Evidence map›Paper›PMID 38742466›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Gut Microbiota-Derived 3-Hydroxybutyrate Blocks GPR43-Mediated IL6 Signaling to Ameliorate Radiation Proctopathy.

Zhenhuang Ge, Chun Chen, Junyi Chen, Zhou Jiang, Lingming Chen, Yingqi Wei, Haiyang Chen, Lei He, Yi Zou, Xiaoxuan Long and 4 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

27 citing papers in PubMed.

  1. Gut microbes · 2026
    Article
  2. Article
  3. Metabolic Engineering of ProbioticFoods (Basel, Switzerland) · 2026
    Article
  4. Article
  5. Review
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  18. Acta pharmaceutica Sinica. B · 2025
    Article
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  20. Review
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.

Zhenhuang GeRun Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Chun ChenDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Junyi ChenRun Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Zhou JiangRun Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Lingming ChenSchool of Medical Technology, Guangdong Medical University, Dongguan, 523808, China.
Yingqi WeiDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Haiyang ChenDepartment of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Lei HeAffiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, China.
Yi ZouRun Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Xiaoxuan LongRun Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Hongyu ZhanRun Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
Huaiming WangDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Hui WangDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Yongjun LuRun Ze Laboratory for Gastrointestinal Microbiome Study, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.ORCID 0000-0002-3030-5724

Funding

Guang Dong Cheung Kong Philanthropy Foundation E2018096Guangdong key areas R & D projects 2018B020205002Guangdong key areas R & D projects 202206080008National Natural Science Foundation of China 82103084Sun Yat-sen University Clinical Research 5010 Program 2019021The Project of The State Key Laboratory of Respiratory Disease SKLRD-Z-202008
6 · The paper itself

Abstract

Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota-derived 3-hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6-mediated radiation damage. Irradiated cell-fecal microbiota co-culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43-mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut-immune axis in radiation pathophysiology, with potential therapeutic applications.

Indexed as

3-Hydroxybutyric AcidGastrointestinal MicrobiomeInterleukin-6Receptors, G-Protein-CoupledSignal TransductionAkkermansiaAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLProctitisRadiation Injuries3-Hydroxybutyric AcidFfar2 protein, mouseInterleukin-6Receptors, G-Protein-Coupled3HBakkermansia muciniphilaGPR43IL6radiation proctopathyradioprotection

Identifiers

PMID38742466
PMCPMC11267371

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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.