Ecosystem Nourishment for Gut Restoration After Fecal Transplantation

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.

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.