Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jul 14;15(7):1005.
doi: 10.3390/biom15071005.

The Impact of the Microbiota on the Immune Response Modulation in Colorectal Cancer

Ana Iulia Neagu  1   2 , Marinela Bostan  3   4 , Vlad Alexandru Ionescu  1   5 , Gina Gheorghe  1   5 , Camelia Mia Hotnog  3   6 , Viviana Roman  3 , Mirela Mihaila  3   7 , Simona Isabelle Stoica  1 , Camelia Cristina Diaconu  1   5   8 , Carmen Cristina Diaconu  2 , Simona Maria Ruta  1   9 , Coralia Bleotu  2   8   10
Affiliations
Review

The Impact of the Microbiota on the Immune Response Modulation in Colorectal Cancer

Ana Iulia Neagu et al. Biomolecules. .

Abstract

Colorectal cancer (CRC) is a multifactorial disease increasingly recognized for its complex interplay with the gut microbiota. The disruption of microbial homeostasis-dysbiosis-has profound implications for intestinal barrier integrity and host immune function. Pathogenic bacterial species such as Fusobacterium nucleatum, Escherichia coli harboring polyketide synthase (pks) island, and enterotoxigenic Bacteroides fragilis are implicated in CRC through mechanisms involving mucosal inflammation, epithelial barrier disruption, and immune evasion. These pathogens promote pro-tumorigenic inflammation, enhance DNA damage, and suppress effective anti-tumor immunity. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, exert protective effects by preserving epithelial barrier function and priming host immune responses. These beneficial microbes can promote the maturation of dendritic cells, stimulate CD8+ T cell cytotoxicity, and modulate regulatory T cell populations, thereby enhancing anti-tumor immunity. The dichotomous role of the microbiota underscores its potential as both a biomarker and a therapeutic target in CRC. Recent advances in studies have explored microbiota-modulating strategies-ranging from dietary interventions and prebiotics to fecal microbiota transplantation (FMT) and microbial consortia-as adjuncts to conventional therapies. Moreover, the composition of the gut microbiome has been shown to influence the responses to immunotherapy and chemotherapy, raising the possibility of microbiome-informed precision oncology therapy. This review synthesizes the current findings on the pathogenic and protective roles of bacteria in CRC and evaluates the translational potential of microbiome-based interventions in shaping future therapeutic paradigms.

Keywords: colorectal cancer; immune response; intestinal barrier integrity; microbiota; therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Pathogen bacterial species from microbiome impact on immune response and intestinal barrier integrity in CRC (TLRs—Toll-like Receptors, NLRs—Nucleotide-binding and Oligomerization Domain (NOD)-like Receptors, TJ—Tight Junction, PAMPs—Pathogen-Associated Molecular Patterns (bacteria, viruses, fungi), IL—Interleukin, IFNg—Interferon Gamma, TGFb—Transforming Growth Factor Beta, ROS—Reactive Oxygen Species, RNS—Reactive Nitrogen Species, Treg—Regulatory T cells, CTLs—Cytotoxic T Lymphocytes, NKs—Natural Killer Cells).
Figure 2
Figure 2
Mechanisms by which pathogenic bacteria compromise the integrity of the intestinal barrier in colorectal cancer CRC.
Figure 3
Figure 3
The correlation between pathogenic bacteria, ROS production, immune response, and barrier disruption in CRC; (ROS—reactive oxygen species).
Figure 4
Figure 4
The impact of beneficial bacterial species on immune response and intestinal barrier integrity in CRC.
See this image and copyright information in PMC

References

    1. Zhang W., An Y., Qin X., Wu X., Wang X., Hou H., Song X., Liu T., Wang B., Huang X., et al. Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges. Front. Oncol. 2021;11:739648. doi: 10.3389/fonc.2021.739648. - DOI - PMC - PubMed
    1. Nobels A., van Marcke C., Jordan B.F., Van Hul M., Cani P.D. The gut microbiome and cancer: From tumorigenesis to therapy. Nat. Metab. 2025;7:895–917. doi: 10.1038/s42255-025-01287-w. - DOI - PubMed
    1. Petersen C., Round J.L. Defining dysbiosis and its influence on host immunity and disease. Cell. Microbiol. 2014;16:1024–1033. doi: 10.1111/cmi.12308. - DOI - PMC - PubMed
    1. Strati F., Pujolassos M., Burrello C., Giuffrè M.R., Lattanzi G., Caprioli F., Troisi J., Facciotti F. Antibiotic-Associated Dysbiosis Affects the Ability of the Gut Microbiota to Control Intestinal Inflammation upon Fecal Microbiota Transplantation in Experimental Colitis Models. Microbiome. 2021;9:39. doi: 10.1186/s40168-020-00991-x. - DOI - PMC - PubMed
    1. Pfeilmeier S., Werz A., Ote M., Bortfeld-Miller M., Kirner P., Keppler A., Hemmerle L., Gäbelein C.G., Petti G.C., Wolf S., et al. Leaf microbiome dysbiosis triggered by T2SS-dependent enzyme secretion from opportunistic Xanthomonas pathogens. Nat. Microbiol. 2024;9:136–149. doi: 10.1038/s41564-023-01555-z. - DOI - PMC - PubMed

MeSH terms