Review for 10.1186/s12876-025-03914-y (2025)

Title: Evaluation of the efficacy of probiotics in the chemoradiotherapy of colorectal cancer#a
meta-analysis of Randomized Controlled Trials
Version: 3 Date: 10 Mar 2025
Reviewer's report:
This paper presents a comprehensive meta-analysis evaluating the efficacy of probiotics in
mitigating adverse effects during chemoradiotherapy for colorectal cancer. The study is well-
structured and contributes valuable insights to the field; however, several areas require further
clarification and revision. Below are key points that should be addressed to enhance the scientific
rigor and clarity of the manuscript.
Elaboration on the Molecular Mechanisms of Probiotic Action
The Background section provides a broad discussion of probiotics' anti-tumor effects across
various cancer types. However, the manuscript lacks a detailed explanation of the molecular
and cellular mechanisms underlying these effects. The authors should consider incorporating
a discussion on how probiotics modulate immune responses, influence gut microbiota
composition, and affect metabolic pathways that contribute to tumor suppression. Including
references to key signaling pathways such as NF-#B inhibition, apoptosis induction, and immune
checkpoint modulation would strengthen the scientific basis of the study.
Refinement of Repetitive Terminology
The phrase "The administration of probiotics" appears frequently throughout the manuscript.
To improve readability and avoid redundancy, alternative expressions such as "probiotic
supplementation," "probiotic intervention," or "probiotic intake" should be employed where
appropriate. Additionally, restructuring some sentences to reduce repetition would enhance the
overall flow of the text.
Clarification of Chemoradiotherapy Regimens
While the manuscript provides details on the chemotherapy and radiotherapy protocols used in
the included studies, there is limited discussion on how variations in treatment regimens might
affect the outcomes of probiotic intervention. Were there significant differences in response
to probiotics based on the specific chemotherapeutic agents or radiation doses? A stratified
analysis, if available, would provide more nuanced insights into the effectiveness of probiotics
in different treatment contexts.
Discussion on Heterogeneity Among Included Studies
The meta-analysis includes studies with different probiotic strains, dosages, and administration
durations, which could introduce heterogeneity into the results. While statistical heterogeneity
is briefly mentioned, a more in-depth discussion on the potential clinical implications of these
variations is warranted. Were specific probiotic strains more effective than others? Did the
duration of probiotic administration influence outcomes? Addressing these questions would
improve the interpretability of the findings.
Clarification of Quality of Life (QOL) Assessment
The manuscript states that probiotics did not significantly improve quality of life (QOL)
in colorectal cancer patients undergoing chemoradiotherapy. However, it is unclear whether
differences in QOL assessment tools among studies influenced this result. Did all studies
use the same validated QOL questionnaire, such as EORTC QLQ-C30? If not, how was
data harmonization achieved for meta-analysis? Providing this clarification would enhance the
credibility of the conclusions regarding QOL outcomes.