Cell Host Microbe
Gut microbiome still pre-cancerous a decade after polypectomy
Clinical takeaway: Polypectomy alone doesn't restore a low-risk gut environment, reinforcing the case for ongoing surveillance and lifestyle counseling in post-adenoma patients.
Adenoma removal at colonoscopy is one of the most effective tools for preventing colorectal cancer, yet patients with a history of resected adenomas continue to face elevated risk. Earlier microbiome work captured snapshots near the time of resection, leaving open the question of whether microbial alterations were transient or sustained.
The current analysis profiled stool metagenomes from 354 women a mean 12 years after adenoma resection and from 354 polyp-free controls matched on age, endoscopy timing, and other clinical factors. Microbial profiles were compared with those from 14 publicly available colorectal cancer (CRC) case-control studies covering 2,112 individuals. Metabolomic profiling was performed in a subset of 184 pairs, weighted toward cases with more advanced histology.
Adenoma cases showed microbial differences from controls that moderately correlated with CRC-associated alterations. Thirty-one species were shifted in the same direction in both adenoma and CRC, including enrichment of Ruminococcus gnavus, Ruminococcus torques, and Flavonifractor plautii and depletion of Faecalibacterium prausnitzii and Gemmiger formicilis. Relative abundance shifts were generally smaller in adenoma than in CRC, consistent with progressive dysbiosis across the adenoma-carcinoma continuum.
Notably, oral-typical microbes implicated in advanced CRC, including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus stomatis, were rarely detected at the adenoma stage, suggesting oral microbial introgression is largely a later event.
Among adenoma cases, abundance of the shared microbes correlated with diet and lifestyle: enrichment tracked with red meat, sugar-sweetened beverages, and higher BMI; depletion tracked with whole grains, fruits, vegetables, nuts and legumes, and physical activity. These correlations were stronger in cases than in polyp-free controls. Adjustment for lifestyle had minimal effect on the case-control microbial differences, suggesting lifestyle shapes but does not fully explain the signature.
Fecal metabolomics identified 30 metabolites and seven sub-pathways altered in adenoma, with enrichment of secondary bile acids, sphingolipids, and polypeptides, and depletion of medium-chain, long-chain polyunsaturated, and dicarboxylic fatty acids. Sphingolipid enrichment, linked elsewhere to inflammation and pro-tumorigenic signaling, was a recurring feature. Disease-specific microbe-metabolite associations also emerged, including correlations between Bilophila wadsworthia and alanine-containing dipeptides seen only in cases.
The findings argue that adenoma resection removes the lesion but not the surrounding microbial and metabolic environment that may contribute to recurrent risk. They also reframe lifestyle counseling after polypectomy from a generic recommendation to a plausible mechanism-linked intervention.
"Our study was the first to address whether gut microbial and metabolic alterations are still detectable many years after adenoma removal," said Mingyang Song, MD, ScD, associate professor of clinical epidemiology and nutrition at the Harvard T.H. Chan School of Public Health. "The answer is yes — suggesting that removing an adenoma doesn't return the gut to a low-risk state, and that the gut microbiome may therefore be a significant biological contributor to sustained CRC risk."
Source: Nogal A. Cell Host Microbe. 2026 May 27. Long-lasting gut microbiome and fecal metabolome alterations after colorectal adenoma removal and their relationship to colorectal cancer