Deciphering Scope of Probiotics in Managing PPI induced SIBO: A Clinical Review

Small intestinal bacterial overgrowth (SIBO) is characterized by an excessive overgrowth of bacteria in the small intestine. The manifestation of signs and symptoms of overgrowth depends on the absolute number of organisms, and the type of microbial flora present. (1) While motility disorders, structural anomalies, and reduced gastric acid output are some of the common causes (1), interestingly, drugs like PPIs (proton pump inhibitors) are now being increasingly linked to SIBO.

Proton-pump inhibitors (PPIs) are used widely to treat acid peptic diseases and cause substantial acid suppression in the stomach. PPIs are often co-prescribed with non-steroidal anti-inflammatory drugs(NSAIDs) to prevent NSAID-induced gastroduodenal injury. But emerging research now indicates that PPI-induced gut dysbiosis promotes NSAID-induced small intestinal injury rather than suppressing it (2,3), thus raising a unique clinical concern.

For a long time now, broad-spectrum antibiotics have been in use for managing SIBO, but with limited results (4). This article aims to shed light on the emergence of PPI-induced SIBO and the rationale for considering probiotics to mitigate the same.

Understanding Gut Dysbiosis-

Gut dysbiosis has recently garnered a lot of interest in various biological domains. "Microbial dysbiosis" is a term used to describe ''alterations'' in intestinal bacteria' variety, density, and metabolic activity. Small intestine bacterial overgrowth(SIBO) is the most well-described form of small intestinal dysbiosis in the medical literature, characterized by aberrant microbial density and associated with an increase in atypical species. (5)

Though the term "dysbiosis" has been in use (initially in German studies on intestinal bacteria flora) since the 1960s, it has been recently linked to disorders like diabetes mellitus, obesity, non-alcoholic fatty liver diseases, as well as autoimmune diseases; attracting an exponential surge of interest and research in this direction. (2,6,7,8,9)

PPI Causing SIBO -The Connection and Association:

In 2008, the first report of a putative link between PPIs and small intestinal bacterial overgrowth (SIBO) was reported. (2) Since then, scientific research continues to reinforce that chronic acid suppression and resulting hypochlorhydria associated with PPI usage modify the intraluminal environment, allowing the bacterial flora in the small intestine to flourish (10). Several studies have now connected hypochlorhydria to increased bacterial colonization in the stomach and duodenum, predisposing individuals to SIBO development (10).

Confirming the above fact, PPI usage was found to be substantially greater among patients with positive culture findings compared to those with negative culture results (52.6 percent vs 30.2 percent, respectively) in a recently published retrospective analysis (11). In yet another 2018 meta-analysis of 19 trials (N = 7,055), it was reported that long-term use of PPIs increases the risk of small intestine bacterial overgrowth (SIBO).

Combating PPI-induced SIBO: Potential Opportunity for Probiotics

Research highlights that when treating a patient with SIBO, the focus should first be on detecting and eliminating any underlying cause and then on correcting any nutritional deficits that arise (4).

Probiotics are living organisms that have a beneficial effect on the host's gut microbiome. Given the ability of probiotics to modulate and repopulate the intestinal microbiota, considerable interest has been put in them.

Decoding the Mechanism of action of Probiotics in SIBO:

Among the various mechanisms that make probiotics an effective choice for PPI-induced SIBO, the most prominent benefits have been summarized below.

• Probiotics directly or indirectly influence intestinal physiology by modulating the endogenous environment and immune system (13).
• Probiotics have also been shown to act by lowering pro-inflammatory cytokines, modifying gut microbiota, maintaining intestinal epithelial integrity, and changing visceral hypersensitivity (12).
• Probiotics prevent disease-causing bacteria from colonizing through nutritional competition, immune system activation, and the creation of antitoxins (13,14).

Probiotics in SIBO: Clinical Evidence Indicating Benefits of Lactobacillus strains

Global research has yielded encouraging results in favor of utilizing probiotics in SIBO.

• According to a recent meta-analysis, probiotics are beneficial in lowering the bacterial load and alleviating symptoms in SIBO patients. (11)
• Probiotics may boost the efficacy of antibiotics, as concluded by recent research in which patients were treated with rifaximin and probiotics (Lactobacillus casei). Patients on combined therapy saw better relief in their symptoms than those treated with antibiotics monotherapy. (11)
• An interesting study noted that both Lactobacillus casei and Lactobacillus acidophilus strains were beneficial in treating chronic diarrhea caused by bacterial overgrowth (4).
• Another study by Khalighi et al (15) supported the use of probiotics as maintenance therapy in SIBO by testing individuals with symptoms indicative of SIBO with a positive hydrogen breath test (HBT) and after initial antibiotic treatment.

Compared to the control group, those in the probiotic group saw a substantial reduction in discomfort, bloating, belching, and diarrhea. Noteworthy was a complete alleviation of stomachache reported in the probiotic group.

Considering the extensive wealth of evidence supporting probiotics and prebiotics, it is comprehensible that they play a major role in modulating gut flora favorably in PPI-induced SIBO.

Summary and Way Forward

• The extensive use of PPIs has now been linked to the development of SIBO.
• Probiotics (living microorganisms with positive physiological or therapeutic characteristics) and prebiotics (dietary components that foster the growth of beneficial bacteria) have exhibited promising results in managing PPI-induced SIBO, with clinical evidence supporting Lactobacillus-containing species.
• Extensive research-based evidence on probiotics' efficacy in restoring a healthy microbiome in SIBO patients justifies its clinical applicability in this indication.

Considering the risks of continuous antibiotic therapy in treating PPI-induced SIBO, replacing antibiotic therapy with probiotics is acknowledged unanimously as a significant step forward.

With durable scientific evidence favoring probiotics, the management of PPI-induced SIBO treads forward in the best interest of patients.

The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Probiotics, click here.

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