Changes In The Gut Microbiota And Their Effect On Pathogenesis In Obese Patients With Colorectal Cancer

The gut microbiota is affected by dietary patterns and obesity, which are known as some of the key risk factors for colorectal cancer (CRC) development.Several studies have shown the mechanisms by which some bacteria might influence CRC development; however, the characteristics of the gut microbiota in obese (Ob) patients with CRC have not been discovered.Therefore, we evaluated the gut microbiota profile and its relationship with metabolic markers in Ob patients with CRC.Methods: From June 2016 to July 2019, we obtained fecal samples from consecutive patients with CRC (p-CRC, n = 36) at Yamagata University Hospital and individuals without CRC (controls, n = 38) as confirmed with total colonoscopy as part of the health checkup conducted at Tohoku Central Hospital.16S rRNA gene amplicon sequencing was performed to identify the microbiotic variations between the p-CRC and the controls, as well as between the non-obese (nOb) and Ob individuals (BMI >25 kg/m 2 ).Results: In p-CRC, the number of current smokers and patients with diabetes or hyperlipidemia; the median age; the levels of fasting plasma glucose, insulin, and HbA1c; and HOMA-IR were significantly higher, whereas the levels of total cholesterol, HDL, and LDL were significantly lower than those in the controls.Between the p-CRC and controls, no significant differences were observed in the number of males, Ob patients, and current drinkers and triglyceride levels.The median Chao-1 (177 vs. 142, p < 0.01) and Shannon index (2.70 vs 2.64, p = 0.08) were higher in p-CRC than in the controls.A principal coordinate analysis demonstrated that there is a significant difference in the overall structure of the microbiota between the p-CRC and the controls or between the Ob and the nOb patients in each group.The relative abundance rates of the phyla Actinobacteria, Fusobacteria, and Tenericutes were higher in the CRCs than in the controls ( p < 0.05).The relative abundance rates of 38 genera were significantly higher, whereas those of 9 genera were significantly lower in the p-CRC than in the controls.The comparison of these genera between the Ob and nOb in p-CRC showed that the relative abundance of the genus Enterococcus was significantly lower in the Ob patients.The relative abundance of the genus Enterococcus positively correlated with LDL level in the p-CRC, particularly in the Ob patients (r = 0.74).In the genus Enterococcus, the most abundant species in p-CRC was E. fecalis, which was observed in lower relative abundance in Ob patients than in nOb patients ( p < 0.01).Conclusion: Our study demonstrated several compositional alterations of the gut microbiota in patients with CRC and suggested that decreased E. faecalis is associated with the obesity-related CRC development.The gut microbiota could provide potential mechanistic insights into obesity-related colorectal carcinogenesis.