Ornithine α-Ketoglutarate Alleviates Inflammation via Regulating Ileal Mucosa Microbiota and Metabolites in Enterotoxigenic Escherichia coli-Infected Pigs

Yuying Li; Xuetai Bao; Fan Yang; Junquan Tian; Wenxuan Su; Jie Yin; Kang Yao; Tiejun Li; Yulong Yin

doi:10.3389/fnut.2022.862498

Ornithine α-Ketoglutarate Alleviates Inflammation via Regulating Ileal Mucosa Microbiota and Metabolites in Enterotoxigenic Escherichia coli-Infected Pigs

Front Nutr. 2022 Jun 7:9:862498. doi: 10.3389/fnut.2022.862498. eCollection 2022.

Authors

Yuying Li^{1

2}, Xuetai Bao^{1

2}, Fan Yang^{1

2}, Junquan Tian^{1

2}, Wenxuan Su^{1

2}, Jie Yin³, Kang Yao¹, Tiejun Li^{1

2}, Yulong Yin^{1

2}

Affiliations

¹ Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Changsha, China.
² College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China.
³ College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

Abstract

Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of diarrhea in weaned piglets, and ornithine α-ketoglutarate (OKG) as a food supplement has been shown to improve intestinal immune status in animals and humans. However, it remains unknown whether OKG alleviates inflammation through the regulation of gut microbiota and its metabolites on ETEC-infected piglets. This study was conducted to explore the impact of OKG on growth performance, immunity, and ileal mucosa microbiota and its metabolites in piglets infected with ETEC. On a total of 40 pigs, a 2 × 2 factor design was performed; the major factors were diet (basal diet or 1% OKG diet) and challenge (E. coli or LB Broth). The results showed that ETEC-infection inhibited growth performance, and OKG supplementation alleviated growth performance. Interestingly, ETEC-infection increased the serum TNF-α and IL-6, decreased the serum IL-10, downregulated the mRNA expression of IL-1β, IL-6, MyD88, and improved the mRNA expression of IL-8, IL-18, and TLR4. OKG inhibited serum IL-6, suppressed the phosphorylation of downstream signals of NF-κB/JNK in the ileum, and enhanced serum IL-10 and ileum SIgA in ETEC-challenged piglets. OKG supplementation enhanced the mRNA expression of IL-1β and IL-10 and reduced NF-κB and MyD88 in the ileum. Importantly, OKG reversed intestinal microbiota dysfunction, including the diversity of ileal microbiota, the relative abundances of Actinobacillus, Turicibacter, and [Acetivibrio]_ethanolgignens_group, which significantly affected arachidonic acid metabolism and primary bile acid biosynthesis. Collectively, our results suggest that OKG improves growth performance, regulates immunity, and ileal mucosa microbiota and its metabolites in ETEC-infected piglets.

Keywords: enterotoxigenic Escherichia coli; ileal mucosa metabolites; ileal mucosa microbiota; immune status; inflammation; ornithine α-ketoglutarate.