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Dietary fat alters goblet cell function and microbial bile acid metabolism to promote intestinal lipid absorption in mice.

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Title: Dietary fat alters goblet cell function and microbial bile acid metabolism to promote intestinal lipid absorption in mice.
Authors: Liang X; Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China., Zhang Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, P. R. China., Xie W; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; University of Chinese Academy of Sciences, Beijing, P. R. China., Xiong J; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, P. R. China., Lin S; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, P. R. China., Wen Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; School of Life Sciences and Technology, Tongji University, Shanghai, P. R. China., Cao Y; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, P. R. China., Yu S; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; University of Chinese Academy of Sciences, Beijing, P. R. China., Wang K; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China., Deng J; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, P. R. China., Zhao J; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; ShanghaiTech University, School of Life Science and Technology, Shanghai, P. R. China.; Lingang Laboratory, Shanghai, P. R. China., Xu J; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, P. R. China., Hu Y; Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China., Liu Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China. yameng_liu@simm.ac.cn., Feng Q; Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China. fengqin@shutcm.edu.cn., Zhong Y; Division of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China. sh_zhongyifei@shutcm.edu.cn., Gonzalez FJ; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Xie C; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China. xiecen@simm.ac.cn.; University of Chinese Academy of Sciences, Beijing, P. R. China. xiecen@simm.ac.cn.; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, P. R. China. xiecen@simm.ac.cn.
Source: Nature microbiology [Nat Microbiol] 2026 Jul; Vol. 11 (7), pp. 1833-1849. Date of Electronic Publication: 2026 Jun 10.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101674869 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2058-5276 (Electronic) Linking ISSN: 20585276 NLM ISO Abbreviation: Nat Microbiol Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : Nature Publishing Group, [2016]-
MeSH Terms: Bile Acids and Salts*/metabolism , Goblet Cells*/metabolism , Goblet Cells*/drug effects , Dietary Fats*/metabolism , Intestinal Absorption* , Lipid Metabolism* , Gastrointestinal Microbiome*, Receptors, Cytoplasmic and Nuclear/metabolism ; Glutamine/metabolism ; Obesity/metabolism ; Obesity/microbiology ; Clostridium/metabolism ; PPAR alpha/metabolism ; Akkermansia/metabolism ; Intestinal Mucosa/metabolism ; Intestine, Small/metabolism ; Animals ; Mice ; Mice, Inbred C57BL ; Receptor, Farnesoid X-Activated ; Male
Abstract: Dietary fat reshapes host-microbiota interactions, yet the upstream events that mediate overnutrition-driven microbiome alterations and metabolic dysfunction remain unclear. Here we compared mouse models of diet-induced and genetic obesity using multi-omics to identify the colonic mucus niche as an early, diet-sensitive driver of metabolic dysfunction. Excessive dietary lipids impaired glutamine metabolism and redox homeostasis in goblet cells, thinning the mucus layer and depleting the mucus-adapted symbiont Akkermansia muciniphila while expanding the bile-acid-transforming bacterium Clostridium scindens. Altered bile acid composition along the enterohepatic axis activates FXR-PLIN2 signalling in the small intestine and increases fat absorption. In parallel, enterocytes upregulate the PPARα-dependent uptake pathway that supports luminal lipid entry. Supplementation with glutamine restored goblet cell function and the gut microbiota-derived bile acid pool, thereby reducing intestinal FXR activation and lipid uptake. These findings reveal that dietary fat impairs colonic goblet cell function and reshapes microbial bile acid metabolism, influencing small-intestinal fat absorption.
(© 2026. The Author(s), under exclusive licence to Springer Nature Limited.)
Competing Interests: Competing interests: The authors declare no competing interests.
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Grant Information: 92557304 National Natural Science Foundation of China (National Science Foundation of China); 82530024 National Natural Science Foundation of China (National Science Foundation of China); 82521004 National Natural Science Foundation of China (National Science Foundation of China); 82570954 National Natural Science Foundation of China (National Science Foundation of China)
Substance Nomenclature: 0 (Bile Acids and Salts)
0 (Dietary Fats)
0 (Receptors, Cytoplasmic and Nuclear)
0 (Receptor, Farnesoid X-Activated)
0RH81L854J (Glutamine)
0 (PPAR alpha)
SCR Organism: Akkermansia muciniphila
Entry Date(s): Date Created: 20260610 Date Completed: 20260702 Latest Revision: 20260702
Update Code: 20260702
DOI: 10.1038/s41564-026-02381-9
PMID: 42271159
Database: MEDLINE
Description
ISSN:2058-5276
DOI:10.1038/s41564-026-02381-9