Engineered organoid platforms for mechanistic studies of gut microbiota-cancer interactions
- 1epartment of Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China
Abstract
Associations between the gut microbiota and cancer are increasingly reproducible at the cohort level, but association alone cannot establish whether a microorganism, microbial product, or metabolite directly alters tumor-relevant host biology. Engineered organoid systems address this gap by placing defined microbial exposures against human or genetically specified epithelia under experimentally controlled conditions. The strength of the resulting inference depends on platform architecture. Three-dimensional organoids preserve epithelial organization but restrict luminal access; microinjection and apical-out configurations enable direct microbial exposure; organoid-derived monolayers permit directional sampling and barrier measurements; and microfluidic systems add flow, oxygen gradients, and longer-term host-microbe co-culture. Tumor organoids and defined immune or stromal co-cultures can be added when the biological question requires cancer-specific or multicellular readouts. This review evaluates these platforms according to the mechanistic questions they can answer and distinguishes evidence from live microorganisms, complex communities, cell-free microbial products, purified metabolites, and clinical associations. The strongest organoid-based evidence currently concerns microbial genotoxicity, epithelial transformation, barrier and repair responses, selected tumor-growth phenotypes, and intestinal treatment toxicity. Direct organoid evidence linking the gut microbiota to distant, non-gastrointestinal tumors remains limited despite substantial clinical and animal data. We further discuss how physicochemical control, omics-based benchmarking, and standardized reporting can improve reproducibility without adding unnecessary model complexity. The central requirement is explicit matching of experimental architecture to the causal claim being tested.
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BibTeX
@article{sun2026engineered,
title = {{Engineered organoid platforms for mechanistic studies of gut microbiota-cancer interactions}},
author = {Man Sun and Jing-Mian Jiao and Dan Zang and Mei-Xi Lin and Huan Zhou and Jun Chen},
journal = {Frontiers in Bioengineering and Biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1905559},
url = {https://doi.org/10.3389/fbioe.2026.1905559},
note = {CC BY},
}
RIS
TY - JOUR
TI - Engineered organoid platforms for mechanistic studies of gut microbiota-cancer interactions
AU - Man Sun
AU - Jing-Mian Jiao
AU - Dan Zang
AU - Mei-Xi Lin
AU - Huan Zhou
AU - Jun Chen
PY - 2026
DA - 2026/10/26
JO - Frontiers in Bioengineering and Biotechnology
DO - 10.3389/fbioe.2026.1905559
UR - https://doi.org/10.3389/fbioe.2026.1905559
AB - Associations between the gut microbiota and cancer are increasingly reproducible at the cohort level, but association alone cannot establish whether a microorganism, microbial product, or metabolite directly alters tumor-relevant host biology. Engineered organoid systems address this gap by placing defined microbial exposures against human or genetically specified epithelia under experimentally controlled conditions. The strength of the resulting inference depends on platform architecture. Three-dimensional organoids preserve epithelial organization but restrict luminal access; microinjection and apical-out configurations enable direct microbial exposure; organoid-derived monolayers permit directional sampling and barrier measurements; and microfluidic systems add flow, oxygen gradients, and longer-term host-microbe co-culture. Tumor organoids and defined immune or stromal co-cultures can be added when the biological question requires cancer-specific or multicellular readouts. This review evaluates these platforms according to the mechanistic questions they can answer and distinguishes evidence from live microorganisms, complex communities, cell-free microbial products, purified metabolites, and clinical associations. The strongest organoid-based evidence currently concerns microbial genotoxicity, epithelial transformation, barrier and repair responses, selected tumor-growth phenotypes, and intestinal treatment toxicity. Direct organoid evidence linking the gut microbiota to distant, non-gastrointestinal tumors remains limited despite substantial clinical and animal data. We further discuss how physicochemical control, omics-based benchmarking, and standardized reporting can improve reproducibility without adding unnecessary model complexity. The central requirement is explicit matching of experimental architecture to the causal claim being tested.
SN - 2296-4185
ER -