Oct. 22, 2024
First described over a century ago, small intestinal bacterial overgrowth (SIBO) is broadly defined as excessive bacteria in the small intestine, which can be seen in patients with impaired motility of the small intestine. The most common presentation is diarrhea, though patients may have additional gastrointestinal symptoms associated with diarrhea, such as bloating, flatulence and abdominal pain. Patients with severe symptoms are at risk of malabsorption leading to weight loss and malnutrition.
More than 20 years ago, researchers hypothesized that increased numbers of small intestine bacteria also might account for symptoms in the absence of malabsorption in irritable bowel syndrome (IBS) and other disorders of the gut-brain interaction (DGBI).
The SIBO-IBS hypothesis prompted important research examining the role of the microbiota as a potential pathophysiological mechanism in IBS and other DGBI. However, in a review article published in Neurogastroenterology and Motility in 2024, Purna C. Kashyap, M.B.B.S., and co-authors note that after two decades, this hypothesis remains unproved and has had significant unintended consequences. In particular, the SIBO-IBS hypothesis has led to widespread use of breath tests to diagnose SIBO in patients with IBS and the resulting injudicious use of antibiotics. Dr. Kashyap is a gastroenterologist and researcher at Mayo Clinic in Minnesota, where he also serves as the Bernard and Edith Waterman Director, Microbiomics Program, Center for Individualized Medicine.
Limitations of breath testing
In Part 1 of their review article, Dr. Kashyap and co-authors discuss the concept of breath testing, its serious limitations, and why attributing IBS and unexplained gastrointestinal symptoms to SIBO remains problematic. They describe the available evidence demonstrating the fundamental flaw underlying the use of the lactulose hydrogen breath test (LHBT) — the fact that this test is primarily a measure of intestinal transit and has very low sensitivity and specificity to diagnose SIBO. Because transit time is highly variable in healthy people, an early rise in H2 levels can be wrongly attributed to increased bacteria in the small intestine. The authors explain that transit time to the cecum is remarkably short in many healthy people and in people diagnosed with IBS. Thus, breath testing can yield false-positive results in a very high proportion of individuals.
The authors explain that the glucose hydrogen breath test (GHBT) also lacks sufficient accuracy to diagnose SIBO in patients with IBS. Their review of GHBT studies reveals that GHBT has a lower false-positive rate than LHBT, which makes it suitable to use in patients at risk of SIBO, such as those with disordered gastrointestinal motility. However, the poor performance characteristics of GHBT in patients with suspected disorders of the gut-brain axis makes it unacceptable for routine clinical use in patients with IBS.
In a detailed review of studies examining the potential role of SIBO in IBS, Dr. Kashyap and co-authors explain that proponents of breath testing for IBS have based their recommendation on principles that lack supporting evidence from relevant studies. The controversy over the use of breath tests in diagnosing SIBO also is evident in the conflicting guidelines and consensus statements on this topic issued by major societies.
Understanding the small intestinal microbial environment
"We need to better understand the role of specific small intestinal bacteria and their products in driving GI disease. These efforts will allow us to develop both more targeted diagnostics and therapeutics."
In Part 2 of their article, Dr. Kashyap and co-authors describe the dynamic state of bacterial communities in the small intestine and their interactions with the host, and their potential role in the generation of IBS symptoms. They describe the small intestine as having "a fragile equilibrium," where diet and the luminal environment shape microbial composition and function. And they explain that all of these elements impact digestion, absorption and how the mucosal immune system functions.
The authors conclude by expressing their concern that the inaccurate attribution of symptoms to SIBO has led to administration of unnecessary and potentially harmful antibiotics in some instances. They recommend shifting the focus away from simply testing for SIBO in all patients with GI symptoms to a more targeted approach of identifying patients at risk of SIBO. Further, the authors support efforts to identify specific changes in microbial composition and function.
"We need to better understand the role of specific small intestinal bacteria and their products in driving GI disease," says Dr. Kashyap. "These efforts will allow us to develop both more targeted diagnostics and therapeutics."
The review article builds on multiple years of research that Dr. Kashyap and Mayo Clinic colleagues have conducted. In a 2019 publication in Nature Communications, Dr. Kashyap and co-authors demonstrated that common GI symptoms such as abdominal pain and diarrhea are likely due to a shift in the types of bacteria in the small intestine rather than SIBO. Their findings highlighted the potential clinical benefit of characterizing the small intestinal microbiome.
For more information
Kashyap P, et al. Critical appraisal of the SIBO hypothesis and breath testing: A clinical practice update endorsed by the European Society of Neurogastroenterology and Motility (ESNM) and the American Neurogastroenterology and Motility Society (ANMS). Neurogastroenterology and Motility. 2024;36:e14817.
Saffouri GB, et al. Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders. Nature Communications. 2019;10:2012.
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