Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review.

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Metabolites Pub Date : 2025-06-18 DOI:10.3390/metabo15060412
Ielmina Domilescu, Bogdan Miutescu, Florin George Horhat, Alina Popescu, Camelia Nica, Ana Maria Ghiuchici, Eyad Gadour, Ioan Sîrbu, Delia Hutanu
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引用次数: 0

Abstract

Background and objectives: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC).

Methods: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous.

Results: Twelve studies (n = 1354 unique patients, median sample = 73, range 22-735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a "butyrate-rich" baseline profile was 44% (95% CI 35-54) versus 21% (95% CI 15-29) in controls (I2 = 18%).

Conclusions: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment.

肠道微生物特征预测局部晚期直肠癌对新辅助放化疗的反应:一项系统综述。
背景和目的:直肠癌的治疗越来越依赖于新辅助放化疗(nCRT)后的观察和等待策略。准确的、无创的病理完全反应(pCR)预测仍然难以捉摸。新出现的证据表明,肠道微生物组成调节放射化学敏感性。我们系统地回顾了将局部晚期直肠癌(LARC)的基线或治疗期间肠道微生物组特征与nCRT反应相关的初步研究。方法:检索自成立至2025年4月30日的MEDLINE、Embase和PubMed。资格要求:(i) LARC的前瞻性或回顾性人体研究,(ii)通过16S、宏基因组学或宏转录组学分析粪便或粘膜微生物组,以及(iii)使用肿瘤消退等级或pCR进行反应评估。在数据均质的情况下进行叙事综合和随机效应比例荟萃分析。结果:12项研究(n = 1354例独特患者,中位数样本= 73,范围22-735)符合纳入。四个独立的机器学习模型实现了受试者工作特征曲线下面积AUROC≥0.85的pCR预测。在应答者中持续富集的分类群包括毛螺杆菌科细菌、蓝芽孢杆菌、Roseburia spp和产丁酸肠单胞菌。无应答者显示出核梭杆菌、脆弱拟杆菌和普雷沃氏菌的过度代表。两项研究将丁酸盐产生模块与辐射敏感性联系起来,而核苷酸生物合成途径则赋予了抗性。“富含丁酸盐”基线谱患者的聚合pCR率为44% (95% CI 35-54),对照组为21% (95% CI 15-29) (I2 = 18%)。结论:尽管存在异质性,但趋同的功能和分类信号支撑着LARC中基于微生物组的放射敏感性轴。在临床应用之前,需要进行多中心验证队列和干预试验,如益生元或活体生物治疗药物。
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来源期刊
Metabolites
Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
5.70
自引率
7.30%
发文量
1070
审稿时长
17.17 days
期刊介绍: Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.
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