Gut microbiota-germline interactions and epigenetic inheritance

Denboba Lab

Gametogenesis process is sensitive to environmental perturbations and could underlie some aspects of disease susceptibility in offspring. During development, germ cells undergo rapid proliferation and epigenome remodelling, requiring a high intake of micronutrients and metabolic resources. Particularly, oogenesis is a metabolically demanding process. A maturing oocyte increases 100-300 folds in volume (varies by species), during which several biomolecules accumulate that are crucial for oocyte growth, fertilization, and embryonic development. Microbiota in the gut produce thousands of known and unknown essential metabolites, suggesting the vulnerability of germline cells to dysbiosis-induced systemic metabolic changes.

Recently, we showed that the gut microbiota acts as a key interface between the paternal preconception environment and intergenerational health risks in offspring. This study revealed previously unknown mechanisms of intergenerational inheritance through the gut-germline axis. Currently, we are investigating the role of maternal gut microbiota in oogenesis and their impact on offspring phenotypes. In this project, we use an inducible animal model that allows us to carefully manipulate microbial factors during female reproductive development. Through this novel approach, we aim to determine the regulatory role of gut microbiota during oogenesis and embryonic development. We will also investigate the impacts of gut dysbiosis on epigenetic inheritance and identify mechanisms that explain specific and reproducible phenotypic changes in offspring.