Physiological relevance of food grade microcapsules: Impact of milk protein based microcapsules on inflammation in mouse models for inflammatory bowel diseases.

In order to increase beneficial effects of bioactive compounds in functional food and dietary supplements, enormous efforts are put in the technological development of microcapsules. Although these products are often tailor-made for disease susceptible consumer, the physiological impact of microcapsule uptake on the respective target consumer has never been addressed. The present study aimed to assess the relevance of this aspect by analyzing the impact of milk protein based microcapsules on experimental inflammatory bowel disease. Long-term feeding of sodium caseinate or rennet gel microcapsules resulted in significant alterations in the intestinal microbiota of healthy mice. In TNFΔARE/wt mice, a model for chronic ileal inflammation, rennet gel microcapsules resulted in further increased splenomegaly, whereas ileal inflammation was unchanged. In IL10(-/-) mice, a model for chronic colitis, both types of microcapsules induced a local increase of the intestinal inflammation. The present study is the first to demonstrate that, independent of their cargo, microcapsules have the potential to affect the intestinal microbiota and to exert unprecedented detrimental effects on disease-susceptible individuals. In conclusion, the impact of microcapsule uptake on the respective target consumer groups should be thoroughly investigated in advance to their commercial use in functional food or dietary supplements.

An unusual method of diagnosing a common disease.

A 34-year-old woman presented with non-bloody diarrhoea of 14 days duration and vomiting. Physical examination was unremarkable. She had hypokalaemia and metabolic acidosis. Stool studies were negative for Clostridium difficile toxin, faecal leucocytes and parasites. Colon appeared normal on colonoscopy. Pronounced scalloping of ileal folds was noted on ileoscopy. Ileal biopsies revealed villous blunting, crypt hyperplasia, marked intraepithelial lymphocytosis and lymphocytic infiltration of the lamina propria, consistent with lymphocytic ileitis in coeliac disease. Serology revealed elevated antitissue transglutaminase IgA antibodies (>100 U/ml). Institution of a strict gluten free diet resulted in complete resolution of symptoms. Although rare, coeliac disease can present as an acute diarrhoeal illness and should be considered after infectious aetiologies are excluded.

Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions.

A study was conducted in healthy elderly living independently in senior housing to assess the impact of a probiotic yoghurt supplement on small intestinal bacterial overgrowth. Twenty-three participants with positive and thirteen participants with negative hydrogen breath test were studied before and after a period of 4 weeks of probiotic yoghurt administration. Intestinal permeability, plasma endotoxin levels, phagocytic activity of leucocytes, cytokine production by monocytes and free radical response of neutrophils were determined. Intestinal permeability was similar for the two groups and was unaffected by probiotic treatment. Both plasma endotoxin levels and the basal phagocytic activity of leucocytes decreased after yoghurt intake in the two groups. Exposure of monocytes and neutrophils ex vivo led to an increased cytokine response and free radical response, respectively. The normalisation of the various cytokine responses was more apparent in the group with positive breath test. In addition, the plasma levels of lipoplysaccharide binding protein and soluble CD14, lipoplysaccharide pattern recognition receptors and surrogate markers of lipoplysaccharide permeability were diminished by the end of the study. In conclusion, probiotic administration in the elderly normalises the response to endotoxin, and modulates activation markers in blood phagocytes, and therefore may help reduce low-grade chronic inflammation.

Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation?

Intestinal glutamine utilization is integral to mucosal regeneration. We analyzed the systemic and intestinal glutamine status in Crohn's disease (CD) and evaluated the therapeutic effect of glutamine supplementation in an animal model of ileitis. In CD, glutamine concentrations were decreased systemically and in noninflamed and inflamed ileal/colonic mucosa. Mucosal glutaminase activities were depressed in the ileum independent of inflammation but were not different from controls in the colon. In experimental ileitis, oral glutamine feeding prevented macroscopic inflammation, enhanced ileal and colonic glutaminase activities above controls, and normalized the intestinal glutathione redox status. However, glutamine supplementation enhanced myeloperoxidase activity along the gastrointestinal tract and potentiated lipid peroxidation in the colon. In conclusion, glutamine metabolism is impaired in CD. In experimental ileitis, glutamine supplementation prevents inflammatory tissue damage. In the colon, however, which does not use glutamine as its principal energy source, immune enhancement of inflammatory cells by glutamine increases oxidative tissue injury.

Simultaneous diagnosis of ulcerative jejunoileitis and coeliac disease in an elderly man.

Ulcerative jejunoileitis (UJI) is a rare condition which usually develops in patients with established or simultaneously diagnosed coeliac disease (CD) and has been suggested to represent cryptic low-grade enteropathy-associated T-cell lymphoma (EATL). We report a case of a 78-year-old male patient with UJI and CD diagnosed at the same time. He presented with abdominal pain, diarrhoea and weight loss and had serological, endoscopical, radiological and histological findings compatible with the diagnoses of both UJI and CD. The possibility of EATL was carefully excluded. The patient exhibited significant symptomatic improvement with a gluten-free diet, probably indicating an early stage of disease despite his old age. In conclusion, this rather unusual case of an elderly patient presenting with UJI and CD without evidence of EATL supports the great heterogeneity of these diseases not only in their clinical presentation but even in their course and complications.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

BACKGROUND AND AIMS: Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. METHODS: Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. RESULTS: Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. CONCLUSIONS: Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.

Medium-chain triglycerides modulate ileitis induced by trinitrobenzene sulfonic acid.

BACKGROUND: It is important to develop an appropriate animal model for further investigation into inflammatory bowel disease (IBD). We therefore investigated a trinitrobenzene sulfonic acid (TNBS) ileitis model. Dietary fat in Crohn's disease is still a controversial risk factor for IBD. We therefore also studied the effects of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) on TNBS ileitis. METHODS AND RESULTS: An intraileal injection of TNBS induced ulceration and inflammation with thickening of the intestinal wall, which were characterized histologically by infiltration of polymorphic nuclear leucocytes and by granuloma formation. The mucosal damage score and serum sialic acid levels reached their highest 7 days after the TNBS injection and then gradually decreased. The mucosal damage series in the MCT group was significantly lower than in the LCT group, and levels of tumour necrosis factor-alpha (TNF-alpha) and leukotriene B4 (LTB4) tended to be lower in the MCT group. CONCLUSIONS: These results suggested that TNBS enteritis might be useful as an IBD animal model and that MCT modulates intestinal inflammation and is less damaging than LCT.

Angioimmunoblastic lymphadenopathy, sulphasalazine exposure and villous atrophy.

A woman with inflammatory lesions in the terminal ileum was treated with sulphasalazine. Nine months later she developed angioimmunoblastic lymphadenopathy and was found to have intestinal villous atrophy. Her systemic illness partially responded to oral steroids but a gluten free diet restored clinical and biochemical well being coincident with a return of her villous pattern.