Adults with Crohn's disease exhibit elevated gynoid fat and reduced android fat irrespective of disease relapse or remission.

Crohn's disease (CD) is a debilitating inflammatory bowel condition of unknown aetiology that is growing in prevalence globally. Large-scale studies have determined associations between female obesity or low body mass index (BMI) with risk of CD at all ages or 8- < 40 years, respectively. For males, low BMI entering adult life is associated with increased incidence of CD or ulcerative colitis up to 40 years later. Body composition analysis has shown that combinations of lean tissue loss and high visceral fat predict poor CD outcomes. Here, we assessed dietary intake, physical activity and whole or regional body composition of patients with CD relapse or remission. This anthropometric approach found people with CD, irrespective of relapse or remission, differed from a large representative healthy population sample in exhibiting elevated gynoid fat and reduced android fat. CD is associated with mesenteric adipose tissue, or "creeping fat", that envelops affected intestine exclusive of other tissue; that fat is localised to the android region of the body. In this context, CD mesenteric adiposity represents a stark juxtaposition of organ-specific and regional adiposity. Although our study population was relatively small, we suggest tentatively that there is a rationale to refer to Crohn's disease as a fatty intestine condition, akin to fatty liver conditions. We suggest that our data provide early insight into a subject that potentially warrants further investigation across a larger patient cohort.

Disruption of colonic barrier function and induction of mediator release by strains of Campylobacter jejuni that invade epithelial cells.

AIM: To study the mechanisms by which Campylobacter jejuni (C. jejuni) causes inflammation and diarrhea. In particular, direct interactions with intestinal epithelial cells and effects on barrier function are poorly under-stood. METHODS: To model the initial pathogenic effects of C. jejuni on intestinal epithelium, polarized human colonic HCA-7 monolayers were grown on permeabilized filters and infected apically with clinical isolates of C. jejuni. Integrity of the monolayer was monitored by changes in monolayer resistance, release of lactate dehydrogenase, mannitol fluxes and electron microscopy. Invasion of HCA-7 cells was assessed by a modified gentamicin protection assay, translocation by counting colony forming units in the basal chamber, stimulation of mediator release by immunoassays and secretory responses in monolayers stimulated by bradykinin in an Ussing chamber. RESULTS: All strains translocated across monolayers but only a minority invaded HCA-7 cells. Strains that invaded HCA-7 cells destroyed monolayer resistance over 6 h, accompanied by increased release of lactate dehydrogenase, a four-fold increase in permeability to [(3)H] mannitol, and ultrastructural disruption of tight junctions, with rounding and lifting of cells off the filter membrane. Synthesis of interleukin (IL)-8 and prostaglandin E(2) was increased with strains that invaded the monolayer but not with those that did not. CONCLUSION: These data demonstrate two distinct effects of C. jejuni on colonic epithelial cells and provide an informative model for further investigation of initial host cell responses to C. jejuni.

Toxicity of mycophenolate mofetil in patients with inflammatory bowel disease.

Trials of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) suggest that it may be useful in patients intolerant of azathioprine. We examined the safety and efficacy of MMF in IBD patients intolerant of or unresponsive to azathioprine. Twelve patients [seven with Crohn's disease (CD); seven women; mean age 40 years, range 14-76 years] were treated with MMF 500 mg b.i.d. for a mean of 12.5 weeks. Intolerance was defined as the development of side effects that resolved on discontinuing MMF. Improvement was described as symptomatic improvement, decreased steroid use, or disease entering endoscopic remission. Four patients responded with symptomatic improvement and reduced steroids or mesalazine requirement. Three patients developed headache, nausea, or arthralgia. Three patients developed profuse bloody diarrhea, and in two cases with previously quiescent ulcerative colitis (UC), the source was shown to be ulcers in a drug-induced colitis with histologic features similar to those previously reported in four renal transplant patients on MMF. There is no clear evidence of efficacy of MMF in the treatment of IBD, and its use in this condition should be confined to a randomized controlled trial. Moreover, as patients with UC may be unduly prone to colonic injury, MMF may not be a suitable drug for its treatment.