A possible role for bile acid in the control of methanogenesis and the accumulation of hydrogen gas in the human colon

Abstract This study investigated a possible role for primary bile acid in the control of methanogenesis in the human colon. Production of hydrogen and methane was measured in anaerobic faecal cultures derived from faeces of six ‘non‐methanogenic’ and three methanogenic healthy humans. Using a sensitive technique for gas measurement, methane was detected in all faecal cultures, including those from ‘non‐methanogenic’ humans. Bile acid inhibited methanogenesis in a dose‐response fashion in the in vitro‘non‐methanogenic’ and methanogenic faecal cultures. Inhibition was significant at bile acid concentrations > 0.05%. Methanogenesis correlated with methanogen (methanogenic bacteria) numbers. If this inhibition occurs in vivo, then it would explain much of the epidemiology of non‐methanogenesis in humans. From an analysis of net hydrogen production by the faecal cultures, it is inferred that bile acid inhibits other hydrogen‐consuming bacteria in addition to methanogens. These in vitro data suggest a major role for bile acid in the accumulation of hydrogen gas in the colon. Possible links between bile acid induced accumulation of gas and irritable bowel syndrome are discussed

Inhibition of methanogenesis by human bile

The factors that regulate methanogenesis in humans have not been established. The presence of bile acid, which is lost into the colon from the small intestine, may be an important regulatory factor of methanogenesis. To examine this possibility, the effect of human bile on methane production by faecal cultures, and the in vivo effect of biliary diversion on breath methane excretion in a methanogenic choledochostomy patient, were investigated. Faecal suspensions (0.1%) from five methanogenic humans were incubated anaerobically with bile (0.3-30%) from three choledochostomy patients, and headspace methane measured by gas chromatography. All biles inhibited headspace methane. Inhibition of methanogenesis was dose dependent, plateaued at 10-30% bile concentration, and was abolished by 0.6% cholestyramine. The maximum inhibition by bile, median (range), was 38 (0.9-56%) of control methane values. Reversal of the bile fistula in the fourth choledochostomy patient converted that subject from methanogenic to 'non-methanogenic' status. It is concluded that inhibition of methanogens in the caecum by bile acid could significantly reduce the number of methanogens in the colon. This and the effect of transit time could explain much of the known epidemiology of 'non-methanogenesis', which has been related to obesity, (comparatively) fast colonic transit in healthy persons, and to small intestinal Crohn's disease

Metabolism of dietary sulphate: absorption and excretion in humans

Dietary sulphate may affect colonic pathophysiology because sulphate availability determines in part the activity of sulphate reducing bacteria in the bowel. The main product of sulphate reducing bacterial oxidative metabolism, hydrogen sulphide, is potentially toxic. Although it is generally believed that the sulphate ion is poorly absorbed, there are no available data on how much sulphate reaches the colon nor on the relative contributions from diet and endogenous sources. To resolve these questions, balance studies were performed on six healthy ileostomists and three normal subjects chosen because they did not have detectable sulphate reducing bacteria in their faeces. The subjects were fed diets which varied in sulphate content from 1.6-16.6 mmol/day. Sulphate was measured in diets, faeces (ileal effluent in ileostomists), and urine by anion exchange chromatography with conductivity detection. Overall there was net absorption of dietary sulphate, with the absorptive capacity of the gastrointestinal tract plateauing at 5 mmol/day in the ileostomists and exceeding 16 mmol/day in the normal subjects. Endogenous secretion of sulphate in the upper gastrointestinal tract was from 0.96-2.6 mmol/day. The dietary contribution to the colonic sulphate pool ranged up to 9 mmol/day, there being linear identity between diet and upper gastrointestinal losses for intakes above 7 mmol/day. Faecal losses of sulphate were trivial (less than 0.5 mmol/day) in the normal subjects at all doses. It is concluded that diet and intestinal absorption are the principal factors affecting the amounts of sulphate reaching the colon. Endogenous secretion of sulphate by colonic mucosa may also be important in determining amounts of sulphate in the colon

