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Antibiotic Use as a Risk Factor for IBS
TAKE-HOME MESSAGE
- This case–control study collected data from 29,111 patients with IBS and 135,172 controls to assess the risk of developing IBS after antibiotic exposure. The investigators limited their analysis to only antibiotic exposure beyond a year before IBS diagnosis. They found that any history of antibiotic exposure was significantly associated with subsequent IBS diagnosis. The number of historical antibiotic prescriptions demonstrated a dose–response relationship with the risk of IBS, with three or more historical antibiotic prescriptions resulting in 2.36- to 3.36-times increased odds of being diagnosed with IBS across antibiotic classes.
- Antibiotic exposure may be a risk factor for the subsequent development of IBS, which would agree with the dysbiosis pathophysiological theory. However, further studies are needed given the diversity in both IBS and the microbiome.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
The microbiome plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Antibiotic use can fundamentally alter gut microbial ecology. We examined the association of antibiotic use with IBS in a large population-based investigation.
METHODS
A case-control study with prospectively collected data on 29,111 adult patients diagnosed with IBS in Sweden between 2007 and 2016 matched with 135,172 controls. Using a comprehensive histopathology cohort, the Swedish Patient Register, and the Prescribed Drug Register, we identified all consecutive cases of IBS in addition to cumulative antibiotic dispensations accrued until 1 year prior to IBS (exclusionary period) for cases and time of matching for up to five general population controls matched on the basis of age, sex, country and calendar year. Conditional logistic regression estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of IBS.
RESULTS
Patients with IBS (n = 29,111) were more likely than controls (n = 135,172) to have used antibiotics up to 1 year prior to diagnosis (74.9% vs. 57.8%). After multivariable adjustment, this translated to a more than twofold increased odds of IBS (OR 2.21, 95% CI 2.14-2.28) that did not differ according to age, sex, year of IBS diagnosis or IBS subtype. Compared to none, 1-2 (OR 1.67, 95% CI 1.61-1.73) and ≥3 antibiotics dispensations (OR 3.36, 95% CI 3.24-3.49) were associated with increased odds of IBS (p for trend <0.001) regardless of the antibiotic class.
CONCLUSIONS
Prior antibiotics use was associated with an increased odds of IBS with the highest risk among people with multiple antibiotics dispensations.
Additional Info
Disclosure statements are available on the authors' profiles:
Antibiotic use as a risk factor for irritable bowel syndrome: Results from a nationwide, case-control study
Aliment. Pharmacol. Ther. 2023 Sep 28;[EPub Ahead of Print], K Staller, O Olén, J Söderling, B Roelstraete, H Törnblom, B Kuo, LH Nguyen, JF LudvigssonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Antibiotic use is a strong risk factor for IBS
Increasing evidence implicates the intestinal microbiome in the pathogenesis of IBS.1,2 The study by Staller et al (2023) confirms in a very large population-based nested case–control study that antibiotic use is a strong risk factor for the development of IBS. Furthermore, they identified a dose–response relationship with the odds of developing IBS increasing with higher antibiotic dispensation (OR, 3.36 with three or more dispensations controlling for confounders on multivariate analysis). While all classes of antibiotics were associated with the development of IBS, tetracyclines were associated with the greatest risk (OR, 2.18).
Of note, a personal history of GI infection up to 1 year prior to IBS diagnosis did not appear to alter the likelihood of developing IBS. A meta-analysis of other studies indicates that a history of GI infection is associated with the risk of IBS development beyond 1 year.3 It is possible that acute GI infection sets the scene for IBS (and the infection often later forgotten), and antibiotic exposure provides the second hit to the microbiome initiating immune activation and disease onset.
The proportion of IBS with diarrhea (57.7%) in the Staller study was higher than expected.4 The methodology of choosing cases from a population that has undergone colonoscopy and biopsy likely skewed the results because fewer with IBS with constipation may have been offered colonoscopy (as the yield of finding underlying organic disease in constipation is less).
Psychiatric illness is a risk factor for IBS, but was not documented in the patients' previous comorbidity list. Data on the use of antidepressant medication in this population would also be noteworthy given the association of depression and anxiety with IBS. Those seeking healthcare more often, which may be driven by underlying psychological distress, may be more likely to receive other prescriptions (eg, unnecessary antibiotics), confounding the association. Supporting this idea, the patients with IBS in this study had a higher number of outpatient visits than controls.
Inappropriate use of antibiotics continues to increase worldwide.5 However, the incidence of IBS is not established to be increasing, although the exact impact of postinfectious IBS after SARS-CoV-2 has yet to be ascertained.6 The microbiome is also altered by diet, medications, environment, and genetics; therefore, any impact of antibiotic use is likely to be complex. Further studies are needed to explore exactly why antibiotic use is a risk factor for IBS, which is no longer in dispute. Is it an alteration of many or a few (even one) bacteria? Can it be prevented with prebiotics or probiotics or diet change, and when is the optimal time to intervene? In the meantime, limiting unnecessary prescription of antibiotics should be a public health priority.
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