Diet and microbiota in inflammatory bowel disease: The gut in disharmony

Bacterial colonization of the gut shapes both the local and the systemic immune response and is implicated in the modulation of immunity in both healthy and disease states. Recently, quantitative and qualitative changes in the composition of the gut microbiota have been detected in Crohn's disease and ulcerative colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism underlying inflammatory bowel disease(IBD) pathogenesis. Humans and microbes have coexisted and co-evolved for a long time in a mutually beneficial symbiotic association essential for maintaining homeostasis. However, the microbiome is dynamic, changing with age and in response to environmental modifications. Among such environmental factors, food and alimentary habits, progressively altered in modern societies, appear to be critical modulators of the microbiota, contributing to or co-participating in dysbiosis. In addition, food constituents such as micronutrients are important regulators of mucosal immunity, with direct or indirect effects on the gut microbiota. Moreover, food constituents have recently been shown to modulate epigenetic mechanisms, which can result in increased risk for the development and progression of IBD. Therefore, it is likely that a better understanding of the role of different food components in intestinal homeostasis and the resident microbiota will be essential for unravelling the complex molecular basis of the epigenetic, genetic and environment interactions underlying IBD pathogenesis as well as for offering dietary interventions with minimal side effects.

Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production

AIM： To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α （TNF-α）, IL-12, and vascular endothelial growth factor （VEGF）, hallmarks of intestinal inflammation in Crohn＇s disease （CD）. METHODS： Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4＋ T cells, macrophages, and VEGF＋ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS： Significant reduction in the inflammatory score and in the percentage of VEGF＋ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF＋ cells. CONCLUSION： Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

High prevalence of vitamin A deficiency in Crohn's disease patients according to serum retinol levels and the relative dose-response test

AIM:To assess the vitamin A status of patients with Crohn's disease(CD) by evaluating serum retinol levels and the relative dose response(RDR) test(liver retinol stores).METHODS:Vitamin A nutritional status was measured by serum retinol obtained by high performance liquid chromatography and the RDR test for evaluation of the hepatic stores.Body composition was performed by densitometry by dual-energy X-ray absorptiometry.Vitamin A dietary intake was assessed from a semiquantitative food frequency questionnaire.RESULTS:This study included 38 CD patients and 33 controls.Low serum retinol concentrations were detected in 29% of CD patients vs 15% in controls(P < 0.005).The RDR test was positive in 37% of CD patients vs 12% in controls,which indicated inadequate hepatic vitamin A stores(P < 0.005).Individuals with hypovitaminosis A had lower BMI and body fat compared with those without this deficiency.There was no association between vitamin A deficiency and its dietary intake,ileal location,presence of disease activity and prior bowel resections.CONCLUSION:Patients with CD have higher prevalence of vitamin A deficiency,as assessed by two independent methods.