From the Journals

VIDEO: Infectious enteritis quadrupled short-term risk of IBS

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Phenomenon has long been under study

The phenomenon of IBS developing after a bout of gastroenteritis (postinfectious [PI]–IBS) was first reported in 1950 and subsequently elaborated by studies from Oxford (Q J Med. 1962;123:307-22), Sheffield (Gut. 1999;44:400-6), and Nottingham (BMJ 1997;314:779-82; Gut. 2000;47:804-11). It has proven to be a fertile area for research, which is the basis for this excellent meta-analysis.

The authors identified 45 studies, 29 in the last decade including a total of 21,421 participants with exposure to gastroenteritis. The pooled prevalence for PI-IBS was 11.5% (95% CI, 8.2%-15.8%) but with considerable heterogeneity, which the authors attempted to explain by a number of subgroup analyses. The authors report that protozoal infection seems to have a higher rate of PI-IBS than bacterial or viral infection, though some caution is warranted, since these figures rely on reports from just one outbreak of giardiasis in Bergen, Norway (Scand J Gastroenterol. 2012;47:956-61). However, if true, this might suggest that a different immune response could be responsible, a feature which others have suggested might predispose particular individuals to PI-IBS (Gut. 2016;65[8]1279-88).

Dr. Robin Spiller

Other notable findings were the higher incidence of PI-IBS in studies with low response rates, suggesting important bias is such studies. Thirty of the studies included controls to allow relative risk (RR) estimation. Pediatric series showed similar RRs to adults at 4.1 versus 3.8, respectively. Age strongly influences immune response and older age was protective in several studies (Clin Gastroenterol Hepatol 2007;5:465-9; J Travel Med. 2014;21:153-8; BMJ 1997;314:779-82) but other studies found no effect. This may relate to an inadequate age range since the differences were most marked in those older than 60 years (BMJ 1997;314:779-82).

The meta-analysis confirms the consistent increased risk in female patients (odds ratio, 1.69), anxiety (OR, 1.97), and somatization (greatest RR, 4.05), all common risks for the development of IBS but not specific to PI-IBS. Initial disease severity indicators, including bloody stool and more than 7 days of initial illness, which might indicate the severity of underlying damage to the gut, were shown to be significant risk factors. Animal studies of acute infection, particularly parasitic infestation, indicate that significant changes can be seen in both nerve and muscle, but routine histology in PI-IBS patients is normal. Infection produces a striking increase in gut permeability (Gut 2000;47:804-11), a feature of IBS whose molecular basis has been demonstrated by a series of elegant studies (Gut. 2017 Jan 12 [Epub ahead of print]; Gut. 2015;64:1379-88) demonstrating altered tight junctions and immune activation in IBS with diarrhea. The authors found treatment with antibiotics increased the risk of PI-IBS but whether this is attributable to confounding by indication is unclear.

This meta-analysis indicates that PI-IBS also potentially is the most common cause of IBS, given that both the Centers for Disease Control and Prevention in the United States and community surveys in the United Kingdom (BMJ. 1999;318:1046-50) indicate that gastroenteritis affects around 1 in 5 of the population each year. If the incidence of PI-IBS is around 10%, modeling suggests PI-IBS could account for the majority of new cases (J Neurogastroenterol Motil. 2012;18:200-4).

Dr. Robin Spiller is professor of gastroenterology, NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham Digestive Diseases Centre, University of Nottingham, England. He has no relevant conflicts of interest.


 

FROM GASTROENTEROLOGY

More than 10% of patients developed irritable bowel syndrome (IBS) within a year after infectious enteritis, which gave them a more than fourfold greater risk than that of controls, according to a systematic review and meta-analysis of 45 studies.

Postinfectious IBS can last at least a decade after resolution of campylobacteriosis, shigellosis, salmonellosis, giardiasis, and norovirus infections, even when patients have no other risk factors for IBS, the researchers noted. To update and expand the most recent meta-analysis of this topic (Aliment Pharmacol Ther. 2007;26:535-44), the investigators searched Ovid Medline, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews for studies published from 2006 through Aug. 31, 2015. This search yielded 45 studies, including 30 studies comparing infected patients with controls, who were usually matched by age, sex, and geographic location (Gastroenterology. 2017 Jan 6. doi: 10.1053/j.gastro.2016.12.039).

In all, 10.1% of patients with infectious enteritis developed IBS in the next 12 months (95% confidence interval, 7.2-14.1) – a 4.2-fold increase in risk, compared with that of controls (risk ratio, 4.2; 95% CI, 3.2-5.7). This risk subsequently dropped, but remained significantly elevated (RR, 2.3; 95% CI, 1.8-3.0), compared with controls. “Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS; of patients with enteritis caused by bacterial infection, 13.8% developed IBS,” the researchers emphasized. Patients with these infections remained at elevated risk of PI-IBS even after 1 year. Viral enteritis also significantly increased the risk of PI-IBS, but risk dropped to baseline levels after a year.

Among 10 pooled studies of IBS subtypes, 46% of patients had mixed IBS, 39% had diarrhea-predominant IBS, and 15% had constipation-predominant IBS. Female sex doubled the odds of PI-IBS (odds ratio, 2.2; 95% CI, 1.6-3.1) in 11 pooled studies. Significant clinical risk factors for PI-IBS included diarrhea lasting more than 7 days (eight studies; OR, 2.6; 95% CI, 1.5-4.6), bloody stool (four studies; OR, 1.9; 95% CI, 1.1-3.0), and antibiotic therapy during infectious enteritis (seven studies; OR, 1.7; 95% CI, 1.2-2.4).

Multiple reports linked PI-IBS to clinical psychological distress at the time of infectious enteritis. Specific risk factors included depression based on the Hospitalization Anxiety and Depression Scale (five studies; OR, 1.5; 95% CI, 1.2-1.9), anxiety based on the Hospital Anxiety and Depression Scale (four studies; OR, 2.0; 95% CI, 1.3-2.9), somatization (four studies; OR, 4.1; 95% CI, 2.7-6.0), and neuroticism (two studies; OR, 3.3; 95% CI, 1.6-6.6). Isolated studies also implicated hypochondriasis, extroversion, negative illness beliefs, stress, sleep disturbance, and adverse life events in the preceding year, the researchers said.

They found no evidence of publication bias, but noted a substantial amount of heterogeneity among studies. Also, some studies did not report multivariate analyses, so individual odds ratios might reflect “a conglomeration of factors,” they said.

The National Institutes of Health and the American Gastroenterological Association funded the work. The investigators reported having no conflicts of interest.

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