacae


H. himalayensis


H. fennelliae


H. jaachi


H. saguini


H. aurati


H. monodelphidis   Shen et al. 2020


H. didelphidarum


H. acinonychis


H. pylori


H. cetorum


H. delphinicola   Segawa et al. 2021


H. suis


H. labacensis


H. bizzozeronii


H. felis


H. salomonis


H. cynogastricus


H. baculiformis


H. ailurogastricus


H. heilmannii


H. mehlei


H. vulpis


" Helicobacter burdigaliensis "  Berthenet et al. 2019


Helicobacter valdiviensis   Collado, Jara & Gonzalez 2014


Helicobacter turcicus   Aydin et al. 2022


" Helicobacter winghamensis "  Melito et al.


Helicobacter ganmani   Robertson et al. 2001


" P. rodentium "  (Shen et al. 1997) Waite, Chuvochina & Hugenholtz 2019


Helicobacter apodemus   Jeon et al. 2015


Helicobacter mesocricetorum   Simmons et al. 2000


" P. canadensis "  (Fox et al. 2002) Waite, Chuvochina & Hugenholtz 2019


" P. pullorum "  (Stanley et al. 1995) Waite, Chuvochina & Hugenholtz 2019


H. saguini   Shen et al. 2017


H. aurati   Patterson et al. 2002


H. muridarum   Lee et al. 1992


H. didelphidarum   Shen et al. 2020


H. trogontum   Mendes et al. 1996


H. bilis   Fox et al. 1997


" H. rappini "  Dewhirst et al. 2000


H. enhydrae   Shen et al. 2020


H. kayseriensis   Aydin et al. 2022


H. pametensis   Dewhirst et al. 1994


H. brantae   Fox et al. 2006


" Ca.  H. avistercoris"  Gilroy et al. 2021


H. cholecystus   Franklin et al. 1997


" Ca.  H. avicola"  Gilroy et al. 2021


H. himalayensis   Hu et al. 2015


" H. labetoulli "  Berthenet et al. 2019


H. cinaedi   (Totten et al. 1988) Vandamme et al. 1991


" H. magdeburgensis "  Traverso et al. 2010


H. jaachi   Shen et al. 2017


H. hepaticus   Fox et al. 1994


H. marmotae   Fox et al. 2006


H. japonicus   corrig. Shen et al. 2017


H. typhlonius   Franklin et al. 2002


H. fennelliae   (Totten et al. 1988) Vandamme et al. 1991


H. macacae   Fox et al. 2013


H. canis   Stanley et al. 1994


H. anseris   Fox et al. 2006


H. anatolicus   Aydin et al. 2023


H. mustelae   (Fox et al. 1988) Goodwin et al. 1989


H. cetorum   Harper et al. 2006


H. acinonychis   corrig. Eaton et al. 1993


H. pylori   (Marshall et al. 1985) Goodwin et al. 1989


H. bizzozeronii   Hanninen et al. 1996


H. mehlei   Gruntar et al. 2020


H. suis   Baele et al. 2008


H. ailurogastricus   Joosten et al. 2017


H. heilmannii   Smet et al. 2012


H. cynogastricus   Van den Bulck et al. 2006


H. felis   Paster et al. 1991


H. salomonis   Jalava et al. 1997


H. baculiformis   Baele et al. 2008


H. labacensis   Gruntar et al. 2020


H. vulpis   Gruntar et al. 2020


Species incertae sedis:


Hemostatic Powder Spray TC-325  ( Hemospray  or  TC-325 ) is an inert, highly absorptive mineral agent which is used for the treatment of  gastrointestinal bleeding .  Applied during  endoscopy  to bleeding lesions, TC-325 is derived from  bentonite , and is used to achieve  hemostasis  (control of bleeding) by absorbing water and creating a barrier that leads to mechanical tamponade (pressure) and concentration of  clotting factors , resulting in enhanced  coagulation  (clotting of blood). [ 1 ]  TC-325 was approved for gastrointestinal bleeding from causes other than  gastric  or  esophageal varices  (e.g., nonvariceal bleeding). TC-325 results in immediate control of bleeding in 91-93% of cases. [ 2 ] [ 3 ]  Technical success has gradually increased between 2011 and 2019, which may be due to device improvements or physician familiarity with the application of TC-325. [ 2 ]


