Depicting the landscape of gut microbial-metabolic interaction and microbial-host immune heterogeneity in deficient and proficient DNA mismatch repair colorectal cancersOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
Researchers compared gut microbiome and metabolome profiles between colorectal cancers with deficient versus proficient DNA mismatch repair (dMMR and pMMR CRC), and linked these to tumor immune features.
How was it studied?
Metagenomic sequencing and metabolomic analysis were performed on fecal samples from 455 participants (21 dMMR CRC, 207 pMMR CRC, 227 healthy controls). Bulk RNA sequencing was done on 50 tumor samples (5 dMMR, 45 pMMR).
What did they find?
dMMR CRC showed 211 enriched species, including Fusobacterium nucleatum and Akkermansia muciniphila, plus enriched retinoic acid and depleted short chain organic acids like lactic and succinic acid. Flavonifractor plautii was depleted in dMMR but enriched in pMMR CRC, linked to fatty acid degradation and lactate buildup. MMR-specific metabolic patterns tracked with distinct immune cell profiles, including CD8+ T cells, dendritic cells, and M2-like macrophages.
Why it matters
The findings suggest gut microbiota and their metabolites shape distinct antitumor immune environments in dMMR versus pMMR colorectal cancer, pointing to mechanisms behind their differing immune responses.