Fiber Metabolism in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title: Fiber Metabolism in Chronic Obstructive Pulmonary Disease

Status Recruiting

Clinical Trial Summary

The impact of fiber intake on short chain fatty acid (SCFA) metabolism has not been studied in subjects suffering from COPD. The purpose of this study is to compare changes in SCFA metabolism after inulin vs. placebo intake in COPD patients to healthy matched controls. This protocol is an extension of a recent study about whole-body SCFA production rates in COPD patients. The investigators hypothesize that a short-term fiber supplementation increases SCFA production in COPD patients.

Clinical Trial Description

Dietary fibers are indigestible carbohydrates, which are present in several daily foods such as beans, legumes, whole grain products, and whole fruits and vegetables. The Food and Drug Administration recommends a daily fiber uptake of 25 g. However, in 2009-2010 the mean fiber intake of US adults was 17 g/day. Fiber cannot be digested by human enzymes and reach the colon undigested. Depending on the chemical structure (solubility, degree of polymerization) of the fiber, it can or cannot be fermented by the intestinal bacteria. Insoluble, unfermented fibers such as cellulose help to prevent constipation by enhancing bowel movement and the transit time of the feces. Most soluble fibers like inulin can be fermented by intestinal bacteria. During the bacterial fermentation short-chain fatty acids (SCFA) such as acetate (C2), propionate (C3), and butyrate (C4) are produced. The production is highest in the proximal colon where the abundance of fiber is the highest. The colonocytes absorb more than 90 % of the SCFAs, the rest is excreted with the feces. Most of the butyrate is oxidized in the colonocytes, being their main energy source. Propionate gets metabolized by the liver. In particular acetate enters the systemic circulation and might have anti-inflammatory and immune modulating effects. Indole and isovalerate are products of bacterial amino acid fermentation. Indole is solely produced by bacterial enzymes from the essential amino acid tryptophan (TRP) and isovalerate from branched-chain amino acids.

In COPD an enhanced pulmonary inflammatory response causes a combination of small airways disease (e.g., obstructive bronchiolitis) and/or a destruction of lung parenchyma (emphysema). This leads to a progressive and persistent airflow limitation. It has been shown that a healthy overall diet as well as a diet high in fiber can be associated with a good lung function and a decreased COPD prevalence. A diet rich in fermentable fiber altered the gut and lung microbiota composition in mice, mainly through a decrease in the Firmicutes-to-Bacteroidetes-ratio, which was accompanied by elevated concentrations of circulating SCFAs. These mice were protected against allergic inflammation in the lungs. Previous human research has demonstrated that the composition of the intestinal microbiota influences the asthma risk and it was associated with early life exacerbations in cystic fibrosis, which demonstrates a gut-lung cross-talk. Halnes et al. found a significantly reduced airway inflammation in asthma patients four hours after the ingestion of a meal containing soluble fiber and prebiotics compared to a placebo meal. Stable tracer studies are needed to examine the colonic production and metabolic fate of SCFAs in healthy and ill subjects.

The intestinal microbiota of older individuals is less diverse, has a higher interindividual variability, and lower SCFA production capacity compared to younger adults. Hence, a dysbiosis of the intestinal microbiota could be involved in the development of several age-related chronic systemic diseases, such as sarcopenia and lower muscle quality or cognitive dysfunction. These age-related impairments are associated with a reduced physical performance and elevated risk for falls, fractures, physical disability and mortality. Dysbiosis of the intestinal microbiota (i.e. an altered microbial composition and function) might contribute to the development of sarcopenia by modulating muscle size, composition, and function. Moreover, SCFAs, metabolites produced by beneficial bacteria, help maintaining cognitive function and psychological well-being through their anti-inflammatory and gene regulating properties. Hence, nutritional interventions, such as fiber supplementation, must be studies as a modulator of microbial composition and SCFA production rate, as well as the subsequent effects on muscle and cognitive health and overall well-being. ;

Related Conditions & MeSH terms

• Aging
• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

• NCT number: NCT04459156
• Study type: Interventional
• Source: Texas A&M University
• Contact: Marielle M Engelen, PhD
• Phone: 9792202282
• Email: mpkj.engelen@ctral.org
• Status: Recruiting
• Phase: N/A
• Start date: June 23, 2020
• Completion date: December 2023