Fecal microbiota transplantation for improved Fructose catabolism and Insulin sensiTivity In patients with metabolic syndrome : the FFIT study

The incidence and progression of insulin resistance to subsequent type 2
diabetes (DM2) is different between Surinamese-Hindoestani versus Caucusian .
metabolic syndrome patients in The Netherlands. Based on our previous research
(Deschaschaux/Nieuwdorp, Nature Medicine 2018) we showed that altered
catabolism of dietary fructose by diferent gut microbiota in these patients
groups is associated with this different insulin resistance/DM2 progression and
that desulfivibrio strains are important in maintaining gut microbiota
diversity and stabitillity. .Previous research from our group has shown that
donor fecal transplantation has beneficial effects on increasing gut microbiota
diversity and subsequent insulin sensitivity in Caucasian metabolic syndrome
subjects (MEC 07/114, 11/023 en 13/090)., however this is not known for
Surinamese-asian metabolic syndrome subjects We thus expect that using donor
fecal transplantations enriched in desulfovibrio strains will improve (dietary)
fructose catabolism and insulin sensitivity (driven by improved gut microbiota
diversity and plasma metabolites) in both surinamese asian and caucasian dutch
metabolic syndrome subjects. An approach by which gutmicrobiota diversity
and insulin sensitivity improvement is targeted by using a selected specific
fecal donor has never been done before. We expect to find ethnicity specific
involved gut microbial strains as well as (dietary fructose derived) plasma
metabolites that are involved in insulin sensitivity in Surinamse-hindoestaan
tversus Caucasian Dutch metabolic syndrome subjects. This could lead to new
diagnostic and therapeutic (dietary) approaches based on personalized medicine
to alleviate insulin resistance / Dm2 disparities in these different ethnic
groups .

We would like to investigate if use of donor FMT enriched desulfovibrio
bacterial strains has a beneficial effect on gut microbiota diversity and
subsequent improvement of (diet derived) fructose catabolism and insulin
sensitivity in patients with metabolic syndrome from either Surinamese
hindustani or caucasian douch descent. . By identifying which involved
bacterial strains and their (from dietary fructose) produced plasma metabolites
are associated with changes in glucose metabolism, we hope to pave the way for
new personalized treatment (using either specific diet of cocktail of
identified bacterial strains) to treat these specific patiënt groups against
diabetes.

double blinded randomized controlled intervention trial

donor fecestransplantaton (allogenic) or fecal transplantation with own feces
(autologous)

2x gastroduodenoscopy (<0.01% chance of complications), hypersinulinemic clamp
with energy expenditure (REE) as well as fructose test using stabiele isotopen
(no complications in AMC in the last 20 years). fecal transplant using
screened donor feces was also safe in the last 15 years when few hundred of
these have been performed at AMC .use of freestyle libre sensor and MRI have
not been associated with complications either. In conclusion, we feel that the
new insight that we will gain by dissecting the role of specific gutmicrobiota
strains and their produced metabolites on ethnic differences in insulin
resistance/DM2 and the role of dietary fructose herein outweighs the risks and
time investment of this study.