Galacto-oligosaccharides enrich galactosidase-encoded rather than all Lachnospiraceae bacteria to redress abnormal gut microbiota and lipid metabolism in pregnancy.

Among the various pregnancy complications, gestational diabetes mellitus (GDM) is one of the most prevalent and damaging adverse conditions. GDM is characterised by dysregulated gut microbiota and dysglycaemia. There is a keen search for active ingredients that can modify gut dysbiosis and glycaemic imbalances. In this study, the effects of dietary supplementation with high fibre and galacto-oligosaccharides (GOS) on GDM were evaluated. We found that GOS effectively alleviated blood glucose, hepatic inflammatory response, and lipid metabolism in high-fat-induced GDM mice. Furthermore, GOS redressed GDM-associated gut dysbiosis and altered glycerolipid metabolic pathways. GOS supplementation significantly downregulated the levels of fat synthesis genes and inflammatory factors in the liver and upregulated the expression of lipolytic catabolic genes (Cyp4a10). In dietary GOS supplementation, Lachnospiraceae bacteria strongly co-occurred with saturated lysophosphatidylcholine in the glycerolipid metabolic pathway. Metagenomic analyses illustrated that Lachnospiraceae bacteria-hosted α-galactosidase genes enriched upon GOS intake. GOS supplementation reduces lipopolysaccharide (LPS) entry into the systemic circulation by repairing intestinal mucosal damage, inhibits inflammatory cell production by reducing hepatic and intestinal Toll-like receptor-4 (TLR-4) expression and potentially ameliorates blood glucose dysregulation in GDM by modulating glycerophospholipid metabolism. These results revealed that dietary supplementation of GOS during pregnancy may be a promising intervention against GDM.