Short-term consumption of a high-fat diet increases host susceptibility to Listeria monocytogenes infection

Vanessa Las Heras,Paul D Cotter,Pat G Casey,Raul Cabrera-Rubio,Feargal J Ryan,Colin Hill,Justine K Rudkin,Cormac G M Gahan,Silvia Melgar,Cara M Hueston,Adam G Clooney,Jorge Pinheiro

doi:10.1186/s40168-019-0621-x

Abstract

BackgroundA westernized diet comprising a high caloric intake from animal fats is known to influence the development of pathological inflammatory conditions. However, there has been relatively little focus upon the implications of such diets for the progression of infectious disease. Here, we investigated the influence of a high-fat (HF) diet upon parameters that influence Listeria monocytogenes infection in mice.ResultsWe determined that short-term administration of a HF diet increases the number of goblet cells, a known binding site for the pathogen, in the gut and also induces profound changes to the microbiota and promotes a pro-inflammatory gene expression profile in the host. Host physiological changes were concordant with significantly increased susceptibility to oral L. monocytogenes infection in mice fed a HF diet relative to low fat (LF)- or chow-fed animals. Prior to Listeria infection, short-term consumption of HF diet elevated levels of Firmicutes including Coprococcus, Butyricicoccus, Turicibacter and Clostridium XIVa species. During active infection with L. monocytogenes, microbiota changes were further exaggerated but host inflammatory responses were significantly downregulated relative to Listeria-infected LF- or chow-fed groups, suggestive of a profound tempering of the host response influenced by infection in the context of a HF diet. The effects of diet were seen beyond the gut, as a HF diet also increased the sensitivity of mice to systemic infection and altered gene expression profiles in the liver.ConclusionsWe adopted a systems approach to identify the effects of HF diet upon L. monocytogenes infection through analysis of host responses and microbiota changes (both pre- and post-infection). Overall, the results indicate that short-term consumption of a westernized diet has the capacity to significantly alter host susceptibility to L. monocytogenes infection concomitant with changes to the host physiological landscape. The findings suggest that diet should be a consideration when developing models that reflect human infectious disease.

Highlights

A westernized diet comprising a high caloric intake from animal fats is known to influence the development of pathological inflammatory conditions
It is known that wild-type L. monocytogenes internalin A (InlA) interacts poorly with murine E-cad [4], most likely translocates passively at Peyer’s patches in non-permissive models [15] and is incapable of significant invasive disease in normal mice
Others, recognize the limitations of both models [10] and appreciate that the altered InlA expressed in L. monocytogenes EGDem in addition to enhancing interaction with E-cadherin may interact with murine N-cadherin [16]

Summary

Introduction

A westernized diet comprising a high caloric intake from animal fats is known to influence the development of pathological inflammatory conditions. Increased consumption of a ‘westernized’ diet, comprising high caloric intake from fats and reduced consumption of fermentable fibre, has been linked to the current pandemic of chronic inflammatory conditions such as obesity, type 2 diabetes, inflammatory bowel disease and allergic asthma [1]. L. monocytogenes has been extensively investigated as a model intracellular pathogen to uncover the biological mechanisms involved in host cell invasion, intracellular parasitism and resultant host immunity [4]. The majority of such studies have utilized cell culture models or systemic murine infection. There is a role for the microbiota in providing a barrier to infection and in modifying the host immune response to the pathogen locally [6, 9,10,11]

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Results

Conclusion