Lactiplantibacillus plantarum promotes intestinal goblet cell differentiation via indole-3-lactic acid–AHR signaling in pigs
6 affiliations
- 1College of Animal Science, South China Agricultural University, State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Guangzhou, China
- 2Department of Animal Science, University of Arkansas, Fayetteville, AR USA
- 3State Key Laboratory for Quality and Safety of Agro-Products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
- 4Department of Biological and Agriculture Engineering, University of Arkansas, Fayetteville, AR USA
- 5Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR USA
- 6Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB Canada
Abstract
The swine intestinal microbiota dynamically remodels during development and supports gut homeostasis. However, whether stage-specific microbial shifts, are associated with epithelial development remains poorly understood. Here, longitudinal metagenomic profiling of the swine gut microbiome identified Lactiplantibacillus plantarum as a transiently enriched nursery-stage bacterium positively associated with goblet cell numbers. Dietary supplementation with L. plantarum validated this association, showing increased goblet cell numbers and MUC2 expression in the ileum of nursery piglets. Co-culture with porcine ileum organoids further demonstrated that L. plantarum cell-free supernatant promoted ileal organoid growth and goblet cell differentiation. Integrated untargeted metabolomic analyses of ileal samples and bacterial culture supernatants identified indole-3-lactic acid (ILA) as a potential key microbial metabolite from L. plantarum. Mechanistically, ILA promoted intestinal stem cell proliferation and MUC2 expression, accompanied by increased expression of aryl hydrocarbon receptor (AHR) and its downstream target CYP1A1 in ileal organoids. Consistently, activation of AHR using FICZ increased MUC2 expression, whereas inhibition with CH-223191 suppressed MUC2 expression in ileal organoids. Collectively, these findings uncover a L. plantarum–ILA–AHR signaling axis that promotes intestinal goblet cell differentiation, providing mechanistic insight into microbial metabolite–mediated regulation of epithelial homeostasis during post-weaning period in pigs.
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BibTeX
@article{liu2026lactiplantibacillus,
title = {{Lactiplantibacillus plantarum promotes intestinal goblet cell differentiation via indole-3-lactic acid–AHR signaling in pigs}},
author = {Ziyu Liu and Haiqin Wu and Samantha Howe and Bin Zuo and Yang Tian and Xiaofan Wang and Hailemariam Abrha Assress and Renny Shang-Lun Lan and Chunlong Mu and Yingping Xiao and Yan Huang and Michael Looper and Tsungcheng Tsai and Jiangchao Zhao},
journal = {NPJ Biofilms and Microbiomes},
year = {2026},
month = jul,
doi = {10.1038/s41522-026-01085-6},
url = {https://doi.org/10.1038/s41522-026-01085-6},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Lactiplantibacillus plantarum promotes intestinal goblet cell differentiation via indole-3-lactic acid–AHR signaling in pigs
AU - Ziyu Liu
AU - Haiqin Wu
AU - Samantha Howe
AU - Bin Zuo
AU - Yang Tian
AU - Xiaofan Wang
AU - Hailemariam Abrha Assress
AU - Renny Shang-Lun Lan
AU - Chunlong Mu
AU - Yingping Xiao
AU - Yan Huang
AU - Michael Looper
AU - Tsungcheng Tsai
AU - Jiangchao Zhao
PY - 2026
DA - 2026/07/11
JO - NPJ Biofilms and Microbiomes
DO - 10.1038/s41522-026-01085-6
UR - https://doi.org/10.1038/s41522-026-01085-6
AB - The swine intestinal microbiota dynamically remodels during development and supports gut homeostasis. However, whether stage-specific microbial shifts, are associated with epithelial development remains poorly understood. Here, longitudinal metagenomic profiling of the swine gut microbiome identified Lactiplantibacillus plantarum as a transiently enriched nursery-stage bacterium positively associated with goblet cell numbers. Dietary supplementation with L. plantarum validated this association, showing increased goblet cell numbers and MUC2 expression in the ileum of nursery piglets. Co-culture with porcine ileum organoids further demonstrated that L. plantarum cell-free supernatant promoted ileal organoid growth and goblet cell differentiation. Integrated untargeted metabolomic analyses of ileal samples and bacterial culture supernatants identified indole-3-lactic acid (ILA) as a potential key microbial metabolite from L. plantarum. Mechanistically, ILA promoted intestinal stem cell proliferation and MUC2 expression, accompanied by increased expression of aryl hydrocarbon receptor (AHR) and its downstream target CYP1A1 in ileal organoids. Consistently, activation of AHR using FICZ increased MUC2 expression, whereas inhibition with CH-223191 suppressed MUC2 expression in ileal organoids. Collectively, these findings uncover a L. plantarum–ILA–AHR signaling axis that promotes intestinal goblet cell differentiation, providing mechanistic insight into microbial metabolite–mediated regulation of epithelial homeostasis during post-weaning period in pigs.
SN - 2055-5008
ER -