Gut Microbiota as a Modulator of Paneth Cells During Parenteral Nutrition in Mice

Background Parenteral nutrition (PN) leads to decreased production of Paneth cell-derived antimicrobial peptides and is accompanied by dysbiosis of the gut. The role of gut microbiota in regulating Paneth cell function during PN is unknown. Methods Results Male C57BL/6 mice received either an antibiotic cocktail (Abx) or nothing (Normal) in their drinking water for 2 weeks before being fed either standard laboratory chow (Abx-Chow and Normal-Chow) or a continuous infusion of PN solution (Abx-PN and Normal-PN) for 7 days. In a separate experiment, the intestinal contents of mice having received 7 days of Chow or PN were transferred by gavage to germ-free (GF) mice. Antibiotic treatment decreased the protein levels of lysozyme and RegIII gamma and the mRNA level of alpha-defensin 5, with no further effect by PN compared with chow. However, these measurements were higher in Abx-PN mice than in Normal-PN mice. When compared with Chow -> GF, PN -> GF mice demonstrated lower body weight, shorter intestinal length, severe atrophy of the ileum villus, and lower levels of lysozyme and RegIII gamma protein and alpha-defensin 5 mRNA. Interleukin (IL)-22 and IL-17 mRNA levels declined in the ileum. Principal component analysis revealed major differences between the metabolite compositions of the Chow and PN, as well as the Chow -> GF and PN -> GF groups that appears to indicate aberrant tryptophan metabolism. Conclusions Gut microbiota plays a vital role in PN-related Paneth cell dysfunction. Dysbiosis during PN might alter the production of microbial metabolites, thereby influencing the production of Paneth cell-derived antimicrobial peptides.