Researchers Investigate FMT in Metabolic Syndrome

In a new literature review, researchers from the Netherlands postulate that studying fecal microbiota transplantation (FMT) can assist in the identification of novel therapeutic targets for metabolic syndromes.

In the review, the researchers took a closer look at the history of FMT as well as the present evidence on its role in the pathophysiology of metabolic syndrome; they analyzed its efficacy, limitations and future prospects. First documented in China, as early as 300 AD, it was known as “yellow soup” or “golden syrup” and was applied in cases of food poisoning and diarrhea.

By the 16th century, China developed feces-derived products to cure gastrointestinal ailments, fever, and pain. Upon examining FMT in the modern era, they discovered that the earliest record of FMT for a non-infectious disease involved a 45-year-old male who had refractory ulcerative colitis—he achieved a “full and lasting clinical recovery.”

FMT is sometimes used to treat Clostridium difficile (C. difficile) infection; 3 randomized controlled studies have shown cure rates of 90% or higher with this treatment method. Other reports have detailed alleviated symptoms after FMTs for patients with multiple sclerosis, Parkinson’s disease, and chronic fatigue. Furthermore, in another study involving mice, FMT was theorized to potentially be utilized to help children with severe malnutrition.

In the review, the researchers also detailed the rise of “new onset obesity” among FMT patients, and discussed the trend in studies that suggest a causal relation between the gut microbiota and the metabolic syndrome. However, they wrote, the pathophysiologic pathways have yet to be explained.

“There is a firm base of evidence linking the spectrum of metabolic dysfunction seen in metabolic syndrome to inflammation,” the researchers wrote.

Furthermore, a “leaky gut,” or intestinal permeability, was also attributed to a decline in metabolic function. This theory involves an impaired gut barrier functionality and leakage of gut microbiota and/or bacterial components into the system, resulting in a variety of negative effects. One way researchers suggested to test for a leaky gut was to look for bacterial signatures in the circulation.

The gut microbiota can contribute to the metabolic system in several ways, including: the production of signaling molecules from the gut microbes affecting gut integrity, poor mediation of bile acids, and malevolent microbes that contribute to insulin resistance—namely, Prevotella copri and Bacteroides vulgates.

The researchers noted that gut microbes are involved in many aspects of the metabolic syndrome and can contribute to atherosclerosis, hepatic steatosis, elevated blood pressure, and dyslipidemia.

Upon examining this evidence, the researchers wrote that now is "the time to further investigate these claims using well-designed randomized placebo-controlled studies featuring FMT that focus on unraveling the mechanisms through which gut bacteria interact with host metabolism."

They suggest doing this through the monitoring of microbiotal changes, genetic and epigenic effects, and exploring dietary habits; doing this can pave the way for more personalized strategies for manipulating the microbiota, they wrote.

Although there are still some obstacle to overcome when it comes to FMTs—such as risk infection, or microbiota associated disease, or the “yuck factor”—the US Food and Drug Administration (FDA) has determined that FMT is classified as a biologic product, thus, the process remains under FDA jurisdiction. In Europe, that is not the case, leaving the burden of additional research on investigators in that part of the world.

Feature Picture Source: MD Magazine