Lifestyle influences of the gut microbiota and implications on vascular health

Abstract

Background: The gut microbiota provides multiple physiological functions to facilitate the health of an individual and its dysbiosis is related to the pathophysiology of multiple diseases. Previous studies have shown that diet has a major role in shaping the gut microbiota of an individual, specific food groups and nutrients are shown to induce alterations of gut microbiome diversity and compositions. These studies mainly focused on the diet of Caucasian cohorts while little has been done to characterize the interactions between the local Chinese diet with the gut microbiota. Sodium, a known independent risk factor of hypertension, is shown to be associated with gut microbiota changes in the literature. However, human studies regarding this topic are very limited. Objectives: In this thesis, I firstly aimed to determine the dietary profile of Hong Kong Chinese, as well as its associations with blood pressure and vascular health. I then aimed to determine the sodium intake of Hong Kong Chinese and correlate these with blood pressure, vascular health, long-term estimated stroke risk, the gut microbiota and gut microbiota mediated short chain fatty acids (SCFA). Finally, I aimed to determine whether various vascular health parameters, gut microbiota and gut-mediated SCFAs differs in Hong Kong Chinese with different dietary patterns, such as those categorized using the Healthy Eating Index (HEI) or adhering to the Mediterranean diet (MD) and Dietary Approach to Stop Hypertension (DASH) diet. Methods: I conducted a cross-sectional study during the period 1st July 2018 and 30th June 2020 and recruited 241 Hong Kong Chinese subjects satisfying the inclusion and exclusion criteria. All subjects had vascular assessments including clinic blood pressure, 24-hour ambulatory blood pressure, and arterial stiffness represented by pulse wave velocity. A 7-day dietary recall was performed for all subjects, and their intake of various macronutrients, micronutrients and food groups determined. Dietary pattern scores including HEI, MD and DASH diet scores were calculated accordingly. All recruited subjects had blood drawn under fasting conditions for biochemical and SCFAs estimations. Urine samples were collected for spot urine sodium estimation. Stool sample was submitted by all subjects for gut microbiome analysis. Downstream processing including DNA extraction and next generation sequencing (NGS) were performed in collaboration with the Centre for PanorOmic Sciences (CPOS) of the University of Hong Kong. Taxonomic and functional profiling, and bioinformatics analysis were subsequently performed to determine the associations of dietary components and dietary patterns scores with the gut microbiota. Results: Hypertensive subjects were more likely to be older, of male sex, eversmokers, had a higher body mass index and waist hip ratio, worse vascular health and a higher stroke risk. A higher red and organ meat intake were significant independent predictors of raised systolic and diastolic blood pressure; whilst fruit intake were significant negative independent predictors of blood pressure. The mean estimated sodium intake estimated from spot urine was much higher than the World Health Organisation (WHO) intake recommendations. Consistent with the literature, the sodium intake estimated from spot urine of a subject was shown to be significantly correlated with blood pressure, vascular health and stroke risk. Interestingly, there were no significant associations between sodium intake with gut microbiota diversity nor with individual gut microbiota phylum and species. Similarly, except for a significant positive correlation with butyric acid (only when stratified by sex) and iso-butyric acid, no significant associations between sodium intake with stool and plasma SCFAs were noted. In the analysis of the dietary pattern scores including the HEI, MD and DASH, results of the HEI were the most significant, negative associations with body mass index, ever smoking history, sodium intake and blood pressure were established. Given its negative association with blood pressure, further multivariate adjusted linear regression analysis showed that HEI is a significant negative predictor on blood pressure. In the analysis with the gut microbiome, significant differences in the beta diversity of the gut microbiome between high and low HEI scorers were observed. Despite no significant associations with Shannon diversity, Firmicutes to Bacteroidetes ratio and the abundance of bacteria phyla were seen, at the species level, Eubacterium sp CAG 251, Anaerostipes hardus and Eubacterium eligens species were significantly enriched in individuals with a high HEI scores, whilst Bifidobacterium adolescentis and Acidaminococcus intestine and Collinsella aerofaciens (only male) were significantly enriched in those with a low HEI score. A higher HEI was also independently associated with a lower propionic acid level, after adjusting for other confounding factors. Conclusions: The identification of key dietary predictors of blood pressure can help guide future public health measures to improve the cardiovascular health of the population. No significant associations between sodium intake and the gut microbiome in this cohort provides new information in understanding the sodium-gut microbiome interaction in human subjects. Among the dietary pattern scores, HEI is possibly the most comprehensive score as a dietary quality assessment tool to guide healthy diet of the local population. The changes in the gut microbiome identified fill in the knowledge gap on the associations of HEI with the gut microbiome in a Chinese cohort and help explain how adherence to HEI brings health to an individual.