| Autor: |
Xuehua Li, Shixian Hu, Xiaodi Shen, Ruonan Zhang, Caiguang Liu, Lin Xiao, Jinjiang Lin, Li Huang, Weitao He, Xinyue Wang, Lili Huang, Qingzhu Zheng, Luyao Wu, Canhui Sun, Zhenpeng Peng, Minhu Chen, Ziping Li, Rui Feng, Yijun Zhu, Yangdi Wang, Zhoulei Li, Ren Mao, Shi-Ting Feng |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
EMBO Molecular Medicine, Vol 16, Iss 10, Pp 2427-2449 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1757-4684 |
| DOI: |
10.1038/s44321-024-00129-8 |
| Popis: |
Abstract Intestinal fibrosis is the primary cause of disability in patients with Crohn’s disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g., Lachnospiraceae, Ruminococcaceae, Muribaculaceae, Saccharimonadales) and metabolites (e.g., L-aspartic acid, glutamine, ethylmethylacetic acid) in moderate-severe intestinal fibrosis. By integrating multiomics data with magnetic resonance enterography features, putative links between microbial metabolites and intestinal fibrosis-associated morphological alterations were established. These potential associations were mediated by specific combinations of amino acids (e.g., L-aspartic acid), primary bile acids, and glutamine. Finally, we provided causal evidence that L-aspartic acid aggravated intestinal fibrosis both in vitro and in vivo. Overall, we offer a biologically plausible explanation for the hypothesis that gut microbiota and its metabolites promote intestinal fibrosis in CD while also identifying potential targets for therapeutic trials. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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