The Gut Microbiome and IBS
Irritable bowel syndrome (IBS), which affects more than 11% of the global population, is one of the most commonly diagnosed gastrointestinal (GI) conditions. Previous research has shown that IBS may be attributable to a combination of internal and external conditions specific to individual patients, including genetics, environment, stress, diet, and gut microbiome.
Michael C. Hoaglin, MD, and Melissa Agnello, PhD, cofounders of microbiome consultancy M2Biome in San Francisco, California, and colleagues conducted a study1 of a large cross-section of patients with self-reported IBS to investigate the connections between microbiome composition and IBS. They answered some of our questions about their research and its implications for future research and therapies for IBS.
CONSULTANT360: You mention in your study that evidence points to the importance of the gut microbiome in the etiology of IBS, but the association remains poorly defined. Can you explain why this is the case, and how has your research sought to clarify that relationship?
Michael Hoaglin: IBS is a heterogeneous disease entity that is typically thought of as a diagnosis of exclusion. Unlike other causes of chronic GI distress, such as inflammatory bowel disease or celiac disease—which can be ruled out by biopsy—there is no test for IBS. Diagnosing IBS, as a result, can prove to be a costly workup. We wanted to see if there was some signal in the human gut microbiome that was consistent in people with IBS, despite the likelihood of multiple etiologies. As with other diseases, we have not found a direct causal relationship between the microbiome and IBS, but rather an association.
Only relatively recently has technology become advanced enough to allow for in-depth analysis of the human gut microbiome. Although the overall importance of the microbiome in health and disease is now clear, characterizing the specific features associated with a disorder such as IBS has proven challenging. This is due to the complexity of the gut microbiome and also to the challenges of collecting and analyzing the large number of samples required to enable valid conclusions. The importance of our study in helping to further clarify and define both the clinical features of IBS and the microbiome associations stems from the uniquely large collection of samples and patient data that we had available.
C360: What did your research reveal about the extent of IBS in different populations in the United States according to demographics, microbiome composition, and risk factors? Which populations are at highest risk for IBS?
MH: Our large IBS cohort was consistent with what might be expected from the well-known epidemiological features of IBS. The disorder predominantly affected women and those with a family history of IBS; it also was more prevalent in people who had taken antibiotics in the previous year, especially fluoroquinolones. We were able to control for these factors in a multivariate analysis to look at the microbiome composition. Our aim was to take our analysis a bit beyond the “one bug, one disease” paradigm, because we know a single microbe association with a disease does not occur in a vacuum. It is an ecosystem of microbes that influence each other.
C360: How did the gut microbiomes of patients with IBS compare with individuals without IBS? What implications do these findings hold for advancing the diagnosis and treatment of IBS?
Melissa Agnello: We performed a pairwise analysis, which is a pretty novel analysis for this type of study, to reflect the reality that each species does not exist alone in the gut microbiome. In a complex, highly adapted ecosystem, the abundance of each species is directly related to, and has a direct effect on, the abundance of the other organisms. We found some interesting pairwise associations. For example, we found that increased Lactobacillus salivarius at the expense of Staphylococcus aureus showed the largest association on the odds of IBS. This may reflect increased probiotic and antibiotic use in the IBS group or a potential ecological interdependence that has not been explored. Although our results suggest an ecological shift, this primarily generates hypotheses for further study.
While our cross-sectional study was able to significantly associate certain features and risk factors for IBS, more studies are needed, specifically longitudinal, in order to more fully associate specific microbiome features with the risk of IBS.
C360: What are the key takeaways for practicing gastroenterologists that they can apply in diagnosing and treating patients with symptoms of IBS?
MH: Consider a microbial imbalance or “dysbiosis” in the gut microbiota as a potential contributor to chronic gastrointestinal distress. With more advanced data science and machine learning, the future will likely hold more robust gut microbiome diagnostic tests that will focus on the ecosystem of the microbiome, not just the level of a single microbe.
- Agnello M, Carroll LN, Imam N, et al. Gut microbiome composition and risk factors in a large cross-sectional IBS cohort. BMJ Open Gastroenterol. 2020;7(1):e000345. doi:10.1136/bmjgast-2019-000345