Colorectal cancer and inulin supplementation: the good, the bad, and the unhelpful.

The prebiotic inulin has been vaunted for its potential to reduce the risk of colorectal cancer. Inulin fermentation resulting in the production of short-chain fatty acids, primarily butyrate, has been reported to be associated with properties that are beneficial for gut health and has led to an increased consumption of inulin in the Western population through processed food and over-the-counter dietary supplements. However, in clinical trials, there is limited evidence of the efficacy of inulin in preventing colorectal cancer. Moreover, recent data suggest that improper inulin consumption may even be harmful for gastro-intestinal health under certain circumstances. The main objective of this review is to provide insight into the beneficial and potentially detrimental effects of inulin supplementation in the context of colorectal cancer prevention and enhancement of treatment efficacy.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

PURPOSE: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. EXPERIMENTAL DESIGN: We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. RESULTS: Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. CONCLUSIONS: Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.

Gut microbiota influence anastomotic healing in colorectal cancer surgery through modulation of mucosal proinflammatory cytokines.

OBJECTIVE: Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing. DESIGN: The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo. RESULTS: Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery. CONCLUSION: Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.

Clinical validation of the SIMPLE classification for optical diagnosis of colorectal polyps.

Background and study aims A novel endoscopic optical diagnosis classification system (SIMPLE) has recently been developed. This study aimed to evaluate the SIMPLE classification in a clinical cohort. Patients and methods All diminutive and small colorectal polyps found in a cohort of individuals undergoing screening, diagnostic, or surveillance colonoscopies underwent optical diagnosis using image-enhanced endoscopy (IEE) and the SIMPLE classification. The primary outcome was the agreement of surveillance intervals determined by optical diagnosis compared with pathology-based results for diminutive polyps. Secondary outcomes included the negative predictive value (NPV) for rectosigmoid adenomas, the percentage of pathology exams avoided, and the percentage of immediate surveillance interval recommendations. Analysis of optical diagnosis for polyps ≤ 10 mm was also performed. Results 399 patients (median age 62.6 years; 55.6 % female) were enrolled. For patients with at least one polyp ≤ 5 mm undergoing optical diagnosis, agreement with pathology-based surveillance intervals was 93.5 % (95 % confidence interval [CI] 91.4-95.6). The NPV for rectosigmoid adenomas was 86.7 % (95 %CI 77.5-93.2). When using optical diagnosis, pathology analysis could be avoided in 61.5 % (95 %CI 56.9-66.2) of diminutive polyps, and post-colonoscopy surveillance intervals could be given immediately to 70.9 % (95 %CI 66.5-75.4) of patients. For patients with at least one ≤ 10 mm polyp, agreement with pathology-based surveillance intervals was 92.7 % (95 %CI 89.7-95.1). NPV for rectosigmoid adenomas ≤ 10 mm was 85.1 % (95 %CI CI 76.3-91.6). Conclusions IEE with the SIMPLE classification achieved the quality benchmark for the resect and discard strategy; however, the NPV for rectosigmoid polyps requires improvement.