High-Density Lipoprotein Cholesterol as a Potential Medium between Depletion of Lachnospiraceae Genera and Hypertension under a 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 people who resided in Sunan County in China’s nomadic steppes, with little population movement. To investigate gut microbial contributions to this high incidence of 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 to 43.3%) than the average in China (23.2%), under a special high-calorie diet based on wheat, cattle, mutton, and animal offal. Investigations of the fecal microbiota of another cohort of 153 individuals revealed that certain Lachnospiraceae genera were positively correlated with high-density lipoprotein cholesterol (HDL-C) but negatively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP). HDL-C was negatively correlated with SBP and DBP. We further observed that the serum butyrate content was lower in both Han and Yugur people with hypertension than in those without hypertension. This study gives 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. IMPORTANCE Dietary nutrients can be converted by the gut microbiota into metabolites such as short-chain fatty acids, which may serve as disease-preventing agents in hypertension. Due to the limited population mobility and unique high-calorie dietary habits, the cohort of this study can serve as a representative cohort for elucidating the associations between the gut microbiota and hypertension under a 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 new insight showing that low levels of HDL-C may be a potential medium between the depletion of Lachnospiraceae genera and hypertension under a high-calorie diet, which might also be a potential candidate for other CVDs.