Probiotics can help or hinder gut recovery after antibiotic treatment

All probiotics are not created equal, according to new research from North Carolina State University. In a mouse model, researchers found that different probiotic strains can either accelerate or delay the gut microbiome’s recovery after antibiotic treatment. The work adds to the body of evidence suggesting that probiotic efficacy is specific and situational, and that more research is needed to understand the strain-specific impacts of different probiotics.

Probiotic supplements are often consumed after antibiotic treatment to prevent antibiotic-associated diarrheal disease, most commonly caused by Clostridioides difficile (C. diff). However, the actual impact of individual probiotic strains on the gut’s microbiota, or bacterial environment, is poorly understood.

“Colonization resistance or the ability to prevent colonization of pathogens is a function of a healthy microbiota,” says Casey Theriot, professor of infectious disease at NC State and co-corresponding author of the research. “This study looked at how long it took resistance against C. diff colonization to return after antibiotics and the impact of two of the most commonly used commercial strains of Lactobacillus probiotic on that return.”

The research team looked at three groups of mice that had been treated with cefoperazone, a commonly used broad-spectrum cephalosporin antibiotic. The first group received no probiotic treatment. The second group received L. acidophilus, and the third received L. gasseri. Each group was challenged with C. diff weekly for four weeks and the microbiota of each group was examined to measure bacterial load and C. diff resistance.   

Mice that received no probiotic showed decreased bacterial load and resistance to C. diff infection by four weeks after stopping antibiotics. However, the L. acidophilus mice had an increased bacterial load in weeks two and three, while the L. gasseri group had no detectible C.diff after two weeks.

Additionally, the researchers found that L. gasseri did not colonize or remain in the gut. Instead, it was involved in the production of bacteriocins, or antimicrobial peptides, and it encouraged the growth of Muribaculaceae, another potentially beneficial bacteria.

“We have always known that it’s important to understand the strain-specific impact of probiotic strains,” says Rodolphe Barrangou, Todd R. Klaenhammer Distinguished Professor of Food, Bioprocessing and Nutrition Sciences at NC State and co-corresponding author of the research. “Depending on the condition and composition of the individual’s microbiome, the disease, and the probiotic strain, you will have different effects and outcomes.

“What’s interesting is that this study indicates it’s more complicated than people think, because probiotics can have transient or indirect effects on the microbiome. L. gasseri doesn’t prevent infection, it transiently promotes recovery of microbiome through Muribaculaceae, which subsequently could provide resistance. This opens new avenues to inform what we should do next.”

“This is the only study out there that is functionally testing resistance in the microbiome,” Theriot adds. “Although this work is in a mouse model, it shows the need for better mechanistic understanding of how probiotics affect the microbiome, because not only can they have effects weeks after they’ve left the body, in certain situations they have the potential to prolong or complicate recovery.” 

The research appears in mBio and was supported by NIH training grants through the University of North Carolina Center for Gastrointestinal Biology and Disease (CGIBD) and the Molecular Biotechnology Training Program (MBTP) at NC State. The UNC CGIBD is an NIH supported center. Other NC State contributors to the work are first author Matthew Foley, Arthur McMillan, Sarah O’Flaherty, Rajani Thanissery, Molly Vanhoy, and Mary Fuller.

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Note to editors: An abstract follows.

“Differential Modulation of Post-Antibiotic Colonization Resistance to Clostridioides difficile by Two Probiotic Lactobacillus Strains”

DOI: 10.1128/mbio.01468-

Authors: Matthew H. Foley, Arthur S. McMillan, Sarah O’Flaherty, Rajani Thanissery, Molly E. Vanhoy, Mary Gracen Fuller, Rodolphe Barrangou, Casey M. Theriot, North Carolina State University

Published: July 21 in mBio

Abstract:
Probiotics are often consumed after antibiotic treatment to prevent antibiotic-associated diarrheal disease, most commonly caused by C. difficile. However, the impact of probiotic bacteria on the post-antibiotic gut microbiota is undetermined and often overlooked. Here, we examined the effect of a single dose of probiotic L. acidophilus NCFM and L. gasseri Lg-36 on colonization resistance against C. difficile in an antibiotic-treated mouse model. We found that L. acidophilus administration increased C. difficile infection and impaired the restoration of colonization resistance. In contrast, L. gasseri decreased C. difficile and promoted the return of colonization resistance, presumably through a putative bacteriocin inhibiting C. difficile. However, L. gasseri transiently colonizes the mouse gut and its administration impacts colonization resistance after it is no longer detectable. We analyzed the gut microbiota of mice and found that members of the understudied Muribaculaceae family were enriched after L. gasseri administration and are associated with colonization resistance. Using M. intestinale and D. muris, we determined that elevated growth of these species can restrict C. difficile growth in vitro, suggesting that these bacteria may play a role in establishing colonization resistance in vivo. These findings highlight the potential pitfalls of specific probiotic strains taken after antibiotic treatment and supports the need for further investigations of their influence on the gut microbiota post antibiotic. Additionally, this work supports the role of the Muribaculaceae as beneficial gut commensals that can contribute to colonization resistance against C. difficile, and illustrates the need to decipher community interactions in complex microbial consortia.