Fiber Metabolism in Chronic Obstructive Pulmonary Disease

  • End date
    Dec 22, 2023
  • participants needed
  • sponsor
    Texas A&M University
Updated on 22 March 2022
Accepts healthy volunteers


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.


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.

Condition Chronic Obstructive Pulmonary Disease, Aging
Treatment placebo maltodextrin, Fiber Inulin
Clinical Study IdentifierNCT04459156
SponsorTexas A&M University
Last Modified on22 March 2022


Yes No Not Sure

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
Age 45 - 100 years for healthy control subjects
Ability to lay in supine or elevated position for 1.5 hours
Age 18 - 30 years for healthy, young adults
No diagnosis of COPD
Willingness and ability to comply with the protocol
Inclusion criteria COPD subjects
Ability to walk, sit down and stand up independently
Ability to lie in supine or elevated position for 1.5 hours
Diagnosis of moderate to very severe chronic airflow limitation and compliant to the following criteria: FEV1 < 70% of reference FEV1
Clinically stable condition and not suffering from a respiratory tract infection or exacerbation of their disease (defined as a combination of increased cough, sputum purulence, shortness of breath, systemic symptoms such as fever, and a decrease in FEV1 > 10% compared with values when clinically stable in the preceding year) at least 4 weeks prior to the first test day
Shortness of breath on exertion
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
(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
Failure to give informed consent or Investigator's uncertainty about the willingness
or ability of the subject to comply with the protocol requirements
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