Ecosystem Nourishment for Gut Restoration After Fecal Transplantation

Phase 2Not Yet RecruitingNCT07826793

Stanford University80 enrolled

Overview

The purpose of this study is to test whether young-donor fecal microbiome transplantation (FMT) and a fermented, plant-rich high-fiber, microbiome rejuvenating diet (MRD) reduce inflammatory and biological aging markers. Participants (≥40 years) will be randomized (1:1:1:1) for 8 weeks with 4-week follow-up to: (A) diet alone, (B) FMT alone, (C) diet + FMT, or (D) Placebo FMT. We will use rigorously screened young and healthy FMT donors and encapsulated delivery. Outcomes include change from baseline to end of dietary intervention (week 8) in markers of aging and inflammation. Secondary outcomes include defining microbiome engraftment/diversity/function, key metabolites, diet adherence, and quality-of-life.

For this study, the research participant will receive a once daily oral dose of healthy young FMT and diet modification to increase fiber and fermented food consumption. Throughout the study's duration, the participant will provide stool, blood and urine samples as well as a series of health questionnaires to track the impact of the intervention. \*PROTOCOL OVERVIEW\* The study will begin with the selection of possible participants through the samples collected through the Stanford Microbiome Bank (IRB 85544), the participants identified will be contacted through the appropriate channels and asked to complete a short online questionnaire if interested in continuing with being a part of the protocol.After completing the questionnaire, those selected will be contacted via phone to schedule an in person appointment in the Clinical and Translational Research Unit (CTRU). During this appointment, the study team will obtain informed consent and one stool sample. Their initial stool sample will be sent outside Stanford for microbiome composition analysis which will determine if the participant is a good candidate for the protocol. After enrollment in the protocol, the participants will be randomized in a 1:1:1:1 ratio to one of four study arms: Placebo, placebo + diet, FMT no diet, or FMT + diet. Those randomized to one of the FMT groups will be instructed to take a single oral dose of young FMT (4 capsules) for two weeks, and those randomized to a diet arm will have an initial appointment with the study's dietitian to establish a microbiome rejuvenating diet (MRD) starting with a one week ramp up period and continued for a total of 8 weeks. The main factors incorporated into the MRD will be \~3 servings/day fermented foods and ≥30-40 g/day or +20g fiber(plant-based whole food), 5g of resistant starch supplements and 5g of psyllium husk. Throughout their enrollment in the protocol, the participants will provide stool samples weekly for analysis and complete general health and lifestyle questionnaires to assess protocol adherence and any changes in their health status. On weeks 0, 2, 4, 8 \& 12 participants will be asked to give a blood, urine and stool sample for further analysis and to complete a Nutrition Data System for Research (NDSR) questionnaire; stool is additionally collected at Week 6. All patient samples will be coded and stored in Stanford facilities for further processing.

Interventions

Fecal Microbiota Transplant CapsulesDRUG

Each dose (4 capsules) will be taken daily in the morning on an empty stomach. Clear liquids are allowed and regular breakfast can follow one hour later. If the dose is skipped, the missed dose should be skipped and the standard 4-capsule dose resumed the following morning; doses must not be doubled. There should be no solid food at the time of ingestion , solid food should be avoided at least 4 hours prior to ingestion of capsules, however, liquid diet is always allowed and a full glass of water should be taken after every dose ingestion. The treatment will be administered daily for 2 weeks.

Microbiome Rejuvenating DietBEHAVIORAL

Fiber intake: participants will be instructed to increase their fiber intake to \>30/40g or +20g per day . There will be a 1 week ramp-up period in which participants will increase their intake progressively. Detailed instructions will be provided to include a variety of fiber sources (legumes, seeds, whole grains, nuts, vegetables, and fruits). Participants will also be instructed to include 5g of resistant starch supplements and 5g of psyllium husk in their diet. Fermented food intake: participants will be instructed to add at least 3 portions of fermented food into their daily diet. There will be a 1 week ramp-up period in which participants will increase their intake progressively and maintain a high level of consumption for the following 8 weeks. Detailed instructions will be provided to include a variety of fermented foods (fermented dairy products, fermented vegetables, fermented non-alcoholic drinks, etc.).

