The role of diet in host susceptibility to listeria monocytogenes infection
Las Heras, Vanessa
University College Cork
Currently the world is facing an epidemic increase in metabolic disorders linked to the Western-diet, a diet consisting of an increased intake of ready-to-eat food products rich in sugar and animal fat. Diet is a significant influencer of gastrointestinal function and the interplay between epithelial physiology, intestinal inflammatory state and commensal bacteria is fundamental to ensure gut homeostasis. Recent epidemiological reports emphasize that diet is a key lifestyle factor driving the rise of gastrointestinal inflammatory diseases. Disease pathology is likely to be linked to aberrant modulation of regulatory events associated with intestinal physiology, inflammatory regulation, nutrient availability in the lumen and microbiota composition and metabolism. Dietary-driven modulation of the environment in the gastrointestinal tract directly affects bacterial adaption in the gut by redirecting bacterial metabolism in response to nutrient availability. This is particularly critical in the context of infection with foodborne pathogens, where diet is beginning to be implicated as an external factor altering host susceptibility to infection. Even though a Westernized-diet has been linked with the development of pathological inflammatory conditions, relatively little is known regarding the implications of such diets in the progression of infectious disease. For this reason, the focus of this research was to investigate the impact of short-term dietary interventions in host susceptibility to infection with an important foodborne pathogen, Listeria monocytogenes. L. monocytogenes is the etiological agent of listeriosis, an invasive foodborne disease with a high fatality rate of 20-30%. By coordinating a complex regulatory gene network, L. monocytogenes is able to sense and adapt to a vast range on environmental stimuli, essential for survival in both saprophytic and gastrointestinal environments. L. monocytogenes is of special concern in ready-to-eat meat products, with several listeriosis outbreaks traced to the consumption of such foodstuffs. Here, we determine the impact of the consumption of a Western-diet upon susceptibility to L. monocytogenes in a murine disease model. We adopted a systems approach to identify the effects of a two-week dietary supplementation with either animal fat or L-carnitine, through analysing changes in host physiology and microbiota composition. In the present study we evaluate the effects of a high-fat diet on modulation of the host physiological landscape and microbiota composition, parameters associated with the L. monocytogenes infectious process, both before and after oral infection. Our data indicate that a short-term increase in dietary fat intake results in an increased susceptibility to infection, related to significant alterations in host microbiota composition, epithelial cell and immune cell function in both the ileum and liver. In addition, we analyse the role of L-carnitine in the L. monocytogenes transcriptomic profile in response to osmotic stress and determine the role of OpuC (part of L. monocytogenes osmotic stress response machinery) in the pathogens growth and virulence in vitro. Our results show that L-carnitine ameliorates the effects of the osmotic stress response on L. monocytogenes fitness and cellular homeostasis and induces virulence gene expression. Furthermore, we demonstrate that L-carnitine uptake trough OpuC is fundamental for L. monocytogenes growth and invasion of epithelial cells during the osmotic stress response under conditions mimicking the gut environment. Finally, we analysed the role of dietary supplementation with L-carnitine on the ability of L. monocytogenes to adapt to the high osmolarity environment of the gastrointestinal tract and establish oral infection in the murine model. The results suggest that additional L-carnitine in the diet does not increase susceptibility to oral L. monocytogenes infection, though the OpuC system does play a significant role in the infectious process. Overall the work significantly enhances our understanding of how diet may influence host parameters which are significant for the progression of L. monocytogenes infection.
Host-pathogen interaction , Listeria monocytogenes , High-fat diet , Dietary L-carnitine , Immune modulation , Microbiota dysbiosis , Intestinal landscape
Las Heras, V. 2019. The role of diet in host susceptibility to listeria monocytogenes infection. PhD Thesis, University College Cork.