Inflammation-associated gut microbiota and their mediating role in colorectal neoplasia: evidence from a multi-cohort study
1
Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
2
Center for Prevention and Early Intervention, Peking Union Medical College Hospital, Beijing, China
Popul. Med. 2026;8(Supplement Supplement 1):
ABSTRACT
INTRODUCTION:
Most studies on gut microbiota and inflammation rely on single cohorts and have not focused on inflammation-related microbiota in relation to colorectal tumor risk. This study identifies inflammation-associated bacteria and examines their roles in colorectal neoplasia.
METHODS:
From a CRC screening trial, we included 26 CRC, 376 advanced adenoma (AA), 322 non-advanced adenoma (NAA), and 324 healthy controls (HC). Pre-diagnostic fecal and plasma samples underwent shotgun metagenomic sequencing and hs-CRP measurement. Multivariate linear models identified inflammation-associated microbes and their associations with colorectal neoplasia. A cohort of 97 healthy individuals validated microbiota–inflammation links, and eight colorectal tumor cohorts validated inflammation-related microbiota–tumor associations.
RESULTS:
We identified three anti-inflammatory species—Eubacteriaceae bacterium, GGB79734 SGB15291, and Mediterraneibacter butyricigenes—and two pro-inflammatory species—Flavonifractor plautii (FP) and Clostridium butyricum. Mendelian randomization supported a causal relationship between FP and CRP levels. To assess their combined effects, we developed a microbiome inflammation score by weighting the relative abundances of the five species. This score was significantly associated with AA risk. Individually, FP positively correlated with risks of AA and advanced neoplasm (AN), whereas GGB79734 SGB15291 showed negative associations. Across six validation cohorts, FP was consistently enriched and GGB79734 SGB15291 consistently depleted in AA and AN. Mediation analysis showed that CRP partially mediated the associations of FP and GGB79734 SGB15291 with AA. Microbial pathway analysis further suggested that the methylerythritol phosphate pathway may reduce AA risk by lowering CRP, while the all-trans farnesol biosynthesis pathway may increase CRC risk by elevating CRP.
CONCLUSIONS:
This study demonstrates that gut microbiota influence colorectal neoplasia by modulating systemic inflammation and reveals potential mechanisms through which inflammatory bacteria promote carcinogenesis, offering new insights into the microbiota–inflammation–cancer axis.
Most studies on gut microbiota and inflammation rely on single cohorts and have not focused on inflammation-related microbiota in relation to colorectal tumor risk. This study identifies inflammation-associated bacteria and examines their roles in colorectal neoplasia.
METHODS:
From a CRC screening trial, we included 26 CRC, 376 advanced adenoma (AA), 322 non-advanced adenoma (NAA), and 324 healthy controls (HC). Pre-diagnostic fecal and plasma samples underwent shotgun metagenomic sequencing and hs-CRP measurement. Multivariate linear models identified inflammation-associated microbes and their associations with colorectal neoplasia. A cohort of 97 healthy individuals validated microbiota–inflammation links, and eight colorectal tumor cohorts validated inflammation-related microbiota–tumor associations.
RESULTS:
We identified three anti-inflammatory species—Eubacteriaceae bacterium, GGB79734 SGB15291, and Mediterraneibacter butyricigenes—and two pro-inflammatory species—Flavonifractor plautii (FP) and Clostridium butyricum. Mendelian randomization supported a causal relationship between FP and CRP levels. To assess their combined effects, we developed a microbiome inflammation score by weighting the relative abundances of the five species. This score was significantly associated with AA risk. Individually, FP positively correlated with risks of AA and advanced neoplasm (AN), whereas GGB79734 SGB15291 showed negative associations. Across six validation cohorts, FP was consistently enriched and GGB79734 SGB15291 consistently depleted in AA and AN. Mediation analysis showed that CRP partially mediated the associations of FP and GGB79734 SGB15291 with AA. Microbial pathway analysis further suggested that the methylerythritol phosphate pathway may reduce AA risk by lowering CRP, while the all-trans farnesol biosynthesis pathway may increase CRC risk by elevating CRP.
CONCLUSIONS:
This study demonstrates that gut microbiota influence colorectal neoplasia by modulating systemic inflammation and reveals potential mechanisms through which inflammatory bacteria promote carcinogenesis, offering new insights into the microbiota–inflammation–cancer axis.
| eISSN: | 2654-1459 |
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