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Gut Microbiota‐Derived Hyocholic Acid Enhances Type 3 Immunity and Protects Against Salmonella enterica Serovar Typhimurium in Neonatal Rats
This study investigates how microbiome colonization influences the development of intestinal type 3 immunity in neonates. The results showed that reduced oxygen levels in the small intestine of neonatal rats induced by Saccharomyces boulardii accelerated microbiome colonization and type 3 immunity development, which protected against Salmonella enterica serovar Typhimurium infection. Microbiome maturation increased the abundance of microbiome‐encoded bile salt hydrolase (BSH) genes and hyocholic acid (HCA) levels. Furthermore, reducing oxygen levels in the intestine increased the abundance of Limosilactobacillus reuteri, a bacterium encoding BSH, and promoted intestinal type 3 immunity. However, inhibition of BSH blocked the L. reuteri‐induced development of intestinal type 3 immunity. Mechanistically, HCA promoted the development of gamma‐delta T cells and type 3 innate lymphoid cells by stabilizing the mRNA expression of RAR‐related orphan receptor C via the farnesoid X receptor–WT1‐associated protein‐N6‐methyl‐adenosine axis. These results reveal that gut microbiota‐derived HCA plays a crucial role in promoting the development of intestinal type 3 immunity in neonates. This discovery introduces potential therapeutic avenues for strengthening intestinal immunity in early life or treating bacterial infections by targeting microbial metabolites.
Gut Microbiota‐Derived Hyocholic Acid Enhances Type 3 Immunity and Protects Against Salmonella enterica Serovar Typhimurium in Neonatal Rats
This study investigates how microbiome colonization influences the development of intestinal type 3 immunity in neonates. The results showed that reduced oxygen levels in the small intestine of neonatal rats induced by Saccharomyces boulardii accelerated microbiome colonization and type 3 immunity development, which protected against Salmonella enterica serovar Typhimurium infection. Microbiome maturation increased the abundance of microbiome‐encoded bile salt hydrolase (BSH) genes and hyocholic acid (HCA) levels. Furthermore, reducing oxygen levels in the intestine increased the abundance of Limosilactobacillus reuteri, a bacterium encoding BSH, and promoted intestinal type 3 immunity. However, inhibition of BSH blocked the L. reuteri‐induced development of intestinal type 3 immunity. Mechanistically, HCA promoted the development of gamma‐delta T cells and type 3 innate lymphoid cells by stabilizing the mRNA expression of RAR‐related orphan receptor C via the farnesoid X receptor–WT1‐associated protein‐N6‐methyl‐adenosine axis. These results reveal that gut microbiota‐derived HCA plays a crucial role in promoting the development of intestinal type 3 immunity in neonates. This discovery introduces potential therapeutic avenues for strengthening intestinal immunity in early life or treating bacterial infections by targeting microbial metabolites.
Gut Microbiota‐Derived Hyocholic Acid Enhances Type 3 Immunity and Protects Against Salmonella enterica Serovar Typhimurium in Neonatal Rats
Yang, Zhipeng (author) / Lin, Zhiyuan (author) / You, Yaojie (author) / Zhang, Mei (author) / Gao, Ning (author) / Wang, Xinru (author) / Peng, Jian (author) / Wei, Hongkui (author)
Advanced Science ; 12
2025-03-01
18 pages
Article (Journal)
Electronic Resource
English
Temperate phages in Salmonella enterica serovar Typhimurium: Implications for epidemiology
| British Library Online Contents | 2002