High-Soluble-Fiber Diet Attenuates Hypoxia-Induced Vascular Remodeling and the Development of Hypoxic Pulmonary Hypertension.

BACKGROUND: Hypoxic pulmonary hypertension is a difficult disease to manage that is characterized by sustained elevation of pulmonary vascular resistance and pulmonary artery pressure due to vasoconstriction, perivascular inflammation, and vascular remodeling. Consumption of soluble-fiber is associated with lower systemic blood pressure, but little is known about its ability to affect the pulmonary circulation. METHODS: Mice were fed either a low- or high-soluble-fiber diet (0% or 16.9% inulin) and then exposed to hypoxia (FiO2, 0.10) for 21 days to induce pulmonary hypertension. The impact of diet on right ventricular systolic pressure and pulmonary vascular resistance was determined in vivo or in ex vivo isolated lungs, respectively, and correlated with alterations in the composition of the gut microbiome, plasma metabolome, pulmonary inflammatory cell phenotype, and lung proteome. RESULTS: High-soluble-fiber diet increased the abundance of short-chain fatty acid-producing bacteria, with parallel increases in plasma propionate levels, and reduced the abundance of disease-related bacterial genera such as Staphylococcus, Clostridioides, and Streptococcus in hypoxic mice with parallel decreases in plasma levels of p-cresol sulfate. High-soluble-fiber diet decreased hypoxia-induced elevations of right ventricular systolic pressure and pulmonary vascular resistance. These changes were associated with reduced proportions of interstitial macrophages, dendritic cells, and nonclassical monocytes. Whole-lung proteomics revealed proteins and molecular pathways that may explain the effect of soluble-fiber supplementation. CONCLUSIONS: This study demonstrates for the first time that a high-soluble-fiber diet attenuates hypoxia-induced pulmonary vascular remodeling and the development of pulmonary hypertension in a mouse model of hypoxic pulmonary hypertension and highlights diet-derived metabolites that may have an immuno-modulatory role in the lung.

Using a Metabotype Framework to Deliver Personalized Nutrition Improves Dietary Quality and Metabolic Health Parameters: A 12-Week Randomized Controlled Trial.

SCOPE: Effective strategies for tailoring dietary advice to individuals are urgently needed. The effectiveness of personalized nutrition advice delivered using a metabotype framework in improving dietary quality and metabolic health biomarkers compared to population-level advice is investigated. MATERIALS AND RESULTS: A 12-week parallel randomized controlled trial is performed with 107 healthy adults. Individuals in the personalized group are classified into metabotypes using four markers (triacylglycerol, high-density lipoprotein [HDL]-cholesterol, total cholesterol [TC], and glucose) and received dietary advice from decision tree algorithms containing metabotypes characteristics and individual traits. Individuals in the control group received generic dietary advice based on national guidelines. The personalized approach results in higher dietary quality assessed by the Alternate Mediterranean Diet Score (effect size [95% confidence interval, CI], 0.77 [0.07, 1.48], 12% versus 3% increase) and significantly lower concentrations of triacylglycerol (-0.17 [-0.28, -0.06] log10 mmol L-1 ), TC (-0.42 [-0.74, -0.10] mmol L-1 ), low-density lipoprotein (LDL)-cholesterol (-0.34, [-0.60, -0.09] mmol L-1 ), and lower triacylglycerol-glucose index (-0.40, [-0.67, -0.13]). Sixteen phosphatidylcholines and six lysophosphatidylcholines, predominately with chain lengths of 30-36 carbons, are lower in the personalized group. CONCLUSIONS: Personalized nutrition advice delivered using the metabotype framework is effective to improve dietary quality, which could result in reduced CVD risk, and metabolic heath biomarkers.