Evidence map›Paper›PMID 42430494›Full record

ArticleScience advances2026

p38 MAP kinase senses short-chain fatty acids to attenuate Toll-like receptor signaling and intestinal inflammation.

Qingang Wu, Rongkai Shi, Liwei Xiao, Xuxiao He, Zhuoneng Chen, Hong Zhao, Junwei Liu, Shudi Luo, Xiaoming Jiang, Dong Guo and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Qingang WuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.ORCID 0000-0002-6928-6268
Rongkai ShiZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Liwei XiaoZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.ORCID 0000-0001-6971-9222
Xuxiao HeZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Zhuoneng ChenDepartment of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.ORCID 0000-0001-6984-1383
Hong ZhaoZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.ORCID 0000-0003-4571-6443
Junwei LiuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Shudi LuoZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Xiaoming JiangZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Dong GuoZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.ORCID 0000-0001-7057-2838
Ying MengZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.ORCID 0000-0002-1165-9009
Rongxuan ZhuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Shan LiZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.ORCID 0000-0002-2146-2453
Min LiZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Guijun LiuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Suyao LiZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Qingqing YangZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.
Zhe ShenDepartment of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China.ORCID 0000-0003-0604-7558
Zhimin LuZhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.ORCID 0000-0002-2859-2736

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Toll-like receptor (TLR) signaling is critical for innate immune system. However, whether it is directly modulated by microbiota-derived metabolites remains unclear. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate suppress TLR signaling by directly binding p38α MAP kinase, promoting its interaction with TAB1, thereby activating p38α via autophosphorylation. Activated p38α then phosphorylates TRAF3 at serine 85, inhibiting K63-linked polyubiquitylation of TRAF3 and disrupting TBK1-IRF3 activation, leading to reduced macrophage activation and intestinal inflammation. In ulcerative colitis patients, fecal levels of propionate and butyrate positively correlate with p38α activity and TRAF3 S85 phosphorylation, but inversely correlate with TBK1 activation, and cytokine levels. Notably, oral administration of propionate in three patients with ulcerative colitis markedly improved intestinal inflammation and clinical symptoms. These findings reveal p38α as a direct sensor for microbiota-derived SCFAs that suppress TLR signaling through nonmetabolic functions of propionate and butyrate, providing the first clinical evidence that propionate supplementation represents a practical dietary strategy for ulcerative colitis management.

Indexed as

Fatty Acids, VolatileInflammationp38 Mitogen-Activated Protein KinasesSignal TransductionToll-Like ReceptorsAnimalsButyratesColitis, UlcerativeFemaleHumansIntestinesMaleMicePhosphorylationPropionatesTNF Receptor-Associated Factor 3ButyratesFatty Acids, Volatilep38 Mitogen-Activated Protein KinasesPropionatesTNF Receptor-Associated Factor 3Toll-Like Receptors

Identifiers

PMID42430494
PMCPMC13353425

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.