Fecal Microbiota Transplantation for Gastrointestinal Disorders

Thomas Malikowski; Sahil Khanna; Darrell S. Pardi

Disclosures

Curr Opin Gastroenterol. 2017;33(1):8-13. 

In This Article

Nonalcoholic Fatty Liver Disease and Alcoholic Liver Disease

The liver is intimately involved with gut function, and serves to filter substances absorbed through the gut before they enter the systemic vascular circulation. The composition of the microbiome contributes to liver homeostasis, and may play a role in the development of NAFLD.[51]

The microbiome influences liver function through energy homeostasis and gut permeability which may expose the liver parenchyma to additional toxins when perturbed.[52–54] Additionally, exposure to bacterial toxins such as lipopolysaccharide (LPS) causes activation of Kupffer and stellate cells, inducing inflammation and fibrosis.[55–57]

NAFLD has been associated with dysbiosis.[51] In NAFLD, the gut microbiome contains fewer Bacteroidetes and Ruminococcaceae.[16] Differences in bile and choline metabolism also exist as a result of differences in microbial composition.[58–60] Alterations in the gut microbiome have also been observed in alcoholic liver disease, with decreased populations of Bacteroidetes. Interestingly, bacterial production of acetaldehyde is also increased in alcoholic liver disease, contributing to increased intestinal permeability.[61]

A few small studies have examined the role of probiotics in attenuation of NAFLD and alcoholic liver disease. The largest study of NAFLD enrolled 66 patients and utilized Bifidobacterium cultures. A statistically significant decrease in AST, LDL, CRP, TNF-a, serum endotoxin levels, and NASH activity index when compared with controls was found.[62] The largest study for alcoholic liver disease enrolled 66 patients and found that Bifidobacterium and Lactobacillus cultures led to a modest improvement in liver enzymes when compared with patients receiving placebo.[63] Interestingly, a meta-analysis of 246 patients by Sawas et al.[64] showed probiotics to benefit patients with cirrhosis undergoing liver transplantation. A statistically significant reduction in the number of infections with a number needed to treat of 3.6 was demonstrated.

With the increasing acceptance and understanding of the impact on the microbiome on liver disease, accompanied by the initial promise of probiotics, interest in FMT has also grown. Perhaps the greatest potential of FMT exists in management of NAFLD. Only one study has been conducted to date, by Vrieze et al.[65] examining the role of FMT in the treatment of insulin sensitivity, metabolic syndrome, and indirectly NAFLD. Patients were given a single FMT via nasoduodenal tube and followed for 6 weeks. Patients who received FMT had improved insulin sensitivity. In theory, this should improve NAFLD indirectly, although this has yet to be shown.

Additional, large-scale randomized, double-blinded, placebo controlled studies are needed, and the current role of FMT in the treatment of liver disease remains unclear. Upon review of clinicaltrials.gov there are currently three randomized control studies underway evaluating the efficacy of FMT for treatment of NAFLD. There is one additional study pending to evaluate the impact of liver transplantation on the gut microbiome.

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