Hemostatic Powder Spray TC-325 was approved by the  United States   Food and Drug Administration  in 2018 for  gastrointestinal bleeding . [ 4 ]
Technical success has gradually increased between 2011 and 2019, which may be due to device improvements or physician familiarity with the application of TC-325. [ 2 ]


TC-325 is recommended for temporary control of gastrointestinal bleeding when other treatments are ineffective or not available. [ 5 ]  TC-325 may also be used for massive bleeding with poor visualization or diffuse bleeding due to cancer. [ 6 ]


The device is not FDA approved for the treatment of gastroesophageal variceal bleeding. [ 7 ]  However, TC-325 is 90.4% effective in achieving initial hemostasis in variceal bleeding, and its use was associated with a 4.2% rate of rebleeding. [ 8 ]  TC-325 use for variceal bleeding is safe. [ 9 ]


TC-325 is 91-93% effective in achieving initial control of bleeding, [ 3 ] [ 2 ]  but does not prevent re-bleeding from occurring. [ 3 ]  Rebleeding is most likely to occur if the initial bleed was brisk (spurting) or  hypotension  was present. [ 10 ]


Risks of TC-325 use include failure to control bleeding, gastrointestinal perforation, bowel obstruction, or malfunction of device or delivery system. If TC-325 is used for the control of bleeding at the site of a sphincterotomy or ampullary resection, there is a risk of biliary obstruction.  Additional risks include allergy to the TC-325 powder. The overall rate of adverse events to TC-325 is 0.7%. [ 11 ]


OR


AND


Hepatology  is the branch of  medicine  that incorporates the study of  liver ,  gallbladder ,  biliary tree , and  pancreas  as well as management of their disorders. Although traditionally considered a sub-specialty of  gastroenterology , rapid expansion has led in some countries to doctors specializing solely on this area, who are called  hepatologists .


Diseases and complications related to  viral hepatitis  and alcohol are the main reason for seeking specialist advice. More than two billion people have been infected with  hepatitis B  virus at some point in their life, and approximately 350 million have become persistent carriers. [ 1 ]   Up to 80% of  liver cancers  can be attributed to either hepatitis B or  hepatitis C  virus. In terms of  mortality , the former is second only to smoking among known agents causing  cancer . With more widespread implementation of  vaccination  and strict  screening  before  blood transfusion , lower  infection  rates are expected in the future. [ citation needed ]  In many countries, however, overall alcohol consumption is increasing, and consequently the number of people with  cirrhosis  and other related complications is commensurately increasing. [ citation needed ]


As for many medical specialties, patients are most likely to be referred by family physicians (i.e., GP) or by physicians from different disciplines. The reasons might be:


Evidence from autopsies on Egyptian  mummies  suggests that liver damage from the  parasitic  infection  bilharziasis  was widespread in the ancient society. [ 2 ]
It is possible that the  Greeks  may have been aware of the liver's ability to exponentially duplicate as illustrated by the story of  Prometheus . However, knowledge about liver disease in  antiquity  is questionable. Most of the important advances in the field have been made in the last 50 years. [ when? ]


The word  hepatology  is from  Ancient Greek  ἧπαρ ( hepar ) or  ἡπατο- ( hepato- ), meaning "liver", and -λογία ( -logia ), meaning "study".


