A comparative study of gut microbiota in the healthy elderly and the elderly with colorectal cancer

Abstract

Colorectal cancer is one of the third most common cancer worldwide. Dysbiosis of the human gut microbiota has been linked to sporadic colorectal cancer (CRC). This study aimed to compare the gut microbiota profile of a total of 80 Thai volunteers, who were above 50 years old, among 25 CRC patients, 33 adenoma patients, and 22 healthy controls (HC). The 16S rRNA sequencing was utilized to characterize the gut microbiome in both mucosal tissue and stool samples. Moreover, absolute quantitative PCR (qPCR) assay was conducted to quantify six CRC-associated bacteria including Fusobacterium nucleatum (FN), Parvimonas micra (PM), colibactin positive strains (EC), Streptococcus gallolyticus (SG), Blautia spp. (Bla) and Fusicatenibacter saccharivorans (FS), in both sample types, and these bacteria were evaluated the performance in CRC and adenoma detections. The results suggested that the fecal microbiota only partially reflected gut microbiota on the mucus layer. The mucosal microbiota of the CRC patients and HC group differed significantly but no difference between adenoma and HC groups was observed. The stepwise increase of Bacteroides and Parabacteroides according to adenomas-carcinomas sequence were found whereas the butyrate-producing genus Faecalibacterium was significantly less abundant in CRC patients. Linear discriminant analysis effect size (LEfSe) showed a higher level of Erysipelatoclostridium ramosum, an opportunistic pathogen, in both sample types of CRC patients. The findings indicated the imbalance of gut microorganisms might be involved in CRC tumorigenesis. In addition, the qPCR assays revealed FN and PM were significantly overrepresented in both sample types of CRC subjects. The combined test of fecal FN and PM with qualitative fecal immunochemical test (FIT) could predict CRC with a sensitivity of 93.8% and a specificity of 95.2%. In a combined test of five fecal bacteria without SG together with the FIT, adenoma was detected with a sensitivity of 83.3% and a specificity of 64.7%. These results indicated E. ramosum may serve as a population-specific biomarker for CRC screening and the quantity of fecal bacteria could complement the current FIT in CRC and adenoma screening. Larger sample size is required for the validation of these candidate biomarkers in CRC and adenoma detections.