The Role of Microbiome Reprogramming on Liver Fat Accumulation

Inclusion Criteria: 1. Age 35-65 years 2. Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) 5%-30% (+0.5%) 3. Liver stiffness \<3.5 kPa by Magnetic Resonance Elastography (MRE) 4. Body mass index (BMI) 27.5-45 kg/m2 5. Weight stable (weight change of no more than 3 kg +0.5 kg) during the 6 months prior to enrollment 6. For individuals with type 2 diabetes: HbA1c ≥6.5 - \<9.5%. If taking allowable diabetes medications, HbA1c can be below 6.5%. 7. Fasting triglycerides 400 mg/dL (4.5 mmol/L) 8. Able to speak and understand written and spoken English 9. Understands the procedures and agrees to participate by giving written informed consent 10. Willing and able to comply with scheduled study days, laboratory tests, and other study procedures Exclusion Criteria: Acute or chronic medical conditions or medication that would contraindicate the participation in the research testing or could potentially affect metabolic function including, but not limited to: 1. Diagnosis of type 1 diabetes mellitus 2. Insulin use 3. Change within 3 months of screening of any medication used to treat insulin resistance or type 2 diabetes 4. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within the previous 6 months (1 drink = 5 ounces \[150 mL\] of wine, 12 ounces \[360 mL\] of beer, or 1.5 ounces \[45 mL\] of hard liquor) 5. A total score of 8 on the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, indicating harmful or hazardous alcohol consumption 6. Clinical evidence of hepatic decompensation, including, but not limited to esophageal varices, ascites, or hepatic encephalopathy 7. Evidence of other forms of chronic liver disease (including laboratory tests and confirmed with a single repeat, if needed): * Hepatitis B virus: defined by presence of hepatitis B surface antigen * Hepatitis C virus: As defined by a clinical history of previous diagnosis of Hepatitis C (treated or untreated) or a positive Hepatitis C antibody. * Known diagnosis of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or overlap syndrome * Alcoholic liver disease * Known diagnosis of hemochromatosis * Prior known drug-induced liver injury * Known or suspected hepatocellular carcinoma or other liver cancer * History of liver transplant, current placement on a liver transplant list, or current model of end-stage liver disease (MELD) score \>12 * Histological presence of cirrhosis on a prior biopsy 8. Bleeding disorders 9. Acute or chronic infections 10. Severe asthma or chronic obstructive pulmonary disease 11. Renal insufficiency or nephritis 12. Thyroid dysfunction (suppressed TSH, elevated TSH \<10 µIU/ml if symptomatic or elevated TSH \>10 µIU/ml if asymptomatic) 13. Uncontrolled hypertension (BP \>160 mmHg systolic or \>100 mmHg diastolic) 14. Prior or planned bariatric surgery 15. Gastrointestinal disorders including: inflammatory bowel disease or malabsorption, swallowing disorders, suspected or known strictures, fistulas or physiological/mechanical GI obstruction, history of gastrointestinal surgery, Crohn's disease or diverticulitis. 16. Participants with intolerance to soluble fiber, sucralose or erythritol. 17. A positive urine drug test for illicit drugs 18. History of major depression within \<5 years from screening or which, in the opinion of a medical investigator, will impact the participant's ability to complete the study. 19. History of eating disorders 20. History of Cushing's disease or syndrome 21. Untreated or inadequately controlled hypo- or hyperthyroidism 22. Active rheumatoid arthritis or other inflammatory rheumatic disorder 23. Pregnant or nursing females or females less than 6 months postpartum from the scheduled date of collection 24. Nicotine use within the past 3 months 25. Had major surgery within 4 weeks prior to Screening. 26. Anemia (hemoglobin \<12 g/dl in men, \<11 g/dl in women) during screening 27. Participation in studies involving investigational drug(s) within 30 days prior to Screening 28. History or presence of cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, presence of cardiac pacemaker, implanted cardiac defibrillator) 29. Human Immunodeficiency Virus (HIV) infection defined as: previous diagnosis of HIV infection, history of positive screening or quantitative HIV testing; positive HIV screen 30. Any malignancy not considered cured, except basal cell carcinoma and squamous cell carcinoma of the skin (a participant is considered cured if there has been no evidence of cancer recurrence in the previous 5 years) 31. Use of drugs historically associated with non-alcoholic fatty liver disease (NAFLD) for 1 month in the previous year prior to Screening; examples include: amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, other known hepatotoxins 32. Participants who fulfill any of the contraindications for MRI; examples include metal implants, devices, paramagnetic objects contained within the body and excessive or metal-containing tattoos 33. Unable to participate in MR assessments due to physical limitations or equipment tolerances (e.g., MRI bore size and 500-pound weight limit) based on Investigator's judgment at screening 34. Any person with history of severe claustrophobia or unable to lie still within the environment of the MRI scanner or unable maintain a breath hold for the required period to acquire images without mild sedation/treatment with an anxiolytic 35. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to Screening (participants may not donate blood any time during the study, through the final study day) 36. Presence of any condition that, in the opinion of the Investigator, compromises participant safety or data integrity or the participant's ability to complete study days