When pregnant rats were exposed to cold temperatures, their male offspring showed better blood sugar control and less liver fat — even into old age. The secret? Breast milk enriched with a bile acid called lithocholic acid (LCA) that reshapes gut microbiota and immune signaling. Human data hint the same may hold true, with winter conceptions linked to lower liver disease risk.
A new study published in npj Biofilms and Microbiomes reveals that exposing pregnant rats to cold temperatures during early gestation can program lasting metabolic health benefits in their male offspring — and the mechanism runs through breast milk. Male pups born to cold-exposed mothers showed significantly better glucose tolerance, insulin sensitivity, and reduced liver fat accumulation when challenged with a high-fat Western diet, with benefits persisting all the way to 18 months of age.
The key mediator appears to be lithocholic acid (LCA), a secondary bile acid found in higher concentrations in the milk of cold-exposed mothers. LCA is converted by gut bacteria — particularly Clostridium scindens — into active metabolites like 3-oxo-LCA, which suppress liver inflammation via the IL-17 (Th17) immune pathway and improve metabolic outcomes. Antibiotic treatment wiped out these benefits, confirming the gut microbiome's essential role.
Supporting the animal findings, human data from over 33,900 UK Biobank participants showed that winter conception — used as a proxy for cold exposure — was associated with a ~25% lower risk of developing metabolic liver disease (MASLD).
Key Takeaways:
Why it matters: This research opens a potential new avenue for preventing metabolic diseases like fatty liver and type 2 diabetes by targeting the maternal microbiome and bile acid pathways — possibly through diet, probiotics, or targeted supplementation during pregnancy and lactation.
