Abstract

The administration of broad-spectrum antibiotics is often associated with antibiotic-associated diarrhea (AAD), and impacts gastrointestinal tract homeostasis, as evidenced by the following: (a) an overall reduction in both the numbers and diversity of the gut microbiota, and (b) decreased short-chain fatty acid (SCFA) production. Evidence in humans that probiotics may enhance the recovery of microbiota populations after antibiotic treatment is equivocal, and few studies have addressed if probiotics improve the recovery of microbial metabolic function. Our aim was to determine if Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-containing yogurt could protect against antibiotic-induced fecal SCFA and microbiota composition disruptions. We conducted a randomized, allocation-concealed, controlled trial of amoxicillin/clavulanate administration (days 1–7), in conjunction with either BB-12-containing or control yogurt (days 1–14). We measured the fecal levels of SCFAs and bacterial composition at baseline and days 7, 14, 21, and 30. Forty-two participants were randomly assigned to the BB-12 group, and 20 participants to the control group. Antibiotic treatment suppressed the fecal acetate levels in both the control and probiotic groups. Following the cessation of antibiotics, the fecal acetate levels in the probiotic group increased over the remainder of the study and returned to the baseline levels on day 30 (−1.6% baseline), whereas, in the control group, the acetate levels remained suppressed. Further, antibiotic treatment reduced the Shannon diversity of the gut microbiota, for all the study participants at day 7. The magnitude of this change was larger and more sustained in the control group compared to the probiotic group, which is consistent with the hypothesis that BB-12 enhanced microbiota recovery. There were no significant baseline clinical differences between the two groups. Concurrent administration of amoxicillin/clavulanate and BB-12 yogurt, to healthy subjects, was associated with a significantly smaller decrease in the fecal SCFA levels and a more stable taxonomic profile of the microbiota over time than the control group.

Highlights

  • The gut microbiota comprises hundreds of bacterial species and is an important factor in determining the health status of the host [1]

  • Acetate is the most abundant short-chain fatty acid (SCFA), produced through anaerobic microbial fermentation in the human colon, and its production is reduced by antibiotic treatment [6,35,36]

  • Since BB-12 produces acetate in vitro, we hypothesized that acetate production by BB12 may mediate, at least in part, the ability of this strain to reduce associated diarrhea (AAD)

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Summary

Introduction

The gut microbiota comprises hundreds of bacterial species and is an important factor in determining the health status of the host [1]. The key species of the gut microbiota ferment undigested carbohydrates that reach the colon, to produce short-chain fatty acids (SCFAs), lactic acid, H2 , and CO2 , as metabolites. SCFAs are essential for gastrointestinal health and are absorbed by colonic epithelial cells, and stimulate Na+ -dependent fluid absorption [2], thereby conserving energy, Na+ , and fluid. The administration of antibiotics impacts gastrointestinal tract homeostasis, and is associated with an overall reduction in the numbers and diversity of the gut microbiota, decreased SCFA production, accumulation of luminal carbohydrate, subsequent pH changes, decreased water absorption, and, potentially, antibiotic-associated diarrhea (AAD) [3,4,5,6,7,8,9,10]. The rate of diarrhea associated with antibiotic usage is 5–25%, with 1–2% of those patients testing positive for Clostridioides difficile, which, in some cases, can result in serious illness [5,11,12,13,14,15,16,17,18,19,20]

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