Paternal gut microbiota and the microbiome−germline axis as a target for prevention and treatment of epigenopathy in the next generation

The paternal pre-conception environment has been demonstrated in preclinical models to alter the sperm epigenome and offspring phenotypes. Recent studies have reported that modulating the paternal gut microbiota through non-absorbable antibiotics altered offspring body weight, survival, brain transcriptomics and behaviour. Other paternal environmental factors including diet composition, stress and pollutant exposure have also been shown to alter the paternal gut microbiome. This review discusses current evidence on the role of the paternal gut microbiome in epigenetic inheritance and explores its potential as a target to prevent alterations in the sperm epigenome and subsequent detrimental effects on offspring outcomes. This nascent research field (at the nexus of microbiology, epigenetics and neuroscience) will facilitate the prevention and treatment of the growing challenge of ‘intergenerational epigenopathy’ in a rapidly changing world.