# Association analysis of the differences in intestinal flora and clinical tumor indicators among colorectal cancer patients

**Authors:** Lijun Ma, Wenjing Wang, Shihu Ma, Yanbai Wang, Hai Li, Ying Gao, Xiaoliang Xie

PMC · DOI: 10.3389/fcimb.2026.1742672 · Frontiers in Cellular and Infection Microbiology · 2026-02-23

## TL;DR

This study explores how gut bacteria differ in colorectal cancer patients compared to healthy individuals and how these differences relate to cancer progression.

## Contribution

The study systematically compares microbial diversity and function in cancerous, paracancerous, and fecal samples from CRC patients and healthy individuals.

## Key findings

- CRC patients show reduced microbial diversity and enrichment of pathogenic bacteria in cancerous tissues.
- Fecal samples from CRC patients have higher gut health index than cancerous tissues.
- Escherichia coli and Methylobacterium/Methylorubrum correlate with tumor size and stage.

## Abstract

Colorectal cancer (CRC) is the third most common malignant tumor globally, and its development is closely related to intestinal flora dysbiosis. However, the heterogeneity of cancerous tissues, paracancerous tissues, and fecal flora, and their clinical significance, has not been fully elucidated.

This study aimed to systematically analyze the diversity, composition, and functional differences of intestinal flora in patients with CRC compared to healthy individuals, and to reveal potential associations between the characteristics of these microbial communities and tumorigenesis and development.

Thirty CRC patients (30 cancerous tissue samples, 30 paracancerous tissue samples, and 30 fecal samples) and 30 healthy volunteers (30 fecal samples) were enrolled in the study. The microbial communities were analyzed using 16S rRNA sequencing, and the status of the bacterial flora was evaluated by combining alpha and beta diversity, species difference analysis, the Gut Microbiome Health Index (GMHI), and the Gut Microbiome Dysbiosis Index (MDI). The correlation of these factors with clinical parameters was then analyzed.

The alpha diversity of the cancerous tissue from patients with CRC was significantly lower than that of the fecal samples (p < 0.05). The intestinal microbiota of patients with CRC was statistically different from that of healthy individuals (p < 0.01). Additionally, there was a statistically significant difference in beta diversity between the cancerous tissue and fecal gut microbiota of patients with CRC (p < 0.01). The microbiota of the paracancerous tissues exhibited significantly higher GMHIs than the cancerous tissues. Healthy individuals demonstrated better gut health than individuals with CRC. The fecal samples from CRC patients had a higher GMHI than the cancerous tissues. The difference was statistically significant (p < 0.001). For MDI, however, the trend was reversed. A statistically significant positive correlation was observed between Escherichia coli and tumor size (p < 0.05). Similarly, Methylobacterium/Methylorubrum exhibited a statistically significant positive correlation with tumor stage (p < 0.05).The research found that Blautia and Faecalibacterium had higher abundances in the feces of healthy individuals and the tissues adjacent to colorectal cancer, while Escherichia-Shigella, Bacteroides, Enterococcus, and Fusobacterium had higher abundances in colorectal cancer tissues.

The intestinal flora of CRC patients is characterized by decreased diversity, an enrichment of pathogenic bacteria, and a reduction in protective flora. these microbial alterations are associated with tumor progression, potentially via inflammatory and metabolic pathways, although causal mechanisms remain to be functionally validated. The flora health index and dysbiosis index have potential for use as adjunctive diagnostic tools. However, individualized preventive intervention strategies need to be developed in the future by combining multi-omics data.

