Cross‐tissue multi‐omics analyses reveal the gut microbiota's absence impacts organ morphology, immune homeostasis, bile acid and lipid metabolism
The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and specific pathogen-free (SPF) mice using spatial transcriptomics, single-cell RNA sequencing, and targeted bile acid metabolomics across multiple organs, we systematically assessed how the gut microbiota's absence affected organ morphology, immune homeostasis, bile acid, and lipid metabolism. Through integrated analysis, we detect marked aberration in B, myeloid, and T/natural killer cells, altered mucosal zonation and nutrient uptake, and significant shifts in bile acid profiles in feces, liver, and circulation, with the alternate synthesis pathway predominant in GF mice and pronounced changes in bile acid enterohepatic circulation. Particularly, autophagy-driven lipid droplet breakdown in ileum epithelium and the liver's zinc finger and BTB domain-containing protein (ZBTB20)-Lipoprotein lipase (LPL) (ZBTB20-LPL) axis are key to plasma lipid homeostasis in GF mice. Our results unveil the complexity of microbiota-host interactions in the crosstalk between commensal gut bacteria and the host.
Authors
- Shanshan Pan (ORCID: https://orcid.org/0000-0001-5977-4914)
- Li Pang (ORCID: https://orcid.org/0000-0002-7163-6255)
- Elaine Lai‐Han Leung (ORCID: https://orcid.org/0000-0002-3705-8084)
- Haohui Deng (ORCID: https://orcid.org/0000-0001-5948-9101)
- Junpu Mei (ORCID: https://orcid.org/0000-0003-4630-0765)
- Yusheng Deng
- S Chen (ORCID: https://orcid.org/0009-0002-5138-9215)
- Xiaodong Fang
- Jiazhe Liu (ORCID: https://orcid.org/0009-0009-3441-0474)
- Wanshun Li
- Tailiang Chai
- Jing‐Jing Ye (ORCID: https://orcid.org/0000-0003-2045-9591)
- Kristiansen Karsten
- Xueting Chen (ORCID: https://orcid.org/0000-0002-5314-0221)
- Huanjie Yang (ORCID: https://orcid.org/0000-0002-2424-4937)
- Yu‐Fen Huang (ORCID: https://orcid.org/0000-0001-7686-8090)
- Lijuan Han (ORCID: https://orcid.org/0000-0003-1190-9634)
- Rouxi Chen (ORCID: https://orcid.org/0000-0001-6050-6626)
- Yang Chen (ORCID: https://orcid.org/0000-0001-6993-4870)
- Lu Zhang (ORCID: https://orcid.org/0000-0002-2794-7371)
- Zhao Zhang (ORCID: https://orcid.org/0000-0002-3209-9071)
- Wen Luo (ORCID: https://orcid.org/0000-0003-4669-9120)
- Xiao Huang (ORCID: https://orcid.org/0000-0002-1533-8093)
- Weiming Liang
- Li Huang (ORCID: https://orcid.org/0000-0003-3668-9770)
- Linying Wang (ORCID: https://orcid.org/0000-0002-4952-3027)
- Juan Shen (ORCID: https://orcid.org/0000-0001-8448-9242)
- Wei Cheng
- Zhen Yue (ORCID: https://orcid.org/0000-0001-8760-7574)
- Yanmin Liu (ORCID: https://orcid.org/0000-0003-3731-0865)
- Qinwei Qiu (ORCID: https://orcid.org/0000-0002-3438-129X)
- Xuanting Jiang
- Ruizhen Zhao
- Zhimin Yang
- Yin Zhang (ORCID: https://orcid.org/0000-0001-5334-0605)
- Hong Wei
Institutions
- BGI Group (China) (CN)
- Guangzhou University of Chinese Medicine (CN)
- University of Copenhagen (DK)
- Hong Kong Baptist University (HK)
- University of Macau (MO)
- Huazhong Agricultural University (CN)
- Beijing Graphene Institute (CN)
- Kangmei Pharmaceutical (China) (CN)
- Zhuhai Institute of Advanced Technology (CN)
- BGI Research (CN)
- City University of Macau (MO)
Publication Details
- Journal
- iMeta
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1002/imt2.272
- Citations
- 18
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 14.51