FELLOW:A TUBBS Impact of Dietary Salt on Inflammation and Infection: Insights into Colitis

Research project

Description

Inflammatory Bowel Disease (IBD) is a group of disorders encompassing Crohn’s disease and ulcerative colitis. As such, IBD represents one of the most prevalent gastrointestinal diseases in the US, costing approximately $1.7 billion annually. Because IBD is incurable, patients are forced to endure repeated hospitalizations and surgeries. Moreover, since IBD disproportionately impacts people of low socio-economic status, the cost burden of IBD falls most heavily on those most susceptible to financial hardship.

Extensive research into the genetics of IBD over the last several decades led to the development of several animal models for Crohn’s disease and ulcerative colitis. By comparison, the study of environmental risk factors like diet has accelerated to equivalent levels only in the last few years. Indeed, while a Western diet low in fiber and high in fat has long been suspected in the development of IBD, it was only recently shown that low dietary fiber results in worsened IBD. Commensurate studies of other dietary factors, including salt remain to be performed.

We specifically propose to examine the role of a high-salt diet (HSD). Recent studies show that dietary salt can exacerbate autoimmune encephalitis, suggesting that a HSD could contribute to other auto-immune diseases like inflammatory bowel disease (IBD). Indeed, in preliminary experiments, we have observed that animals on a HSD display exacerbated inflammation and increased inflammatory cytokine production in two models of murine colitis. Our data thus indicates that a HSD can exacerbate intestinal inflammation in mice.

Based on these data, we propose to characterize the enhanced inflammation induced by a HSD, and to elucidate the underlying molecular mechanisms. We specifically hypothesize that certain immune cell populations respond specifically to dietary salt, increasing their inflammatory output in these models of colitis. To address this hypothesis, we will characterize this HSD exacerbated inflammation, determining whether certain cytokines and/or cell populations are affected (AIM 1). We will also specifically examine the role of the innate immune compartment, as well as the serum and glucocorticoid kinase 1 (SGK1), which has previously been described as an osmosensor in Th17 cells (AIM 2).

The implications of this proposal are far reaching. In determining how dietary salt drives IBD, our research may suggest potential drug targets (e.g. signaling pathways responsible for enhanced immune activation), or prophylactic dietary guidelines (i.e. low-salt diets for people with IBD). The latter public health approach is particularly important, as dietary guidelines are inexpensive and can be implemented immediately to provide relief to those suffering with IBD.
StatusActive
Effective start/end date11/1/1510/31/18

Funding

  • NIH National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDKD)

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Colitis
Inflammatory Bowel Diseases
Salts
Inflammation
Infection
Diet
Nutrition Policy
Ulcerative Colitis
Crohn Disease
Cytokines
Population
Sodium-Restricted Diet
Th17 Cells
Genetic Research
Gastrointestinal Diseases
Immune System Diseases
Dietary Fiber
Glucocorticoids
Hospitalization
Phosphotransferases