Revolutionizing Male Reproductive Health with Probiotics against Endocrine Disruptors

Environmental pollution has emerged as a key contributor to the decline in male fertility, a significant health issue in Western countries. This decline is driven by contaminants of emerging concern that disrupt steroidogenesis and gut microbiota, leading to altered sex hormone levels and nutrient availability. Additionally, these pollutants act as epigenotoxic agents, impacting male germline epigenetics and posing risks to embryo development when such epimutations are inherited by the zygote. In this context, there is an urgent need not only to reduce pollutant emissions but also to develop innovative strategies to mitigate their health impacts, particularly on reproductive disorders and their transgenerational effects. The REPROBATIO project addresses this challenge by focusing on probiotics and postbiotics as a potential solution, leveraging their ability to restore gut microbiota diversity and enhance reproductive health, respectively, thus counteracting the effects of endocrine-disrupting chemicals (EDCs). The project pursues three main objectives: (O1) Conducting high-throughput screening to evaluate EDCs' impact on gut microbiota biodiversity and host-microbe interactions; (O2) Assessing probiotics' efficacy in mitigating EDC-induced gut dysbiosis; and (O3) Investigating probiotics and postbiotics as tools to alleviate EDC-induced reproductive disruptions in steroidogenesis and gametogenesis. Using advanced multi-omics approaches, alongside in vitro 3D (gut and testicular) and in vivo models, the project aims to provide a comprehensive map of how EDCs influence gut microbial biodiversity and hormonal regulation in the host. The outcomes of this research could revolutionize reproductive toxicology by offering novel microbiota-based strategies to combat EDC toxicity, improving overall health and reducing healthcare costs associated with exposome-derived male subfertility.