Identification and Characterization of a Novel Association between Dietary Potassium and Risk of Crohn’s Disease and Ulcerative Colitis

Abstract

BackgroundRecent animal studies have identified that dietary salt intake may modify the risk and progression of autoimmune disorders through modulation of the IL-23/TH17 pathway, which is critical in the pathogenesis of ulcerative colitis (UC) and Crohn’s disease (CD).MethodsWe conducted a prospective study of U.S. women enrolled in the Nurses’ Health Study (NHS) and NHSII who provided detailed and validated information on diet and lifestyle beginning in 1984 in NHS and 1991 in NHSII. We confirmed incident cases of UC and CD reported through 2010 in NHS and 2011 in NHSII. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. In a case–control study nested within these cohorts, we evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes involved in TH17 pathway and dietary potassium on risk of CD and UC. In a cohort of healthy volunteers, we also assessed the effect of supplemental potassium on development of naïve and memory T cells, differentiated with TGFβ1 or TH17 conditions.ResultsAmong a total of 194,711 women over a follow-up of 3,220,247 person-years, we documented 273 cases of CD and 335 cases of UC. Dietary intake of potassium (Ptrend = 0.005) but not sodium (Ptrend = 0.44) was inversely associated with risk of CD. Although, both dietary potassium and sodium were not significantly associated with risk of UC, there was a suggestion of an inverse association with dietary potassium (Ptrend = 0.08). The association of potassium with risk of CD and UC appeared to be modified by loci involved in the TH17 pathway that have previously been associated with susceptibility to CD, particularly SNP rs7657746 (IL21) (Pinteraction = 0.004 and 0.01, respectively). In vitro, potassium enhanced the expression of Foxp3 in both naïve and memory CD4+ T cells via activating Smad2/3 and inhibiting Smad7 in TH17 cells.ConclusionDietary potassium is inversely associated with risk of CD with both in vitro and gene–environment interaction data suggesting a potential role for potassium in regulating immune tolerance through its effect on Tregs and TH17 pathway.

Urinary potassium is a potential biomarker of disease activity in Ulcerative colitis and displays in vitro immunotolerant role

“…Both murine and human studies have depicted the role of NaCl in inducing Th17 related molecules while suppressing the Treg function via SGK1 signaling, thereby developing a more severe colitis in mice and aggravated disease activity in humans 19 . On the contrary, potassium enhanced the generation of FoxP3 + Treg cells in the presence of TGFβ1 and reinforced the Foxp3 expression in Th17 cells by activating Smad2/3 and inhibiting Smad 7 expression 20 . In mouse model of CKD, potassium supplementation down-regulates NF-κB and TGF β pathways and up-regulates Smad 7, thereby shifting the balance against pro-inflammatory state 21 .…”

A nátrium immunmoduláns szerepe

“…A kevés számú humán vizsgálat eredménye sem egybehangzó. A Nurse's Health Study nem talált szignifikáns kapcsolatot a magas sófogyasztás és a Crohn-betegség kialakulásának kockázata között, ellenben érdekes módon a káliumbevitel negatívan korrelált vele [59]. A jelenség magyarázatát adja az az önkénteseken végzett vizsgálat, amelyben Na + -terhelést követően a párhuzamosan adott kálium az SGK1-útvonalon hatva csökkentette a Na + által okozott IL17A-termelést [60].…”

The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview

“…Introductory analyses of gene-environmental interplay in studies involving dietary factors in IBD have been increasingly promising [236][237][238][239]. A study from the NHS and NHSII, which involved 169 patients with CD and 202 cases with UC matched to 740 participants as control, analyzed the reciprocal action between total dietary consumption of iron and heam iron and genetic variants related with risk factors of IBD [240].…”

“…In an identical population, in a NCC (nested case-control) study of 202 cases with UC and 169 patients with CD in the NHS and NHSII cohorts matched to 740 participants as control based on age, menopausal situation, period of blood withdrawal collection and fasting status, an interplay between dietary potassium consumption and genetic variants in the IL-23 pathway that have been previously related with risk of IBD in GWAS was identified [234,236]. Particularly, the rs7657746 variant of IL21 (which encodes IL-21) appeared to modify the relationship between potassium consumption and risk of IBD pathogenesis.…”