Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans

The gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella , which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7–15, 2011, https://doi.org/10.3201/eid1701.P11101 ), and opportunistic pathogens like Candida , which causes an estimated 46,000 cases of invasive candidiasis each year in the United States (Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United State s, 2013 , 2013). Using a gnotobiotic mouse model, we investigate potential changes in gut microbial community structure and function during infection using metagenomics and metabolomics. We observe that changes in the community and in biosynthetic gene cluster potential occur within 3 days for the virulent Salmonella enterica serovar Typhimurium, but there are minimal changes with a poorly colonizing Candida albicans . In addition, the metabolome shifts depending on infection status, including changes in glutathione metabolites in response to Salmonell a infection, potentially in response to host oxidative stress.