Serious infective complications associated with anti-TNF alpha therapy in inflammatory bowel disease

Background: Anti-TNFαmedications are effective in the management of patients with difficult Crohn’s disease (CD) and ulcerative colitis/IBDU(UC/IBDU). They are, however, associated with an increased risk of tuberculosis (TB) reactivation, initial TB infection, and potentially other bacterial, viral or fungal infections. Aims: To examine the Australasian experience of TB and serious infective complications in IBD patients treated with an anti-TNFα. Methods: Data was collected from eight sites across Australia and New Zealand specialising in IBD management. Overall IBD patient numbers managed, patient numbers ever treated with an anti-TNFα, and patients suffering TB, or a serious infection while receiving anti-TNFαtherapy were analysed. A serious infection was defined as ‘an infection requiring hospital admission’. Patient demographics, concurrent IBD medications, the anti-TNFαmedication used, time on the anti-TNFα, infection type and infection outcome was also collected. Results: A total of 5613 IBD patients (2904 CD, 2709 UC/IBDU) were managed across the centers. Anti-TNFαtherapy was used in 16.9% of CD(491; 442-infliximab, 94-adalimumab, 45-both) and 3.7% of UC/IBDU patients (100 UC/IBDU; 94-infliximab, 14-adalimumab, 8-both). There were no cases of reactivation of latent TB and no new cases reported. There were nine serious infections (4M/5F, 1 UC/IBDU/8 CD, average 36.1 years, range 14–57 years). Infections occurred in three patients receiving 24 months of an anti-TNFα. All these patients were receiving additional immunosuppressive (IS) medication: 2-pred, 1-pred/AZA, 2-AZA, 1-methotrexate (MTX), 1-pred/MTX, 1-pred/AZA/MTX and 1-pred/MTX/mycophenolate mofetil. Seven of the infections occurred while on an anti-TNFαand two within 3 months of the last treatment. There were two primary varicella zoster, one Pneumocysits carnii peunmonia, one UTI with enterobacteraerogenes, and five infections where no organ-ism was identified (1 pneumonia, one diverticular abscess, one conjunc-tivitis and two unidentified source). All infections resolved. Conclusion: TB does not appear to be a problem with anti-TNFα therapy in Australasia. Infections, resulting in a hospital admission, are low occur-ring in only 1.8% of patients receiving anti-TNFαtherapy, but all those patients were also on other IS medications. All the infections were successfully treated.IC Lawrance, Pabampton, M Sparrow, RB Gearry, RW Leong, JM Andrews, THJ Florin, A Croft, And GL Radford-Smit

Molecular characterization of the microbial species that colonize human ileal and colonic mucosa by using 16S rDNA sequence analysis

Aim: The aim of this study was to characterize the bacterial community adhering to the mucosa of the terminal ileum, and proximal and distal colon of the human digestive tract. Methods and Results: Pinch samples of the terminal ileum, proximal and distal colon were taken from a healthy 35-year-old, and a 68-year-old subject with mild diverticulosis. The 16S rDNA genes were amplified using a low number of PCR cycles, cloned, and sequenced. In total, 361 sequences were obtained comprising 70 operational taxonomic units (OTU), with a calculated coverage of 82.6%. Twenty-three per cent of OTU were common to the terminal ileum, proximal colon and distal colon, but 14% OTU were only found in the terminal ileum, and 43% were only associated with the proximal or distal colon. The most frequently represented clones were from the Clostridium group XIVa (24.7%), and the Bacteroidetes (Cytophaga-Flavobacteria-Bacteroides ) cluster (27.7%). Conclusion: Comparison of 16S rDNA clone libraries of the hindgut across mammalian species confirms that the distribution of phylogenetic groups is similar irrespective of the host species. Lesser site-related differences within groups or clusters of organisms, are probable. Significance and Impact: This study provides further evidence of the distribution of the bacteria on the mucosal surfaces of the human hindgut. Data contribute to the benchmarking of the microbial composition of the human digestive tract