AUTHOR=Liao Wenhao , Cao Lei , Jiang Xuemei , Che Lianqiang , Fang Zhengfeng , Xu Shengyu , Lin Yan , Zhuo Yong , Hua Lun , Li Jian , Liu Guangmang , Sun Mengmeng , Wu De , Wang Hairui , Feng Bin TITLE=Intestinal overexpression of Pla2g10 alters the composition, diversity and function of gut microbiota in mice JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1535204 DOI=10.3389/fcimb.2025.1535204 ISSN=2235-2988 ABSTRACT=The intestinal microbiota is important for the health of the host and recent studies have shown that some genes of the host regulated the composition of the intestinal microbiota. Group 10 phospholipase A2 (PLA2G10) is a member of the lipolytic enzyme family PLA2, which hydrolyze the ester bond at the sn-2 position of phospholipids to produce free fatty acids and lysophospholipids. PLA2G10 is secreted into the intestinal lumen, but its impact on the gut microbiota remains unclear. In this study, we generated intestine-specific Pla2g10 knock-in mice, and used 16S RNA sequencing to compare their gut microbiota with that of their wild-type (WT) littermates. Results showed that gut-specific Pla2g10 knock-in induced both PLA2G10 mRNA and protein levels in the colon. Moreover, intestinal Pla2g10 overexpression reduced the α-diversity of the gut microbiota relative to that of WT mice. The abundance of Bacteroidetes was lower in the Pla2g10 knock-in mice than that in the control mice, while the ratio of Firmicutes/Bacteroidetes was higher. Furthermore, the abundance of the genus Allobaculum was reduced, whereas the abundance of beneficial bacteria genera, including Enterorhabdus, Dubosiella, and Lactobacillus, was increased by host intestinal Pla2g10 overexpression. In summary, intestinal Pla2g10 overexpression increased the proportions of beneficial bacterial in the colonic chyme of mice, providing a potential therapeutic target for future improvement of the gut microbiota.