Page 7 - Introduction to FMT

FMT Introduction

FMT FOR EXTRA-INTESTINAL DISORDERS

It seems to be serendipitous that the CDI epidemic facilitated the application of FMT to many other
diseases (Table 1). The pathogenesis of gut microbiota in extra-intestinal diseases was inspired by
massive studies in germ-free (GF) animals. Complete construction of the hypothalamic-pituitary- adrenal
axis requires the participation of gut microbiota[45]. GF mice exhibit a dysregulation of the axis, thereby
resulting in altered brain-derived hormones (e.g., norepinephrine and tryptophan) and increased caloric
intake[45]. Aside from the crucial role of intestinal microbiota in central nervous system activity, another
concept is emerging which was termed as “bidirectional brain-gut-microbiota axis”[46-48]. The
destruction of the axis leads to altered behaviors and various neurologic conditions[49,50]. Identically,
ample human studies have provided evidence for the critical role of the gut microbiota in extra-intestinal
disorders.

Table 1

Summary of extra-intestinal disorders associated with gut microbiota

Extra-intestinal disorders Ref. Publication year Study type

Metabolic diseases

Metabolic syndrome Vrieze et al[61] 2012 RCT

Obesity Turnbaugh et al[54] 2009 Observational study

There is compelling evidence that the intestinal microbiota is closely linked to a series of metabolic
conditions. Obesity, diabetes mellitus, and metabolic syndrome are epidemic in modern society. There
have been extensive investigations concerning microbiota reaction acting as a pivotal role in the
pathogenesis of these endocrine diseases in animal models[51,52]. Changes in gut microbiota
composition have also been reported in obese humans[53-55], with a shift in the ratio of Firmicutes and
Bacteroidetes[56]. Meanwhile, increased levels of bacteria and their metabolic products were found in the
plasma of obese individuals, with one likely mechanism thought to be increased intestinal
permeability[57,58]. Recent studies have shown that short chain fatty acid (including butyrate) producing
Clostridiales strains (Roseburia and Faecalibacterium prausnitzii) were found to be decreased in patients
with type 2 diabetes mellitus, but non-butyrate producing Clostridiales and pathogens such as
Clostridium clostridioforme were increased[59,60]. Vrieze et al[61] conducted a double blind, randomized
controlled trial of FMT in 18 male patients with metabolic syndrome. Half of them received fecal
microbiota infusion from lean male donors (allogenic group), while the other half received auto-fecal
transplants (control group). The results showed that both insulin sensitivity and levels of butyrate-
producing intestinal microbiota (Roseburia intestinalis and Eubacterium hallii) were markedly increased
after a six-week infusion of microbiota from lean donors, while no significant changes were found in the
control group[61]. In the group following allogenic gut microbiota transfer, the median rate of glucose
disappearance increased from 26.2 to 45.3 μmol/kg per minute, while the median endogenous glucose
production increased from 51.5% to 61.6%. Hence, it can be speculated that FMT could be developed as a
potential therapeutic strategy for increasing insulin sensitivity in humans.

FMT Introduction