The Microbiome and Chronic Disease: The SIBO Hypothesis "Hope, Deception, and Transformation"

| 30 January 2023

Written by: Abby Mocherniak, MSc Candidate, TMED 801 Student

On January 26th, the Department of Medicine had the pleasure to hear from Dr. Stephen Vanner, MD, MSc during Medical Grand Rounds, giving us the scoop on our poop. Dr. Vanner is the co-founder of the Translational Institute of Medicine (TIME) at Queen's University, director of the Gastrointestinal Disease Research Unit (GIDRU) at KGH and a practicing clinician scientist. Dr. Vanner shared his expertise in the field of gastroenterology, discussing the role of the gut microbiome in gastrointestinal (GI) disorders and the small intestine bacterial overgrowth (SIBO) hypothesis, including the hope, deception and transformation of research surrounding this topic.

Dr. Vanner discussed the role of the gut microbiome in chronic GI disorders, including irritable bowel syndrome (IBS). He explained the SIBO hypothesis as one manifestation of dysbiosis of the gut microbiome in which abnormal growth of bacteria may occur in the small intestine. Further, this hypothesis suggests that the altered bacterial colonization in the small intestine can elicit an immune response, that in turn produces symptoms in a subset of patients (1). However, Dr. Vanner explained that this theory has sparked debate amongst researchers and clinicians as the hypothesis is largely based on unvalidated breath tests.

Breath tests have been suggested as a method for detecting SIBO (2). These tests analyze the composition of expired breath following the ingestion of sugar. After ingestion, sugar undergoes fermentation by bacteria in the gut microbiome, producing hydrogen and methane gas as a byproduct that is exhaled in the breath (3). Collecting and quantifying the gas products of microbial fermentation in expired breath is suggested to vary between individuals with SIBO and healthy individuals, both in the timing of gas detection and quantity to allow for identification of SIBO1. In addition to breath tests, studies have suggested the use of the antibiotic rifaximin as a new therapeutic for GI disorders (4). Together, breath testing and antibiotic treatment contributed to the hope experienced by patients suffering from chronic GI disorders.

Now comes the deception. Dr. Vanner explained that perception of breath tests by patients and clinicians is problematic, as the test has low sensitivity and specificity, as well as highly subjective criteria used to classify test results as normal or abnormal (1). Thus, breath tests have been widely implemented without sufficient evidence supporting their accurate detection of IBS or SIBO, leading to incorrect diagnosis and treatment for patients experiencing GI symptoms (1). Thus, Dr. Vanner emphasized that the use of breath tests for SIBO in GI disorders should be abandoned completely.

Further complicating clinical management is the unfounded use of the antibiotic rifaximin in patients with IBS (4). The significance of SIBO in IBS remains largely unclear due to challenges associated with scientific analysis of bacterial contents of the small intestine, influence of confounding factors, and vast differences observed between studies (1). The validity of studies supporting the therapeutic use of rifaximin in this context raise concerns due to the conflicts of interest associated with lead investigators, insufficient symptom relief for a majority of IBS patients, as well as potential for antibiotic resistance (5). Dr. Vanner further discussed how clinicians endorsing the use of rifaximin are highly motivated by their relationships with pharmaceutical companies that directly benefit from rifaximin drug-sales.

Finally, Dr. Vanner discussed the transformation necessary in approaching chronic GI disorders, including research and clinical practice. He indicated that this transformation should include no longer using the term SIBO, as well as discontinuing the use of breath tests for IBS, and other GI disorders. Further, we should highlight the importance for future research to be driven by mechanistic studies rather than by associations. Dr. Vanner also emphasized how guidelines should be improved by medical societies and regulatory bodies to prevent conflicts of interest from influencing research that has potential to guide clinical practice. Further, he explained the low FODMAP diet as a safe and effective alternative to antibiotic use that shows greater promise in improving patient’s GI symptoms (6).

Following his lecture, Dr. Vanner met with the TMED students to discuss how this topic has influenced patient care. He explained the challenges of managing symptoms experienced by patients and how misconceptions surrounding treatment have been problematic in the field of gastroenterology. Additionally, he explained how social media has impacted patient perceptions of GI disorders. Dr. Vanner also shared his career journey and provided advice for how he maintains work-life balance as a clinician scientist.

On behalf of the TMED class, I would like to thank Dr. Vanner for his insightful, thought-provoking lecture and for taking the time to answer our questions.

REFERENCES

1. Simrén M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62(1):159-176. doi:10.1136/gutjnl-2012-302167

2. Vijay A, Valdes AM. Role of the gut microbiome in chronic diseases: a narrative review. European Journal of Clinical Nutrition. 2022;76(4):489-501. doi:10.1038/s41430-021-00991-6

3. Ogunrinola GA, Oyewale JO, Oshamika OO, Olasehinde GI. The Human Microbiome and Its Impacts on Health. International Journal of Microbiology. 2020;2020:1-7. doi:10.1155/2020/8045646

4. Saadi M, McCallum RW. Rifaximin in irritable bowel syndrome: rationale, evidence and clinical use. Therapeutic Advances in Chronic Disease. 2013;4(2):71-75. doi:10.1177/2040622312472008

5. Rezaie A, Buresi M, Lembo A, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. American Journal of Gastroenterology. 2017;112(5):775-784. doi:10.1038/ajg.2017.46

6. Gearry R, Skidmore P, O'Brien L, Wilkinson T, Nanayakkara W. Efficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to date. Clinical and Experimental Gastroenterology. 2016:131. doi:10.2147/ceg.s86798