To determine if the microbiota inhabiting the small intestine in morbidly obese patients with T2DM is comparable to those without T2DM and, if not, what are the deviations and what is their impact
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Appetite and general nutritional disorders
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Microbiota composition:
- adherent microbiota at site of ileum
- luminary small intestinal microbiota composition
- faecal microbiota composition
Insulin resistance (plasma):
- Glucose
- Insulin
- HbA1C
Inflammation:
- CRP (plasma)
- histological staining
Secondary outcome
- BMI
- Diet
Background summary
Obesity and type 2 diabetes (T2DM) are characterized by altered gut microbiota
composition and systemic inflammation. These have in turn been associated with
gut barrier disruption.
Specific bacteria such as the Akkermansia muciniphila reside in the mucus layer
of the intestinal wall and degrade mucin. Akkermansia muciniphila has been
found to correlates inversely with body weight and increase intestinal barrier
function in mice studies (9). Moreover, in human T2DM we found the mucus
composition to be altered, and adherent bacteria at the site of the small
intestine to induce a systemic inflammatory reaction. Altogether, these studies
plead for a role of gut bacteria and impaired barrier function in
obesity-induced T2DM. Up until now, microbiota studies are all based on faecal
analysis, which mainly reflects the colonic microbiota composition. The large
intestine contains around one kilogram of mainly bacteria, and the colonic wall
is relatively thick and well-protected against potential bacterial
infiltration. In contrast, the small intestinal wall is relatively thin and
less well protected against bacterial infiltration. Marked differences exist
between the bacterial numbers, composition and activity of the small and large
intestine.
In the context of T2DM, several studies emphasize the pivotal role of the small
intestine. First, exclusion of the first part of the small intestine results in
almost immediate improvement of T2DM. More convincing evidence for the role of
the small intestine in development of T2DM is provided by the success of newest
incretin-based medical therapy for T2DM, which are based upon gut hormones
secreted through receptor signalling in the small intestine. In addition, small
intestinal bacterial overgrowth (SIBO) has been associated with human T2DM.
Current therapeutic studies even focus on improving diabetes by influencing
microbiota composition.
Study objective
To determine if the microbiota inhabiting the small intestine in morbidly obese
patients with T2DM is comparable to those without T2DM and, if not, what are
the deviations and what is their impact
Study design
In this observational cross-sectional study, we intend to include 50 subjects
and investigate their small intestinal and colonic flora in relation to their
glycaemic and inflammatory status.
Study burden and risks
Patients are asked to collect faeces in a faecal collector for one day
preoperative. also, they are asked to register their diet in a diary for one
week.
During surgery, a small biopsy will be taken from the intestinal wall, a
procedure which showed nog adverse events in a previous study.
Blood samples will be taken regarding the current protocol, providing the
necessary amount of blood for the determination of CRP, HbA1c, insulin and
glucose. Patients do not have to visit the hospital more frequent then patients
who do not participate in this study. In addition, hospitalization time will
not be extended because of this study.
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
- BMI> 40 or BMI> 35 kg/m2 with or without co-morbidities
- undergoing hastric bypass surgery
- Age 18-60 years (in line with the indication criteria for bariatric surgery)
- Caucasian race (previous research showed that people of different ethnicity vary in intestinal microbiota composition)
Exclusion criteria
- Age <18 or> 60 years
- Alcohol abuse (>10 standard international units/week) or any drug use (Cannabis, cocaine, etc)
- Auto-immune and / or inflammatory diseases (eg sarcoidosis, diabetes mellitus type I, liver disease, or intestinal diseases such as inflammatory bowel disease)
- Antibiotics usage <6mnd prior to inclusion (because of their effect on the intestinal microbiota)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL46559.100.13 |