Alterations in Intestinal Microbial Flora and Human Disease

Mohamed Othman; Roberto Agüero; Henry C. Lin

Disclosures

Curr Opin Gastroenterol. 2008;24(1):11-16. 

In This Article

Acute Bacterial Gastroenteritis and Microflora in Irritable Bowel Syndrome

There are numerous pathogenic organisms responsible for acute bacterial gastroenteritis. These microbes not only activate the immune response of the host but also alter the composition of the gut microflora.[21••] A complication of acute gastrointestinal infection is the subsequent development of irritable bowel syndrome (IBS). About a quarter of IBS patients recall an episode of acute gastroenteritis prior to the onset of their IBS. Furthermore, the incidence of IBS is higher among patients who experienced an episode of acute bacterial gastroenteritis relative to those who have not.[22] In a large prospectively conducted cohort study, the relative risk for developing IBS following bacterial gastroenteritis was 11-fold greater than that of the control population.[23] The relationship between acute gastroenteritis and IBS may be due to either altered gut microbiota, bacterial overgrowth (SIBO), or a change in the part of the host as a consequence of an acute episode of gastrointestinal infection. Three months following recovery from an acute gastroenteritis caused by Campylobacter jejuni, 27% of rats had SIBO as confirmed by quantitative PCR targeting microbial DNA.[24] This finding in animals recovering from acute bacterial gastroenteritis is consistent with a growing body of evidence pointing to SIBO as the underlying cause of IBS.[10] There is also evidence of abnormal microbial fermentation in IBS patients as shown by increased excretion of microbially produced gases (hydrogen or methane) on the exhaled breath of IBS patients, compared with controls, after ingestion of lactulose, a nondigestible substrate during a lactulose breath test (LBT).[9,25,26] Although prevalence of an abnormal lactulose breath test in IBS patients varies, in a randomized, placebo-controlled study of patients meeting Rome I criteria for IBS, the prevalence of an abnormal LBT was 84%.[27] Different breath test methods and instrumentation place the prevalence of an abnormal breath test in IBS patients in the range of 30-78%.[28,29] Treating IBS patients with nonabsorbable antibiotics resulted in complete resolution of IBS symptoms in those patients who achieved a normalized breath test.[28] Similarly, in the RCT, patients reported 75% global improvement in their symptoms if they were randomized to the antibiotic group and their post-treatment breath test was found to be normal.[27] In contrast, patients who were treated but failed to achieve a normalized breath test still reported a 32% global improvement, which was significantly higher than the 10% improvement reported by patients randomized to placebo.

The contribution of gut microbes to symptoms of IBS is further supported by the role of microbial gases in altered bowel patterns. In the RCT,[27] the finding of breath excretion of methane alone was associated exclusively with constipation; and this observation was confirmed in a larger study.[30] In addition, the mean constipation severity-scores correlated directly with the concentration of methane detected on LBT in a study of 87 IBS patients.[31•] Furthermore, improvement of symptoms for patients with constipation-predominant IBS correlated with a reduction in methane production by neomycin.[32]

Methane is a biologically active gas that is capable of slowing intestinal transit by shifting the pattern of motility from peristaltic to nonperistaltic.[33] In a recent RCT,[34••] 87 IBS patients were given either rifaximin, a nonabsorbed oral antibiotic that acted primarily in the small intestine, or placebo. In this study, symptom improvement persisted through the entire 10-week observation period following discontinuation of the 10-day antibiotic treatment. Since symptom-directed treatment rapidly disappears upon cessation of treatment, such sustained improvement is only possible if the treatment were to be directed, instead, at the underlying cause of the symptoms of IBS and that cause were to be an antibiotic-sensitive mechanism such as SIBO. The relationship between SIBO and intestinal motility was supported by the finding of reduced frequency of cycling of interdigestive motility in patients with IBS.[35] Impaired intestinal motility may be a key element in the loss of containment of the microflora, resulting in SIBO.

The relationship between acute gastroenteritis, SIBO and IBS can be understood by considering the activation of host immunity by microbes and symptoms as consequences of immune activation. An additional piece of evidence supporting the idea of altered gut microbiota is the histological finding of immune activation in both IBS patients with a history of acute gastroenteritis and in IBS patients without such history.[36] In animal models, infection of the gastrointestinal tract by nematodes resulted in an alteration of the intestinal myenteric neurons, suggesting an additional mechanism for symptoms in IBS patients.[37]

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