APOA2 Gene, Diet, Inflammation and Gut Health
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/13/2019 |
| Start Date: | October 13, 2017 |
| End Date: | September 2020 |
| Contact: | Jose M Ordovas, PHD |
| Email: | jose.ordovas@tufts.edu |
| Phone: | 617 556 3102 |
Nutrients and chemicals in food are able to regulate expression of genetic elements.
Gene-nutrient interaction in response to unhealthy diets can increase an individual's risk,
shifting the individual from health toward the development of chronic disease. The
apolipoprotein A2 (APOA2) gene may either put individuals at risk for or protect from obesity
in the presence of certain fats in food. The main purpose of this four-week study is to
examine diet induced gene-nutrient interaction, with a focus on gut health, gut microbiota
and inflammation in individuals who have either the CC or the TT form within a specific
variant of the APOA2 Gene. The (2) one-week study diets, one plant based and the other animal
based are separated by a (1) week return to your regular habitual without probiotic or
prebiotic food products.
Gene-nutrient interaction in response to unhealthy diets can increase an individual's risk,
shifting the individual from health toward the development of chronic disease. The
apolipoprotein A2 (APOA2) gene may either put individuals at risk for or protect from obesity
in the presence of certain fats in food. The main purpose of this four-week study is to
examine diet induced gene-nutrient interaction, with a focus on gut health, gut microbiota
and inflammation in individuals who have either the CC or the TT form within a specific
variant of the APOA2 Gene. The (2) one-week study diets, one plant based and the other animal
based are separated by a (1) week return to your regular habitual without probiotic or
prebiotic food products.
The primary objectives of this application are 1. To use a diet intervention setting to
rigorously evaluate the mechanisms responsible for the previously observed effects, focusing
on gut microbiota and markers of gut health and inflammation and 2. To prove that targeted
dietary intervention based on genes can provide additional, tailored benefit to genetically
vulnerable individuals. The overall hypothesis proposes that significant cross-talk between
the human host genome, the microbiome, and the diet, defines the observed inter-individual
variation in metabolic and physiological responses. Accordingly, the investigators propose
the following specific aims and hypotheses.
AIM 1: To catalog the response of the plasma metabolome to diets differing in saturated fat
and prebiotics content (animal-based diet versus plant-based diet) in individuals from the
USA carrying CC (n=20) and TT (n=20) genotypes at the common APOA2 −265T>C SNP using a
crossover, randomized dietary intervention study.
Our primary hypothesis states: A significant and biologically relevant proportion of the
individual variation in changes in the plasma metabolome in response to dietary saturated fat
and prebiotic intake will be due to APOA2−265T>C genotypes. Specifically, subjects homozygous
(CC) for the less common C allele will respond to decreases in total dietary saturated fat
and increases in prebiotics (i.e., plant-based diet) with significantly greater improvement
of metabolites related to gut health, inflammation and other cardiometabolic traits than
subjects homozygous (TT) for the common T allele.
AIM 2: To characterize differential impacts of low SFA/high prebiotic (plant-based) diet vs.
high SFA/low prebiotic (animal-based) diets on gut microbiota patterns between CC and TT
persons at APOA2-265T>C.
Our primary hypothesis states: CC subjects have a preference for high-fat and -protein foods
and therefore high levels of Bacteroidetes, Actinobacteria and similar species in the gut are
expected. Moreover, reducing intake of saturated fat and increasing prebiotics will be more
effective in inducing a healthier gut microflora profile in CC subjects than in those with
the TT genotype, with opposite effects observed when the diet is switched to one high in
saturated fat.
AIM 3: To integrate the metabolomic and gut microflora taxonomic information generated in
AIM1 and AIM2 in order to elucidate the physiological mechanism(s) by which diet impinges on
metabolic pathways through APOA2 genotypes.
