Colonic methane production modifies gastrointestinal toxicity associated with adjuvant 5-fluorouracil chemotherapy for colorectal cancer.

GOALS: To investigate the association of colonic methane, formed by methanogenic achaea, and pH with gastrointestinal symptoms during colorectal cancer chemotherapy. BACKGROUND: Adjuvant 5-fluorouracil chemotherapy reduces recurrences in colorectal cancer, but causes severe gastrointestinal toxicity, partly related to disturbed intestinal microbiota. STUDY: Resected colorectal cancer patients (n=143) were analyzed for colonic methanogenesis and pH before and during the 24 weeks of 5-fluorouracil chemotherapy and for gastrointestinal symptoms during chemotherapy. This study was performed within the setting of an intervention study on the effects of Lactobacillus on chemotherapy-related gastrointestinal toxicity. The site of resected cancer, resection type, stoma, chemotherapy regimen, hypolactasia, and Lactobacillus intervention were considered as possible confounding factors, and multivariate models were constructed. RESULTS: Baseline methane producers had less frequent diarrhea (more than or equal to moderate) during chemotherapy than nonproducers [odds ratio (OR), 0.42; 95% confidence interval (CI), 0.20 to 0.88; P=0.022] and more frequent constipation (OR, 4.56; 95% CI, 2.01 to 10.32; P<0.001). Baseline fecal pH was also associated with symptoms during chemotherapy; higher the pH, the lower the risk of diarrhea (OR, 0.56; 95% CI, 0.31 to 1.02; P=0.058) and higher the risk of constipation (OR, 2.23; 95% CI, 1.35 to 3.68; P=0.002). In multivariate stepwise models, methanogenesis was a significant explaining factor with inverse association with diarrhea and positive association with constipation. Fecal pH, which was significantly associated with methane production, was no longer a significant explaining factor when methanogensis was included in the model. CONCLUSIONS: Methane producer status has a role in determining whether patient experiences diarrhea or constipation during 5-fluorouracil therapy. This underscores the importance of intestinal microbiota in the development of intestinal toxicity during 5-fluorouracil therapy.

Colonic methanogenesis in vivo and in vitro and fecal pH after resection of colorectal cancer and in healthy intact colon.

PURPOSE: We compared colonic methanogenesis in vivo and in vitro as well as fecal pH in healthy subjects and in patients with resected colorectal cancer thus without the possible confounding effects of the tumor. METHODS: A total of 144 subjects, 96 with resected colorectal cancer (of whom, 48 were with metastatic disease), 48 healthy subjects with intact colon, were analyzed for breath methane, fecal methanogenesis in vitro and fecal pH. In addition, the association between methanogenesis and pH with cancer site, operation technique and abdominal discomfort was investigated. RESULTS: In vivo and in vitro methane measurements were in agreement. The percentage of breath methane excretors and fecal pH did not significantly differ in participants resected for colorectal cancer, either with (46%, 6.76) or without (46%, 6.77) metastatic disease, from healthy participants (40%, 6.80). Breath methane excretors had higher fecal pH than nonexcretors (7.05 versus 6.57, P< 0.001) and less abdominal discomfort (30% versus 54%, P = 0.016). Among patients with resected right-sided cancer (n = 15), there were less breath methane excretors (20%) than among those with resected left-sided cancer (51%, n = 81, P = 0.029) as well as lower fecal pH than among those with resected left-sided cancer (6.27 versus 6.86, P = 0.002) and among healthy subjects (6.80, P = 0.010). CONCLUSIONS: Patients with resected colorectal cancer were as frequently methane producers as healthy subjects with intact colon, and there was no difference in their fecal pH. Low methanogenesis was found in patients with abdominal discomfort and is a possible characteristic, along with low fecal pH, to right-sided colorectal cancer.