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ResearchIn-Press PreviewGastroenterologyMicrobiology Open Access | 10.1172/JCI196788

Colonic Engyodontium fungus triggers neutrophil antimicrobial activity to suppress Lactobacillus johnsonii-derived glutamic acid-maintained Tregs

Xinying Wang,1 Haiyang Sun,2 Ying Tan,2 Shaoting Xu,2 Zishan Liu,1 Kaile Ji,2 Ding Qiu,2 Jianping Deng,2 Bingbing Feng,2 Xueting Wu,1 Yoichiro Iwakura,3 Minhu Chen,1 Rui Feng,1 Chanyan Huang,4 and Ce Tang1

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Wang, X. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Sun, H. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Tan, Y. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Xu, S. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Liu, Z. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Ji, K. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Qiu, D. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Deng, J. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Feng, B. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Wu, X. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Iwakura, Y. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Chen, M. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Feng, R. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Huang, C. in: PubMed | Google Scholar

1Department of Gastroenterology and Hepatology, Sun Yat-sen University, Guangzhou, China

2Institute of Precision Medicine, Sun Yat-sen University, Guangzhou, China

3Center for Animal Disease Models, Tokyo University of Science, Noda, Japan

4Department of Anesthesiology, Sun Yat-sen University, Guangzhou, China

Find articles by Tang, C. in: PubMed | Google Scholar

Published March 2, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI196788.
Copyright © 2026, Wang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 2, 2026 - Version history
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Abstract

Isolating commensal fungi from mouse intestines has been challenging, limiting our understanding of their role in intestinal immune homeostasis and diseases. Using an Fc fusion protein of the C-type lectin Dectin-2, we successfully purified the commensal Ascomycota fungus Engyodontium sp. from mouse feces. Engyodontium enhances the antimicrobial activity of colonic neutrophils via CARD9 pathway, and exacerbates colitis by impairing the colonization of intestinal Lactobacillus johnsonii (L. johnsonii) WXY strain. L. johnsonii produces high levels of L-glutamic acid by expressing the glutaminase-encoding gene glsA to facilitate Treg expansion via enhancing IL-2 receptor signaling. Patients with Crohn’s disease (CD) and ulcerative colitis harbored increased Engyodontium and decreased L. johnsonii abundance. Engyodontium directly induced calprotectin in human colonic neutrophils, and CD patients exhibited lower levels of L-glutamic acid which also promoted human Treg expansion. These findings highlight the Engyodontium-calprotectin axis against the Lactobacillus-glutamate-Treg cascade to aggravate colitis, suggesting commensal Engyodontium-triggered signaling as a therapeutic target for mucosal inflammatory diseases.

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