Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review
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 modul...
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2025-06-01
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| author | Ielmina Domilescu Bogdan Miutescu Florin George Horhat Alina Popescu Camelia Nica Ana Maria Ghiuchici Eyad Gadour Ioan Sîrbu Delia Hutanu |
| author_facet | Ielmina Domilescu Bogdan Miutescu Florin George Horhat Alina Popescu Camelia Nica Ana Maria Ghiuchici Eyad Gadour Ioan Sîrbu Delia Hutanu |
| author_sort | Ielmina Domilescu |
| collection | DOAJ |
| description | 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 <i>Lachnospiraceae bacterium</i>, <i>Blautia wexlerae</i>, <i>Roseburia</i> spp., and <i>Intestinimonas butyriciproducens</i>. Non-responders showed over-representation of <i>Fusobacterium nucleatum</i>, <i>Bacteroides fragilis</i>, and <i>Prevotella</i> 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 (I<sup>2</sup> = 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. |
| format | Article |
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| spelling | doaj-art-43e67d6b0ff14112b19b7c3cd3ead4d92025-08-20T02:21:13ZengMDPI AGMetabolites2218-19892025-06-0115641210.3390/metabo15060412Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic ReviewIelmina Domilescu0Bogdan Miutescu1Florin George Horhat2Alina Popescu3Camelia Nica4Ana Maria Ghiuchici5Eyad Gadour6Ioan Sîrbu7Delia Hutanu8Doctoral School, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDivision of Gastroenterology and Hepatology, Department of Internal Medicine II, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDepartment of Microbiology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDivision of Gastroenterology and Hepatology, Department of Internal Medicine II, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDivision of Gastroenterology and Hepatology, Department of Internal Medicine II, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaDivision of Gastroenterology and Hepatology, Department of Internal Medicine II, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, RomaniaMulti-Organ Transplant Centre of Excellence, Liver Transplantation Unit, King Fahad Specialist Hospital, Dammam 32253, Saudi ArabiaDepartment of Oral Implantology, Faculty of Dental Medicine, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, RomaniaBiology Department, Chemistry-Biology-Geography Faculty, West University of Timisoara, 300115 Timisoara, RomaniaBackground 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 <i>Lachnospiraceae bacterium</i>, <i>Blautia wexlerae</i>, <i>Roseburia</i> spp., and <i>Intestinimonas butyriciproducens</i>. Non-responders showed over-representation of <i>Fusobacterium nucleatum</i>, <i>Bacteroides fragilis</i>, and <i>Prevotella</i> 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 (I<sup>2</sup> = 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.https://www.mdpi.com/2218-1989/15/6/412rectal cancergut microbiomechemoradiotherapypathologic complete responsepredictive biomarkermetagenomics |
| spellingShingle | Ielmina Domilescu Bogdan Miutescu Florin George Horhat Alina Popescu Camelia Nica Ana Maria Ghiuchici Eyad Gadour Ioan Sîrbu Delia Hutanu Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review Metabolites rectal cancer gut microbiome chemoradiotherapy pathologic complete response predictive biomarker metagenomics |
| title | Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review |
| title_full | Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review |
| title_fullStr | Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review |
| title_full_unstemmed | Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review |
| title_short | Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review |
| title_sort | gut microbiome signatures predicting response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer a systematic review |
| topic | rectal cancer gut microbiome chemoradiotherapy pathologic complete response predictive biomarker metagenomics |
| url | https://www.mdpi.com/2218-1989/15/6/412 |
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