Deciphering the role of sex hormones in host-microbiome interactions in the human oral mucosa - Project Summary The human body houses many distinct, but interconnected microbial populations which can exert long-lasting systemic effects. Understanding how microbial communities interact with the host and how these interactions influence host physiology is critical to defining their roles in health and disease states. In particular, the oral microbiota serves as a reservoir for opportunistic pathogens, potentially contributing to a wide range of oral and systemic diseases. My lab has been focusing on developing benchtop experimental tools to provide a mechanistic framework of oral host-microbial interactions and modulation in early dysbiosis to support therapeutic interventions. The bidirectionality of these interactions has been hypothesized to be attributed to microbial metabolites, diet, immune, and endocrine factors. Specifically, sex as a biological variable has been historically omitted from preclinical and clinical studies, resulting in a knowledge gap regarding how biological systems respond to hormones and their fluctuations and, potentially, how therapeutic regimes can be tailored to account for hormonal alterations. In particular, clinical studies have suggested that several microbiome-related diseases display a sex bias, some of which have been shown to be associated with sex hormones. Specifically, clinical evidence in common oral signs has been observed during menstruation, pregnancy, and hormonal contraception use, however, mechanistic links between hormonal fluctuation, oral dysbiosis, and host tissue health still need to be elucidated. Therefore, underscoring how sex hormone signaling affects disease progression in the context of host-microbiome interactions is critical to support fundamental studies of disease pathogenesis and to open the door to therapeutic strategies targeting both the microbiome, sex hormones and the bidirectionality of those interactions. The mission of my research program is to address these fundamental gaps in bidirectionality of host-microbiome cross-talks and underpinning the role of sex-bias in these interactions and how it affects the onset and progression of inflammatory diseases, in a tractable in vitro model of the oral mucosa. Over the next five years, I will expand the scientific knowledge over the following three themes of research: (1) profiling human host tissue baseline as a function of sex difference and investigating tissue responses to sex hormones changes, (2) underscoring the causal relationships between sex difference and fluctuations of sex hormones and microbiome diversity and spatial organization, (3) dissecting the bidirectionality of human host-microbiome interactions accounting for sex differences, hormonal changes under healthy and inflamed clinically relevant conditions. The outcomes from this research program will provide insights into the role of sex differences and hormonal fluctuations on human host-microbial interactions, opening the doors to therapeutic approaches targeting both the microbiome, endocrine factors, and their mutual interactions.
