Serotonin Variants & Gut Microbiota in Mental Health

N/ANot Yet RecruitingNCT07634458

Neurobiologix30 enrolled

Overview

This observational pilot study investigates whether a broad panel of genetic variants relevant to the serotonin pathway (including serotonergic system, methylation cycle, intestinal barrier integrity, and inflammatory response genes) are associated with distinct gut microbiome compositional and functional signatures in adults aged 18-44 years with self-reported mental health conditions (Major Depressive Disorder, Generalized Anxiety Disorder, PTSD, or Panic Disorder). This is a decentralized, participant-funded (Citizen Science) study. Eligible participants provide at-home saliva (buccal swab) and stool samples. Genomic analysis is performed using the NeuroBiologix GenePro+ SNP Panel (Illumina Infinium Global Screening Array-24, \~654,000 SNPs) via Gene By Gene, a CLIA/CAP-accredited laboratory. Gut microbiome analysis is performed by Tiny Health using deep whole-genome shotgun metagenomics (≥20 million reads) on a NextGen Illumina Platform. The study is non-interventional and hypothesis-generating, aiming to identify potential genotype-microbiome associations and estimate effect sizes to inform a future interventional trial. N=30 participants. Study Start: July 2026.

Background: The gut-brain-microbiota axis (GBA) represents a complex, bidirectional communication system. Microbial tryptophan metabolism is a key mechanism within this axis - approximately 95% of the body's serotonin is synthesized peripherally in the gut. Host genetic variants can influence both serotonin biology and gut microbiome composition. Objective: To explore correlations between multi-system genetic variants (TPH2, SLC6A4, MTHFR, FUT2, MUC1, IL-6, and others) and gut microbiome compositional and functional profiles (particularly tryptophan metabolism pathways) in adults with self-reported mental health conditions. Design: Decentralized observational pilot study. Participants complete digital questionnaires and provide at-home biospecimen collections (saliva and stool) using prepaid medical-grade kits. Genomic Methodology: Saliva samples undergo DNA extraction and array-based genotyping (Illumina GSA-24 v3.0) at Gene By Gene (CLIA No. 45D1102202, CAP-accredited). Data processed via OmicsEdge bioinformatics platform. Metagenomic Methodology: Stool samples analyzed by Tiny Health using whole-genome shotgun metagenomics. Human reads are depleted against GRCh38. Taxonomic profiling via GTDB/GenBank database (111,000+ genomes). Functional annotation via KEGG Orthology and CAZy. Statistical Analysis: Descriptive statistics; alpha diversity (Shannon index); beta diversity (Bray-Curtis dissimilarity); PERMANOVA; exploratory non-parametric comparisons between genotype-defined groups. Effect sizes calculated for future study design. IRB: Approved by Sterling Institutional Review Board (Atlanta, GA), IRB ID 16153.

Interventions

SNP Genotyping and Gut MetagenomicsDIAGNOSTIC_TEST

Genomic analysis using NeuroBiologix GenePro+ SNP Panel: Illumina Infinium Global Screening Array-24 v3.0 (\~654,000 SNPs), genotyped at Gene By Gene (CLIA No. 45D1102202, CAP-accredited). Data processed via OmicsEdge bioinformatics platform analyzing serotonergic, methylation, intestinal barrier, and inflammatory pathway variants. Gut microbiome analysis using Tiny Health deep whole-genome shotgun metagenomics (NextGen Illumina Platform, ≥20 million reads), with taxonomic profiling (GTDB/GenBank) and functional annotation (KEGG Orthology, CAZy).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 44 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age: Adults aged 18 to 44 years. 2. Residency: Current legal residents of the United States. 3. Clinical Phenotype: Self-report of Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), Post-Traumatic Stress Disorder (PTSD), or Panic Disorder. 4. Medication Stability: If currently prescribed psychotropic medications (e.g., SSRIs, SNRIs, benzodiazepines), the dosage must remain stable with no changes in molecule or quantity for at least 3 months prior to enrollment. 5. Language and Technology: Proficiency in English and access to a smartphone or computer for digital data entry. 6. Financial Commitment: Explicit agreement to the "Citizen Science" model, including payment for discounted testing kits. Kit shipping (both directions) is prepaid by the study. Exclusion Criteria: 1. Use of systemic antibiotics, antifungals, or antivirals within the 8 weeks prior to specimen collection. 2. Regular use of commercial probiotics or concentrated prebiotic supplements within 4 weeks of collection. 3. Frequent use of osmotic or stimulant laxatives, or motility agents, within 4 weeks of collection. 4. Chronic use (\>3 times/week) of NSAIDs, systemic corticosteroids, or high-dose Omega-3 supplementation (\>2g/day) within 4 weeks of enrollment. 5. Use of weight-loss medications or GLP-1 receptor agonists (e.g., semaglutide, liraglutide, tirzepatide) within the 3 months prior to enrollment. 6. Confirmed diagnosis of Irritable Bowel Syndrome (IBS), Inflammatory Bowel Disease (Crohn's or Ulcerative Colitis), Celiac Disease, or history of major gastric/intestinal resection. 7. Current pregnancy or lactation. 8. Presence of cognitive impairments that preclude the ability to provide informed consent. 9. Individuals undergoing active cancer treatment.

Serotonin Variants & Gut Microbiota in Mental Health

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Central Contacts