Evidence map›Paper›PMID 42275581›Full record

ArticleHepatology communications2026

Gut microbiota-derived indole-3-propionic acid alleviates endoplasmic reticulum stress by regulating FMO2 in MASLD.

Yue Luo, Yuefeng Zhang, Qian Zhang, Xiaohan Li, Kaiwei Cai, Yaning Xu, Ruirui Zhao, Saixuan Zhang, Xinyu Bai, Haopeng Chen and 4 more

Abstract read
In one paragraph

Article in Hepatology communications, 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
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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

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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

14 authors.

Yue LuoSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0009-0001-4458-7101
Yuefeng ZhangSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0000-0002-1536-9359
Qian ZhangSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0000-0002-5652-1345
Xiaohan LiSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0009-0000-5835-5101
Kaiwei CaiSchool of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China.ORCID 0009-0001-8926-4437
Yaning XuSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0009-0007-0497-7969
Ruirui ZhaoSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0009-0008-3073-4845
Saixuan ZhangSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0009-0003-8150-7558
Xinyu BaiSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0009-0002-9117-5684
Haopeng ChenSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0009-0009-3887-3695
Hao LiSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0000-0003-1661-7139
Yanjun HongSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0000-0003-3059-8130
Qiongfeng LiaoSchool of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, China.ORCID 0009-0005-2684-5129
Zhiyong XieSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.ORCID 0000-0001-8578-3275

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) has become a global health challenge for which there are currently no approved drugs. Indole-3-propionic acid (IPA), as one of the primary metabolites of gut microbiota, can influence the development of liver diseases through the gut-liver axis, but how it contributes to liver diseases remains unclear. The present study was conducted to explore the possible molecular mechanisms of IPA in the development of MASLD.

methodsMetabolomic analysis compared serum and fecal metabolite profiles between MASLD and normal mice. The effects of microbial metabolite IPA on MASLD were evaluated through the utilization of a mouse model and cell models. Transcriptome data analysis was used, and further validation was conducted through flow cytometry, western blotting, RNA interference, and immunoprecipitation.

resultsSerum and fecal IPA levels in high-fat diet-fed mice were significantly decreased compared with those of normal chow diet-fed mice. IPA supplementation reduced hepatic lipid accumulation and alleviated insulin resistance, liver damage, and steatosis development in high-fat diet-fed mice, while gut microbiota dysbiosis was restored. Mechanistic analysis suggested that IPA promoted FMO2 expression, enhancing the interaction between FMO2 and protein kinase R-like endoplasmic reticulum kinase (PERK) and inhibiting the PERK/eIF2α/ATF4/CHOP signaling cascade, then mitigating endoplasmic reticulum (ER) stress, such as reducing hepatocyte apoptosis and reactive oxygen species levels, ultimately improving MASLD.

conclusionsIPA can promote the expression of FMO2, which binds to PERK within the ER of hepatocytes. This binding process inhibits the phosphorylation of PERK, thereby affecting PERK-mediated ER stress, and subsequently leading to a reduction in hepatocyte apoptosis and oxidation. This study puts forward the IPA/FMO2/PERK axis as a potential therapeutic target in ER stress for MASLD.

Indexed as

Endoplasmic Reticulum StressFatty LiverGastrointestinal MicrobiomeIndolesOxygenasesPropionatesActivating Transcription Factor 4AnimalsApoptosisDiet, High-FatDisease Models, AnimaleIF-2 KinaseHepatocytesLiverMaleMiceActivating Transcription Factor 4dimethylaniline monooxygenase (N-oxide forming)eIF-2 Kinaseindolepropionic acidIndolesOxygenasesPropionatesFMO2gut microbiota metaboliteliver diseaseoxidative stressPERK/eIF2α/ATF4/CHOP

Identifiers

PMID42275581
PMCPMC13263094

What Socratic holds

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Registered trials

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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 Socratic graph.