1.  International Classification of Disease  ( ICD 2007) – WHO classification :


2.  MeSH (medical subject heading) :sam


3.  National Library of Medicine Catalogue [ 18 ]


Also see  Hepato-biliary diseases


Seven  cholera  pandemics have occurred in the past 200 years, with the first  pandemic  originating in  India  in 1817. The  seventh cholera pandemic  is officially a current pandemic and has been ongoing since 1961, according to a  World Health Organization  factsheet in March 2022. [ 1 ]   Additionally, there have been many documented major local cholera outbreaks, such as a 1991–1994 outbreak in South America and, more recently, the  2016–2021 Yemen cholera outbreak . [ 2 ]


Although much is known about the mechanisms behind the spread of  cholera , this has not led to a full understanding of what makes cholera outbreaks happen in some places and not others. Lack of treatment of human  feces  and lack of treatment of drinking water greatly facilitate its spread. Bodies of water have been found to serve as a  reservoir , and seafood shipped long distances can spread the disease.


Between 1816 and 1923, the first six cholera pandemics occurred consecutively and continuously over time. Increased commerce, migration, and pilgrimage are credited for its transmission. [ 3 ]  Late in this period (particularly 1879–1883), major scientific breakthroughs toward the treatment of cholera develop: the first immunization by  Pasteur , the development of the first cholera vaccine, and identification of the bacterium  Vibrio cholerae  by  Filippo Pacini  and  Robert Koch . After a long hiatus, a  seventh cholera pandemic  spread in 1961. The pandemic subsided in the 1970s, but continued on a smaller scale. Outbreaks occur across the developing world to the current day. Epidemics occurred after wars, civil unrest, or natural disasters, when water and food supplies had become contaminated with  Vibrio cholerae , and also due to crowded living conditions and poor sanitation. [ 4 ]


Deaths in  India  between 1817 and 1860 in the first three pandemics of the nineteenth century, are estimated to have exceeded 15 million people. Another 23 million died between 1865 and 1917, during the next three pandemics. Cholera deaths in the  Russian Empire  during a similar time period exceeded 2 million. [ 5 ]


The  first cholera pandemic  occurred in the Bengal region of India, near  Calcutta  (now Kolkata), starting in 1817 through 1824. The disease dispersed from India to Southeast Asia, the Middle East, Europe, and Eastern Africa through trade routes. [ 6 ]  The  second pandemic  lasted from 1826 to 1837 and particularly affected North America and Europe, due to the result of advancements in transportation and global trade, and increased human migration, including soldiers. [ 7 ]   The  third pandemic  erupted in 1846, persisted until 1860, extended to North Africa, and reached South America, for the first time specifically affecting Brazil. The  fourth pandemic  lasted from 1863 to 1875, and spread from India to Naples and  Spain , and to the United States in 1873. The  fifth  pandemic was from 1881 to 1896 and started in India and spread to Europe, Asia, and South America. The  sixth pandemic  started in India and lasted from 1899 to 1923. These epidemics were less fatal due to a greater understanding of the cholera bacteria. Egypt, the Arabian peninsula, Persia, India, and the Philippines were hit hardest during these epidemics, while other areas, such as Germany in 1892 and Naples from 1910 to 1911, also suffered severe outbreaks. The  seventh pandemic  originated in 1961 in Indonesia and is marked by the emergence of a new strain, nicknamed  El Tor , which still persists (as of 2019 [ 8 ] ) in developing countries. [ 9 ]


Cholera did not occur in the  Americas  for most of the 20th century after the early 1900s in New York City. It reappeared in the Caribbean toward the end of that century and seems likely to persist. [ 10 ]


The  first cholera pandemic , though previously restricted, began in  Bengal , and then spread across  India  by 1820. Hundreds of thousands of Indians and ten thousand  British troops  died during this pandemic. [ 11 ]  The cholera outbreak extended as far as  China ,  Indonesia  (where more than 100,000 people succumbed on the island of  Java  alone) and the  Caspian Sea  in Europe, before receding. [ 12 ] [ 13 ]  In 1821, it is estimated that up to 100,000 deaths occurred in  Korea . [ 14 ]


