HDL-C as a potential medium between depletion of Lachnospiraceae genera and hypertension under high-calorie diet

Gut microbial dysbiosis has been associated with hypertension. An extremely high incidence of essential hypertension was found in the Han and the Yugur who resided in Sunan county in East Asias nomadic steppes with little population movement. In attempt to investigate the gut microbial role in hypertension, we recruited a total of 1, 242 Yugur and Han people, who had resided in Sunan County for more than 15 years and accounted for 3% of the local population. The epidemiological survey of 1,089 individuals indicated their nearly 1.8 times higher prevalence of hypertension (38.2-43.3%) than the average in China (23.2%), under a special high-calorie diet based on wheat, cattle, mutton, and animal offal. The 16S rRNA gene sequencing on the fecal samples of 153 individuals revealed that certain Lachnospiraceae genera were negatively correlated with high-density lipoprotein cholesterol (HDL-C, P = 5.46 x 10-6), systolic blood pressure (SBP, P = 7.22 x 10-3), diastolic blood pressure (DBP, P = 1.8 x 10-3). HDL-C was positively correlated with SBP (P = 0.023). We further observed that serum butyrate content was lower in both Han (P = 1.99 x 10-3) and Yugur people (P = 0.031) with hypertension than those without hypertension. This study gives a novel insight into the role of gut microbial dysbiosis in hypertension modulation under a high-calorie diet, where the notable depletion of Lachnospiraceae genera might lead to less production of butyrate, contributing to the lower level of HDL-C, and elevating blood pressure in hypertension. IMPORTANCEDietary nutrients can be converted by gut microbiota into metabolites such as short-chain fatty acids, which may serve as disease-preventing agents in hypertension. Due to limited population mobility and a unique high-calorie dietary habit, the recruited cohort in this study could be a representative for elucidating the associations between gut microbiota and hypertension under high-calorie diet. Moreover, low levels of HDL-C have previously been associated with an increased risk of various cardiovascular diseases (CVDs). Our findings provide a new insight that low levels of HDL-C may be a potential medium between depletion of Lachnospiraceae genera and hypertension under high-calorie diet, which might also be a potential candidate for other CVDs.