Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May;66(10):e2100955.
doi: 10.1002/mnfr.202100955. Epub 2022 Mar 20.

Alpha-Ketoglutarate Attenuates Colitis in Mice by Increasing Lactobacillus Abundance and Regulating Stem Cell Proliferation via Wnt-Hippo Signaling

Xuemeng Si  1 , Hai Jia  1 , Ning Liu  1   2 , Jun Li  1 , Lina Pan  3 , Jiaqi Wang  3 , Zhenlong Wu  1   2
Affiliations

Alpha-Ketoglutarate Attenuates Colitis in Mice by Increasing Lactobacillus Abundance and Regulating Stem Cell Proliferation via Wnt-Hippo Signaling

Xuemeng Si et al. Mol Nutr Food Res. 2022 May.

Abstract

Scope: Inflammatory bowel disease is an inflammatory gastrointestinal disorder associated with intestinal barrier damage, cell proliferation disorder, and dysbiosis of the intestinal microbiota. It remains unknown whether alpha-ketoglutarate (α-KG) can alleviate colitis in mice.

Methods and results: Six-week-old male C57BL/6 mice supplemented with or without 0.5% α-KG (delivered in the form of sodium salt) are subjected to drinking water or 2.5% DSS to induce colitis. The results show that α-KG administration is attenuated the severity of colitis, as is indicated by reduced body-weight loss, colon shortening and colonic hyperplasia, and repressed proinflammatory cytokine secretion in DSS-challenged mice. Additionally, DSS-induced increases in malondialdehyde (MDA) and hydrogen peroxide (H2 O2 ), and decreases in glutathione (GSH) levels are attenuated by α-KG administration. Further study shows that the protective effect of α-KG is associated with restoring gut barrier integrity by enhancing the expression of tight junction proteins, increasing Lactobacillus levels, and regulating gut hyperplasia by the Wnt-Hippo signaling pathway in DSS-induced colitis.

Conclusion: Collectively, the data provided herein demonstrate that α-KG administration is attenuated mucosal inflammation, barrier dysfunction, and gut microflora dysbiosis. This beneficial effect is associated with increased Lactobacillus levels and regulated colon hyperplasia by the Wnt-Hippo signaling pathway.

Keywords: DSS-induced colitis; Lactobacillus; Wnt/β-catenin-Hippo signaling; alpha-ketoglutarate; intestinal stem cell.

PubMed Disclaimer

References

    1. S. C. Ng, H. Y. Shi, N. Hamidi, F. E. Underwood, W. Tang, E. I. Benchimol, R. Panaccione, S. Ghosh, J. C. Y. Wu, F. K. L. Chan, J. J. Y. Sung, G. G. Kaplan, Lancet 2017, 390, 2769.
    1. M. F. Neurath, Nat. Immunol. 2019, 20, 970.
    1. T. Kobayashi, B. Siegmund, C. Le Berre, S. C. Wei, M. Ferrante, B. Shen, C. N. Bernstein, S. Danese, L. Peyrin-Biroulet, T. Hibi, Nat. Rev. Dis. Primers 2020, 6, 74.
    1. E. A. Franzosa, A. Sirota-Madi, J. Avila-Pacheco, N. Fornelos, H. J. Haiser, S. Reinker, T. Vatanen, A. B. Hall, H. Mallick, L. J. McIver, J. S. Sauk, R. G. Wilson, B. W. Stevens, J. M. Scott, K. Pierce, A. A. Deik, K. Bullock, F. Imhann, J. A. Porter, A. Zhernakova, J. Fu, R. K. Weersma, C. Wijmenga, C. B. Clish, H. Vlamakis, C. Huttenhower, R. J. Xavier, Nat. Microbiol. 2019, 4, 293.
    1. T. Hibi, H. Ogata, J. Gastroenterol. 2006, 41, 10.

Publication types

LinkOut - more resources