# Great Review of Research on the role of infection/microbiota on IBS and the Brain



## betterthroughscience (Jan 13, 2006)

Dig Liver Dis. 2009 Sep 7. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/pubmed/19740713The putative role of the intestinal microbiota in the irritable bowel syndrome.Collins S, Denou E, Verdu E, Bercik P.The Farncombe Digestive Health Research Institute, The Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.The irritable bowel syndrome (IBS) is a chronic abdominal symptom complex that is heterogeneous in terms of its clinical presentation and underlying pathophysiology and pathogenesis. It is now established that enteric infection can trigger the syndrome in at least a subset of patients. In addition, there is growing evidence of low grade inflammation and immune activation in the distal bowel of some IBS patients. These observations now prompt the question as to what maintains gut dysfunction in these patients. The intestinal microbiota influences a broad array of host organs that include the gut and the brain, and is an important determinant of normal function in these systems. Disruption of the delicate balance between the host and its intestinal microbiota (termed dysbiosis) results in changes in the mucosal immune system that range from overt inflammation as seen in Crohn's Disease, to low grade inflammation without tissue injury, as seen in a subset of IBS patients. Under experimental conditions, disruption of the microbiota also produces changes in gut sensory-motor function and immune activity. Thus, dysbiosis induced by infection, dietary change or drugs such as antibiotics could produce low grade inflammation and chronic gut dysfunction, reminiscent of that seen in IBS. Fluctuations in gut physiology destabilize the habitat of commensal bacteria and provide a basis for chronic dysbiosis. Recent observations in animal models that changes in gut flora influence behavior provide a basis for a novel unifying hypothesis that accommodates both gut dysfunction and behavioral changes that characterize many IBS patients. This hypothesis states that dysbiosis exists in at least a subset of IBS patients, as a result of infection, dietary change or drugs and contributes to gut inflammatory and functional change in addition to psychiatric co-morbidity.PMID: 19740713 [PubMed - as supplied by publisher]


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## eric (Jul 8, 1999)

This is talking about POST INFECTIOUS IBS like people who develop IBS after an enteric infection has already been erdicated. So far no link has been found to any specific bacteria or that any drug causes IBS.Betterthrough science what exactly are these experimnetal conditions?"Under experimental conditions, disruption of the microbiota also produces changes in gut sensory-motor function and immune activity."Since gut bacteria are constantly changing to a certain extent yet everyone doesn't get IBS.


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## eric (Jul 8, 1999)

Dig Liver Dis. 2009 Aug 27. [Epub ahead of print] LinksInfection, inflammation, and the irritable bowel syndrome.Spiller R, Garsed K.Nottingham Digestive Diseases Centre Biomedical Research Unit, University Hospital, Nottingham, United Kingdom.Gastrointestinal infection is ubiquitous worldwide though the pattern of infection varies widely. Poor hygiene and lack of piped water is associated with a high incidence of childhood infection, both viral and bacterial. However in developed countries bacterial infection is commoner in young adults. Studies of bacterial infections in developed countries suggest 75% of adults fully recover, however around 25% have long lasting changes in bowel habit and a smaller number develop the irritable bowel syndrome (IBS). Whether the incidence is similar in developing countries is unknown. Post-infective IBS (PI-IBS) shares many features with unselected IBS but by having a defined onset allows better definition of risk factors. These are in order of importance: severity of initial illness, smoking, female gender and adverse psychological factors. Symptoms may last many years for reasons which are unclear. They are likely to include genetic factors controlling the immune response, alterations in serotonin signaling, low grade mucosal inflammation maintained by psychological stressors and alterations in gut microbiota. As yet there are no proven specific treatments, though 5HT(3) receptor antagonists, anti-inflammatory agents and probiotics are all logical treatments which should be examined in large well-designed randomised placebo controlled trials.PMID: 19716778


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## Kathleen M. (Nov 16, 1999)

I was able to see the epublished version of the first paper mentioned.Here are the papers that they used to back up the sentance the authors of the paper put in the abstract.[50] V. Lesniewska, I. Rowland and H.N. Laerke et al., Relationship between dietary-induced changes in intestinal commensal microflora and duodenojejunal myoelectric activity monitored by radiotelemetry in the rat in vivo, Exp Physiol 91 (2006), pp. 229-237. View Record in Scopus | Cited By in Scopus (3)[51] E.F. Verdu, P. Bercik and M. Verma-Gandhu et al., Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice, Gut 55 (2006), pp. 182-190. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (46)How to translate that to the human conditions I don't know, but there is always some interplay between our bacteria and us as the host so I do not think that this sort of thing only happens in rodents.Generally if they mention something like that in a peer reviewed paper in the literature someone double checked they actually referred to real experiments in the paper. Sometimes the abstract isn't all that representative of the paper, or leaves important details out, but rarely can they make statements that are not backed up by something in the paper.I think everyone can agree that by whatever mechanism probiotics do seem to be a promising treatment for at least some people with IBS.


