Harnessing the Gut Commensal Bifidobacterium spp. to Modulate Anti-Tumour Immune Responses

Mitchell, Luke J. (2025) Harnessing the Gut Commensal Bifidobacterium spp. to Modulate Anti-Tumour Immune Responses. Doctoral thesis, University of East Anglia.

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Abstract

The gut microbiome plays a critical role in shaping host immunity, and specific commensal bacteria, including Bifidobacterium, have been implicated in modulating anti-tumour immune responses. However, the immunoregulatory properties of bacteria are highly strain-specific, and systematic methods for identifying therapeutic strains are lacking. This thesis aimed to develop a functional screening pipeline to characterise immunomodulatory activity across diverse Bifidobacterium isolates and to evaluate selected strains in murine cancer models.

A multi-tiered in vitro and ex vivo screening platform was established, incorporating THP-1 monocyte NF-κB activation assays, dendritic cell cytokine profiling, DCCD8+ T cell cocultures, and human PBMC immune phenotyping. Screening of >150 Bifidobacterium isolates from both human and animal gastrointestinal sources revealed substantial heterogeneity in their ability to stimulate innate and adaptive immune populations, enabling prioritisation of candidate strains for in vivo study.

In a luminal A-like breast cancer model, selected B. bifidum strains significantly reduced tumour growth and were associated with enrichment of cDC1 in tumour-draining lymph nodes, increased costimulatory molecule expression on dendritic cells, and enhanced CD8+ T cell effector responses. In an orthotopic pancreatic ductal adenocarcinoma model, distinct strains exerted divergent effects on tumour progression, with several strains markedly reducing hepatic metastatic burden in the absence of consistent primary tumour control, consistent with systemic immune modulation.

Collectively, these findings demonstrate that Bifidobacterium strains exhibit distinct, strain-dependent immunomodulatory profiles with divergent effects on tumour immunity. By integrating high-throughput functional screening with in vivo validation across multiple cancer models, this thesis establishes a coherent framework for linking strain-level immunomodulatory heterogeneity to anti-tumour immune outcomes, underscoring the importance of strain-level resolution in microbiome-based cancer research.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	29 Jan 2026 08:31
Last Modified:	29 Jan 2026 08:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101782
DOI:

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