A diet-specific microbiota drives Salmonella Typhimurium to adapt its in vivo response to plant-derived substrates

Nicoletta Prax,Thilo M Fuchs,Klaus Neuhaus,Thomas Clavel,Stefanie Wagner,Jakob Schardt

doi:10.1186/s42523-021-00082-8

Abstract

BackgroundLittle is known about the complex interactions between the diet, the gut microbiota, and enteropathogens. Here, the impact of two specific diets on the composition of the mouse gut microbiota and on the transcriptional response of Salmonella Typhimurium (S. Typhimurium) was analyzed in an enteritis model.ResultsMice were fed for two weeks a fibre-rich, plant-based diet (PD), or a Westernized diet (WD) rich in animal fat and proteins and in simple sugars, and then infected with an invasin-negative S. Typhimurium strain ST4/74 following streptomycin-treatment. Seventy-two hours post infection, fecal pathogen loads were equal in both diet groups, suggesting that neither of the diets had negatively influenced the ability of this ST4/74 strain to colonize and proliferate in the gut at this time point. To define its diet-dependent gene expression pattern, S. Typhimurium was immunomagnetically isolated from the gut content, and its transcriptome was analyzed. A total of 66 genes were more strongly expressed in mice fed the plant-based diet. The majority of these genes was involved in metabolic functions degrading substrates of fruits and plants. Four of them are part of the gat gene cluster responsible for the uptake and metabolism of galactitol and D-tagatose. In line with this finding, 16S rRNA gene amplicon analysis revealed higher relative abundance of bacterial families able to degrade fiber and nutritive carbohydrates in PD-fed mice in comparison with those nourished with a WD. Competitive mice infection experiments performed with strain ST4/74 and ST4/74 ΔSTM3254 lacking tagatose-1,6-biphosphate aldolase, which is essential for galactitol and tagatose utilization, did not reveal a growth advantage of strain ST4/74 in the gastrointestinal tract of mice fed plant-based diet as compared to the deletion mutant.ConclusionA Westernized diet and a plant-based diet evoke distinct transcriptional responses of S. Typhimurium during infection that allows the pathogen to adapt its metabolic activities to the diet-derived nutrients. This study therefore provides new insights into the dynamic interplay between nutrient availability, indigenous gut microbiota, and proliferation of S. Typhimurium.

Highlights

Little is known about the complex interactions between the diet, the gut microbiota, and enteropathogens
The microbiota of plant-based diet (PD) fed mice were characterized by significantly higher species richness and higher Shannon effective counts compared with that of mice in the Westernized diet (WD) group (Fig. 1a)
Typhimurium for the benefit of the in vivo transcriptome. This experimental step possibly perturbed the digestion of the diet, the post-streptomycin analysis of the microbiota demonstrated that families involved in the degradation of carbohydrates were still present in the mouse gut (Additional file 5)

Summary

Introduction

Little is known about the complex interactions between the diet, the gut microbiota, and enteropathogens. Typhimurium) is a Gram-negative, facultative anaerobic microorganism that causes non-thypoidal gastroenteritis in humans and typhoid-like disease in mice [1]. It is a food-borne pathogen that invades its host by contaminated food or water, eventually leading to salmonellosis [2]. Typhimurium due to colonization resistance of the commensal microbiota This complex bacterial community forms a highly competitive environment via for instance the production of antimicrobial peptides and growth-inhibiting metabolites, and by reducing the amount of substrates freely available in the gut [3]. Typhimurium is urged to rapidly switch from one nutrient to another, and to adapt its metabolic profile according to the metabolic status of each microenvironment encountered during infection

Methods

Results

Discussion

Conclusion