Abstract
Reducing food intake is a common host response to infection, yet it remains unclear whether fasting is detrimental or beneficial to an infected host. Despite the gastrointestinal tract being the primary site of nutrient uptake and a common route for infection, studies have yet to examine how fasting alters the host’s response to an enteric infection. To test this, mice were fasted before and during oral infection with the invasive bacterium Salmonella enterica serovar Typhimurium. Fasting dramatically interrupted infection and subsequent gastroenteritis by suppressing Salmonella’s SPI-1 virulence program, preventing invasion of the gut epithelium. Virulence suppression depended on the gut microbiota, as Salmonella’s invasion of the epithelium proceeded in fasting gnotobiotic mice. Despite Salmonella’s restored virulence within the intestines of gnotobiotic mice, fasting downregulated pro-inflammatory signaling, greatly reducing intestinal pathology. Our study highlights how food intake controls the complex relationship between host, pathogen and gut microbiota during an enteric infection.
Highlights
When a mammalian host becomes infected, concerted metabolic programs are activated at both the cellular and organ level to combat the invading pathogen, distributing energy resources away from growth and towards an effective immune response [1]
Fasting therapies have become popular in recent years and show promise for treating chronic inflammatory diseases, but it is uncertain whether fasting-induced immunosuppression could leave an already fasted host more vulnerable to infection than a fed host
Typhimurium model of infectious gastroenteritis, mice are pre-treated with the antibiotic streptomycin to overcome microbiota-based colonization resistance [16]
Summary
When a mammalian host becomes infected, concerted metabolic programs are activated at both the cellular and organ level to combat the invading pathogen, distributing energy resources away from growth and towards an effective immune response [1] These internal metabolic adaptations are accompanied by external sickness behaviors such as fever, malaise, lethargy, social withdrawal and loss of appetite [2]. Rao et al found that the bacterial pathogen Salmonella enterica serovar Typhimurium has potentially evolved adaptive counter measures, limiting systemic infection-induced anorexia at the cost of its own virulence, as a means to ensure host survival and its own transmission [7] In line with these findings are observations from severely food deprived populations that malnutrition, especially protein deficiency, is the primary cause of immunodeficiency worldwide. Chronic undernutrition impairs both innate and adaptive immune responses, leading to the deaths of millions of children from otherwise non-lethal infections [8]
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