A  second cholera pandemic  reached Russia (see  Cholera Riots ),  Hungary  (about 100,000 deaths) and  Germany  in 1831; [ 15 ]  it killed 130,000 people in  Egypt  that year. [ 16 ]   In 1832 it reached  London  and the United Kingdom (where more than 55,000 people died) [ 17 ]  and  Paris . In London, the disease claimed 6,536 victims and came to be known as "King Cholera"; in Paris, 20,000 died (of a population of 650,000), and total deaths in France amounted to 100,000. [ 18 ]  In 1833, a cholera epidemic killed many  Pomo , which are a Native American tribe. The epidemic reached  Quebec ,  Ontario ,  Nova Scotia , [ 19 ]  and  New York  in the same year, and the Pacific coast of North America by 1834. In the center of the country [ clarification needed ] , it spread through the cities linked by the rivers and steamboat traffic. [ 20 ]


In Washington D.C.  Michael Shiner , an enslaved laborer at the  Washington Navy Yard  recorded, "The time the colery [cholera] broke out in about June and July August and September 1832 it Raged in the City of Washington and every day they wher [were] twelve or 13 carried out to they [their] graves a day." [ 21 ]  By late July 1832, cholera had spread to Virginia and on 7 August 1832, Commodore  Lewis Warrington  confirmed to the Secretary of the Navy  Levi Woodbury  cholera was at the  Gosport Navy Yard , "Between noon of that day, [1 August] and the morning of Friday [3 August], when all work on board her  USS  Fairchild  stopped, several deaths by cholera occurred and fifteen or sixteen cases (of less violence) were reported." [ 22 ]


The epidemic of cholera, cause unknown and prognosis dire, had reached its peak. [ 23 ]  Cholera afflicted Mexico's populations in 1833 and 1850, prompting officials to quarantine some populations and fumigate buildings, particularly in major urban centers, but nonetheless the epidemics were disastrous. [ 24 ] [ 25 ]


In response to the  second cholera pandemic , the  Ottoman Empire  and  Egypt  reformed their quarantine systems, following the western Mediterranean model. In 1831, the Egyptian Quarantine Board was established. It constructed Egypt’s first modern lazaretto in  Alexandria  in 1833. In 1831, the Ottoman government set up the first permanent quarantine complex in  Istanbul . In 1838, the Ottoman government established the Supreme Council of Health, which oversaw 59 quarantines. While largely useless against cholera, these quarantines shored up the two countries' epidemiological defenses against  bubonic plague . [ 26 ]


During this pandemic, the scientific community varied in its beliefs about the causes of cholera. In France, doctors believed cholera was associated with the poverty of certain communities or poor environment. Russians believed the disease was contagious, although doctors did not understand how it spread. The United States believed that cholera was brought by recent immigrants, specifically the Irish, and epidemiologists understand they were carrying disease from British ports. Lastly, some British thought the disease might rise from divine intervention. [ 6 ]


The  third cholera pandemic  deeply affected Russia, with over one million deaths.  Over 15,000 people died of cholera in  Mecca  in 1846. [ 27 ]  A two-year outbreak began in  England and Wales  in 1848, and claimed 52,000 lives. [ 12 ]


In 1849, a second major outbreak occurred in France. In London, it was the worst outbreak in the city's history, claiming 14,137 lives, over twice as many as the 1832 outbreak. Cholera hit  Ireland  in 1849 and killed many of the  Irish Famine  survivors, already weakened by starvation and fever. [ 28 ]  In 1849, cholera claimed 5,308 lives in the major port city of  Liverpool ,  England , an embarkation point for immigrants to North America, and 1,834 in  Hull , England. [ 18 ]  In Vietnam and Cambodia, cholera hit in summer 1849, killing approximately 589,000 to 800,000 people within one year, along with its consequential famine. [ 29 ] [ 30 ]


An  outbreak in North America  took the life of former  U.S. President   James K. Polk . Cholera, believed spread from Irish immigrant ships from England, spread throughout the  Mississippi river system , killing over 4,500 in  St. Louis [ 18 ]  and over 3,000 in  New Orleans . [ 18 ]  Thousands died in  New York , a major destination for Irish immigrants. [ 18 ]  Cholera claimed 200,000 victims in  Mexico . [ 31 ]


