Immunomodulatory functions of the gut protist Pentatrichomonas hominis in health and disease

Abstract Protists have been identified as part of the mammalian gut microbiome and are known to impact gut immunity and complex intestinal diseases such as inflammatory bowel disease (IBD). In humans, studies mainly describe host interactions with disease-causing species, while little is known about how commensal protists impact the immune system. Protists from the Parabasalid family, including Pentatrichomonas hominis (P. hominis), have been identified in about 30% of healthy individuals; however, the role of these non-pathogenic commensal Parabasalids remains unstudied. Our data shows that P. hominis promotes Treg differentiation in vitro. Interestingly, this ability was found to be contact-independent, as culture supernatant was sufficient to induce Tregs. Moreover, by doing de-novo genome and transcriptome assembly and high-resolution mass spectrometry we have identified immunomodulatory candidate pathways and metabolites that might be mediating this effect. Re-establishment of tolerance is a major therapeutic strategy for treating intestinal diseases. Hence, we were interested in studying P. hominis impact on the gut immune landscape. To that aim, we successfully and stably colonized mice with P. hominis in gnotobiotic housing conditions and under antibiotic regimen and we are testing P. hominis role under steady state and IBD mouse models. Altogether, our research will address a present gap in knowledge, potentiating the study of protists in the microbiome and their association with intestinal disorders.