The goal of this project is to determine an individual's ability to generate active gut microbial metabolites called urolithins upon consumption of pomegranate dietary supplements. Recent publications have reported that urolithins are the major active metabolites responsible for the beneficial effects of eating pomegranates, berries, or walnuts. However, the production of urolithins from the parent compound ellagic acid (EA) is dependent upon the presence of certain bacteria in the human gut. In this trial, we propose to investigate variations in gut microbiota and their capacity to metabolize pomegranate dietary supplements (PDS) into active urolithins. We will measure the levels of urolithins in blood as well as inflammatory cytokines in plasma samples upon consumption of PDS.

A large body of anecdotal evidence suggests beneficial effects for many botanical dietary supplements (BDS) on human health. The U.S. alone spent ~$7.5 billion on BDS in 2016, suggesting significant interest in the consumption of such products. Since ancient times, pomegranate has been known as a 'healing food', with numerous health benefits, including prevention of health risk factors for high blood pressure, arthritis, high cholesterol, oxidative stress, and hyperglycemia (1-4). Despite reported benefits from consumption of pomegranate dietary supplements (PDS), the overall outcomes of clinical trials were not uniform, and the results were inconclusive (5-7). However, gut microbial metabolites derived from polyphenolics of pomegranate have been shown to promote many beneficial activities, including anti-oxidative and anti-inflammatory activities (8- 12). Thus, the inter-individual variation in human gut microbiota compositions and their metabolic capacities may hamper the predicted PDS-mediated benefits. We postulate that harboring the specific gut microbiota responsible for metabolizing PDS into beneficial metabolites is critical to manifesting the complete benefits of PDS consumption. Recently, we reported one such microbial metabolite, 'urolithin A' (UroA), derived from ellagic acid-rich diets (e.g., pomegranate), significantly enhanced gut barrier function in addition to blocking unwarranted inflammation in colitis models (13) and protected from alcoholic liver disease (ALD) in mouse models (unpublished data). UroA is produced only in 40-50% of humans, who harbor the appropriate microbiota capable of converting consumed ellagic acid-rich diets (such as pomegranates, berries, and walnuts). UroA levels varied significantly among populations, to micromolar levels in some individuals. The direct correlations between UroA levels and human health/disease conditions are not yet available.

This project aims to determine an individual's ability to generate active gut microbial metabolites called urolithins upon consumption of pomegranate dietary supplements. We, and others, reported that urolithins are the major active metabolites that are responsible for the beneficial activities that are rendered from eating pomegranates, berries, or walnuts. However, the production of urolithins from the parent compound ellagic acid (EA) is dependent upon the presence of certain bacteria in the human gut. In this trial, we propose to investigate variations in gut microbiota and their capacity to metabolize pomegranate dietary supplements (PDS) into active urolithins. We will measure the levels of urolithins in blood as well as inflammatory cytokines in plasma samples upon consumption of PDS.

Healthy Group:

Inclusion: Healthy individuals, Exclusion: AUD, ALD, AC, and inflammatory conditions,

Alcohol Use Disorder Group:

Inclusion: AUD diagnosis Exclusion: alcohol-associated systemic conditions

Alcohol-associated liver disease Group:

Inclusion: early-stage ALD comorbid with AUD Exclusion: Only AUD or AUD with AC

Alcohol-associated cirrhosis Inclusion: AC with AUD Exclusion: AUD, and early stage ALD, as well as determined by the study cohort criteria

Young adults and up with open population specifics, qualifying for each cohort requirements

Study data can be obtained by contacting the NIH NDA system

2034 Onwards

Contact the Investigators for approval to upload the NDA issuance data.