Overview of “Salt-responsive gut commensal modulates TH17 axis and disease”, by Katie Golden

High salt intake is a known contributor to the development of hypertension. The mechanisms through which salt induces elevated blood pressures are still under investigation, and the majority of research has focused on the renal and nervous systems as key players. Despite a well established link between dietary salt and hypertension, however, we know surprisingly little about the role of the gastrointestinal system in disease progression.

In a paper recently published in Nature, Wilck et.al. explain how high salt intake affects gut microbiomes, and propose a mechanism through which this may contribute to the pathophysiology of hypertension. They start with prior evidence that pathologic activation of T cells (TH17, specifically) plays a role in development of hypertension. Given we also know that induction of TH17 cells is linked to the microbial environment of the gut, researchers asked the next logical question: how does salt intake affect the intestinal microbiome?

Investigators began with a mouse model, and used genetic sequencing to study the fecal microbial profiles of mice fed with high salt versus normal salt loads. After analysis of multiple bacterial populations, they found the Lactobacillus species to be particularly sensitive to this change in diet, with significantly decreased levels detectable as early Day 1 of the study, and continued decline throughout the 14 day length of the study. In the next phase of the study, researchers used flow cytometry to show that mice fed with high salt diets also had significantly higher frequency of TH17 cells, an effect that was then ameliorated when the mice were treated with Lactobacillus supplementation. This supplementation also effectively treated the elevated blood pressures in the high salt group.

In an effort to better understand the link between Lactobacillus species and T cell populations, investigators elaborated on prior research suggesting the disease-protective role of indole metabolites, a known byproduct of Lactobacillus metabolism. As expected, the high salt diet mice had significantly reduced levels of fecal indoles, an effect that again was eliminated with Lactobacillus supplementation. They then used in vitro studies to show that indoles significant reduced TH17 polarization in a dose-dependent manner, uncovering a possible mechanism through with Lactobacillus species prevents pathologic T cell proliferation.

Their findings prompted the investigators to study these effects in humans. Similar to the mouse model, they subjected a small number of healthy male volunteers to a high salt diet for 14 days. In comparison to a control group, the high salt intake group had higher nocturnal blood pressures, an increase in TH17 cells in blood samples, and decreased lactobacillus species in fecal samples (and again, this species was more depleted than other bacterial species.) While the sample size was small, this provided exciting evidence that their findings may have important implications for disease progression in humans.