Effect of Mediterranean Diet During Pregnancy on Gut Microbiota and on the Epigenetics (PREMEDI)
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|ClinicalTrials.gov Identifier: NCT03337802|
Recruitment Status : Unknown
Verified February 2020 by Roberto Berni Canani, Federico II University.
Recruitment status was: Recruiting
First Posted : November 9, 2017
Last Update Posted : February 18, 2020
Food allergies (AA) are adverse reactions to food. Over the last decade, the AA scenario has changed profoundly. In many countries, there has been a significant increase in the prevalence, persistence and severity of AAs and a consequent increase in the socio-economic impact associated with these conditions. For these reasons, there is a strong need to develop effective strategies to prevent these conditions. To date, the AA etiopathogenesis is not yet fully defined. Genetic factors may predispose certain subjects to the development of AA, but these alone can not explain the change observed in the AA scenario over the last few years, renewing interest in environmental factors.
Numerous scientific evidence demonstrate the role of eating habits in influencing human health. Many of the effects of the diet on human health are due to a modulation of intestinal microbiosis. The regulation of the immune system is one of the pathways through which dietary modifications from the earliest times of life can alter the susceptibility of the individual to the development of allergic manifestations. The diet during pregnancy and lactation represents the earliest possible influence on the development of the baby's immune system. Observational studies suggest the association between maternal diet during pregnancy and lactation and development of allergic pathologies in the unborn, but the data are still preliminary. Often, other important parameters such as the atopic status of the parents, the type of delivery, the number of brothers, exposure to common allergens, maternal infections or early life, smoking exposure were not taken into account of cigarettes. The Mediterranean diet (MD) is characterized by a high intake of fruit and vegetables, legumes and whole grains combined with a moderate consumption of red wine, and the use of olive oil as the main source of lipids. In some studies adherence to MD was inversely related to the incidence of asthma and allergic rhinitis, especially in children. High adherence to MD was associated with a positive change in intestinal microbiosis and the production of short chain fatty acids (SCFA), particularly butyrate, the main SCFA produced by intestinal fermentation of food fibers. SCFA regulates mucosal integrity and the immunological and non-immunological mechanisms involved in the development of oral tolerance.
MD mechanisms during pregnancy in the prevention of childhood allergies are not yet fully known.
|Condition or disease||Intervention/treatment||Phase|
|Food Allergy||Behavioral: mediterranean diet||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effects of the Mediterranean Diet During Pregnancy on Maternal Gut Microbiota Composition and Function and on Neonatal Epigenetic Modulation on Food Allergy and Obesity|
|Actual Study Start Date :||March 31, 2017|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||March 31, 2021|
No Intervention: Pregnant women at standard diet
obstetrical and gynecological follow-up
Experimental: Pregnant women at mediterranean diet
obstetrical and gynecological follow-up + nutritional counseling
Behavioral: mediterranean diet
The Mediterranean diet (MD) is highly regarded as a healthy balanced diet. It is distinguished by a beneficial fatty acid profile that is rich in both monounsaturated and polyunsaturated fatty acids, high levels of polyphenols and other antioxidants, high intake of fiber and other low glycemic carbohydrates, and relatively greater vegetable than animal protein intake. Specifically, olive oil, assorted fruits, vegetables, cereals, legumes, and nuts; moderate consumption of fish, poultry, and red wine; and a lower intake of dairy products, red meat, processed meat and sweets characterize the traditional MD.
- The effects of Mediterranean diet in pregnancy on epigenetic mechanisms that regulate the expression of the genes involved in the allergic response in the offspring through epigenetic analysis on cord blood [ Time Frame: after 9 months (at the end of the pregnancy) ]The cord blood (5 ml) will be harvested in heparin tubes and transported immediately to the laboratory for extraction of peripheral blood lymphocytes by Ficoll gradient. The epigenetic mechanisms that will be explored are: DNA methylation of the major cytokines involved in Th1 / Th2 (IL-4, IL-5, IL-13, IL-10, IFN-γ and Treg-specific demethylated region of FoxP3 transcriptional factor) , Using the High Resolution melting (RealMore) method and confirmed by sequencing; Expression analysis of the major miRNAs involved in the pathogenesis of allergic pathologies (miR-125b, miR-146, miR-155, miR-29a / b, miR-27, miR-128, let-7b, miR-21, miR-126 , MiR-145, miR-106a, miR-375) on RNA extracted from peripheral blood lymphocytes by Real Time PCR; Analysis of the activity of Histone deacetylases (HDAC) 6 and 9, involved in the equilibrium of Th1 / Th2 cells by Real Time PCR.
