Two recent case reports of ulcerative colitis 1,2 demonstrated the ef fi cacy of a new therapeutic option for ulcerative colitis. Both cases of ulcerative colitis had failed treatment with salazopyrin and all forms of immunotherapy so that a panproctocolectomy had been recommended. Before proceeding with surgery, the cases were offered fecal microbial transplants (FMT) followed by intake of a low sulfur amino acid diet. Both cases healed all mucosal ulcers and have been in remission for 18 and 24 months, respec-tively. These results were rapidly reproduced by others 3 who how-ever used a different diet but still low in sulfur amino acids.

Most models of experimental colitis do not replicate human ulcerative colitis and do not help in defining the causation of human ulcerative colitis. Inducing pantothenic acid deficiency in pigs produces an ideal model in terms of extent, histology, and chronicity of human ulcerative colitis. Comparing metabolic changes in human ulcerative colitis with metabolic changes in experimental colitis in pigs provided a guide for the search of initiating factors of human ulcerative colitis. Observations showed that bacterial nitric oxide with bacterial hydrogen sulphide reproduced the metabolic changes of human ulcerative colitis. Decreasing colon-produced nitric oxide and hydrogen sulphide by bacteria through diet and medication resulted in pronounced therapeutic improvement, both clinically and histologically, of human ulcerative colitis.

Introduction Diversion colitis, a nutritional deficiency disease of short chain fatty acids (SCFAs) in the defunctioned rectum, responds to butyrate enemas but these are impracticable due to unpleasant malodour. Treatment with rapidly fermentable fibre to SCFAs as suppositories, seemed a preferable option and was tested. Methods “Hi-maize 260” which is naturally high in resistant starch and is optimally fermented to n-butyrate in the colon1 was formulated into 2.0 g suppositories with a binding agent of cocoa butter. Patients were selected on symptoms (blood stained discharge, or anorectal discomfort) for treatment. Suppositories were used on alternative nights for 14 days. Colonoscopic examination of the rectum was performed before and 6 days after completion of treatment. Results “Hi-maize 260” produces a concentration of 20.3 mmol of butyrate in the colon. The diverted rectum of three patients showed severe macroscopic proctitis and mucosal appearances returned to normal after 2 weeks treatment. Long term recovery was not assessed as two patients had the diversion reversed. Conclusion Dietary fibre suppositories are a convenient treatment for diversion colitis. The healing capacity of fermentable fibre should enable distinction between diversion colitis and ulcerative colitis or Crohn9s Disease in a diverted rectum where further reconnection or proctectomy might be contemplated. Competing interests None declared. Reference 1. Le Leu RK,et al. Effect of high amylose maize starches on colonic fermentation and apoptotic response to DNA-damage in the colon of rats. Nutr Metab 2009;6:11–20.

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BACKGROUND:Factors initiating human ulcerative colitis (UC) are unknown. Dysbiosis of bacteria has been hypothesized to initiate UC but, to date, neither the nature of the dysbiosis nor mucosal breakdown has been explained.AIM:To assess whether a dysbiosis of anaerobic nitrate respiration could explain the microscopic, biochemical and functional changes observed in colonocytes of UC.METHODS:Published results in the gastroenterological, biochemical and microbiological literature were reviewed concerning colonocytes, nitrate respiration and nitric oxide in the colon in health and UC. A best-fit explanation of results was made regarding the pathogenesis and new treatments of UC.RESULTS:Anaerobic nitrate respiration yields nitrite, nitric oxide (NO) and nitrous oxide. Colonic bacteria produce NO and UC in remission has a higher lumenal NO level than control cases. NO with sulphide, but not NO alone, impairs beta-oxidation, lipid and protein synthesis explaining the membrane, tight junctional and ion channel changes observed in colonocytes of UC. The observations complement therapeutic mechanisms of those probiotics, prebiotics and antibiotics useful in treating UC.CONCLUSIONS:The prolonged production of bacterial NO with sulphide can explain the initiation and barrier breakdown, which is central to the pathogenesis of UC. Therapies to alter bacterial nitrate respiration and NO production need to evolve. The production of NO by colonic bacteria and that of the mucosa need to be separated to pinpoint the sequential nature of NO damage in UC.

Tissue lipogenesis is variably controlled by substrate supply and hormones. The possibility that nitric oxide (NO) might regulate lipogenesis derives from the action of NO on coenzyme A (CoA) to produce metabolically inactive S-nitrosoCoA. The effect of the nitric oxide donor S-nitrosoglutathione (GSNO) on long chain fatty acid and cholesterol synthesis was measured in isolated cultured rat hepatocytes. [1-14C] Butyrate was used as substrate to measure 14C incorporation into lipids as butyrate is twice as effective as acetate in hepatic lipogenesis and is ketogenic via the Lynen cycle. NO very significantly (P < 0.01) impaired long chain fatty acid and cholesterol synthesis an observation dependent upon time of exposure (3 h pre-incubation or 6 h continuous exposure) and concentration of GSNO (500 microM to 2.0 mM). Decrease in hepatic lipogenesis was paralleled by decrease in ketogenesis. ATP levels remained unchanged following short-term exposure to GSNO. Exposure of hepatocytes to GSNO together with 2.0 mM glutathione significantly diminished the inhibition of lipogenesis induced by GSNO alone. Impairment of lipogenesis by GSNO appears not to be limited by energy supply and now adduced, but not proven, to be operative via the degree of inactivation of cytosolic CoA. NO control of lipogenesis could be clinically important where NO production is increased as in demyelinating diseases, chronic arthritis or colitis and in wasting diseases such as AIDS.

Intestinal diversion with reconnection in active Crohn's disease (CD) indicates that luminal contents or bacteria contribute to the formation of CD lesions. Fluorescent staining for mycoplasma in freshly resected Crohn's tissue and electron microscopy reveal intracellular organisms akin to mycoplasma. Historically, tissue culture of CD has shown mycoplasma described as contaminants. Mycoplasma are surface epithelial parasites requiring exogenous cholesterol for membrane stability and cell entry. PCR of intestinal tissue has shown Mycoplasma pneumoniae to be detectable more significantly in CD. Oral M. iowae in experimental poultry localizes to the distal small bowel and colon. Hypothetically, lipopeptides of mycoplasmal membranes are proposed to cause chronicity and stronger immune responses than by other bacteria. 'Intestinal' mycoplasmas, from a number of observations, deserve consideration as organisms mediating inflammation of acute and chronic CD.

OBJECTIVE: Treatment of diverticulitis may change when associated with mucosal inflammation of either ulcerative-like or Crohns-like colitis. To determine effective treatment of diverticular colitis, four cases were analysed. Mechanisms to account for the colitis associated with diverticulitis are put forward. PATIENTS AND TREATMENT: Four cases had colitis and active diverticulitis established by clinical, colonoscopic or CT evidence of active inflammation. Biopsies confirmed mucosal inflammation: two with ulcerative colitis-like and two with granulomata suggestive of Crohns-like colitis. Treatment for colitis in all cases included sulphasalazine and steroids in two cases. RESULTS: Colitis subsided in three cases but one had continuing inflammatory polyps and one case did not resolve. Segmental resection was performed in two cases one with continuing colitis and one with inflammatory polyps. No further attacks of colitis have occurred since the initial observations were made or operations performed. CONCLUSION: An association of colitis with diverticulitis has been confirmed by present observations and case reports of others. Colitis requires medical treatment and if inflammation fails to resolve, segmental resection is indicated. Diverticular colitis, either ulcerative colitis-like or Crohns-like, is part of the spectrum of acute diverticulitis.