2. Academic Validation
  3. Lactobacillus paragasseri LPG-9 reduces placental inflammation in intrahepatic cholestasis of pregnancy by regulating TGR5 in mice

Lactobacillus paragasseri LPG-9 reduces placental inflammation in intrahepatic cholestasis of pregnancy by regulating TGR5 in mice

  • Commun Biol. 2026 Mar 26;9(1):679. doi: 10.1038/s42003-026-09869-4.
Wanwen Huang 1,  Jiechang Zhang 2,  Jiamin Shan 2,  Wei Shen 3,  Pingping Du 4,  Jiaxin Liu 2,  Xiaotong Guo 2,  Zhenhui Chen 2,  Weisen Zeng 5,  Qiongxi Lin 6,  Hongying Fan 7
Affiliations

Affiliations

  • 1 Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
  • 2 Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
  • 3 Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 4 Department of Obstetrics and Gynaecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 5 Department of Cell Biology, School of Basic Medicine Sciences, Southern Medical University, Guangzhou, China. [email protected].
  • 6 Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China. [email protected].
  • 7 Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China. [email protected].
PMID: 41888318 DOI: 10.1038/s42003-026-09869-4
Abstract

Intrahepatic cholestasis of pregnancy (ICP), a liver disorder associated with adverse fetal outcomes, is characterized by elevated bile acid levels and placental inflammation by the TGR5. However, the interplay among the gut microbiome, bile acid metabolism, and ICP-associated placental inflammation remains unexplored. We aimed to investigate the role of the gut microbiota in regulating bile acid metabolism and placental inflammation, and to identify potential probiotic-based therapies for ICP in C57BL/6 mice. Immunohistochemical analysis of human placentas revealed significantly higher inflammation and decreased TGR5 expression in ICP compared with controls. In vivo and in vitro assays confirmed the anti-inflammatory effects of TGR5 activation. Using 16S rRNA Sequencing and metabolomics, ICP mice exhibited a distinct gut microbiota composition and reduced abundance of bile salt hydrolase (BSH)-producing bacteria (e.g., Lactobacillus), accompanied by a significant decrease in the proportion of secondary bile acids. Transplanting fecal microbiota from ICP donors into healthy mice reproduced the disease phenotype of ICP, confirming the pathogenic role of gut microbiota dysbiosis. Supplementation with BSH-enriched Lactobacillus paragasseri LPG-9 remodeled the bile acid profile, thereby activating placental TGR5 to inhibit TLR4-NF-κB signaling and promoting hepatic bile acid excretion via BSEP.

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