Maternal Metformin Exposure Induces Gut Microbial Shifts in Non-Diabetic Dams and Sex-Stratified Changes in Mouse Offspring

Beyond being one of the most widely prescribed medications for type 2 diabetes, metformin has been increasingly used during pregnancy for gestational diabetes and polyendocrine metabolic ovarian syndrome. While it is considered safe for pregnancy and lactation, metformin is known to induce gut microbial changes in non-pregnant individuals with type 2 diabetes, and maternal and offspring microbial alterations are known to influence offspring development. Therefore, understanding whether metformin drives microbiota changes beyond the confounding effects of maternal hyperglycaemia holds significant implications for maternal–foetal health. In this study, non-diabetic C57BL/6 mouse dams received either control or metformin treatment (5 mg/mL) in drinking water during pregnancy and lactation. Microbial profiling from faecal samples of dams at gestational day 15 and offspring at 6 weeks of age was analysed using 16S rRNA sequencing and an R-based pipeline. Metformin positively restructured dominant taxa associated with healthy pregnancy in dams, while inducing broad taxonomic changes in males and Bacteroidetes-dominant shifts in female offspring. Overall, maternal metformin treatment promoted short-chain fatty acid-producing taxa while suppressing potentially opportunistic bacteria, without compromising community richness. Further studies are required to elucidate the functional mechanisms underlying these shifts and their long-term implications for maternal–foetal health.