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## Patman75 (Mar 9, 2008)

> in at least a *subset* of IBS patients


Good info everyone. If we all had the same problem it would be easy to correct the problem. How have you been Eric? we have not seen you around in a long time. I hope all is well.


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## eric (Jul 8, 1999)

I am doing okay Patman.No doubt probiotics can be helpful to some and understanding the different gut micro-organisms. But in post infectious IBS there are also structural issues they have found that can cause the symptoms. If I am not mistaken only one strain of bacteria has been shown in research to help somewhat. They have known about intestinal permeability in IBS for quite sometime now from Post infectious IBS studies. Low grade tissue inflammation without tissue injury from degrandulation of mast cells and histimine can also be achived through activation of the bodies the stress system. Mast cells and EC cells embedded in the gut wall have been and are being investigated. They have found problems with post infectious IBSers and IBSers with these cells.


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## Puppy3D (Jul 28, 2004)

I`m PI-IBS, with mild C and a lot of pain. I tried everything in the last 10 years, also probiotics. Microbacterias are no harm, but I felt no change in symptoms. I had email contact with one of the best IBS researcher in Europe. Dr. Scheemann and his team from Germany. He is sure that inflammation damage gut lining in IBS. And after inflammation the gut lining is altered and produces more TRPV1 receptores, an ezyme called Serine protease, and serotonin. A whole mixture that is irritating gut nerves. This leads to motility issues and of course visceral sensibilty and pain. After his opinion a lot people with IBS have altered gut lining, even people who had no inflammation process- (PI IBS). What is also interessting is that, there are also people with IBS, who have no altered gut lining. They are completly normal healthy. That`s probably because IBS is no real illness but only a syndrome. So this means that a person who infection with inflammation and chronic pain 24/7has the same IBS diagnosis like a person who have once bout of diarrhea (for expample) before a math test in school. If this makes sense is disputable. ALso that up to 20% of population have IBS is not true in my opion. They are much less. But probably 20% have digestion issues like bloating or C. Also Scheemann remakrs that today prescribded drugs are more or less useless for IBS. They do nothing at the key-mechanisms of IBS, like trpv1 and serine protease. This will need new drugs.


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## eric (Jul 8, 1999)

