Transplantation of Microbes of Fecal Origin for Prevention and Treatment of Metabolic Syndrome and Non Alcoholic Fatty Liver Disease
Implementation & Integration
Highlights (Transformation, Adoptability, and/or Outcomes)
AMO-15-008 Abnormal intestinal permeability (IP) is a central pathway in the development of many autoimmune diseases (Type I Diabetes, Systemic lupus, Multiple sclerosis, Rheumatoid arthritis), metabolic diseases (Obesity, Metabolic syndrome, Non Alcoholic Fatty Liver Disease (NAFLD), Atherosclerosis) and impacts on the gut-brain axis (Depression, Psychosis, Autism). To date no interventions have been available to improve abnormal IP. We conducted a randomized clinical trial that demonstrates that Fecal Microbial Transplantation (FMT) can correct the abnormal IP in NAFLD patients. This raises the possibility of intervening to prevent and treat many clinical syndromes via manipulation of the gut microbiome. We hope to refine this technology furthur and develop disease specific interventions.
AMO-15-008 NAFLD is the most common liver disease worldwide. Many factors contribute to progression including; intestinal dysbiosis, diet, genetic factors, endoplasmic reticulum stress and intestinal permeability [IP]. Animal and Clinical studies show that IP is increased in NAFLD. This exposes the liver to potentially harmful substances including translocated bacteria, Lipopolysaccharides, endotoxins, and cytokines via portal blood flow. The aim of the study was to determine if FMT improves insulin resistance, hepatic fat percentage and alters intestinal permeability in NAFLD. This double blind, randomized study enrolled 21 NAFLD patients (Jun 2016 – Aug 2017). 15 patients were randomized to receive FMT from healthy donors (allogeneic) or control (autologous) FMT (n = 6). FMT was administered by duodenoscopy. Insulin resistance was measured using HOMA Score and MRI for hepatic fat. The ratio of the lactulose/mannitol urinary excretion determined IP. There were no significant changes in insulin resistance or percentage of hepatic fat in patients that received the allogenic or autologous FMT. Patients with elevated IP (>0.03 lactulose:mannitol) had a significant reduction 6 weeks’ post-allogenic FMT. Blood triglycerides and Cholesterol:HDL ratio decreased post-FMT in the allogenic group. This study indicates that FMT can improve IP in NAFLD. Due to lack of available medications, current treatment focuses on lifestyle intervention which has limited success. FMT shows promise in replacing gut dysbiosis and improving factors involved in NAFLD pathogenesis. The information from this pilot study is being used to design several other clinical trials for safety and efficacy of FMT in relapsing Multiple Sclerosis, immunotherapy in Melanoma patients, Unexplained Resistant Atherosclerosis and Psychosis.