Writing in The American Journal of Gastroenterology, the research team also observe a significant in significant reduction in intestinal permeability that is one of the hallmarks seen in NAFLD patients.
“Intestinal permeability plays a role in the development of metabolic syndrome which is a major cause of coronary and cerebrovascular disease,” explains Dr Michael Silverman, associate scientist at Lawson Health Research Institute.
“It has also been associated with autoimmune diseases like multiple sclerosis (MS), rheumatoid arthritis, systemic lupus and type 1 diabetes,” adds Dr Silverman, also a professor at Western University’s Schulich School of Medicine & Dentistry.
The trial, carried out on 21 patients with NAFLD, hypothesised that a change in the gut microbiome of these patients could reduce intestinal permeability – a condition that allows intestinal microorganisms and/or their products to enter the blood more readily.
Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic form of metabolic syndrome.
The gut microbiome plays a role in metabolism and maintaining gut barrier integrity and studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD.
Faecal microbiota transplantation (FMT) can be used to alter the gut microbiome with the research team suggesting an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR) and intestinal permeability.
Along with colleagues from Duke University in the US, the research team began recruiting and randomising the 21 patients in a ratio of 3:1 to receive either a faecal transplant using stool from a healthy donor (sample size = 15) or a placebo (the patient’s own stool. Sample size = 6).
Patients were then followed for six months to assess changes to their gut microbiome, intestinal permeability, percentage of liver fat and insulin resistance.
The team found no significant changes in measurements for insulin resistance or liver fat in patients, who received either FMT,
However, patients with elevated small intestinal permeability, who received a healthy donor FMT at the start of the trial exhibited significant reduction six weeks later. Two patients had a decrease that fell into the normal range of permeability.
“Our study demonstrates that intestinal permeability can be improved through faecal transplant from a healthy donor,” says Dr Laura Craven, first author on the published study.
“This suggests that faecal transplant could be used as an early intervention in the treatment of NAFLD to reduce intestinal permeability and prevent inflammation.”
Dr Silverman adds, “Our findings have implications for other conditions too. Changing the gut microbiome could hold promise in preventing and treating metabolic syndrome and autoimmune diseases associated with increased gut permeability.”
Further investigation warranted
Commenting on the study’s findings, Dr Atif Zaman, associate editor for NEJM Journal Watch Gastroenterology says, “This proof-of-concept study is the first reported clinical trial of FMT in patients with NAFLD.
“Although insulin resistance and hepatic steatosis did not improve, small intestinal permeability apparently did. Since elevated intestinal permeability has been implicated in liver disease, further investigation of FMT in this population is warranted.”
The research team now hope to conduct a large multi-centre trial to further investigate FMT as an intervention for NAFLD and as a therapy to reduce intestinal permeability.
Source: The American Journal of Gastroenterology
Published online ahead of print: doi: 10.14309/ajg.0000000000000661
“Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability.”
Authors: Craven, Laura et al.