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.
Gut microbiota-associated predictors as biomarkers of neoadjuvant treatment response in rectal cancer-a systematic review / Stepanyan, Astghik; Kotsafti, Andromachi; Rosato, Antonio; Castagliuolo, Ignazio; Scarpa, Marco; Scarpa, Melania; Null, Null; Agostini, Marco; Angriman, Imerio; Antoniutti, Michele; Bao, Quoc Riccardo; Baldo, Andrea; Barbareschi, Mattia; Bardini, Romeo; Becherucci, Giulia; Bergamo, Francesca; Bertalot, Giovanni; Bordignon, Giovanni; Brignola, Stefano; Brolese, Alberto; Brolese, Marco; Businello, Gianluca; Buzzi, Gianluca; Campi, Michela; Candioli, Salvatore; Capelli, Giulia; Cataldo, Ivana; Cavallin, Francesco; Ceccarini, Lavinia; Ceccon, Carlotta; Cipollari, Chiara; Chiminazzo, Valentina; Cola, Roberto; Da Lio, Corrado; Dal Santo, Luca; D'Angelo, Antonella; De Simoni, Ottavia; Dei Tos, Angelo Paolo; Di Camillo, Barbara; Di Cristofaro, Loretta; Facci, Luca; Fassan, Matteo; Franzato, Boris; Gavagna, Laura; Godina, Mario; Gregori, Dario; Guerrieri, Mario; Guerriero, Silvio; Guzzardo, Vincenza; Laurino, Licia; Marchegiani, Francesco; Maretto, Isacco; Marinelli, Laura; Massani, Marco; Merenda, Roberto; Mondi, Isabella; Negro, Silvia; Noaro, Giulia; Ortenzi, Monica; Parini, Dario; Pellegrini, Valerio; Piccioli, Alessandra; Pilati, Pierluigi; Pirozzolo, Giovanni; Porzionato, Andrea; Portale, Giuseppe; Pozza, Anna; Pozza, Giulia; Prando, Daniela; Pucciarelli, Salvatore; Recordare, Alfonso; Ricagna, Fabio; Rivella, Giorgio; Romiti, Chiara; Ruffolo, Cesare; Saadeh, Luca; Salmaso, Beatrice; Salmaso, Roberta; Scapinello, Antonio; Scognamiglio, Federico; Spolverato, Gaya; Spolverato, Ylenia Camilla; Stecca, Tommaso; Tagliente, Giovanni; Tomassi, Monica; Tedeschi, Umberto; Tussardi, Gaia; Vignotto, Chiara; Verdi, Daunia; Zagonel, Vittorina; Zizzo, Maurizio; Zuin, Matteo. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - 2026:(2026). [10.1038/s41416-026-03443-9]
Gut microbiota-associated predictors as biomarkers of neoadjuvant treatment response in rectal cancer-a systematic review
Barbareschi, Mattia;Bertalot, Giovanni;
2026-01-01
Abstract
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.| File | Dimensione | Formato | |
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BJC 2026 Gut-microbiota associated predictors as biomarkers of neoadjuvant treatment.pdf
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