IL-17A-dependent gut microbiota is essential for regulating diet-induced disorders in mice

The gut microbiota plays a key role in obesity and related metabolic disorders, and multiple factors including diet, host genotype, and age regulate it. Many studies have examined the contribution of extrinsic factors to the regulation of the gut microbiota, but the importance of the host genetic constitution cannot be ignored. Interleukin 17A (IL-17A), a pro-inflammatory cytokine, is important in the defense against infection and diseases. Here, we investigated the association among IL-17, a high-fat diet (HFD), and the gut microbiota. Mice deficient in IL-17A were resistant to diet-induced obesity and related diseases. Compared with the Il-17a^-/- mice, wild-type (WT) mice challenged with HFD showed obvious weight fluctuations, such as those seen in type 2 diabetes, and hematological changes similar to those associated with metabolic syndrome. However, housing WT mice and Il-17a^-/- mice together significantly alleviated these symptoms in the WT mice. A metagenomic analysis of the mouse feces indicated that the microbial community compositions of these two groups differed before HFD feeding. The HFD mediated shifts in the gut microbial compositions, which were associated with the mouse phenotypes. We also identified potentially beneficial and harmful species present during this period, and drew networks of the most abundant species. A functional analysis indicated pathway changes in the WT and Il-17a^-/- mice when fed the HFD. Collectively, these data underscore the importance of the host factor IL-17A in shaping and regulating the gut microbiota, which conversely, influences the host health.