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



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+ CD44low) 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.


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.


Our results suggest that d-serine not only can prevent, but also has efficacious effects as a treatment for IBD.

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We acknowledge the IMSUT FACS Core laboratory for assistance with cell sorting and Techno-Suruga Laboratory Co., Ltd. (Sizuoka, Japan) for microbiome analysis. We thank Bao Duong for editing a draft of this manuscript. This work was supported by JSPS KAKENHI (JP17H04024, JP17K19675, JP19H01050).

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Authors and Affiliations



TA planned, performed majority of the experiments and wrote the manuscript. MO performed the initial experiments, wrote the manuscript and directed the research. CS, RH, DY, AM, TM and SA performed the experiments. YK, SO, TN, KT, HO and RO planned the experiments and provided technical assistance. MW directed the research.

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Correspondence to Michio Onizawa or Mamoru Watanabe.

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The authors have declared that no competing interests exist.

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Asakawa, T., Onizawa, M., Saito, C. et al. Oral administration of d-serine prevents the onset and progression of colitis in mice. J Gastroenterol 56, 732–745 (2021).

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  • Mouse IBD model
  • Colitis
  • d-amino acids
  • d-serine