Clinical translation of gut microbiome biomarkers and host immune dysregulation in colorectal neoplasia: a systematic review with Clinical and Molecular Pathology Prioritisation

Aims Gut microbiome signatures are promising non-invasive biomarkers for colorectal neoplasia, but clinical translation is limited by heterogeneity in populations, platforms, validation and comparator tests. We evaluated microbiome-based biomarkers and microbiome–host immune associations, emphasising applicability. Methods We systematically reviewed human studies published from 1 January 2020 to 15 July 2026 evaluating gut microbiome-associated biomarkers in colorectal adenoma or colorectal cancer. Diagnostic studies were summarised by biomarker, target lesion, comparator, validation and performance, with Quality Assessment of Diagnostic Accuracy Studies-2 appraisal. A predefined seven-domain framework provided secondary translational prioritisation. Mechanistic and prognostic microbiome–immune studies were synthesised separately. Results Recurrent signals included Fusobacterium nucleatum , multispecies panels, microbial gene and single-nucleotide-variant classifiers, multikingdom signatures and metabolite profiles. Some integrated models combining microbial biomarkers with faecal immunochemical testing, methylated DNA, clinical variables or metabolomics showed improved performance measures, but benefits were inconsistent. External validation was limited. Microbiome–immune studies linked microbial profiles with immune-related expression, immune-cell infiltration and treatment–response phenotypes without establishing improved screening accuracy. Conclusions Microbiome biomarkers show promise for colorectal neoplasia detection, but evidence does not establish universal multimodal superiority. Routine translation requires prospective validation, analytical standardisation, reproducibility, cost-effectiveness and demonstrated incremental utility. PROSPERO registration number CRD420261457983.