Maternal cold exposure improves offspring metabolic health via a milk lithocholic acid–microbiota–Th17 axis
5 affiliations
- 1Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin, China
- 2State Key Laboratory of Frigid Zone Cardiovascular Disease, Harbin Medical University, Harbin, Heilongjiang China
- 3Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, China
- 4Arongqi People’s Hospital, Arong Banner, Hulunbuir, Inner Mongolia China
- 5Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui China
Abstract
Metabolic diseases are rising with a trend toward earlier onset, yet effective preventive strategies remain limited. While cold exposure improves metabolic health in adults, its role during pregnancy in shaping offspring metabolic outcomes remains unknown. Herein, we demonstrate that maternal cold exposure in early pregnancy markedly improved offspring glucose tolerance, insulin sensitivity, and hepatic lipid metabolism when challenged with a Western diet, and the benefits persisted into late adulthood. Transcriptomic and immunophenotyping analyses revealed that offspring with cold-exposed dams exhibited suppressed Th17 activity and IL-17 signaling. Cross-fostering and metabolomics identified elevated lithocholic acid (LCA) in maternal milk as a critical mediator of these effects. LCA supplementation recapitulates these benefits through gut microbiota-dependent conversion to 3-oxo-LCA. Furthermore, Clostridium scindens supplementation enhanced 3-oxo-LCA production, suppressed Th17 responses, and alleviated diet-induced hepatic steatosis. Clinically, analysis of the UK Biobank cohort showed that winter conception was associated with a lower risk of metabolic dysfunction-associated steatotic liver disease in offspring. A similar association was observed in the CHARLS cohort in colder northern China. Together, these results identify a maternal cold–microbiota–bile acid–Th17 axis that programs offspring metabolic health and highlight microbial bile acid metabolism as a potential therapeutic target for metabolic diseases.
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BibTeX
@article{han2026maternal,
title = {{Maternal cold exposure improves offspring metabolic health via a milk lithocholic acid–microbiota–Th17 axis}},
author = {Xuejie Han and Hui Yu and Qianhui Gao and Dongze Li and Linwei Zhang and Qi Kang and Chaowen Sui and Qian Zhao and Xuanrui Ji and Hanwen Liu and Yuchen Wang and Changming Zhao and Shuting Li and Li Sun and Yun Zhang and Yue Li},
journal = {NPJ Biofilms and Microbiomes},
year = {2026},
month = jul,
doi = {10.1038/s41522-026-01092-7},
url = {https://doi.org/10.1038/s41522-026-01092-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Maternal cold exposure improves offspring metabolic health via a milk lithocholic acid–microbiota–Th17 axis
AU - Xuejie Han
AU - Hui Yu
AU - Qianhui Gao
AU - Dongze Li
AU - Linwei Zhang
AU - Qi Kang
AU - Chaowen Sui
AU - Qian Zhao
AU - Xuanrui Ji
AU - Hanwen Liu
AU - Yuchen Wang
AU - Changming Zhao
AU - Shuting Li
AU - Li Sun
AU - Yun Zhang
AU - Yue Li
PY - 2026
DA - 2026/07/09
JO - NPJ Biofilms and Microbiomes
DO - 10.1038/s41522-026-01092-7
UR - https://doi.org/10.1038/s41522-026-01092-7
AB - Metabolic diseases are rising with a trend toward earlier onset, yet effective preventive strategies remain limited. While cold exposure improves metabolic health in adults, its role during pregnancy in shaping offspring metabolic outcomes remains unknown. Herein, we demonstrate that maternal cold exposure in early pregnancy markedly improved offspring glucose tolerance, insulin sensitivity, and hepatic lipid metabolism when challenged with a Western diet, and the benefits persisted into late adulthood. Transcriptomic and immunophenotyping analyses revealed that offspring with cold-exposed dams exhibited suppressed Th17 activity and IL-17 signaling. Cross-fostering and metabolomics identified elevated lithocholic acid (LCA) in maternal milk as a critical mediator of these effects. LCA supplementation recapitulates these benefits through gut microbiota-dependent conversion to 3-oxo-LCA. Furthermore, Clostridium scindens supplementation enhanced 3-oxo-LCA production, suppressed Th17 responses, and alleviated diet-induced hepatic steatosis. Clinically, analysis of the UK Biobank cohort showed that winter conception was associated with a lower risk of metabolic dysfunction-associated steatotic liver disease in offspring. A similar association was observed in the CHARLS cohort in colder northern China. Together, these results identify a maternal cold–microbiota–bile acid–Th17 axis that programs offspring metabolic health and highlight microbial bile acid metabolism as a potential therapeutic target for metabolic diseases.
SN - 2055-5008
ER -