Unveiling the impact of tritrichomonas musculus colonization and its interplay with host metabolism and immunity

The murine eukaryotic protozoa, Tritrichomonas musculus, is a commensal member of the gut microbiota that was initially considered non-pathogenic. Recent research has delved into the adverse effects of various Tritrichomonad protists upon colonization in their rodent hosts. However, the implications of chronic T. musculus colonization on metabolic health and mucosal immunity are not yet fully understood. By utilizing a chow- and high-fat diet (HFD)fed wild-type mouse model, we aim to study the metabolic and mucosal immunological consequences of T. musculus colonization. Alongside monitoring the in vivo metabolic phenotype, we assessed gut mucosal immune cells via flow cytometry and conducted caecal microbiota sequencing to evaluate microbial composition.
Our results indicated that T. musculus colonization in wild-type C57BL/6N mice substantially impaired the metabolic state and induces a pro-inflammatory shift in mucosal immune cells. This impairment was initiated at an earlier timepoint and further exacerbated by HFD feeding. The engraftment of T. musculus influences mucosal immunity, with significant expansions in pro-inflammatory macrophages and CD4+ T-cell responses. Crucially, the Nlrp3 inflammasome and IL-1β play key roles in these phenotypes, as demonstrated through genetic knockout and pharmacological inhibition models. Microbiota composition analysis revealed significant shifts in the abundances of the Bacteroides, Akkermansia, and Desulfovibrio bacterial families in T. mu-colonized mice. The increased abundance of choline-processing bacterial families, such as Desulfovibrio and Lachnoclostridium, upon T. musculus colonization suggests a potential involvement of the choline-TMAO pathway in the metabolic phenotype. Administering choline to uncolonized HFD-fed mice significantly impairs glycemic control, leading to hyperinsulinemia and the development of insulin resistance.
Overall, T. musculus colonization adversely affects mucosal immune cell homeostasis and glycemic control through IL-1β secretion and choline metabolism, with these effects accentuated by HFD feeding. Our findings provide additional evidence that the integration of T. musculus into the gut microbiome induces substantial alterations in bacterial communities, with these changes being dependent on dietary nutrients. This study sheds new light and builds upon previous research regarding the metabolic and immunological implications of T. musculus colonization in rodent hosts.