A positive breath hydrogen test does not predict the occurrence of a spontaneous bacterial peritonitis in cirrhotic patients with ascites.

BACKGROUND/AIMS: A positive breath hydrogen test (BH(2) T) suggesting the presence of a small intestinal bacterial overgrowth (SIBO) might be a factor increasing the risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. In this prospective observational study, we aimed to determine whether a positive BH(2) T was associated in time with the development of SBP in cirrhotics with ascites. METHODS: During a 3-year period, we prospectively included 29 consecutive cirrhotics with ascites but without previous episodes of SBP or recent antibiotherapy. Every 3 months or before in the event of cirrhosis complications, patients underwent clinical examination, routine laboratory tests, analysis of ascitic fluid and a BH(2) T after ingestion of 50 g D-glucose. RESULTS: During a mean follow-up of 12 months (range 3-33), 11 patients were prematurely withdrawn from the study without SBP (3 transplantations, 2 lost to follow-up, 6 deaths from hepatorenal syndrome, terminal liver failure, variceal bleeding or septic shock) and 9 developed SBP. In the 29 patients, 116 BH(2) T were performed and were positive 12 times in 8 patients; however, in the same patient the positivity was not constant during the follow-up and not related to the clinical presence of ascites. Among the 9 patients who developed SBP, only 2 had a previous transitory positive BH(2) T, which became negative at least 3 months before the occurrence of SBP. CONCLUSION: In cirrhotics with ascites the diagnosis of SBP is not associated in time with a recent positive BH(2) T.

Tumor necrosis factor alpha reduces butyrate oxidation in vitro in human colonic mucosa: a link from inflammatory process to mucosal damage?

BACKGROUND: Butyrate produced by colonic bacterial fermentation is the main fuel for colonocytes, glucose being an alternative fuel. During inflammatory bowel disease, butyrate oxidation by colonocytes is impaired, and increased production of proinflammatory cytokines is detected in the colonic mucosa. We hypothesized that proinflammatory cytokines might reduce butyrate oxidation, and we assessed the in vitro effects of 3 proinflammatory cytokines on butyrate and glucose oxidation in colonic mucosa. METHODS: Colonic biopsies were obtained from normal mucosa in 42 patients who underwent a colonoscopy. Biopsies were incubated in RPMI 1640 with [1-14C]-butyrate or [U-14C]-glucose with or without 1 of the 3 following proinflammatory cytokines: tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6. For each cytokine, 4 different concentrations were tested in 8 subjects. Concentrations overlapped those commonly found in inflamed mucosa and had no cytotoxicity as assessed in preliminary experiments using both the trypan blue exclusion test and lactate dehydrogenase release. Production of 14CO2 (picomoles per microgram dry weight per hour) was measured after a 2-hour incubation and expressed as a percentage of the control [14C]-substrate oxidation without cytokines. RESULTS: Whereas glucose oxidation was not affected, butyrate oxidation was reduced significantly (P < 0.05) by TNFalpha at concentrations of 100 (-26 +/- 6%), 1000 (-32 +/- 7%), and 5000 pg/mL (-34 +/- 5%). IL-1beta (0, 500, 5000, and 25,000 pg/mL) and IL-6 (0, 100, 1000, and 5000 pg/mL) did not affect either substrate oxidation. CONCLUSIONS: TNFalpha at concentrations found in inflamed mucosa reduces butyrate oxidation in vitro in mucosa from healthy controls. This result is not caused by a cytotoxic effect of TNFalpha and is not balanced by an increased oxidation of glucose. Reduced butyrate oxidation results in a decreased energy supply to colonocytes and may explain, in part, mucosal damage occurring during attacks of inflammatory bowel disease.