Evidence map›Paper›PMID 40624638›Full record

ArticleBMC medicine2025

Mitigation of chemotherapy-induced gut dysbiosis and diarrhea by supplementation with heat-killed Bacteroides fragilis.

Xinwen Yan, Xinlong Lin, Jianhua Wu, Lijun Zheng, Yangyang Liu, Fang Wu, Ying Lin, Yishi Lu, Chongyang Huang, Binhai Shen and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

23 authors.

Xinwen Yan *Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Xinlong Lin *Guangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Jianhua WuDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Lijun ZhengGuangzhou ZhiYi Biotechnology Co. Ltd, Guangzhou, 510530, China.
Yangyang LiuGuangzhou ZhiYi Biotechnology Co. Ltd, Guangzhou, 510530, China.
Fang WuDepartment of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Ying LinGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Yishi LuGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Chongyang HuangGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Binhai ShenGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Hongbin LiuGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Ruo HuangGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Fengyi HouGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Qian ZhouGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Mengyao SongGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Ke LiuGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Fangqing ZhuGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Sheng LiGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Yuqing LinGuangzhou ZhiYi Biotechnology Co. Ltd, Guangzhou, 510530, China.
Wei WangGuangzhou ZhiYi Biotechnology Co. Ltd, Guangzhou, 510530, China.
Ping LiGuangzhou ZhiYi Biotechnology Co. Ltd, Guangzhou, 510530, China.
Wangjun LiaoDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. nfyylwj@163.com.
Fachao ZhiGuangdong Provincial Key Laboratory of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. zhifc41532@163.com.

Funding

Innovation Leading Team Project in Guangzhou NO. 201809010014Key Technology Project in Guangzhou NO.2024B03J1282Study on the Mechanism of FUT7 regulating CD15s+eTreg cells in the Pathogenesis of Ulcerative Colitis Y20190159
6 · The paper itself

Abstract

backgroundThe role of gut microbial dysbiosis in chemotherapy-induced diarrhea (CID) pathogenesis remains unclear in humans. This study investigates gut microbiota alterations in CID patients and evaluates the therapeutic potential of probiotic supplementation.

methodsTo establish a paired cohort for longitudinal comparison and minimize confounding factors in assessing CID-related microbiota changes, strict inclusion/exclusion criteria were applied to gastrointestinal cancer patients. Fecal samples from eligible participants underwent shotgun metagenomic sequencing to comprehensively profile the gut microbiome composition and function. To evaluate probiotic efficacy and mechanisms, we utilized 6-8-week-old male BALB/c and C57BL/6 mice in established 5-FU- or CPT-11-induced CID models. Probiotic efficacy was assessed using primary (diarrhea severity) and secondary endpoints (body weight change, intestinal permeability). Mechanistic studies were conducted in murine models, complemented by IEC-6 cells and intestinal organoid experiments to elucidate microbiota-host interactions.

resultsAnalysis of paired fecal samples (pre- and post-chemotherapy) from 30 gastrointestinal cancer patients (n = 60) revealed chemotherapy-induced reduction of Bacteroides fragilis (B. f) via metagenomics sequencing, with baseline B. f relative abundance negatively correlating with CID severity (r =  - 0.93, p = 3.1e - 12). Building on these clinical observations, in 5-FU/CPT-11-induced CID murine models, oral gavage of heat-killed B. f (hk-B. f) outperformed live bacteria in diarrhea alleviation. Mechanistically, B. f-derived succinate exacerbated diarrhea, while its capsular polysaccharide (PSA) ameliorated mice diarrhea. This discovery explains the discrepant therapeutic effect between hk-B. f and live B. f. Fluorescence tracing confirmed hk-B. f transiently localized to the upper gastrointestinal tract without extraintestinal colonization. hk-B. f preserved epithelial integrity, mitochondrial function, and intestinal organoid development (higher budding count and larger organoid surface area). Moreover, hk-B. f upregulated the expression of BCL2 and downregulated the expression of BAX. Shifting the balance between BCL2 and BAX alleviates intestinal epithelial apoptosis. Caspase-3 inhibition or BCL2 silencing abrogated hk-B. f's anti-apoptotic effects in IEC-6 cells.

conclusionsPathological process of CID can be partially explained by compositional alterations in the gut microbiota. Supplementation with hk-B. f reduces 5-FU-stimulated epithelial injury through mitochondrial apoptotic pathway in CID murine models. These preclinical findings suggest hk-B. f merits further investigation as a potential strategy for improving CID, pending clinical validation.

Indexed as

Antineoplastic AgentsBacteroides fragilisDiarrheaDysbiosisGastrointestinal MicrobiomeProbioticsAgedAnimalsFecesFemaleFluorouracilHumansMaleMiceMice, Inbred BALB CMice, Inbred C57BLAntineoplastic AgentsFluorouracilApoptosisBacteroides fragilisChemotherapyDiarrheaMitochondriaProbiotics

Identifiers

PMID40624638
PMCPMC12235877

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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.