To investigate whether postprandial bacterial translocation and the subsequent inflammatory response can be modulated by oral vancomycin in lean versus obese subjects. Moreover, we will study the role of platelets in postprandial inflammation.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To investigate the effect of oral vancomycin in lean versus obese, insulin
resistant subjects on postprandial bacterial translocation, as measured by
plasma LPS, LBP and sCD14 as well as 16S DNA concentrations in whole blood,
isolated platelets and isolated monocytes.
Secondary outcome
To investigate postprandial platelet activation, as measured by P-selectin
expression and platelet-monocyte interaction in flow cytometric analyses.
All measurements will be related to postprandial inflammation, as measured by
monocyte phenotyping using flow cytrometric and histopathological analyses and
plasma cytokine concentrations, and gut microbiota composition before and after
treatment with oral vancomycin. Moreover, we will assess postprandial
concentrations of plasma bile acids, FGF-19 and glucagon-like peptide 1
(GLP-1). Finally, we will determine the effect of oral vancomycin on satiety as
measured by time taken to eat a standardized meal and intestinal transit time
as measured by 24 hour Sitzmark capsule clearance.
Background summary
The human gastro-intestinal tract harbors a complex and diverse ecosystem of
bacteria that affect the host in several beneficial ways. However, the gut
microbiota also comprises a source of potentially toxic molecules, such as
lipopolysaccharide (LPS). Chronic exposure to LPS has been associated with
obesity, development of insulin resistance and type 2 diabetes and
cardiovascular disease. Following ingestion of a high-fat meal, a systemic
inflammatory response with activation of monocytes occurs that is more severe
in obese subjects. However, the underlying mechanisms of this postprandial
inflammatory response have not been fully elucidated. Based on previous data by
our group, we propose that modulation of the gut microbiota by oral vancomycin
influences bacterial translocation and postprandial inflammation, and that the
response differs between lean and obese subjects. Moreover, we hypothesize that
translocation of Gram-negative bacteria and LPS induces activation of
platelets, that in turn activate monocytes and trigger the low-grade
inflammatory response that is associated with metabolic diseases.
Study objective
To investigate whether postprandial bacterial translocation and the subsequent
inflammatory response can be modulated by oral vancomycin in lean versus obese
subjects. Moreover, we will study the role of platelets in postprandial
inflammation.
Study design
Prospective, single center intervention study.
Intervention
Subjects will receive oral vancomycin 500 mg 4 times a day for 7 days.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Participants will receive oral vancomycin for 7
days. Moreover, they will undergo 2 separate 4 hour oral fat load tests and 3
abdominal X-rays. All interventions are associated with negligible risks and
have been approved by the METC in previous studies (MEC 10/265, and 2015_014).
Thus, the risks and burden associated with participation can be considered
minimal. Moreover, this study will provide valuable insight into the
relationship of the intestinal microbiota composition and postprandial
bacterial translocation in metabolic syndrome. Subjects will receive 300 euro
as compensation for their participation as well as reimbursement of their
travel expenses.
Meiberdreef 9
Amsterdam 1105AZ
NL
Meiberdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Metabolic syndrome patients:
* Caucasian male
* BMI *30 kg/m2
* At least 2 of the following criteria:
o fasting plasma glucose *5.6 mmol/L
o waist-circumference *102 cm
o HDL-cholesterol *1.02 mmol/L
o Blood pressure *130/85 mmHg
o HOMA-IR index *2.5 (HOMA-IR is measured as (fasting insulin (pmol/L) x fasting glucose (mmol/L)) / 135)
* Triglycerides *1.7 mmol/L
* Subjects should be able to give informed consent;Healthy controls:
* Caucasian male
* BMI 18,5-25 kg/m2
* HOMA-IR index *2.0
* Subjects should be able to give informed consent
Exclusion criteria
Metabolic syndrome patients:
* A history of cardiovascular event (CVI, MI) or pacemaker implantation
* Use of any medication including PPI and antibiotics in the past three months or during the study period
* (Expected) prolonged compromised immunity (due to recent cytotoxic chemotherapy or HIV infection with a CD4 count < 240/mm3)
* Presence of type 1 diabetes mellitus (T1DM) or T2D
* Smoking
* Use of >5 units of alcohol daily or use of alcohol during the study period
* History of cholecystectomy;Healthy controls:
* A history of cardiovascular event (CVI, MI) or pacemaker implantation
* Use of any medication including PPI and antibiotics in the past three months or during the study period
* (Expected) prolonged compromised immunity (due to recent cytotoxic chemotherapy or HIV infection with a CD4 count < 240/mm3)
* Presence of type 1 diabetes mellitus (T1DM) or T2D
* Smoking
* Use of >5 units of alcohol daily or use of alcohol during the study period
* History of cholecystectomy
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 | NL58739.018.16 |