## Linked entities

- **Diseases:** colorectal cancer (MONDO:0005575)
- **Species:** Escherichia coli (taxon 562), Blautia (taxon 572511), Faecalibacterium (taxon 216851), Bacteroides (taxon 816), Enterococcus (taxon 1350), Fusobacterium (taxon 848)

## Full-text entities

- **Genes:** GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, Cea (carcinoembryonic antigen gene family) [NCBI Gene 111518], ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) [NCBI Gene 5167] {aka ARHR2, COLED, M6S1, NPP1, NPPS, PC-1}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, mucin [NCBI Gene 100508689], GGTLC4P (gamma-glutamyltransferase light chain 4 pseudogene) [NCBI Gene 729838] {aka GGT}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, MAFD2 (major affective disorder 2) [NCBI Gene 4096] {aka BPAD, MDI, MDX}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** infectious diseases (MESH:D003141), inflammatory bowel disease (MESH:D015212), Tumor, Node, Metastasis (MESH:D008207), infection (MESH:D007239), Adenomatous Polyposis Coli (MESH:D011125), GMHI (OMIM:603663), metastasis (MESH:D009362), carcinogenic (MESH:D011230), tumorigenic (MESH:D002471), CRC (MESH:D015179), ischemia (MESH:D007511), OSCC (MESH:D000077195), hypoxia (MESH:D000860), gastric cancer (MESH:D013274), adenomas (MESH:D000236), carcinogenesis (MESH:D063646), TBIL (MESH:D007647), lung cancer (MESH:D008175), adenocarcinomas (MESH:D000230), Cancerous (MESH:D009369), Dysbiosis (MESH:D064806), chronic inflammation (MESH:D007249), HL (MESH:C538324), dysplasia (MESH:D015792)
- **Chemicals:** creatinine (MESH:D003404), formaldehyde (MESH:D005557), SCFAs (MESH:D005232), urea nitrogen (MESH:C530477), agarose (MESH:D012685), Butyrate (MESH:D002087), propionate (MESH:D011422), APCMin (-), bile acids (MESH:D001647), nucleotide (MESH:D009711), bilirubin (MESH:D001663), lactate (MESH:D019344), colibactin (MESH:C569566), sialic acid (MESH:D019158), methylmalonic acid (MESH:D008764)
- **Species:** Enterococcus faecium (species) [taxon 1352], Methylorubrum (genus) [taxon 2282523], gut metagenome (species) [taxon 749906], Fusicatenibacter (genus) [taxon 1407607], Blautia (genus) [taxon 572511], Peptostreptococcus stomatis (species) [taxon 341694], Anaerobutyricum (genus) [taxon 2569097], Micrococcus (genus) [taxon 1269], Enterobacteriaceae (enterobacteria, family) [taxon 543], Fusobacterium nucleatum (species) [taxon 851], Shigella dysenteriae (species) [taxon 622], Bacteroides fragilis (species) [taxon 817], Fusobacterium (genus) [taxon 848], Bacteroides (genus) [taxon 816], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Faecalibacterium prausnitzii (species) [taxon 853], Homo sapiens (human, species) [taxon 9606], Akkermansia muciniphila (species) [taxon 239935], Streptococcus (genus) [taxon 1301], Pasteurella stomatis (species) [taxon 760], Methylobacterium (genus) [taxon 407], Fusobacterium varium (species) [taxon 856], Enterococcus (genus) [taxon 1350], Roseburia (genus) [taxon 841], Mediterraneibacter (genus) [taxon 2316020], Parvimonas micra (species) [taxon 33033], Shigella flexneri (species) [taxon 623], Bifidobacterium pseudocatenulatum (species) [taxon 28026], Pantoea agglomerans (species) [taxon 549], Mediterraneibacter torques (species) [taxon 33039], Gemella morbillorum (species) [taxon 29391], Shigella sonnei (species) [taxon 624], Prevotella (genus) [taxon 838], Stenotrophomonas (genus) [taxon 40323], Mus musculus (house mouse, species) [taxon 10090], Acinetobacter (genus) [taxon 469], Shigella boydii (species) [taxon 621], Phocaeicola (genus) [taxon 909656], Faecalibacterium (genus) [taxon 216851], Escherichia coli (E. coli, species) [taxon 562], Peptostreptococcus anaerobius (species) [taxon 1261]

## Full text

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## Figures

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## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12968219/full.md

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Source: https://tomesphere.com/paper/PMC12968219