Long-term exclusive enteral nutrition remodels the gut microbiota and alleviates TNBS-induced colitis in mice

Abstract

Background: Exclusive enteral nutrition (EEN) provides an effective strategy for the induction of clinical remission in pediatric Crohn's disease. However, the feasibility of long-term EEN in the management of disease and the underlying mechanism whereby long-term EEN prevents intestinal inflammation are still not fully understood. Methods: Paired male and female adult wild-type (WT) mice were mated to breed littermates, and these pups were then weaned at 3 weeks of age and randomly allocated into regular diet (RT) feeding group and EEN feeding group (Peptisorb; NUTRICIA), respectively. After feeding until adulthood at the age of 8 weeks, mice were sacrificed and phenotypic analysis of immune cells in spleens and mesenteric lymph nodes (MLNs) was performed by flow cytometry. Fecal pellets were also collected to determine the levels of immunoglobulins and gut microbiota by ELISA and 16S rRNA sequencing. The role of long-term EEN in the development of colitis and its underlying mechanisms were evaluated in a TNBS-induced colitis model in mice. Results: Feeding with EEN decreased the percentages of IgA- and IgG-coated bacteria and the levels of soluble IgA and IgG in the feces of EEN-feeding mice compared with the controls, but did not affect the compositions of different immune cells including CD4⁺, CD8⁺ T cells and B220⁺ B cells in the spleens and MLNs. An in-depth analysis of the gut microbiota revealed a decrease of the general diversity of the gut microbiota, but a significant change of the composition of the gut microbiota after EEN feeding, characterized by an increase of the beneficial bacteria including Bacteroides, Parabacteroides, and Alistipes, but a decrease of the detrimental bacteria such as Escherichia–Shigella. Moreover, we found that EEN feeding markedly improved intestinal inflammation in the TNBS-induced colitis model compared to RT feeding, as evidenced by decreased levels of inflammatory cytokines and fecal soluble immunoglobulins and improved microbial community composition. Conclusions: Our data indicate that long-term EEN feeding remodels the composition of gut microbiota and alleviates intestinal mucosal inflammation. It provides new guidance using EEN for the management of gut inflammation.