Jury still out on causes of, treatment for small intestinal bacterial overgrowth
Mitchell B.Cohen, M.D., FAAP and William J.Steinbach, M.D., FAAP
Focus on Subspecialties
Small intestinal bacterial overgrowth (SIBO) is hard to diagnose, and the very definition
of SIBO is controversial.
There is agreement that bacterial overgrowth, or an abundance of microbes in the small
intestine, is the definition of SIBO. However, difficulty obtaining cultures from
this site, uncertainty about the quantity and diversity of “normal” flora, and lack
of a good surrogate marker, including breath tests, all contribute to the murky definition.
Symptoms ascribed to SIBO are protean and include abdominal pain, malnutrition, diarrhea,
weight loss, bloating, growth stunting, flatulence, steatorrhea, malabsorption, anemia
and fat-soluble vitamin deficiency (Sieczkowska A, et al. J Pediatr Gastroenterol Nutr. 2016;62:196-207).
Moreover, in part because it is difficult to identify comparable control study subjects,
it is not known whether SIBO is a condition causing a clinical disease or simply an
observation in search of a disease.
There are no broadly reproducible data on the true prevalence of SIBO in the overall
population or even in specific groups thought to be at high risk. Several proposed
risk factors make intuitive sense. Factors that reduce the movement of intestinal
contents “downstream” and might result in SIBO from stasis include dysmotility and
altered anatomy including but not limited to the loss of the ileocecal valve, which
separates the bacteria-rich colon and the small intestine. Reduced gastric acid, including
treatment with proton pump inhibitors, interruption of pancreatic and biliary secretion,
and mucosal immune deficiency all remove limits on bacterial growth in the intestine
and are plausible causes of SIBO.
A high burden of contaminated food and water in children in low- and middle-income
countries also has been postulated to cause SIBO (Donowitz JR and Petri WA. Trends Mol Med. 2015;21:6-15).
While countless attempts have been made to relate SIBO to a long list of underlying
disorders, those links have not been established conclusively, and bona fide mechanistic
studies are lacking.
However, the greatest controversy surrounding SIBO likely has been the proposed connection
between SIBO and irritable bowel syndrome (IBS) (Aziz I, et al. Curr Opin Gastroenterol. 2017:33:196-202). The complicating issues have been the heterogeneous nature of
IBS, the lack of consistently robust control groups and the many factors that confound
any attempt to ascribe causality as well as attribute empiric treatment success. Because
of widely discordant diagnostic and treatment results in both children and adults,
a relationship between SIBO and IBS is not clearly established in the view of many
gastroenterologists and infectious disease experts.
Empiric treatment of SIBO, classically through use of enteral antimicrobials, is not
without pitfalls. Some clinicians use this treatment approach especially in high-risk
patients (e.g., those with short gut syndrome) (Youssef NN, et al. Curr Gastroenterol Rep. 2012;14:243-252).
In children without known risk factors, it is difficult to evaluate the therapeutic
index (benefit vs. harm). While clear efficacy has not been established conclusively
for many conditions, such as IBS or in functional abdominal pain, clinicians have
to consider the negative impact to the patient as well as the public surrounding the
persistent use, often in rotating fashion, of empiric antimicrobials. This is especially
critical as we learn more about the importance and spectrum of the human microbiome;
there are conclusive studies that even a single dose of an antimicrobial can alter
the diversity and composition of the microbiome for extended periods.
Our nascent understanding of the importance of the microbiome to overall human health
is at odds with a therapeutic strategy that aims to grossly reduce overall bacterial
counts without understanding the specific consequences, especially in the absence
of data supporting this intervention. Antimicrobial stewardship — the idea of using
the correct drug for a specific diagnosis — has taught us that antibiotics should
not be used indiscriminately to avoid antimicrobial resistance and mitigate other
Medicine is littered with examples where actions or interventions were implemented
prematurely without a robust evidence base. For example, the use of proton pump inhibitors
to treat infant reflux initially was greeted with great enthusiasm and originally
was thought to carry no major adverse effects, only to fall out of favor with regard
to both efficacy and potential side effects (Rosen R, et al. J Pediatr Gastroenterol Nutr. 2018;66:516-554).
Data are not yet at hand to support widespread and first-line use of antimicrobials
to treat presumed SIBO for many gastrointestinal symptoms.
Dr. Cohen is chair-elect of the AAP Section on Gastroenterology, Hepatology and Nutrition
Executive Committee. Dr. Steinbach is a member of the AAP Committee on Infectious