Understanding the Efficacy of Dietary Supplement on Fungal Mycobiota in Healthy Volunteers: A Pilot Study

The purpose of this study is to explore how the dietary supplement L-Phenylalanine affects the production of the metabolite phenylpropionic acid (PPA) and changes fungal populations of the gut microbiome.

Study Overview

• Status: Recruiting
• Conditions: Gut Microbiome; Dietary Supplement; Gut Health; L-Phenylalanine; Phenylpropionic Acid
• Intervention / Treatment: Drug: L-Phenylalanine 500 mg Veg Capsule product

Detailed Description

The human gastrointestinal tract hosts a diverse microbial community that has a role in influencing the host's pathophysiological responses. Although there is an abundance of metagenomic data available, the functional dynamics of the gut microbiota still need exploration in different conditions. The microbiota produces various metabolites from dietary products, impacting both host health and pathophysiological functions. The metabolites produced by different microbiota may selectively suppress or stimulate the growth of some components of the gut microbiome, ultimately influencing the dynamic of gut bacterial and fungal populations. Our lab is specifically interested in a metabolite, known as phenylpropionic acid (PPA) produced by a human gut resident bacteria known as Clostridium sporogenes. C. sporogenes produces PPA by metabolizing the amino acid, L-phenylalanine, which is sourced from human diet. Many studies have observed the antimicrobial and antifungal effects of PPA. Our lab determined PPA holds antifungal activity of PPA in the gut of mice colonized with Candida albicans. We are interested in investigating how diversity in the mycobiota populations, which focuses on the fungi species in the human gut, are related to changes in PPA levels.

Therefore, this study will asses whether additional oral supplementation of L-phenylalanine has an effect on the way gut mycobiota responds to this amino acid. Healthy subjects received a 14-day supply of L-phenylalanine supplements and provided stool and blood samples to the study team.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tsering D Sherpa-Ngima, BSc; Phone Number: 929-328-9571; Email: tss4002@med.cornell.edu
• Study Contact Backup: Name: Aurelia Li, MS; Phone Number: 732-822-6836; Email: aul4004@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10022
      • Recruiting
      • Belfer Research Building
      • Principal Investigator: Iliyan D Iliev, PhD
      • Contact: Aurelia Li, MS; Phone Number: 732-822-6836; Email: aul4004@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female adults over the age of 18 years

Exclusion Criteria:

• History of a diagnosis of any gastrointestinal condition, such as inflammatory bowel syndrome or disease
• Antibiotic usage within the past two weeks
• Antifungal usage within the past month
• Allergy to L-Phenylalanine or individuals with phenylketonuria (PKU)
• Adults taking medications known to interact with L-phenylalanine supplements, such as Monoamine Oxidase Inhibitors (MOAI), L-DOPA, and some antipsychotic drugs (complete and extensive drug list will be provided to interested participants during screening)
• Pregnant or nursing women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy; Participants will receive one bottle of L-Phenylalanine 500 mg Veg Capsule product on Day 0. All subjects will be asked to start taking the supplement on Day 1 continuing until Day 14. They will be asked to take 2x 500 mg capsules in the morning and 1x 500 mg capsule in the evening daily for 14 days.	Drug: L-Phenylalanine 500 mg Veg Capsule product; 500 mg Veg Capsule product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the number of T cells that react to fungal antigens from baseline in subject blood samples	Blood will be processed through ELISA-based and in vitro restimulation assays to measure T cell reactivity to fungal antigens	Baseline, Week 2 (Day 14)
Changes in phenylpropionic acid levels from baseline in subject fecal material	Metabolite phenylpropionic acid levels will be measured using mass spectrometry before (baseline) and after intervention	Baseline, Week 2 (Day 14)
Change in fungal population levels, specifically gut Candida levels, from baseline in subject fecal material and swabs	Fungal populations, including Candida, will be measured using microbiota sequencing before (baseline) and after intervention. The most abundant fungal populations will be reported; however, the identity of those populations won't be known until sample analysis.	Baseline, Week 2 (Day 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in phenylpropionic acid levels from baseline in subject fecal material	Metabolite phenylpropionic acid levels will be measured using mass spectrometry before (baseline) and after intervention	Baseline, Week 4 (Day 28)
Change in fungal population levels, specifically gut Candida levels, from baseline in subject fecal material	Fungal populations, including Candida, will be measured using microbiota sequencing before (baseline) and after intervention. The most abundant fungal populations will be reported; however, the identity of those populations won't be known until sample analysis.	Baseline, Week 4 (Day 28)
Change in the number of T cells that react to fungal antigens from baseline in subject blood samples	Blood will be processed through ELISA-based and in vitro restimulation assays to measure T cell reactivity to fungal antigens	Baseline, Week 4 (Day 28)

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Iliyan D Iliev, PhD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2024
• Primary Completion (Estimated): December 17, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 22, 2024
• First Submitted That Met QC Criteria: May 22, 2024
• First Posted (Actual): May 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Essential; Amino Acids, Aromatic; Amino Acids, Cyclic; Pharmaceutical Preparations; Phenylalanine
• Other Study ID Numbers: 23-09026469

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No