Protein malnutrition alters tryptophan and angiotensin converting enzyme 2 homeostasis and adaptive immune responses in human rotavirus infected gnotobiotic pigs transplanted with human infant fecal microbiota

Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of five. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets with infected with virulent human rotavirus. After human rotavirus infection, protein deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3+CD4+) and cytotoxic T (CD3+CD8+) lymphocyte frequencies and serum tryptophan and angiotensin I converting enzyme 2. Additionally, deficient diet pigs had impaired tryptophan catabolism post-infection compared with sufficient diet pigs. Tryptophan supplementation was tested as an intervention in additional groups of fecal microbiota-transplanted, rotavirus infected sufficient and deficient diet pigs. Tryptophan supplementation increased the frequencies of regulatory (CD4+ or CD8+CD25+FoxP3+) T cells in pigs on both the sufficient and deficient diets. These results suggest that a protein deficient diet impairs activation of the adaptive immune response following HRV infection and alters tryptophan homeostasis.