Microbiome and Treatment Resistance in Colorectal Cancer: Mechanisms and Solutions
Amália Cinthia Meneses do Rêgo, Irami Araújo-Filho
This review investigates the complex role of the gut microbiome in modulating treatment resistance
in colorectal cancer (CRC), examining mechanisms that influence therapeutic outcomes across
chemotherapy, immunotherapy, and targeted therapies. Through a systematic search of databases,
including PubMed, Scopus, Embase, Web of Science, SciELO, and gray literature from Google Scholar,
we identified relevant studies addressing microbial interactions with cancer treatments. Key insights
reveal how specific microbial species, such as Fusobacterium nucleatum, impact chemotherapy efficacy
by altering drug metabolism and promoting immune evasion. Genetic mutations in patients, notably in
immune-regulatory genes like MSH2 and MLH1, further shape microbiome composition, contributing
to an immunosuppressive environment that fosters CRC progression and resistance. The review also
addresses immunotherapeutic outcomes, highlighting the role of microbial species in modulating immune
checkpoints, such as PD-1 and PD-L1, and influencing CAR-T cell therapy. Microbial metabolites,
including short-chain fatty acids, impact tumor microenvironment signaling pathways associated
with resistance. Therapeutic strategies, such as dietary interventions, probiotics, prebiotics, and fecal
microbiota transplantation, are discussed as potential approaches to modify the microbiome, enhance
treatment responses, and reduce recurrence risks. This synthesis underscores
the need to explore further microbiome-targeted therapies and their integration into precision oncology
for optimized CRC management.
