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Fecal Microbiota and Gut Microbe-Derived Extracellular Vesicles in Colorectal Cancer.

ABSTRACT: The human microbiota comprises trillions of microbes, and the relationship between cancer and microbiota is very complex. The impact of fecal microbiota alterations on colorectal cancer (CRC) pathogenesis is emerging. This study analyzed changes in the microbial composition in CRC subjects with both fecal microbiota and gut microbe-derived extracellular vesicles (EVs). From August 2017 to August 2018, 70 CRC patients and 158 control subjects were enrolled in the study. Metagenomic profiling of fecal microbiota and gut microbe-derived EVs in stool was performed using 16S ribosomal DNA sequencing. Relative abundance, evenness, and diversity in both the gut microbiota and gut microbe-derived EVs were analyzed. Additionally, microbial composition changes according to the stage and location of CRC were analyzed. Microbial composition was significantly changed in CRC subjects compared to control subjects, with evenness and diversity significantly lower in the fecal microbiota of CRC subjects. Gut microbe-derived EVs of stool demonstrated significant differences in the microbial composition, evenness, and diversity in CRC subjects compared to the control subjects. Additionally, microbial composition, evenness, and diversity significantly changed in late CRC subjects compared to early CRC subjects with both fecal microbiota and gut microbe-derived EVs. Alistipes-derived EVs could be novel biomarkers for diagnosing CRC and predicting CRC stages. Ruminococcus 2-derived EVs significantly decreased in distal CRC subjects than in proximal CRC subjects. Gut microbe-derived EVs in CRC had a distinct microbial composition compared to the controls. Profiling of microbe-derived EVs may offer a novel biomarker for detecting and predicting CRC prognosis.

SUBMITTER: Park J

PROVIDER: S-EPMC8477046 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsInvestigation of microbe-metabolite relationships in the gut is needed to understand and potentially reduce colorectal cancer (CRC) risk.MethodsMicrobiota and metabolomics profiling were performed on lyophilized feces from 42 CRC cases and 89 matched controls. Multivariable logistic regression was used to identify statistically independent associations with CRC. First principal coordinate-component pair (PCo1-PC1) and false discovery rate (0.05)-corrected P-values were calculated for 116,000 Pearson correlations between 530 metabolites and 220 microbes in a sex*case/control meta-analysis.ResultsOverall microbe-metabolite PCo1-PC1 was more strongly correlated in cases than in controls (Rho 0.606 vs 0.201, P = 0.01). CRC was independently associated with lower levels of Clostridia, Lachnospiraceae, p-aminobenzoate and conjugated linoleate, and with higher levels of Fusobacterium, Porphyromonas, p-hydroxy-benzaldehyde, and palmitoyl-sphingomyelin. Through postulated effects on cell shedding (palmitoyl-sphingomyelin), inflammation (conjugated linoleate), and innate immunity (p-aminobenzoate), metabolites mediated the CRC association with Fusobacterium and Porphyromonas by 29% and 34%, respectively. Overall, palmitoyl-sphingomyelin correlated directly with abundances of Enterobacteriaceae (Gammaproteobacteria), three Actinobacteria and five Firmicutes. Only Parabacteroides correlated inversely with palmitoyl-sphingomyelin. Other lipids correlated inversely with Alcaligenaceae (Betaproteobacteria). Six Bonferroni-significant correlations were found, including low indolepropionate and threnoylvaline with Actinobacteria and high erythronate and an uncharacterized metabolite with Enterobacteriaceae.ConclusionsFeces from CRC cases had very strong microbe-metabolite correlations that were predominated by Enterobacteriaceae and Actinobacteria. Metabolites mediated a direct CRC association with Fusobacterium and Porphyromonas, but not an inverse association with Clostridia and Lachnospiraceae. This study identifies complex microbe-metabolite networks that may provide insights on neoplasia and targets for intervention.

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Fecal Microbiota and Gut Microbe-Derived Extracellular Vesicles in Colorectal Cancer.

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