The gut microbiota and the bile acid pool play pivotal roles in maintaining intestinal homeostasis. Bile acids are produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. Gut dysbiosis has been reported to be associated with colorectal cancer. However, the interplay between bile acid metabolism and the gut microbiota during intestinal carcinogenesis remains unclear. In the present study, we investigated the potential roles of bile acids and the gut microbiota in the cholic acid (CA; a primary bile acid)‐induced intestinal adenoma‐adenocarcinoma sequence.
Apc
min/+
mice, which spontaneously develop intestinal adenomas, were fed a diet supplemented with 0.4% CA for 12 weeks. Mice that were fed a normal diet were regarded as untreated controls. In CA‐treated
Apc
min/+
mice, the composition of the gut microbiota was significantly altered, and CA was efficiently transformed into deoxycholic acid (a secondary bile acid) by the bacterial 7α‐dehydroxylation reaction. The intestinal adenoma‐adenocarcinoma sequence was observed in CA‐treated
Apc
min/+
mice and was accompanied by an impaired intestinal barrier function and IL‐6/STAT3‐related low‐grade inflammation. More importantly, microbiota depletion using an antibiotic cocktail globally compromised CA‐induced intestinal carcinogenesis, suggesting a leading role for the microbiota during this process. Overall, our data suggested that the crosstalk between bile acids and the gut microbiota mediated intestinal carcinogenesis, which might provide novel therapeutic strategies against intestinal tumor development.
The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.
AimPatients with small serrated adenomas (SAs) (<10 mm) often undergo surveillance colonoscopy before the routine recommended time. We aimed to determine the appropriate surveillance intervals following polypectomy of small SAs for symptomatic patients.MethodWe retrospectively reviewed the data of 638 patients, including 122 cases and 516 controls. Subjects in the case group had small SAs at baseline colonoscopy, including sessile SA/polyps and traditional SAs, while subjects in the control group had negative findings. All patients underwent at least one surveillance colonoscopy during the following 5 years.ResultsThere was no significant difference in the incidence rate of advanced neoplasia between the two groups over a 5-year duration (3.6% vs 2.6%, p=0.455). Moreover, both groups also showed a low prevalence of SA formation over 1–5 years (3.6% vs 1.0%, p=0.145). Patients with baseline SA tended to undergo the first surveillance colonoscopy earlier than those without adenoma (≤1 year vs 1 to ≤3 years). Seventy-one (11.1%) of the total included subjects underwent inadequate initial colonoscopy, and 30 (42.3%) underwent early surveillance of adenoma formation within 1 year. Patients with a family history of colorectal cancer (OR 4.69, 95% CI 1.48 to 14.71, p=0.017) or inadequate baseline colonoscopy (OR 3.17, 95% CI 1.202 to 8.409, p=0.035) were at a higher risk of metachronous adenoma formation during the surveillance period.ConclusionPatients with small SAs at baseline gain little benefit from follow-up of colonoscopy within 5 years after complete polypectomy.
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