Maternal microbiota shapes brain and neuroendocrine development in piglets
9 affiliations
- 1Chinese Academy of Sciences
- 2Chinese Academy of Agricultural Sciences
- 3Shenzhen University of Advanced Technology
- 4Hunan Agricultural University
- 5Chongqing University Three Gorges Hospital, Chongqing University
- 6Hunan Institute of Animal and Veterinary Science
- 7Institute of Medicinal Plant Development
- 8Huazhi Biotechnology Co. Ltd
- 9Ministry of Agriculture
Abstract
The maternal microbiota plays a critical role in early‐life development, yet how maternal microbiota exposure shapes cellular and neuroendocrine programs during mammalian development remains poorly understood. Here, leveraging germ‐free (GF) and maternal microbiota transplantation (MMT) models, we generated an integrated multi‐organ porcine atlas by combining multi‐regional single‐nucleus RNA sequencing, spatial transcriptomics, bulk RNA sequencing of intestinal tissues, and metabolomics. Across five brain regions and the hypothalamic–pituitary–adrenal (HPA) axis, we profiled 673,623 high‐quality nuclei and revealed microbiota‐dependent remodeling of neuronal and glial states across early postnatal developmental stages. MMT reshaped neuronal maturation programs, altered the distribution of immature neuronal states, and elicited region‐specific transcriptional responses in glutamatergic and GABAergic neurons. MMT also reorganized neuron–glia interaction networks, accompanied by trends toward increased plasma glutamic acid and glutamine levels. Across the gut–brain–neuroendocrine axis, MMT was associated with coordinated remodeling of HPA‐axis cellular communication, stress‐response transcriptional programs, and immune signatures, together with reduced circulating cortisol levels. Integrated intestinal analyses revealed segment‐specific transcriptional and metabolic remodeling, including alterations in tryptophan/indole‐related metabolites and immune‐associated pathways. Cross‐species stratified linkage disequilibrium score regression further identified enrichment of human cognitive and neuropsychiatric trait‐associated genetic signals within cell‐type‐specific gene signatures derived from microbiota‐responsive porcine cell populations. Our study establishes a large‐animal cellular atlas linking maternal microbiota‐responsive remodeling across the brain, gut, and neuroendocrine axis, providing a translational framework for understanding how early‐life microbial signals shape mammalian developmental physiology.
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BibTeX
@article{wang2026maternal,
title = {{Maternal microbiota shapes brain and neuroendocrine development in piglets}},
author = {Leli Wang and Chao Yan and Lei Li and Yuankun Deng and Hua Shao and Kuo Long and Cimin Long and Yuanyuan Zhu and Meiqing Chen and Jialu Huang and Jinghua Jiang and Ziyi Lin and Yunying Yao and Tao Yang and Wenbin Guo and Liangpeng Ge and Jing Sun and Yuchun Ding and Zuohua Liu and Mingzhu Yin and Yulong Yin},
journal = {IMeta},
year = {2026},
month = oct,
doi = {10.1002/imt2.70182},
url = {https://europepmc.org/article/PMC/PMC13702092},
note = {CC BY},
}
RIS
TY - JOUR
TI - Maternal microbiota shapes brain and neuroendocrine development in piglets
AU - Leli Wang
AU - Chao Yan
AU - Lei Li
AU - Yuankun Deng
AU - Hua Shao
AU - Kuo Long
AU - Cimin Long
AU - Yuanyuan Zhu
AU - Meiqing Chen
AU - Jialu Huang
AU - Jinghua Jiang
AU - Ziyi Lin
AU - Yunying Yao
AU - Tao Yang
AU - Wenbin Guo
AU - Liangpeng Ge
AU - Jing Sun
AU - Yuchun Ding
AU - Zuohua Liu
AU - Mingzhu Yin
AU - Yulong Yin
PY - 2026
DA - 2026/10/26
JO - IMeta
DO - 10.1002/imt2.70182
UR - https://europepmc.org/article/PMC/PMC13702092
AB - The maternal microbiota plays a critical role in early‐life development, yet how maternal microbiota exposure shapes cellular and neuroendocrine programs during mammalian development remains poorly understood. Here, leveraging germ‐free (GF) and maternal microbiota transplantation (MMT) models, we generated an integrated multi‐organ porcine atlas by combining multi‐regional single‐nucleus RNA sequencing, spatial transcriptomics, bulk RNA sequencing of intestinal tissues, and metabolomics. Across five brain regions and the hypothalamic–pituitary–adrenal (HPA) axis, we profiled 673,623 high‐quality nuclei and revealed microbiota‐dependent remodeling of neuronal and glial states across early postnatal developmental stages. MMT reshaped neuronal maturation programs, altered the distribution of immature neuronal states, and elicited region‐specific transcriptional responses in glutamatergic and GABAergic neurons. MMT also reorganized neuron–glia interaction networks, accompanied by trends toward increased plasma glutamic acid and glutamine levels. Across the gut–brain–neuroendocrine axis, MMT was associated with coordinated remodeling of HPA‐axis cellular communication, stress‐response transcriptional programs, and immune signatures, together with reduced circulating cortisol levels. Integrated intestinal analyses revealed segment‐specific transcriptional and metabolic remodeling, including alterations in tryptophan/indole‐related metabolites and immune‐associated pathways. Cross‐species stratified linkage disequilibrium score regression further identified enrichment of human cognitive and neuropsychiatric trait‐associated genetic signals within cell‐type‐specific gene signatures derived from microbiota‐responsive porcine cell populations. Our study establishes a large‐animal cellular atlas linking maternal microbiota‐responsive remodeling across the brain, gut, and neuroendocrine axis, providing a translational framework for understanding how early‐life microbial signals shape mammalian developmental physiology.
SN - 2770-5986
SN - 2770-596X
ER -