Overview
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.
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.
Eligibility
Inclusion Criteria:
- Healthy male or female according to the investigator's or appointed staff's judgment
- Ability to walk, sit down and stand up independently
- Age 45 - 100 years
- Ability to lay in supine or elevated position for 1.5 hours
- No diagnosis of COPD
- Willingness and ability to comply with the protocol
Exclusion Criteria:
- Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (healthy subjects only)
- Insulin dependent diabetes mellitus
- Established diagnosis of malignancy
- History of untreated metabolic diseases including hepatic or renal disorder
- Presence of acute illness or metabolically unstable chronic illness
- Presence of fever within the last 3 days
- Use of short course of oral corticosteroids within 4 weeks preceding study day
- Dietary or lifestyle characteristics:
- Daily use of fiber supplements 1 week prior to the first test day
- Daily use of protein supplements 5 days prior to each test day
- Indications related to interaction with study products:
- Known allergy to inulin or inulin products
- Known hypersensitivity to inulin or maltodextrin or any of its ingredients
- Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
- (Possible) pregnancy
- Already enrolled in another clinical trial and that clinical trial interferes with participating in this study
- Any other condition according to the PI or nurse that was found during the screening visit, that would interfere with the study or safety of the patient