That year, cholera was transmitted along the  California ,  Mormon , and  Oregon Trails  as 6,000 to 12,000 [ 32 ]  are believed to have died on their way to the  California Gold Rush ,  Utah  and  Oregon  in the cholera years of 1849–1855. [ 18 ]  It is believed more than 150,000 Americans died during the two pandemics between 1832 and 1849. [ 33 ] [ 34 ]


In 1851, a ship coming from Cuba carried the disease to  Gran Canaria . [ 35 ]  It is considered that more than 6,000 people died in the island during summer, [ 36 ]  out of a population of 58,000.


In 1852, cholera spread east to the Dutch East Indies and later was carried to Japan in 1854. The  Philippines  were infected in 1858 and  Korea  in 1859. In 1859, an outbreak in Bengal contributed to transmission of the disease by travelers and troops to  Iran ,  Iraq ,  Arabia , and Russia. [ 27 ]  Japan suffered at least seven major outbreaks of cholera between 1858 and 1902. Between 100,000 and 200,000 people died of cholera in  Tokyo  in an outbreak in 1858–1860. [ 37 ]


In 1854, an outbreak of cholera in  Chicago  took the lives of 5.5 percent of the population (about 3,500 people). [ 18 ] [ 38 ]   Providence, Rhode Island , suffered an outbreak so widespread that for the next thirty years, 1854 was known there as "The Year of Cholera." [ 39 ]  In 1853–1854, London's epidemic claimed 10,739 lives. The  1854 Broad Street Cholera outbreak  in London ended after the physician  John Snow  identified a neighborhood  Broad Street pump  as contaminated and convinced officials to remove its handle to prevent people from drawing water there. [ 40 ]  His study proved contaminated water was the main agent spreading cholera, although he did not identify the contaminant. It would take many years for this message to be believed and fully acted upon. [ 41 ]   In Spain , over 236,000 died of cholera in the epidemic of 1854–1855. [ 42 ]  The disease reached South America in 1854 and 1855, with victims in Venezuela and Brazil. [ 31 ]  During the third pandemic, residents of  Tunisia , which had not been affected by the two previous pandemics, thought Europeans had brought the disease. They blamed their sanitation practices. Some United States scientists began to believe that cholera was somehow associated with African Americans, as the disease was prevalent in the South in areas of black populations. Current researchers note their populations were underserved in terms of sanitation infrastructure and health care, and they lived near the waterways by which travelers and ships carried the disease. [ 43 ]


From November 10, 1855, to December 1856, the disease spread through Puerto Rico, claiming 25,820 victims. [ 44 ]  Cemeteries were expanded to allow for the burial of victims of cholera. [ 45 ]  In  Arecibo , a large municipality of Puerto Rico, the number of people dying in the streets was so great that the city could not keep up. A man named Ulanga made it his responsibility to collect and carry the dead to the provisional  Cementerio de los Coléricos . [ 46 ]


The  fourth cholera pandemic  of the century began in the  Ganges Delta  of the  Bengal  region and traveled with Muslim pilgrims to  Mecca . In its first year, the epidemic claimed 30,000 of 90,000 Mecca pilgrims. [ 47 ]  Cholera spread throughout the Middle East and was carried to Russia, Europe, Africa and North America, in each case spreading from port cities and along inland waterways. [ citation needed ]


The pandemic reached Northern Africa in 1865 and spread to sub-Saharan Africa, killing 70,000 in  Zanzibar  in 1869–1870. [ 48 ]  Cholera claimed 90,000 lives in Russia in 1866. [ 49 ]  The epidemic of cholera that spread with the  Austro-Prussian War  (1866) is estimated to have taken 165,000 lives in the  Austrian Empire , including 30,000 each in Hungary and Belgium and 20,000 in the Netherlands. [ 50 ]  Other deaths from cholera at the time included 115,000 in Germany, 90,000 in Russia, and 30,000 in Belgium. [ 51 ]