Placebo Fecal Microbiota TransplantationOTHER

Participants will receive a once daily dose (4 pills) of inactive pills that are identical in size, shape, color, taste and feel to the active FMT pills

Eligibility

Sex: ALLMin age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Able and willing to provide written informed consent prior to completion of any study procedures. * Age ≥40 years at the time of consent. * In generally good health, as determined by medical history, medication review, and investigator assessment. * Willing and able to comply with all study procedures, assessments, and study-related restrictions for the duration of participation. * Willing to adhere to the study's lifestyle considerations for the duration of the study (maintain usual diet unless assigned to the diet arm; maintain usual physical activity; avoid non-essential systemic antibiotics; avoid probiotic/prebiotic/synbiotic supplements). * Willing and able to attend all required in-person study visits at Stanford University and complete remote assessments, if applicable. Exclusion Criteria: * Moderate or severe irritable bowel syndrome (IBS). * Current or prior diagnosis of inflammatory bowel disease (IBD), including ulcerative colitis, Crohn's disease, or indeterminate colitis. * Active gastrointestinal disease, including infectious gastroenteritis, colitis, gastritis, recurrent Clostridioides difficile infection, untreated Helicobacter pylori infection, or clinically significant malabsorption disorders (e.g., celiac disease). * Major gastrointestinal surgery within the past 5 years (excluding cholecystectomy and appendectomy), or history of major bowel resection at any time. * Body mass index (BMI) ≥40 kg/m². * Diabetes mellitus. * Hyperthyroidism or uncontrolled hypothyroidism. * Clinically significant renal disease. * Clinically significant hepatic disease or significant liver enzyme abnormalities. * Clinically significant cardiovascular disease. * Autoimmune or systemic inflammatory disease. * Current malignancy or history of malignancy within the past 5 years, excluding adequately treated non-melanoma skin cancer. * Current use of immunosuppressive medications, including systemic corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, biologic agents, or other immunosuppressive therapies. * Receipt of fecal microbiota transplantation (FMT) within the previous 12 months. * Use of systemic antibiotic therapy within 30 days prior to enrollment or anticipated antibiotic use during the study period. * Use of probiotic supplements, prebiotic supplements, synbiotics, or live microbial therapeutics within 30 days prior to enrollment. * Current use or use within the previous 6 months of medications prescribed primarily for weight loss. * Current use of medications known to significantly affect body weight unless the medication and dose have remained stable for at least 6 months prior to enrollment. * Neurodevelopmental, psychiatric, neurological, or neuromuscular disorders that, in the opinion of the investigator, may impair the participant's ability to provide informed consent, comply with study procedures, or complete study assessments. * Current diagnosis of schizophrenia, bipolar disorder, or other severe psychiatric illness that may interfere with study participation. * Current substance use disorder. * Current smoking or nicotine use, including cigarettes, cigars, electronic cigarettes, vaping products, or nicotine replacement therapy. * History of anaphylaxis or severe allergic reaction to study-related dietary components. * Planned major dietary change, initiation of a structured weight-loss program, or initiation of a specialized therapeutic diet during the study period. * Concurrent participation in another interventional clinical trial. * Any other medical, psychiatric, or social condition that, in the opinion of the investigator, could compromise participant safety, study compliance, or interpretation of study outcomes. * Pregnancy or breastfeeding * Known immunodeficiency state, including HIV infection, primary immunodeficiency, active hematologic or solid-organ malignancy under treatment, or other clinically significant immunocompromise, independent of medication use. * Dysphagia or any condition impairing the ability to swallow oral capsules.

Outcomes

Primary Outcomes

Difference in DunedinPACE

Difference in the 8-week change from baseline in DunedinPACE among the four randomized groups (FMT + MRD, FMT alone, MRD + placebo FMT, and placebo FMT), assessed by DNA methylation analysis of whole blood. DunedinPACE is a DNA methylation biomarker that quantifies the pace of biological aging, reported as a rate of biological aging per chronological year; higher values indicate a faster pace of aging and lower values indicate a slower pace.