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As the COVID-19 pandemic has engulfed the world, there has never been a time in which topics related to gut health have been more popular. Suddenly self-declared experts from different fields of medicine, nutrition and wellness have all jumped on this new trend to explain old symptoms (such as bloating and abdominal distension) and to promote controversial novel treatments. Podcast, master classes, social media posts and advertisements, bestselling books have all driven the frenzy around topics like SIBO, special gut friendly diets and cleansing protocols, while scientific evidence from well controlled human studies have been lagging behind.

I am convinced that a significant number of individuals striving for improved gut health are suffering from IBS or related disorders of brain gut interactions. In this post, I would like to focus on one such topic: Small intestinal bacterial overgrowth, better known by its acronym SIBO (other references: 1, 2).

“There are few concepts and syndromes in Medicine and particularly in Gastroenterology which have gone through a similarly remarkable historical transformation as SIBO”.

There are few concepts and syndromes in medicine, and particularly in Gastroenterology, which have gone through a similarly remarkable historical transformation as SIBO. The term first emerged in the literature more than 80 years ago and was a relatively rare diagnosis. However, the concept was adopted more recently not only by functional and integrative medicine practitioners and by the lay media, but also by the medical establishment and the pharmaceutical industry. SIBO has been promoted as a diagnosis explaining some of the most common symptoms of abdominal discomfort such as bloating, abdominal distension and altered bowel habits. The concept has fueled a whole new “industry” of breath testing, and most worrisome, has led to the widespread and in my opinion totally unnecessary use of antibiotic treatments for symptoms most likely unrelated to gut microbes.

“…the diagnosis and overall conception of SIBO has become mired in uncertainty and controversy…”

SIBO is a clinical disorder that was first described in the 1930s in patients with serious symptoms of malabsorption, bloating, abdominal pain, and diarrhea, following surgical alterations of the gastrointestinal tract. However, since these early descriptions, the concept of SIBO has undergone significant change and challenges in light of emerging insights and speculations from studies into the gut microbiome. The diagnosis of SIBO which originally was limited to a small number of individuals with a specific medical history, has all of a sudden been given to a large number of patients complaining of such common, non-specific symptoms of abdominal bloating, sensations of gas and irregular bowel movements, and is now widely used as a seemingly plausible explanation for many IBS symptoms. However, as well summarized in a recent review article by Bushyhead and Quigley, the diagnosis and overall conception of SIBO has become mired in uncertainty and controversy, as there remains a lack of consensus or “gold standard” for diagnosis, an absence of causality to clearly link clinical symptoms to alterations in the gut microbiota (“dysbiosis”). In addition, the often-prescribed treatment with antibiotics is highly controversial.

“…there is currently no universally acknowledged or validated ‘gold standard’ for diagnosis, and no FDA-approved medications.”

Although there is no specific symptom of SIBO, patients given this diagnosis generally present with abdominal pain and distension, bloating, flatulence, and diarrhea, a nearly identical symptom complex as reported by IBS patients. Because these symptoms are neither exclusive to, nor predictive of SIBO, and SIBO is often treated with antibiotics, one would expect that such a diagnosis should only be made based on objective, generally accepted, and validated biological tests. However, despite recent advances in the scientific community’s understanding of the microbiome, there is currently no universally acknowledged or validated “gold standard” for diagnosis, and no FD-approved medications. Even though several tests are available and commonly used, including the direct analysis and quantification of small bowel microbiota and various breath tests measuring the production of hydrogen and methane by intestinal microbes, the validity of all these tests has been questioned and has generated substantial controversy. According to a North American Consensus Statement, such test results should be interpreted with caution, and most importantly, in my opinion should never be used as justification to prescribe antibiotics .

