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Background <p>The gut microbiome is increasingly recognized as a modulator of cancer therapy outcomes and a potential predictive biomarker. This systematic review synthesizes current evidence on microbial biomarkers associated with neoadjuvant treatment (NT) response in rectal cancer (RC).</p> Methods <p>PubMed, Embase, and Ovid Medline databases were searched through March 2025. Eligible studies included RC patients treated with NT with baseline microbial analysis stratified by treatment response. Two reviewers independently performed screening, data extraction, and quality assessment (NIH and STORMS tools). Due to substantial heterogeneity, a structured qualitative synthesis without meta-analysis was conducted following SWiM guidelines, using a direction-of-effect vote-counting approach.</p> Results <p>Sixteen observational studies (842 patients) were included, covering chemoradiotherapy (nCRT), total neoadjuvant therapy, chemotherapy, and immunochemoradiotherapy. Microbiota composition was investigated by 16S rRNA sequencing, metagenomics, or metatranscriptomics on fecal or tissue samples. While microbial diversity showed inconsistent associations, specific taxa&#xa0;-notably <i>Bacteroides</i>, <i>Fusobacterium</i> and <i>Akkermansia</i>- emerged as recurrent biomarkers of poor response to nCRT. Twelve predictive models reported AUROC values from 0.73 to 0.97, with limited external validation.</p> Conclusions <p>Specific microbial taxa show a consistent association with nCRT resistance across independent cohorts. However, methodological heterogeneity and limited reproducibility warrant standardized prospective validation before clinical implementation. PROSPERO: CRD42023433704.</p>

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Gut microbiota-associated predictors as biomarkers of neoadjuvant treatment response in rectal cancer-a systematic review

  • 期刊论文

  • 发表日期：

    2026年4月13日

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  • Astghik Stepanyan,
  • Andromachi Kotsafti,
  • Antonio Rosato,
  • Ignazio Castagliuolo,
  • Marco Scarpa,
  • Melania Scarpa,
  • Marco Agostini,
  • Imerio Angriman,
  • Michele Antoniutti,
  • Quoc Riccardo Bao,
  • Andrea Baldo,
  • Mattia Barbareschi,
  • Romeo Bardini,
  • Giulia Becherucci,
  • Francesca Bergamo,
  • Giovanni Bertalot,
  • Giovanni Bordignon,
  • Stefano Brignola,
  • Alberto Brolese,
  • Marco Brolese,
  • Gianluca Businello,
  • Gianluca Buzzi,
  • Michela Campi,
  • Salvatore Candioli,
  • Giulia Capelli,
  • Ivana Cataldo,
  • Francesco Cavallin,
  • Lavinia Ceccarini,
  • Carlotta Ceccon,
  • Chiara Cipollari,
  • Valentina Chiminazzo,
  • Roberto Cola,
  • Corrado Da Lio,
  • Luca Dal Santo,
  • Antonella D’Angelo,
  • Ottavia De Simoni,
  • Angelo Paolo Dei Tos,
  • Barbara Di Camillo,
  • Loretta Di Cristofaro,
  • Luca Facci,
  • Matteo Fassan,
  • Boris Franzato,
  • Laura Gavagna,
  • Mario Godina,
  • Dario Gregori,
  • Mario Guerrieri,
  • Silvio Guerriero,
  • Vincenza Guzzardo,
  • Licia Laurino,
  • Francesco Marchegiani,
  • Isacco Maretto,
  • Laura Marinelli,
  • Marco Massani,
  • Roberto Merenda,
  • Isabella Mondi,
  • Silvia Negro,
  • Giulia Noaro,
  • Monica Ortenzi,
  • Dario Parini,
  • Valerio Pellegrini,
  • Alessandra Piccioli,
  • Pierluigi Pilati,
  • Giovanni Pirozzolo,
  • Andrea Porzionato,
  • Giuseppe Portale,
  • Anna Pozza,
  • Giulia Pozza,
  • Daniela Prando,
  • Salvatore Pucciarelli,
  • Alfonso Recordare,
  • Fabio Ricagna,
  • Giorgio Rivella,
  • Chiara Romiti,
  • Cesare Ruffolo,
  • Luca Saadeh,
  • Beatrice Salmaso,
  • Roberta Salmaso,
  • Antonio Scapinello,
  • Federico Scognamiglio,
  • Gaya Spolverato,
  • Ylenia Camilla Spolverato,
  • Tommaso Stecca,
  • Giovanni Tagliente,
  • Monica Tomassi,
  • Umberto Tedeschi,
  • Gaia Tussardi,
  • Chiara Vignotto,
  • Daunia Verdi,
  • Vittorina Zagonel,
  • Maurizio Zizzo,
  • Matteo Zuin

摘要

Background

The gut microbiome is increasingly recognized as a modulator of cancer therapy outcomes and a potential predictive biomarker. This systematic review synthesizes current evidence on microbial biomarkers associated with neoadjuvant treatment (NT) response in rectal cancer (RC).

Methods

PubMed, Embase, and Ovid Medline databases were searched through March 2025. Eligible studies included RC patients treated with NT with baseline microbial analysis stratified by treatment response. Two reviewers independently performed screening, data extraction, and quality assessment (NIH and STORMS tools). Due to substantial heterogeneity, a structured qualitative synthesis without meta-analysis was conducted following SWiM guidelines, using a direction-of-effect vote-counting approach.

Results

Sixteen observational studies (842 patients) were included, covering chemoradiotherapy (nCRT), total neoadjuvant therapy, chemotherapy, and immunochemoradiotherapy. Microbiota composition was investigated by 16S rRNA sequencing, metagenomics, or metatranscriptomics on fecal or tissue samples. While microbial diversity showed inconsistent associations, specific taxa -notably Bacteroides, Fusobacterium and Akkermansia- emerged as recurrent biomarkers of poor response to nCRT. Twelve predictive models reported AUROC values from 0.73 to 0.97, with limited external validation.

Conclusions

Specific microbial taxa show a consistent association with nCRT resistance across independent cohorts. However, methodological heterogeneity and limited reproducibility warrant standardized prospective validation before clinical implementation. PROSPERO: CRD42023433704.