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Meta-Analysis
. 2025 May:89:103151.
doi: 10.1016/j.ctim.2025.103151. Epub 2025 Feb 22.

Oral probiotic supplementation to alleviate diarrhea induced by fluoropyrimidines or irinotecan-based chemotherapy: A systematic review and meta-analysis

Tippawan Siritientong  1 , Daylia Thet  2 , Nattawut Leelakanok  3 , Nutthada Areepium  4
Affiliations
Free article
Meta-Analysis

Oral probiotic supplementation to alleviate diarrhea induced by fluoropyrimidines or irinotecan-based chemotherapy: A systematic review and meta-analysis

Tippawan Siritientong et al. Complement Ther Med. 2025 May.
Free article

Abstract

Background: Fluoropyrimidines and irinotecan cause diarrhea, which can be particularly severe in some cases. Probiotic supplementation is a potential option for managing chemotherapy-induced diarrhea. This study aims to evaluate the efficacy and safety of probiotics in managing diarrhea induced by fluoropyrimidine or irinotecan-based chemotherapy in cancer patients.

Methods: A literature search was conducted in Cochrane Library, PubMed, ScienceDirect, SciFinder, and Scopus in August 2023. Observational and prospective studies of cancer patients receiving 5-fluorouracil, capecitabine, or irinotecan were included. RevMan (version 5.4.1) was used for statistical analysis. The study protocol was registered in PROSPERO.

Results: Of the 9400 records, 24 and 14 studies were included in the systematic review and meta-analysis, respectively. Most studies provided a combination of probiotic strains to patients from the initiation to the completion of chemotherapy cycles. Probiotic supplementation significantly reduced all grade diarrhea (RR = 0.40; 95 % CI: 0.27, 0.60; P < 0.00001, I2: 0 %), nausea and vomiting (RR = 0.49; 95 % CI [0.37, 0.67]; P < 0.00001, I2: 0 %), bloating (RR = 0.27; 95 % CI [0.11, 0.69]; P = 0.006, I2: 0 %) and anorexia (RR = 0.62: 95 % CI [0.43, 0.90]; P = 0.01, I2: 39 %) compared to controls. Absolute risk reductions (ARR) ranged from 22.7 % to 28.5 %, with the number needed to treat (NNT) value of 3-5. Moreover, probiotics improved intestinal microbial balance and symptom scales of quality of life.

Conclusions: Probiotic supplementation is a promising option to manage chemoradiotherapy-induced diarrhea without serious side effects in cancer patients receiving fluoropyrimidines or irinotecan-based regimens. Given the clinically meaningful ARR and favorable NNT values, probiotics may have a role in clinical practice. However, larger trials are needed to standardize probiotic strain, dosage, duration, and target patient subgroups.

Systematic review registration: PROSPERO database (CRD42023473324).

Keywords: 5-fluorouracil; Capecitabine; Chemotherapy-induced diarrhea; Irinotecan; Probiotics.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

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