Oral administration of d-serine prevents the onset and progression of colitis in mice

• Published in: Journal of gastroenterology Vol. 56; no. 8; pp. 732 - 745
• Main Authors: Asakawa, Takehito, Onizawa, Michio, Saito, Chikako, Hikichi, Rie, Yamada, Daiki, Minamidate, Ai, Mochimaru, Tomoaki, Asahara, Shun-ichiro, Kido, Yoshiaki, Oshima, Shigeru, Nagaishi, Takashi, Tsuchiya, Kiichiro, Ohira, Hiromasa, Okamoto, Ryuichi, Watanabe, Mamoru
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.08.2021; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Amino acids; Analysis; Animal models; CD4 antigen; Cell activation; Cell differentiation; Cell proliferation; Colitis; Colorectal Surgery; D-Amino acids; D-Serine; Enantiomers; Gastroenterology; Gastrointestinal diseases; Helper cells; Hepatology; Inflammatory bowel disease; Inflammatory bowel diseases; L-Serine; Lamina propria; Lymphocytes T; Medicine; Medicine & Public Health; Oral administration; Original Article—Alimentary Tract; Prevention; RAG2 protein; Serine; Surgical Oncology; T cells; Mouse IBD model; serine; Colitis; amino acids
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-021-01792-1

Background l -amino acids are the predominant forms of organic molecules on the planet, but recent studies have revealed that various foods contain d -amino acids, the enantiomers of l -amino acids. Though diet plays important roles in both the development and progression of inflammatory bowel disease (IBD), to our best knowledge, there has been no report on any potential interactions between d -amino acids and IBD. In this report, we aim to assess the effects of d -serine in a murine model of IBD. Materials and methods To induce chronic colitis, naïve CD4 T cells (CD4 + CD62 + CD44 low ) from wild-type mice were adoptively transferred into Rag2 −/− mice, after or before the mice were orally administered with d -serine. In vitro proliferation assays were performed to assess naïve CD4 T cell activation under the Th-skewing conditions in the presence of d -serine. Results Mice treated with d -serine prior to the induction of colitis exhibited a reduction in T-cell infiltration into the lamina propria and colonic inflammation that were not seen in mice fed with water alone or l -serine. Moreover, d -serine suppressed the progression of chronic colitis when administered after the disease induction. Under in vitro conditions, d -serine suppressed the proliferation of activated CD4 T cells and limited their ability to differentiate to Th1 and Th17 cells. Conclusion Our results suggest that d -serine not only can prevent, but also has efficacious effects as a treatment for IBD.