- The effects of Mediterranean diet in pregnancy on epigenetic mechanisms that regulate the expression of the genes involved in obesity in the offspring through epigenetic analysis on cord blood [ Time Frame: after 9 months (at the end of the pregnancy) ]The cord blood (5 ml) will be harvested in heparin tubes and transported immediately to the laboratory for extraction of peripheral blood lymphocytes by Ficoll gradient. The epigenetic mechanisms that will be explored are: (leptin, adiponectin, PPAR-γ, PPAR-α, IGF-1, CPTI C / EBPβ) using the HRM (High Resolution melting) Real Time method and confirmed by sequencing.
- The effect of Mediterranean Diet pregnancy on the composition of maternal gut microbiota through analysis of gut microbiota composition. [ Time Frame: after 9 months (at the end of the pregnancy) ]Fecal bacteria DNA will be extracted using standard technique outlined by the Earth Microbiome Project. 16S V4-region amplicon libraries will be produced using previously described primers and sequenced using the IlluminaMiSeqplatform (150bpx2). Bacterial load will be determined by qPCR using a standard curve derived from a plasmid containing a single copy of the 16S rRNAencoding gene. Sequence data has been deposited in MG RAST under accession numbers 4571868.3-4571924.3 and project number 10023. Paired end reads will be quality trimmed and processed for OTU (operational taxonomic unit) clustering using UPARSE pipeline, set at 0.97% identity cutoff. Taxonomic status will be assigned to the high quality (<1% incorrect bases) candidate OTUs using the "parallel_assign_taxonomy_rdp.py" script of QIIME software. Multiple sequence alignment and phylogenetic reconstruction will be performed using PyNast and FastTree.
- The effect of Mediterranean diet in pregnancy on the production of short chain fatty acids (butyrate and propionate) in the intestinal tract. [ Time Frame: after 9 months (at the end of the pregnancy) ]Fecal SCFAs concentration Frozen feces weighing 1g will be diluted with saline solution, vortexed, and centrifuged. Supernatants will be filtered and stored at -20°C until analysis. Frozen fecal extracts will be acidified and extracted in duplicate. A quantity of the pooled extract containing acidified butyrate, propionate or acetate will be transferred into a 2ml glass vial and loaded onto an Agilent Technologies 7890 gas chromatograph (GC) system. Detection will be achieved using a flame ionization detector. Peaks will be identified using a mixed external standard and quantified by peak height/internal standard ratio. To examine whether fecal butyrate levels correlates with bacterial diversity (Shannon diversity index) and evenness (Pielou's evenness index) and abundance patterns across multiple groups we will calculate the Spearman correlation using the cor.test function implemented in R (http://www.r-project.org/
- The adherence to Mediterranean diet in the enrolled women [ Time Frame: from 0 to 9 months (at the end of pregnancy) ]
- The effect of dietary counseling on dietary habits and adherence to Mediterranean diet in pregnancy [ Time Frame: from 0 to 9 months (at the end of pregnancy) ]
- The effect of Mediterranean diet in pregnancy on the maternal weight gain and complications [ Time Frame: from 0 to 9 months (at the end of pregnancy) ]To evaluate the effect of Mediterranean diet in pregnancy on the maternal weight gain and complications (gestational hypertension, infections, gestational diabetes, preeclampsia, use of cesarean)
- the effect of Mediterranean diet in pregnancy on auxological parameters,Apgar score and fetal complications [ Time Frame: from 0 to 9 months (at the end of pregnancy) ]the effect of Mediterranean diet in pregnancy on neonatal weight, length, cranial circumference, Apgar score and fetal complications (natimortality risk, intrauterine growth restriction, preterm delivery, early abortion, shoulder dystocia, fetal macrosomia).
- the effect of Mediterranean Diet in pregnancy on the duration of breastfeeding and the composition of breast milk [ Time Frame: from 0 to 4 months lactation ]the effect of Mediterranean Diet in pregnancy on the duration of breastfeeding and the composition of breast milk (short chain fatty acids, bacterial DNA, adipocytokines.
- the effect of Mediterranean Diet on the growth patterns trends, development of allergies, use of antibiotics, IQ quotient in the first 2 years of life. [ Time Frame: every 6 months from offspring birth to 2 years ]the effect of Mediterranean Diet on the growth patterns trends, development of allergies, use of antibiotics, IQ quotient in the first 2 years of life.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03337802
|Contact: Roberto Berni Canani, MD, PhDemail@example.com|
|University of Naples Federico II||Recruiting|
|Naples, Italy, 80131|
|Contact: Roberto Berni Canani, MD, PhD +390817462680|