Gut-Derived Metabolites from Dietary Tryptophan Supplementation Quench Intestinal Inflammation through the AMPK-SIRT1-Autophagy Pathway.

Abstract

Tryptophan has drawn wide attention due to its involvement in improving intestinal immune defense directly and indirectly by regulating metabolic pathways. The study aims to elucidate the potential modulating roles of tryptophan to protect against intestinal inflammation and elucidate the underlying molecular mechanisms. The protective effects of tryptophan against intestinal inflammation are examined in the lipopolysaccharide (LPS)-induced inflammatory model. We first found that tryptophan markedly (p < 0.01) inhibited proinflammatory cytokines production and nuclear factor κB (NF-κB) pathway activation upon LPS challenge. Next, we demonstrated that tryptophan (p < 0.05) attenuated LPS-caused intestinal mucosal barrier damage by increasing the number of goblet cells, mucins, and antimicrobial peptides (AMPs) in the ileum of mice. In addition, tryptophan (p < 0.05) inhibited LPS-induced autophagic flux through the AMP-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) pathway in the intestinal systems to maintain autophagy homeostasis. Meanwhile, tryptophan also reshaped the gut microbiota composition in LPS-challenge mice by increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria such as Acetivibrio (0.053 ± 0.017 to 0.21 ± 0.0041%). Notably, dietary tryptophan resulted in the activation of metabolic pathways during the inflammatory response. Furthermore, exogenous treatment of tryptophan metabolites kynurenine (Kyn) and 5-HT in porcine intestinal epithelial cells (IPEC-J2 cells) reproduced similar protective effects as tryptophan to attenuate LPS-induced intestinal inflammation through regulating the AMPK-SIRT1-autophagy. Taken together, the present study indicates that tryptophan exhibits intestinal protective and immunoregulatory effects resulting from the activation of metabolic pathways, maintenance of gut mucosal barrier integrity, microbiota composition, and AMPK-SIRT1-autophagy level.

• Authors: Nan Gao, Yang Yang, Siqi Liu, Chunyang Fang, Xiujing Dou, Licong Zhang, Anshan Shan
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 70 Issue 51 Pg. 16080-16095 (Dec 28 2022) ISSN: 1520-5118 [Electronic] United States
• PMID: 36521060 (Publication Type: Journal Article)

Chemical References

• Tryptophan
• Sirtuin 1
• AMP-Activated Protein Kinases
• Lipopolysaccharides
• Sirt1 protein, mouse

Topics

• Swine
• Mice
• Animals
• Tryptophan
• Sirtuin 1 (genetics, metabolism)
• AMP-Activated Protein Kinases (genetics, metabolism)
• Lipopolysaccharides
• Autophagy
• Inflammation (drug therapy, genetics, metabolism)
• Dietary Supplements