Antibiotic-Induced Disruption of Gut Microbiota Alters Local Metabolomes and Immune Responses.

Nan Zhang,Kai Zheng,Zhiyun Chen,Qiaoyan Xiang,Ning Chen,Lin Sun,Junping Zhu,Yuxiao Zhang,Qiushui He,Xiaoyan Zhang

doi:10.3389/fcimb.2019.00099

Abstract

Gut microbiome plays an essential role in modulating host immune responses. However, little is known about the interaction of microbiota, their metabolites and relevant inflammatory responses in the gut. By treating the mice with three different antibiotics (enrofloxacin, vancomycin, and polymixin B sulfate), we aimed to investigate the effects of different antibiotics exposure on gut microbiota, microbial metabolism, inflammation responses in the gut, and most importantly, pinpoint the underlying interactions between them. Although the administration of different antibiotics can lead to different effects on mouse models, the treatment did not affect the average body weight of the mice. A heavier caecum was observed in vancomycin treated mice. Treatment by these three antibiotics significantly up-regulated gene expression of various cytokines in the colon. Enrofloxacin treated mice seemed to have an increased Th1 response in the colon. However, such a difference was not found in mice treated by vancomycin or polymixin B sulfate. Vancomycin treatment induced significant changes in bacterial composition at phylum and family level and decreased richness and diversity at species level. Enrofloxacin treatment only induced changes in composition at family presenting as an increase in Prevotellaceae and Rikenellaceae and a decrease in Bacteroidaceae. However, no significant difference was observed after polymixin B sulfate treatment. When compared with the control group, significant metabolic shift was found in the enrofloxacin and vancomycin treated group. The metabolic changes mainly occurred in Valine, leucine, and isoleucine biosynthesis pathway and beta-Alanine metabolism in enrofloxacin treated group. For vancomycin treatment metabolic changes were mainly found in beta-Alanine metabolism and Alanine, aspartate and glutamate metabolism pathway. Moreover, modifications observed in the microbiota compositions were correlated with the metabolite concentrations. For example, concentration of pentadecanoic acid was positively correlated with richness of Rikenellaceae and Prevotellaceae and negatively correlated with Enterobacteriaceae. This study suggests that the antibiotic-induced changes in gut microbiota might contribute to the inflammation responses through the alternation of metabolic status, providing a novel insight regarding a complex network that integrates the different interactions between gut microbiota, metabolic functions, and immune responses in host.

Highlights

The gut microbiome plays an essential role in health and disease of the host
Antibiotics were administered in drinking water in the following concentrations: enrofloxacin (0.27 mg/ml) (Strzepa et al, 2017), vancomycin (0.5 mg/ml), and polymixin B sulfate (0.1 mg/ml) (Oh et al, 2014)
The histopathological results showed that no structure change of the colon was found in the antibiotic treated mice (Figure 2B)

Summary

Introduction

The gut microbiome plays an essential role in health and disease of the host. It is well-documented that gut microbiome aids the host in modulating immune responses and protecting against pathogens (Holmes et al, 2011). It provides beneficial biological functions via production of vitamin and short-chain fatty acids (SCFAs) (Kasubuchi et al, 2015). A better understanding of the mechanistic roles the gut microbiota play in the regulation of host metabolic and immunological functions will provide useful information on the complex host-gut relationship. There is less attention received on the effects of different kinds of antibiotic usage on the host’s gut microbial function

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Results