Evidence map›Paper›PMID 40285661›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

β-Glucuronidase-Expressing Lactobacillus reuteri Triggers Irinotecan Enterotoxicity Through Depleting the Regenerative Epithelial Stem/Progenitor Pool.

Bei Yue, Ruiyang Gao, Ling Zhao, Donghui Liu, Cheng Lv, Ziyi Wang, Fangbin Ai, Beibei Zhang, Zhilun Yu, Xiaolong Geng and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
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  8. Article
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

16 authors.

Bei YueThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Ruiyang GaoThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Ling ZhaoSchool of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Donghui LiuThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Cheng LvCentre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong, SAR, China.
Ziyi WangThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Fangbin AiThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Beibei ZhangThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Zhilun YuThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Xiaolong GengThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Hao WangThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Kang WangThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Kaixian ChenThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Chenghai LiuDepartment of Hepatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Zhengtao WangThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Wei DouThe MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.ORCID https://orcid.org/0000-0001-6831-2893

Funding

National Natural Science Foundation of China 82130115National Natural Science Foundation of China 82274329National Natural Science Foundation of China 82304991Shanghai Science and Technology Committee Sailing Program Foundation 23YF1442500
6 · The paper itself

Abstract

Irinotecan (CPT11)-induced diarrhea affects 80-90% of cancer patients due to β-glucuronidase (GUS) converting 7-ethyl-10-hydroxycamptothecin glucuronide (SN38G) to 7-ethyl-10-hydroxycamptothecin (SN38). It remains unclear whether SN38 impacts the homeostasis between gut microbiota and mucosal stem cell niche. This study explores the crosstalk between gut microbiota and intestinal stem cells (ISCs) in intestinal mucositis triggered by CPT11 chemotherapy. CPT11-treated mice exhibited significant colon shortening, inflammatory infiltration, intestinal barrier dysfunction, and ISC impairment, which correlated with gut dysbiosis, enrichment of GUS-expressing bacteria, and intraluminal SN38 accumulation. In contrast, antidiarrheal (Xianglian pill) treatment alleviated SN38-induced enterotoxicity and reduced GUS-expressing bacterial populations. Microbiome profiling of clinical patients and mucositis mice revealed a strong correlation between CPT11/SN38 enterotoxicity and GUS-expressing bacteria, particularly Lactobacillus reuteri. PLS-PM modeling further linked L. reuteri to impaired epithelial regeneration, which is validated using a 3D intestinal organoid model. L. reuteri hindered ISC differentiation into secretory lineages within the organoids. Furthermore, L. reuteri colonization in mice exacerbated mucositis and disrupted epithelial differentiation, while its elimination ameliorated colitis symptoms and preserved crypt cell stemness. These findings suggest that selectively targeting GUS-expressing bacteria, particularly L. reuteri, to protect the regenerative epithelial stem/progenitor pool may serve as an effective strategy for mitigating CPT11-induced enterotoxicity.

Indexed as

GlucuronidaseIrinotecanLimosilactobacillus reuteriStem CellsAnimalsDiarrheaFemaleGastrointestinal MicrobiomeHumansIntestinal MucosaMaleMiceMucositisGlucuronidaseIrinotecanepithelial regenerationGUS‐expressing bacteriairinotecan‐induced intestinal toxicitylactobacillus reuteriXianglian pill

Identifiers

PMID40285661
PMCPMC12245021

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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 OpenQuestion graph.