Short-Chain Fatty Acid Metabolism in Aging and Chronic Obstructive Pulmonary Disease Using Novel Stable Tracer Approach

Abstract

Short-chain fatty acids (SCFA) are primarily produced through intestinal microbial fiber fermentation and adequate production appears important to maintain or improve health and well-being in higher age or chronic disease, e.g. Chronic Obstructive Pulmonary Disease (COPD). SCFA production is commonly estimated through fecal or plasma concentration measurements, but these might not represent intestinal microbial production due to extensive SCFA absorption by colonocytes and high first-pass metabolism. Stable tracer methodology is a more suitable, non-invasive approach to measure in vivo SCFA production but previously used continuous infusion methods are too laborious for usage in large human clinical trials. The aim of this dissertation was to develop and apply a novel approach to assess changes in SCFA metabolism in aging and disease, and is divided into 2 parts: Part 1) To develop a stable tracer pulse approach enabling, in combination with compartmental modeling, the estimation of SCFA kinetics (production, disposal, pool sizes) in an accessible pool (systemic circulation and interstitial fluid) and an inaccessible pool (likely the pool SCFAs produced by intestinal microbiota drain into). SCFA kinetics were measured in aging and COPD. Part 2) To quantify the effect of fermentable fiber (inulin) supplementation on SCFA kinetics in aging and COPD and to determine whether fecal and plasma SCFA concentrations are adequate estimates of SCFA production. The study from Part 1) revealed that SCFA kinetics are reduced in aging but comparable between older adults with and without COPD, and that SCFA production measurements in the accessible pool considerably underestimate production in the inaccessible pool. Studies from Part 2) illustrated that a high inulin intake only induces moderate increases in SCFA production, that the effect is diminished in aging, and that presence of COPD alters the response. Plasma but not fecal concentrations were associated with SCFA production but were less sensitive in identifying group differences. I believe the newly developed approach adds substantial value to the status quo of the field as it allows a more accurate evaluation of nutritional and behavioral modifications on in vivo SCFA production and thus facilitates more tailored nutritional recommendations promoting health and well-being in our aging society.