In London in June 1866, a localized epidemic in the East End claimed 5,596 lives, just as the city was completing construction of its major sewage and water treatment systems (see  London sewerage system ); the East End section was not quite complete. [ 52 ]  Epidemiologist  William Farr  identified the  East London Water Company  as the source of the contamination. Farr made use of prior work by  John Snow  and others pointing to contaminated drinking water as the likely cause of cholera in an  1854 outbreak . Quick action prevented further deaths. [ 18 ]  In the same year, the use of contaminated canal water in local water works caused a minor outbreak at  Ystalyfera  in South Wales. Workers associated with the company and their families were most affected, and 119 died. [ 53 ]


In 1867, Italy lost 113,000 lives; and 80,000 died of the disease in Algeria. [ 48 ]  Outbreaks in North America in the 1870s killed some 50,000 Americans as cholera spread from New Orleans to other ports along the Mississippi River and its tributaries. None of the cities had adequate sanitation systems, and cholera spread through the water supply and contact. [ 33 ] [ 54 ]


According to A. J. Wall, the 1883–1887 part of the epidemic cost 250,000 lives in Europe and at least 50,000 in the Americas. Cholera claimed 267,890 lives in Russia (1892); [ 55 ]   120,000 in Spain ; [ 56 ]  90,000 in  Japan , and over 60,000 in  Persia . [ 55 ]  In  Egypt , cholera claimed more than 58,000 lives. The 1892 outbreak in  Hamburg  killed 8,600 people. Although the city government was generally held responsible for the virulence of the epidemic, it was not changed. This was the last serious European cholera outbreak, as cities improved their sanitation and water systems. [ citation needed ]


From the Russian Empire, cholera most likely spread to European countries. In Russia, cholera vibrio was found in  Baku  in 1892. The authorities of the city, despite the mortality of the population from cholera for a long time did not recognize the outbreak of the epidemic. The residents of Baku left the city, including traveling to  Astrakhan , a city located in the delta of the Volga River. After quarantine measures were introduced in Astrakhan, rumors spread among the population that living people were being put in coffins, sprinkled with lime, and buried in cholera hospitals. These rumors provoked riots. During the riots, medical workers were killed, the cholera hospital was burned down, and the infected were sent home. The incidence of the disease increased dramatically after the riots. From June 14 to September 20, 1892, more than 3% of Astrakhan's population died of cholera, with 480 cases and 316 deaths per 10,000 inhabitants. This was the demographic maximum of the 1892 cholera epidemic. An estimate of excess mortality showed an increase of 278% in June and 555% in July over the same months in 1888–1894. Of all those admitted to Astrakhan hospitals, about 73% were workers living in hostels (shelters), about 5% were workers on ships, steamships, and barges, and 12% were artisans. The social composition by estates was as follows: 1983  peasants , 316 soldiers, 262  bourgeois , 12  Cossacks , 8  nobles  and 5 clergymen. Natives of Astrakhan and the province accounted for about 11% of the cases, 89% were seasonal migrants. Many children were orphaned due to the high mortality rate. Because cholera is characterized by waterborne transmission, cholera epidemics were observed in large cities along the Volga River. Much of the empire was infested with cholera vibrio. [ 57 ]


The  sixth cholera pandemic , which was due to the classical strain of O1, had little effect in western Europe because of advances in sanitation and  public health , but major Russian cities and the  Ottoman Empire  particularly suffered a high rate of cholera deaths. More than 500,000 people died of cholera in Russia from 1900 to 1925, which was a time of extreme social disruption because of revolution and warfare. [ 58 ]


