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

• Published in: Cell biochemistry and function Vol. 43; no. 3; pp. e70060 - n/a
• Main Authors: Lu, Xingyu, Xu, Yike, Liu, Yitong, Li, Fang, Feng, Qiong, Gao, Chun, Liu, Dan, Zhou, Li, Yang, Haizhen, Zhang, Ji, Cui, Fengmei, Chen, Qiu
• Format: Journal Article
• Language: English
• Published: England 01.04.2025
• Subjects: Animals; Fatty Acids, Unsaturated - biosynthesis; Gastrointestinal Microbiome; Intestinal Absorption; intestine; Intestines - microbiology; Lipid Metabolism; Male; metagenomics; Mice; Mice, Inbred C57BL; neutrophil; Neutrophils - cytology; Neutrophils - immunology; Neutrophils - metabolism; Rats; unsaturated LCFAs; intestine; unsaturated LCFAs; neutrophil; metagenomics
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.70060

ABSTRACT As 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. Summary Why Was This Work Carried Out? ◦ There are many reports on the effect of lipid metabolism on the function of immune cells, such as foam cells formed by macrophages, but few reports on the effect of immune cells on metabolism. ◦ A recent report by Sullivan et al., γδ T cells regulate the integral response to nutrient sensing, described how γδ T cells indirectly regulate intestinal glucose metabolism through type 3 inner lymphoid cells rather than gut microbiota. What Are the Key Findings? ◦ The importance of our work lies in the discovery that neutrophils regulate unsaturated long‐chain fatty acid metabolism through gut microbiota. Why the Data Matter—What Is the Potential Impact of This Study on Future Research? ◦ These findings have expanded our understanding of neutrophil function and provided new insights into the dysregulation of lipid metabolism in neutropenia, forming a closed‐loop understanding of lipid metabolism–neutrophil–lipid metabolism.