Surprisingly, although there are no Food and Drug Administration–approved medications to treat SIBO, the mainstay of treatment has been oral antibiotics. Given the well-known serious risks of antibiotic therapy– in particular when administered repeatedly- such as reduction of gut microbial diversity, the promotion of drug-resistant bacteria and the development of Clostridium difficile colitis, one would expect that data on the efficacy of antibiotics for SIBO should be unambiguous. Unfortunately, antibiotic regimens for SIBO have, in general, been poorly studied, largely in trials involving small numbers of patients and lack of placebo controls. For example, a systematic review and meta-analysis of rifaximin, a popular, nonabsorbable antibiotic, demonstrated that the overall eradication rate (based on the controversial breath tests mentioned above) was only about 70%. Importantly, the authors of the study noted that the quality of included studies was generally poor, as only a single study was placebo- controlled.

Other treatment modalities that may have a theoretic benefit in restoring healthy GI microbiota such as changes in diet, pro- and prebiotics and even fecal microbiota transplantation (FMT) have not been adequately studied for the treatment of SIBO.

“…the most problematic claim relating to the diagnosis of IBS has been its implication in the pathogenesis of IBS.”

As if the topic of SIBO is not controversial enough, the most problematic claim relating to this diagnosis has been its implication in the pathogenesis of IBS. An early study demonstrating both a higher prevalence of positive lactulose breath tests in patients with IBS (thought to reflect abnormal numbers of gut microbes in the small intestine) in comparison to healthy control subjects and significant improvement in IBS symptoms following normalization of breath tests with antibiotic therapy suggested a strong association between IBS and SIBO. However, a systematic review and meta-analysis of SIBO in IBS challenged the validity of this association, and put both the validity of the breath test as well as the diagnosis of SIBO into question. Significant problems in study design and reporting, as well as the possibility that a positive lactulose breath test may simply signify an abnormally fast transit time through the small intestine.

As there is some suggestion that the pathophysiology of IBS entails abnormal colonic rather than small bowel fermentation of complex carbohydrates, it is possible that the efficacy of antibiotic treatments in reducing bloating symptoms in some IBS patients is due to an impact on colonic rather than small bowel bacterial populations (it is worth noting that a subgroup of IBS patients actually reports a worsening of their symptoms after antibiotic treatment). In view of the well demonstrated hypersensitivity of the colon to distension, even a small reduction of normal intestinal gas production by the colonic microbiota could lead to some reduction in symptoms of bloating and gas. As the involvement and precise mode of action of rifaximin in SIBO remains poorly understood, it has been suggested that the effect of the drug on bacterial numbers may be minimal and effects may be related more to perturbations of bacterial metabolism. However, to date this remains a speculative hypothesis.

“…it is not possible to make any valid conclusions about a putative role of intestinal microbiota, SIBO and IBS”.

In summary, both the relationship between SIBO and altered intestinal gut microbial density, and the association between SIBO and IBS remains controversial. Whether current testing methods accurately reflect SIBO, and whether abnormal breath test results are causally related with IBS or IBS-like symptoms remains open to question. Because SIBO lacks a gold standard for diagnosis, and IBS is a diagnosis based on symptom criteria (the so-called Rome criteria) and of exclusion that lacks a validated biomarker, it is not possible to make any valid conclusions about a putative role of intestinal microbiota, SIBO and IBS.

In my opinion, future research focused on defining the normal small bowel microbiome with novel genomic and metabolomic technologies, and on the clinical utility of breath tests is required before making a valid diagnosis of SIBO and before routinely ordering the available breath test.

It shouldn’t come as a surprise to the readers of this post, that I have never made a diagnosis of SIBO in any of my patients, who did not have any of the established risk factors mentioned above, nor have I treated any IBS or IBS-like symptoms with antibiotics. As explained in a previous post My approach to patients is to take advantage of the gut’s own regulatory mechanisms, including a high fiber diet to assure normal transit of food through the small intestine, reduction or elimination of certain food items that reproducibly increase GI discomfort, and the unique gut cleansing motility patterns (“migrating motor complex”) to keep a normal gradient of microbial density throughout the gut.