Absolute Microbial Abundance and Causal Inference as Foundations for a One Health Roadmap in Colorectal Cancer Diagnostics

Abstract

Abstract The rising global incidence of colorectal cancer (CRC) necessitates a shift toward a functional understanding of the intestinal ecosystem. Although the microbiome is implicated in oncogenesis, most studies rely on relative abundance metrics, which are vulnerable to compositionality bias. To address this limitation, this overview of systematic reviews (Umbrella Review) synthesized evidence from 28 systematic reviews and meta-analyses published between 2021 and 2026, adapting the PRISMA 2020 guidelines for secondary evidence synthesis. By integrating published Mendelian Randomization (MR) findings to appraise causal relationships and summarizing evidence from absolute abundance frameworks, a robust taxonomic consensus was established. Specifically, Fusobacterium nucleatum (Beta: 0.42) was identified as a causal driver, whereas Faecalibacterium prausnitzii (Beta: -0.35) demonstrated a significant causal protective role. Furthermore, multi-kingdom networks revealed that viral families (Microviridae) modulate bacterial fitness and host oncogenes (PCSK5). Absolute abundance approaches have been reported to achieve superior diagnostic performance, with AUC values up to 0.99 in retrospective settings. Ultimately, this synthesis highlights promising frameworks for next-generation CRC screening, showing that integrating absolute quantification with multi-kingdom networks holds strong translational potential, though rigorous clinical validation across diverse populations remains necessary to confirm diagnostic utility.