<p>The effects of diet and nutrition extend beyond individual health: food intake before conception or during pregnancy and lactation can affect the health of offspring. Diet is one of the most powerful modulators of the gut microbiome, influencing gene–environment interactions, with several emerging mechanisms pointing to the microbiome–metabolite–epigenome axis. In this Review, we discuss the effect of dietary changes on the gametes (‘gut–germline axis’) or in utero (‘gut–neonatal axis’) that may change the predisposition of offspring to several non-communicable diseases. Examples of diets discussed are those that detrimentally modulate the parental microbiota and lead to epigenetic changes in the progeny, including Western diets characterized by high saturated fat and low protein or fibre intake. We summarize studies using animal models, which suggest that these diets can have long-lasting effects on the offspring microbiome, epigenome and phenotype, particularly across the cardiometabolic and immune systems, and discuss the limitations of current studies as well as future directions for the field. Translational research investigating the benefits of parental dietary interventions before and during pregnancy, mainly using personalized approaches, is needed. This would, in turn, reduce rates of non-communicable diseases in generations to come.</p>