Our primary hypothesis states: A diet low in saturated fat and high in prebiotics induces
beneficial changes in gut microbiota, metabolic processes and inflammation, which are
significantly more pronounced in CC than in TT subjects.
rigorously evaluate the mechanisms responsible for the previously observed effects, focusing
on gut microbiota and markers of gut health and inflammation and 2. To prove that targeted
dietary intervention based on genes can provide additional, tailored benefit to genetically
vulnerable individuals. The overall hypothesis proposes that significant cross-talk between
the human host genome, the microbiome, and the diet, defines the observed inter-individual
variation in metabolic and physiological responses. Accordingly, the investigators propose
the following specific aims and hypotheses.
AIM 1: To catalog the response of the plasma metabolome to diets differing in saturated fat
and prebiotics content (animal-based diet versus plant-based diet) in individuals from the
USA carrying CC (n=20) and TT (n=20) genotypes at the common APOA2 −265T>C SNP using a
crossover, randomized dietary intervention study.
Our primary hypothesis states: A significant and biologically relevant proportion of the
individual variation in changes in the plasma metabolome in response to dietary saturated fat
and prebiotic intake will be due to APOA2−265T>C genotypes. Specifically, subjects homozygous
(CC) for the less common C allele will respond to decreases in total dietary saturated fat
and increases in prebiotics (i.e., plant-based diet) with significantly greater improvement
of metabolites related to gut health, inflammation and other cardiometabolic traits than
subjects homozygous (TT) for the common T allele.
AIM 2: To characterize differential impacts of low SFA/high prebiotic (plant-based) diet vs.
high SFA/low prebiotic (animal-based) diets on gut microbiota patterns between CC and TT
persons at APOA2-265T>C.
Our primary hypothesis states: CC subjects have a preference for high-fat and -protein foods
and therefore high levels of Bacteroidetes, Actinobacteria and similar species in the gut are
expected. Moreover, reducing intake of saturated fat and increasing prebiotics will be more
effective in inducing a healthier gut microflora profile in CC subjects than in those with
the TT genotype, with opposite effects observed when the diet is switched to one high in
saturated fat.
AIM 3: To integrate the metabolomic and gut microflora taxonomic information generated in
AIM1 and AIM2 in order to elucidate the physiological mechanism(s) by which diet impinges on
metabolic pathways through APOA2 genotypes.
Our primary hypothesis states: A diet low in saturated fat and high in prebiotics induces
beneficial changes in gut microbiota, metabolic processes and inflammation, which are
significantly more pronounced in CC than in TT subjects.
Inclusion Criteria:
- Men and women
- 18 years or older
- Women who are not pregnant
- A BMI ranging between 27 and 34
Exclusion Criteria:
- Unexplained elevation in serum transaminases (i.e. >1.5 times the upper limit of
normal) or with evidence of active liver disease, including primary biliary cirrhosis
or pre-existing gallbladder disease
- Severe renal dysfunction (serum creatinine >2.0mg/dL)
- Excessive alcohol consumption (>2 drinks/day)
- Preexisting cardiovascular disease (CVD)
- Stable exertional angina pectoris requiring sublingual nitroglycerin within the prior
3 months
- Uncontrolled tyoe 2 diabetes (T2D) (fasting glucose >126 mg/dl) or other significant
endocrine disease.
- Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood
pressure >100 mmHg).
- History of pancreatitis within 1 yr. prior to screening.
- Subjects on lipid lowering or diabetes medications.
- Smoking
- Pregnancy
- Body mass index (BMI) below 27 or greater than 34 kg/m2
- Participants will also be excluded for drug abuse, extreme dietary habits, multiple
food allergies, extreme levels of physical or athletic activity, or by changes in body
weight >20 lbs. during the last 6 months
- Current use of antibiotics or during the previous 4 weeks.
- Inability to follow any of the experimental diets (including being vegetarian) or to
perform the sampling required for this study
- Use of herbal supplements that may alter the gut microflora
- Autoimmune diseases
- Recent colonoscopy (within the previous two months)
- Use of antidiarrheal medication
- Thyroid diseases
- Use of omega-3 supplements (unless it is discontinued one month prior to the beginning
of the study).
We found this trial at
1
site
Boston, Massachusetts 02111
Phone: 617-556-3102
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