Neutrophil Depletion Reduced the Relative Abundance of Unsaturated Long‐Chain Fatty Acid Synthesis Microbiota and Intestinal Lipid Absorption

• DOI: 10.1002/cbf.70060
• Publication Date: 2025-03-11T08:40:48Z
• Authors: Xingyu Lu; Yike Xu; Yitong Liu; Fang Li; Qiong Feng; Chun Gao; Dan Liu; Li Zhou; Haizhen Yang; Ji Zhang; Fengmei Cui; Qiu Chen

ABSTRACTAs immune cells, neutrophils serve as the first line of defense against infections; however, the mechanism by which neutrophils regulate lipid metabolism is unknown. The neutrophil depletion group was treated with 100 μg InVivoMAb anti‐mouse Ly6G 6 times, whereas the control group mice were intraperitoneally injected with the same quantity of InVivoMAb rat IgG2a. Body fat content, triglycerides (TGs), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) in the jejunum and ileum, as well as 9 long‐chain fatty acids (LCFAs) in the intestinal contents were significantly decreased. Furthermore, genes involved in the absorption of lipids in each segment of the intestine also showed decreased expression. Neutrophil‐depletion and control models were administered 25 μCi of 3H‐cholesterol by gavage. The distribution of 3H cholesterol in the intestinal segment, heart, liver, serum, and feces was not altered by anti‐Ly6G antibodies. Metagenomics was applied to investigate uncultured microorganisms in the intestinal contents to identify bacteria containing lipid metabolism genes. At the species level, 12 bacteria were involved in unsaturated LCFA synthesis, among which 2 increased and 10 decreased. The overall relative abundance of these bacteria decreased from 3.102% to 0.734%. Many genes involved in lipid metabolism were also reduced as a result, such as fatty acid synthase and peroxisome proliferator‐activated receptor γ. In conclusion, neutrophil depletion does not affect intestinal lipid absorption in the diet but leads to a decrease in the overall relative abundance of gut bacteria involved in unsaturated LCFA synthesis. Consequently, intestinal lipid synthesis and absorption are reduced.