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Aberrant activation of this pathway, often driven by gut microbiota dysbiosis, contributes to tumorigenesis, therapy resistance, and chronic inflammation. Emerging evidence highlights the bidirectional interaction between gut microbiota and NF-\u03baB signalling, suggesting that microbiota modulation may enhance cancer treatment efficacy and reduce treatment-induced inflammation. This review explores the mechanistic underpinnings of gut microbiota-mediated NF-\u03baB regulation, focusing on microbial metabolites such as short-chain fatty acids (SCFAs) and microbial-associated molecular patterns, including lipopolysaccharides (LPS). It examines how conventional cancer treatments, chemotherapy, radiotherapy, and immune checkpoint inhibitors, exacerbate dysbiosis and NF-\u03baB-driven inflammation, further complicating treatment outcomes. Additionally, this review evaluates the therapeutic potential of gut-targeted interventions, including probiotics, prebiotics, faecal microbiota transplantation (FMT), and dietary modifications, in restoring microbial homeostasis and modulating NF-\u03baB signalling. Despite promising findings, challenges remain regarding the clinical translation of microbiota-based therapies, including the need for standardised microbiota profiling, regulatory frameworks, and long-term safety assessments. Advances in metagenomics and metabolomics are proposed as essential tools to personalise gut-targeted interventions and optimise cancer treatment strategies. Integrating gut modulation into oncology represents a paradigm shift, offering a holistic, patient-centric approach to cancer therapy. However, further research is required to validate these strategies and ensure their efficacy in clinical applications.<\/jats:p>","DOI":"10.1007\/s00262-025-04118-9","type":"journal-article","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T10:31:46Z","timestamp":1752316306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Gut modulation to regulate NF-\u03baB in colorectal and gastric cancer therapy and inflammation"],"prefix":"10.1007","volume":"74","author":[{"given":"Rowan","family":"Kearns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"4118_CR1","first-page":"20182020","volume":"144","author":"J Ferlay","year":"2019","unstructured":"Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pi\u00f1eros M, Znaor A, Bray F (2019) Global cancer observatory: cancer tomorrow. 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