Abstract

Antibiotics are a vital and commonly used therapeutic tool, but their use also results in profound changes in the intestinal microbiota that can, in turn, have significant health consequences. Understanding how the microbiota recovers after antibiotic treatment will help to devise strategies for mitigating the adverse effects of antibiotics. Using a mouse model, we have characterized the changes occurring in the intestinal microbiota immediately after five days exposure to ampicillin, and then at three and fourteen days thereafter. During the fourteen day period of antibiotic recovery, groups of mice were fed either water, cows’ milk containing high levels of IgA, or cows’ milk containing low levels of IgA as their sole source of liquid. Effects on microbiota of feeding milks for 14 days were also assessed in groups of mice that had no ampicillin exposure. Changes in microbiota were measured by high throughput sequencing of the V4 to V6 variable regions of the 16S ribosomal RNA gene.As expected, exposure to ampicillin led to profound changes to the types and abundance of bacteria present, along with a loss of diversity. At 14 days following antibiotic exposure, mice fed water had recovered microbiota compositions similar to that prior to antibiotics. However, feeding High-IgA milk to mice that has been exposed to antibiotics was associated with altered microbiota compositions, including increased relative abundance of Lactobacillus and Barnesiella compared to the start of the study. Mice exposed to antibiotics then fed Low-IgA milk also showed increased Barnesiella at day 14. Mice without antibiotic perturbation, showed no change in their microbiota after 14 days of milk feeding. Overall, these findings add to a knowledge platform for optimizing intestinal function after treatment with antibiotics in the human population.

Highlights

  • Antibiotics are administered widely in the human population (Col & O’Connor, 1987) and are a vital therapeutic tool for combating infection

  • Principal coordinate analysis (PCoA) of unweighted Unifrac phylogenetic distances showed no significant changes in microbiota communities following 14 days milk-feeding (Fig. 1B)

  • Groups exposed to ampicillin for five days showed a marked change in their microbiota, leading to communities consisting mainly of Tenericutes, Firmicutes, and Proteobacteria, with mean relative abundances of 76%, 12%, and 9%, respectively (Fig. 2A, Day 0)

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Summary

Introduction

Antibiotics are administered widely in the human population (Col & O’Connor, 1987) and are a vital therapeutic tool for combating infection. The presence of antibiotics within the digestive tract leads to large scale alteration of the intestinal microbiota (Fouhy et al, 2012; Jakobsson et al, 2010; Mikkelsen et al, 2015a). This has been shown to increase susceptibility to further pathogenic infection by making available niches. The use of antibiotics can lead to the persistence of antibiotic-resistant strains of bacteria (Ubeda et al, 2010). There is no consensus for optimal management practises to minimise impact of antibiotic usage on the patient

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