Gert De Hertogh

Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab.

Background: Immune therapies may act in inflammatory bowel diseases (IBD) by modulating regulatory T cells (Tregs). Therefore, we investigated the effect of infliximab (IFX) therapy on Forkhead box protein3 (Foxp3) T cells in blood and intestinal mucosa from Crohns disease (CD) and ulcerative colitis (UC). Methods: Forty patients with active IBD (23 CD / 17 UC) were treated with IFX 5 mg/kg intravenously at weeks 0, 2, 6, and each 8 weeks thereafter. Blood samples were obtained before every infusion and T‐lymphocyte subsets were characterized by flow cytometry. Foxp3 expression in intestinal biopsies from 43 patients with active IBD (19 CD / 24 UC) before and after IFX infusion and from 6 controls were assessed by quantitative reverse‐transcription polymerase chain reaction and immunohistochemistry. Plasma C‐reactive protein (CRP), clinical response, and endoscopic healing data were collected in parallel. Results: IFX therapy resulted in a significant and sustained relative increase of CD4+CD25+Foxp3+ Treg and of CD4+CD25−Foxp3+ Treg cells in peripheral blood (both P < 0.0001 compared to baseline), particularly in responders (both P < 0.05 compared to nonresponders). The change in CRP over time inversely correlated with the increase of CD25+Foxp3+ cells (P < 0.001, r = −0.39) and durable clinical response was associated with a sustained increase of circulating Foxp3+ cells. Surprisingly, IFX therapy downregulated mucosal mRNA and protein expression of Foxp3 in UC and CD responders (both P < 0.001) but not in nonresponders. Conclusions: IFX therapy has opposite effects in Foxp3+ Treg cells in blood and gut mucosa, which suggests a redistribution of this important T‐cell subset. Inflamm Bowel Dis 2010

The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon

In the present study, the production and fate of bacterial metabolites in the colon were investigated in a direct way using two substrates labelled with stable isotopes: lactose [(15)N,(15)N]ureide as a source of labelled ammonia and egg proteins intrinsically labelled with [(2)H4]tyrosine as a precursor of [(2)H4]p-cresol. Both ammonia and phenolic compounds are believed to be carcinogenic. Stimulation of carbohydrate fermentation in order to prevent accumulation of these toxic metabolites was induced by inclusion of inulin in a test meal or by addition of inulin to the daily diet, allowing us to distinguish between changes induced by the actual presence of a fermentable carbohydrate and effects caused by a long-term dietary intervention. When a single dose of inulin was administered together with the labelled substrates, a significant increase in faecal (15)N excretion, accompanied by a proportional decrease in urinary (15)N excretion was observed, probably reflecting an enhanced uptake of ammonia for bacterial biosynthesis, since an increased concentration of labelled N in bacterial pellets was found. A statistically significant reduction of urinary [(2)H4]p-cresol excretion was also noted. Upon supplementation of inulin to the daily diet during 4 weeks, however, only a tendency towards decreased urinary excretion of both labelled and unlabelled p-cresol was noted. Further studies are warranted to confirm these results in a larger cohort.