Glutamine protects intestinal immunity through microbial metabolites rather than microbiota

Shuai Li; Xiaolu Wen; Xuefen Yang; Li Wang; Kaiguo Gao; Xingwei Liang; Hao Xiao

doi:10.1016/j.intimp.2023.110832

Glutamine protects intestinal immunity through microbial metabolites rather than microbiota

Int Immunopharmacol. 2023 Nov;124(Pt A):110832. doi: 10.1016/j.intimp.2023.110832. Epub 2023 Aug 25.

Authors

Shuai Li¹, Xiaolu Wen², Xuefen Yang², Li Wang², Kaiguo Gao², Xingwei Liang³, Hao Xiao⁴

Affiliations

¹ State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; State Key Laboratory of Swine and Poultry Breeding, Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South China, Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Guangzhou 510640, China.
² State Key Laboratory of Swine and Poultry Breeding, Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South China, Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Guangzhou 510640, China.
³ State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, China. Electronic address: xwliang@gxu.edu.cn.
⁴ State Key Laboratory of Swine and Poultry Breeding, Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South China, Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Guangzhou 510640, China. Electronic address: xiaohao@gdaas.cn.

PMID: 37634449
DOI: 10.1016/j.intimp.2023.110832

Abstract

Glutamine has anti-inflammatory properties as well as the ability to maintain the integrity of the intestinal barrier. In our previous study, we found that 1.0% glutamine promoted SIgA (secretory immunoglobulin A) synthesis in the gut via both T cell-dependent and non-dependent processes, as well as via the intestinal microbiota. The purpose of this study was to investigate whether the intestinal microbiota or microbial metabolites regulate SIgA synthesis. In the mouse model, supplementation with 1.0% glutamine had no significant effect on the intestinal microbiota, but KEGG function prediction showed the difference on microbiota metabolites. Therefore, in this study, untargeted metabolomics techniques were used to detect and analyze the metabolic changes of glutamine in intestinal luminal contents. Metabolomics showed that in the positive ion (POS) mode, a total of 1446 metabolic differentials (VIP ≥ 1, P < 0.05, FC ≥ 2 or FC ≤ 0.5) were annotated in samples treated with glutamine-supplemented group compared to control group, of which 922 were up-regulated and 524 down-regulated. In the negative ion (NEG) mode, 370 differential metabolites (VIP ≥ 1, P < 0.05, FC ≥ 2 or FC ≤ 0.5) were screened, of which 220 were up-regulated and 150 down-regulated. These differential metabolites mainly include bile secretion synthesis, ABC transporters, diterpenoids and other secondary metabolites. KEGG analysis showed that propionic acid metabolism, TCA cycle, endoplasmic reticulum protein processing, nitrogen metabolism and other metabolic pathways were active. The above metabolic pathways and differential metabolites have positive effects on intestinal development and intestinal immunity, and combined with our previous studies, we conclude that glutamine supplementation can may maintain intestinal homeostasis and improving intestinal immunity through intestinal microbial metabolites.

Keywords: Glutamine; Intestinal immunity; Intestinal microbiota; Metabolomics profiling; Mice.