The Hidden Link Between Gut Microbiota and Colorectal Cancer: A Scientific Journey of Integrated Analysis

Posted on September 25, 2025   by Han Sun and Ranxin Yan

Han Sun and Ranxin Yan of the Hunan Agricultural University, China, takes us behind the scenes of their latest publication '

Meta-analysis of gut microbiome reveals patterns of dysbiosis in colorectal cancer patients' published in the Journal of Medical Microbiology.

Colorectal cancer (CRC) is a global health crisis, ranking as the fourth deadliest cancer worldwide. Early-stage CRC is often asymptomatic, making timely diagnosis a significant challenge, and its pathogenesis is closely linked to the gut microbiome. When we turn our attention to the human "super-ecosystem," the gut microbiota remains an enigmatic domain. Our recent study, published in the Journal of Medical Microbiology, titled "Meta-analysis of gut microbiome reveals patterns of dysbiosis in colorectal cancer patients," delves deeply into the complex relationship between the gut microbiota and CRC. Our team systematically explored the dysbiosis characteristics of the gut microbiome in CRC patients. This work originated from a critical challenge: although multiple studies suggest that gut microbes may participate in cancer progression through immune modulation and metabolic pathways, technical variations across studies make it difficult to corroborate findings.

At the outset of the research, we collected 1,462 gut microbiome samples (from 674 healthy individuals and 788 CRC patients) across six cohorts, encompassing 320 bacterial genera. This large-scale study could enhance the statistical significance and reliability of the results. When we initially merged multi-batch data, principal component analysis (PCA) revealed that sample distribution was markedly dispersed, which may be due to experimental condition interference—specifically, the presence of a batch effect. This effect likely arose from differences in factors such as time, operators, reagents, and instruments, making preprocessing crucial. To address this challenge, we employed conditional quantile regression for correction. Through repeated validation, we ultimately selected Batch 3 as the reference batch, a decision that increased the explained variance of the principal components from 13% to over 70%. This validated our methodology and laid the groundwork for deeper analysis.

Then, we explored diversity and associations. α-diversity metrics (like the Shannon and Simpson indices) revealed lower species richness in CRC patients—a subtle but critical shift. β-diversity analyses confirmed this, showing distinct microbial communities between groups. Principal coordinate analysis (PCoA) plots visualized these differences: in the raw data, samples from different batches were individually clustered, but after correction, the differences between different batches were reduced. Meanwhile, CRC and healthy samples clustered apart, highlighting the true biological differences. It was thrilling to see statistical tests (PERMANOVA, ANOSIM) unanimously support this, with P-values <0.001. Linear discrimination analysis effect size (LEfSe) analysis acted as a precise molecular probe, capturing the specific enrichment of Enterobacter and Fusobacterium in the gut microbiome of CRC patients. These genera have previously been implicated in CRC progression. Conversely, Bacteroides and Faecalibacterium were confirmed as cornerstone taxa in the healthy gut, renowned for their beneficial roles in maintaining intestinal health. From the taxonomic branching diagram, we could find Fusobacterium light up as a CRC marker, reinforcing its role in cancer progression reported in literature. Here’s the visual proof, with the cladogram and linear discriminant analysis (LDA) scores pinpointing key genera.

These findings provide new perspectives for early CRC diagnosis. By identifying Enterobacter and Fusobacterium as potential diagnostic biomarkers, we could develop non-invasive faecal tests for early CRC screening, particularly in regions lacking advanced medical services. Imagine a future where simple microbiome analysis detects cancer before symptoms manifest. Beyond diagnosis, this opens doors for microbial therapies, such as probiotics or faecal transplantation, to restore healthy gut balance and prevent tumour growth. Our research not only deepens the understanding of microbial roles in CRC but also paves the way for novel interventions.

In summary, our meta-analysis of the gut microbiome in CRC patients provides valuable insights into the microbial features associated with this disease. While much remains to be studied, we are optimistic that these findings will aid in developing more effective diagnostic and therapeutic strategies for CRC. We extend our gratitude to the Microbiology Society for the opportunity to share our work through this blog post and hope it will stimulate further research in this exciting field.