Puppy3-d"After his opinion a lot people with IBS have altered gut lining, even people who had no inflammation process- (PI IBS)."Actually those are the people who had inflammation, from an enteric infection that then develop IBS after the intial infection has resolved, leading to gut changes.Probably one of the most important researchers in PI IBS is DR Spiller if you search pubmed.Dig Liver Dis. 2009 Aug 27. [Epub ahead of print] LinksInfection, inflammation, and the irritable bowel syndrome.Spiller R, Garsed K.Nottingham Digestive Diseases Centre Biomedical Research Unit, University Hospital, Nottingham, United Kingdom.Gastrointestinal infection is ubiquitous worldwide though the pattern of infection varies widely. Poor hygiene and lack of piped water is associated with a high incidence of childhood infection, both viral and bacterial. However in developed countries bacterial infection is commoner in young adults. Studies of bacterial infections in developed countries suggest 75% of adults fully recover, however around 25% have long lasting changes in bowel habit and a smaller number develop the irritable bowel syndrome (IBS). Whether the incidence is similar in developing countries is unknown. Post-infective IBS (PI-IBS) shares many features with unselected IBS but by having a defined onset allows better definition of risk factors. These are in order of importance: severity of initial illness, smoking, female gender and adverse psychological factors. Symptoms may last many years for reasons which are unclear. They are likely to include genetic factors controlling the immune response, alterations in serotonin signaling, low grade mucosal inflammation maintained by psychological stressors and alterations in gut microbiota. As yet there are no proven specific treatments, though 5HT(3) receptor antagonists, anti-inflammatory agents and probiotics are all logical treatments which should be examined in large well-designed randomised placebo controlled trials.PMID: 19716778 Gastroenterology. 2009 May;136(6):1979-88. Epub 2009 May 7. LinksPostinfectious irritable bowel syndrome.Spiller R, Garsed K.Nottingham Digestive Diseases Centre Biomedical Research Unit, University Hospital, Nottingham, England. [email protected] 1 in ten patients with irritable bowel syndrome (IBS) believe their IBS began with an infectious illness. Prospective studies have shown that 3% to 36% of enteric infections lead to persistent new IBS symptoms; the precise incidence depends on the infecting organism. Whereas viral gastroenteritis seems to have only short-term effects, bacterial enteritis and protozoan and helminth infections are followed by prolonged postinfective IBS (PI-IBS). Risk factors for developing PI-IBS include, in order of importance, prolonged duration of initial illness, toxicity of infecting bacterial strain, smoking, mucosal markers of inflammation, female gender, depression, hypochondriasis, and adverse life events in the preceding 3 months. Age older than 60 years might protect against PI-IBS, whereas treatment with antibiotics has been associated with increased risk. The mechanisms that cause PI-IBS are unknown but could include residual inflammation or persistent changes in mucosal immunocytes, enterochromaffin and mast cells, enteric nerves, and the gastrointestinal microbiota. *Adverse psychological factors contribute to persistent low-grade inflammation. *The prognosis for patients with PI-IBS is somewhat better than for those with unselected IBS, but PI-IBS can still take years to resolve. There are no specific treatments for PI-IBS; these should be tailored to the predominant bowel disturbance, which is most frequently diarrhea.PMID: 19457422 Neuropharmacology. 2008 Nov;55(6):1072-80. Epub 2008 Jul 19. LinksSerotonin and GI clinical disorders.Spiller R.Wolfson Digestive Diseases Centre, C Floor South Block, University Hospital, Clifton Boulevard, Nottingham, NG7 2UH, United Kingdom. [email protected] is widely distributed throughout the gut within both the enteric nerves and enterochromaffin (EC) cells. EC cells are located in the gut mucosa with maximal numbers in the duodenum and rectum where they act as signal transducers, responding to pressure and luminal substances both bacterial and dietary. Activation leads to serotonin release which acts on a range of receptors on mucosal afferent and myenteric interneurones to initiate secretomotor reflexes. These cause nausea and vomiting as well as intestinal secretion, propulsion and if pronounced, diarrhoea. Inflammation in animal models acts via T lymphocytes to increase EC cell numbers and mucosal serotonin (5-HT) content while inflammatory cytokines decrease serotonin transporter (SERT) function. Inflammation due to coeliac disease and following gastrointestinal infection increases mucosal 5-HT availability by a combination of increased EC cells and depressed SERT. Irritable bowel syndrome (IBS) developing after gastrointestinal infection and IBS with diarrhoea is associated with excess 5-HT. The associated diarrhoeal symptoms respond well to 5-HT(3) receptor antagonists. These drugs also inhibit the nausea and vomiting occurring in patients undergoing chemotherapy which cause a marked increase in release of 5-HT as well as other mediators. Other conditions including IBS-C and constipation may have inadequate 5-HT release and benefit from both 5-HT(3) and 5-HT(4) receptor agonists.PMID: 18687345Serotonin, inflammation, and IBS: fitting the jigsaw together?Spiller R.Department of Gastroenterology, Wolfson Digestive Diseases Centre, Nottingham, UK. [email protected] diarrhoea is a frequent indication for gastroenterologic referral, and after full investigation the most common final diagnosis is irritable bowel syndrome (IBS). Some patients with IBS describe an acute onset of symptoms following infective gastroenteritis. Postinfective IBS affects 7% to 31% of individuals infected, and appears to be a nonspecific response to injury which has been reported following Salmonella-, Campylobacter-, and Shigella-related IBS. The strongest risk factor for developing postinfective IBS is severity of the initial diarrhoea illness, but toxigenicity of the infected bacteria, age <60 years, and female sex also are important risk factors. Adverse life events, hypochondriasis, and depression are also important, as is increased enteroendocrine cell and lymphocyte numbers in rectal biopsies. Postinfective IBS and IBS with diarrhoea without an infectious onset both show increased postprandial release of serotonin, whilst constipated patients show a depressed release. Several studies suggest impairment of the serotonin transporter in IBS, which in animal studies has been shown to occur following a range of inflammatory insults. Clinical conditions with an inflammatory basis, such as coeliac and Crohn disease, also are characterised by excess postprandial serotonin release. Several studies report evidence of low-grade inflammation in IBS with diarrhoea. However, reliable markers of low-grade inflammation that may predict response to serotonin antagonists or other anti-inflammatory agents remain a goal for future research.PMID: 18185071 Curr Treat Options Gastroenterol. 2007 Aug;10(4):312-21. LinksIrritable bowel syndrome: bacteria and inflammation--clinical relevance now.Spiller RC.Robin C. Spiller, MB BChir, MSc, MD Wolfson Digestive Diseases Centre, University Hospital, Nottingham, NG7 2UH, England. [email protected] bowel syndrome (IBS) is a ubiquitous but heterogeneous syndrome characterized by abdominal pain and erratic bowel habits that affects 5% to 10% of the population. Although current definitions specify that there are no structural or biochemical abnormalities to account for the symptoms, there is growing evidence that in at least a subset of IBS patients, there is low-grade inflammation characterized by increased T lymphocytes and mast cells. Whether this is cause or effect is uncertain, as there is also clear evidence of bidirectional communication between the immune and nervous systems, and at least some of the mucosal changes could be secondary to psychological stress. A small percentage (6%-17%) of patients develop IBS symptoms for the first time after an acute episode of infective gastroenteritis (postinfective IBS), which appears to be directly responsible for low-grade immune activation. *However, even in this group, preexisting psychological factors are as important as mucosal ones.* Specific anti-inflammatory treatments have not been systematically evaluated, but there is no evidence of benefit currently.PMID: 17761124 The bodies stress system is connected to those mast cells and serotonin cells.


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