Salt-sensitive lactobacilli drive down TH17 cells and contribute to normal blood pressure

Most clinically diagnosed hypertensions, high blood pressure, are idiopathic in origin, meaning one can't determine what causes it. First thing patients are asked to do is to modify their diet habits and reduce salt intake. Diet high in salt thought to contribute to hypertension by water retention.

However, it could be that there is another, immunological pathway that contributes to high blood pressure. New study in Nature showed that in mice and maybe in humans as well, high salt diet depletes Lactobacilli, a gut microbiota species shown to lower TH17 differentiation and contributing in maintaining normal blood pressure.

Initially, the authors showed that in mice high salt diet (HSD) depleted several microbiota species, most notable, Lactobacillus murinus (initially identified through sensitive machine learning approach using the AdaBoost classifier from scikit-learn module run on Python).

In autoimmune model, adding Lactobacillus murinus could abolish high salt diet-induced increase in disease severity. Lactobacillus murinus appears to drive down TH17 differentiation (of note, high salt diet did not change TH17 population in germ-free mice).

Mechanistically, the authors showed that Lactobacillus murinus could inhibit TH17 differentiation by producing indole-3-lactic acid (ILA), a product of tryptophan metabolism.

Finally, volunteers on high salt diet display high TH17 differentiation and decrease in gut content for Lactobacilli.

In summary, the authors want to make the case that high salt diet could induce high blood pressure by depleting Lactobacilli and increasing TH17 cells which appear to initiate hypertension-related changes. 

It is clear that depletion of Lactobacilli per se is not sufficient for initiation of hypertension but we don't know what are other remaining microbiota species that actually induce TH17 in humans. Also, it is not clear whether microbiota-derived conserved molecules or metabolites (ILA) are sufficient for initiating hypertension or there are more complex events, such as chronic antigen-specific interactions that are ultimately responsible for sustaining chronicity of TH17 response and hypertension.    

posted by David Usharauli