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Probiotics for prevention of Clostridium difficile infection.

ABSTRACT: PURPOSE OF REVIEW:Probiotics may prevent Clostridium difficile infection (CDI), a leading healthcare-associated infection in the United States. However, prior studies were limited by heterogeneity in products and patient populations. Recent clinical evidence and new approaches to probiotic development are reviewed. RECENT FINDINGS:Probiotic use may reduce incident CDI in high-risk populations by as much as 50%, though prior clinical trials have yielded conflicting results. Combining probiotics with prebiotics improves growth and engraftment in the host. Bacillus clausii and Lactobacillus reuteri secrete compounds that directly inhibit C. difficile. Organisms that produce secondary bile acids, such as Clostridium scindens, enhance C. difficile colonization resistance. Nontoxigenic C. difficile, which provides nutritional niche competition, may prevent CDI. Refinements to fecal microbiota transplantation (FMT) blur the line between probiotics and FMT. These include a quality-controlled stool product (RBX2660), purified Firmicutes spores (SER-109) and sterile fecal filtrate. Bacteriophages may treat CDI but have unknown safety and efficacy in humans. SUMMARY:There have been a number of advances in probiotics and our understanding of their role in prevention of CDI, but a number of important safety and efficacy questions remain. An improved understanding of the native microbiota structure and function will allow for continued development of rationally designed probiotic therapy to provide enhanced protection against CDI.

SUBMITTER: Mills JP

PROVIDER: S-EPMC6335148 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Probiotics for prevention of Clostridium difficile infection.

Mills John P JP Rao Krishna K Young Vincent B VB

Current opinion in gastroenterology 20180101 1

<h4>Purpose of review</h4>Probiotics may prevent Clostridium difficile infection (CDI), a leading healthcare-associated infection in the United States. However, prior studies were limited by heterogeneity in products and patient populations. Recent clinical evidence and new approaches to probiotic development are reviewed.<h4>Recent findings</h4>Probiotic use may reduce incident CDI in high-risk populations by as much as 50%, though prior clinical trials have yielded conflicting results. Combini ...[more]

PMID: 29189354

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Project description:BackgroundRecent meta-analyses of the efficacy of probiotics for preventing diarrhea associated with Clostridium difficile have concluded there is a large effect favouring probiotics. We reexamined this evidence, which contradicts the results of a more recent large randomized controlled trial that found no benefit of Lactobacillus probiotics for preventing C. difficile-associated diarrhea.MethodsWe performed a systematic review of the efficacy of treatment with Lactobacillus probiotics for preventing nosocomial C.?difficile-associated diarrhea in adults and carried out a meta-analysis using a Bayesian hierarchical model. We used credibility analysis and meta-regression to characterize the heterogeneity between studies.ResultsTen studies met our inclusion criteria. The pooled risk ratio was highly statistically significant, at 0.25 (95% credible interval 0.08-0.47). However, the 95% prediction interval for the risk ratio in a future study, 0.02-1.34, was wider than the credible interval, owing to heterogeneity between studies. Furthermore, a credibility analysis showed that the strength of the evidence was weaker than the observed number of cases of C. difficile-associated diarrhea across studies would suggest. Meta-regression suggested that the beneficial effect of probiotics was more likely to be reported in studies with an increased risk of C. difficile-associated diarrhea in the control group, although this association was not statistically significant.InterpretationAccounting for between-study heterogeneity showed that there is considerable uncertainty regarding the apparently large efficacy estimate associated with Lactobacillus probiotic treatment in preventing C. difficile-associated diarrhea. Most studies to date have been carried out in populations with a low risk of C. difficile-associated diarrhea, such that the evidence is inconclusive and inadequate to support a policy concerning routine use of probiotics in to prevent this condition.

Project description:Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials.

Dataset Information

Probiotics for prevention of Clostridium difficile infection.

Publications

Probiotics for prevention of Clostridium difficile infection.

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