Impact of dietary interventions on metabolism and the gut-brain axis in adults with metabolic syndrome traits

Abstract

In recent decades, the incidence of obesity and obesity-associated comorbidities such as the metabolic syndrome has exponentially increased in both developed and developing counties. It is widely accepted that inadequate dietary intake, especially a high consumption of ultra-processed, energy-dense foods and sugar-sweetened beverages, which is defined as ‘Western-type’ dietary pattern, is a main contributor to this global development. The Western-type dietary pattern encourages hyperenergetic nutrition leading to weight gain and increased visceral adipose tissue accumulation, which can result in subclinical, systemic inflammation and whole body insulin resistance. Moreover, the Western-type diet has been associated with a dysbiosis of the gut microbiota and age-related cognitive decline and dementia including Alzheimer’s diseases (AD) in epidemiological studies. The aim of this randomized, controlled intervention trial in obese adults with a habitual Western-type diet is to determine the effects of acute and mid-term, potentially health-promoting, dietary interventions on metabolic functions and brain health elucidating underlying mechanisms. <br /> One hundred and twenty obese, cognitively unimpaired adults aged 45 to 70 years with at least one metabolic syndrome trait including visceral fat distribution, (pre)hypertension, dyslipidemia, and a subclinical inflammation underwent a three hours mixed meal tolerance test (MMTT) for deep metabolic characterization. Fasting and multiple postprandial blood samples were collected to follow the time course of serum/plasma levels of insulin, glucose, blood lipids ((non)-LDL cholesterol, non-esterified fatty acids, and triglycerides), the gut hormone glucagon-like peptide 1 (GLP 1) and AD-related proteins (neurofilament light, glial fibrillary acidic protein, amyloid-beta 42/40, phosphorylated (phospho) tau 181 and 231, total-tau). Furthermore, genetic make-up, gut microbiome composition, and fecal microbial metabolites were analyzed. After completing the baseline visit, participants were randomly assigned to one of three study groups: the Nordic diet (ND) group, the lacto-ovo vegetarian diet (VD) group, or the control group (HD). The key components of the ND were berries, green leafy and root vegetables, whole grain from rye, spelt and oat, boiled potatoes, nuts, fish, and rapeseed oil. The VD comprised plant-derived foods complemented milk(products) and eggs. Both intervention diets were designed isoenergetically to ensure a constant body weight during the six weeks study period and were self-prepared by the participants according to detailed recipes. The HD group was instructed to maintain their habitual Western-type diet, physical activity level and body weight over the six weeks study duration. Compliance with the treatment was monitored using six weeks food diaries and a short-form questionnaire to review the frequency of consuming the key food items of the respective study diet as well as anthropometrics and several blood biomarkers as the fatty acids composition of the phospholipids or vitamin levels. After six weeks of dietary intervention, metabolite and microbiome analyses were repeated. <br /> After six weeks of ND intervention, significant reductions in the concentrations of LDL- and non-LDL cholesterol fractions as well as triglycerides and liver enzymes were observed. Both the ND and VD study diet induced taxonomic alterations of the gut microbiome. Correlation analysis of metabolic markers (lipid metabolism and liver enzymes) and the individual microbes revealed more than 80 significant correlations before and after intervention, suggesting a possible involvement of specific microbes in metabolism and outcome measures of the dietary intervention. The success of the ND in reducing blood lipids was determined by the basal gut microbiota composition, as the largest diet-induced reductions were seen in individuals with a specific microbiome signature. Furthermore, it was observed that individuals with the highest genetic risk for dyslipidemia benefited the most from the ND intervention. In fasting and postprandial levels of GLP-1, glucose, insulin, and AD-related protein concentrations, no ND- or VD induced effects were found. However, poorer long-term glucose control and higher fasting plasma glucose levels were associated with higher fasting and postprandial plasma (phospho) tau levels. The consumption of the standardized meal (MMTT) led to immediate changes in AD-related protein concentrations, which exceeded biomarker dynamics observed in the fasting state and were directly attributed to food intake and associated metabolic events. <br /> We concluded that specific microbial signatures and the individual genetic risk have a strong impact on the success of a dietary change, pointing towards a personalized nutrition approach in preventing cardiometabolic diseases. Because of the observed beneficial effects of the ND study diet on blood lipid profile and liver function, we concluded that the ND was superior to VD in reducing cardiometabolic risk factors. As both study diets were applied isoenergetically, the observed findings can directly be attributed to the specific key foods and nutrient profile of the respective dietary pattern. Furthermore, it was convincingly shown that food intake and glucose control have a decisive impact on the concentration of AD-related biomarkers, which should be considered when using these biomarkers for diagnosis and monitoring of disease progression and drug response