Cholera broke out 27 times during the  hajj  at  Mecca  from the 19th century to 1930. [ 58 ]  The sixth pandemic killed more than 800,000 in  India . [ 12 ]  The 1902–1904 cholera epidemic claimed 200,000 lives in the  Philippines , [ 59 ]  including their revolutionary hero and first prime minister  Apolinario Mabini . A 1905 governmental report mentioned he reappearance of asiatic cholera, characterized that as noteworthy, and described a "very strict marine quarantine" and other measures being imposed in the archipelago to control it. [ 60 ]


The last outbreak of cholera in the United States was in 1910–1911, when the steamship  Moltke  brought infected people from Naples to New York City. Vigilant health authorities isolated the infected in quarantine on  Swinburne Island . Eleven people died, including a health care worker at the hospital on the island. [ 61 ] [ 62 ] [ 63 ]


In 1913, the  Romanian Army , while invading  Bulgaria  during the  Second Balkan War , suffered  a cholera outbreak  that resulted in 1,600 deaths. [ 64 ] [ 65 ] [ 66 ]


During the outbreak, due to cholera frequently being spread by immigrants and tourists, the disease became associated with either outsiders or marginalized groups in societies. In Italy, some blamed  Jews  and  Romani , while in  British India  numerous  Anglo-Indians  ascribed the spread of cholera to  Hindu  pilgrims, and in the  United States  many accused  Filipino immigrants  of introducing the disease. [ 67 ]


As of March 2022, the  World Health Organization  (WHO) continues to define this outbreak as a current  pandemic , noting that cholera has become  endemic  in many countries. In 2017, WHO announced a global strategy aimed at this pandemic with the goal of reducing cholera deaths by 90% by 2030. [ 1 ]


The  seventh cholera pandemic  began in  Indonesia , called  El Tor [ 68 ]  after the strain, and reached  East Pakistan  (now  Bangladesh ) in 1963, India in 1964, and the  Soviet Union  in 1966. From  South America , it spread into Italy by 1973. In the late 1970s, there were small outbreaks in Japan and in the South Pacific. There was an outbreak in  Odessa  in July 1970, and there were also many reports of a cholera outbreak near  Baku  in 1972, but information about it was suppressed in the Soviet Union. [ 69 ]  In 1970, a cholera outbreak struck the  Sağmalcılar  district of  Istanbul , then an impoverished slum, claiming more than 50 lives. Because this incident was notorious, the district was renamed as Bayrampaşa. Also in August 1970, a few cases were reported in  Jerusalem . [ citation needed ]


Vibrio cholerae  has shown to be a very potent pathogenic bacterium causing many pandemics and epidemics over the past three centuries. However, most outbreaks are known to be self-limiting, meaning they come to an end after peaking, without human intervention. One of the mechanisms significantly determining the course of epidemics is phage predation. [ 70 ]  This process is strongly dependent on successful recognition of the bacteria by lytic phages, in which cell surface receptors play a crucial role. Bacteria can reduce their susceptibility by changing their surface receptors and  preventing phage adsorption. In the case of  V. cholerae , the changed receptor gene expression is due to an alteration in cell-density during its infection cycle, a process called quorum sensing (QS). The stool samples collected from patients contain clumps of bacterial cells, demonstrating the occurrence of cell-cell interaction in the latter stage of the infection cycle. QS is strongly regulated by two auto-inducer molecules, AI-2 and CAI-1. [ 71 ]  Evidently, these molecules will have a significant effect on the success of phage predation in  V. cholerae  infections. [ citation needed ]


A previous study has unravelled the mode of action of auto-inducers on preventing predation on the level of phage entry. [ 72 ]  The study has shown that the aforementioned auto-inducers downregulate the ten biosynthetic genes of the surface O-antigen, which is primarily used as a phage receptor for Vibriophages. This mechanism results in an increased phage resistance. It can be stated that the loss of the ability to produce the receptor, reduces the possibility of a phage-dependent limitation or even elimination of  V. cholerae . This should be kept in mind when developing a treatment for enteric bacterial infections with phages as an intervention tool. Future approaches may include additional quorum regulators that operate as “quorum quenchers” to reduce quorum-mediated phage resistance. [ citation needed ]