Elucidating the Dynamics and Impact of the Gut Microbiome on Maternal Nutritional Status During Pregnancy

简要总结

详细描述

This project represents the first systematic investigation of the impact of the microbiome on nutritional status during pregnancy in young women and directly aligns with global health initiatives focused on this vulnerable cohort. The goal of the study is to define the relationships between host nutritional status and microbiome dynamics during pregnancy and how they contribute to birth outcomes. The gut microbiome has a profound influence on host nutritional status. Dysbiosis (loss of diversity/beneficial microbes and gain of pathobionts) has emerged as a major factor in the development of undernutrition. Despite the importance of nutrition during pregnancy, few studies have examined the role of the microbiome on maternal health and birth outcomes. Further, little is known concerning the influence of enteric eukaryotic microbes, such as parasites, on the bacterial microbiome and host nutrition. At the core of this study are two complementary cohorts of young women that provide an exceptional opportunity to obtain longitudinal samples to monitor the dynamic relationships between microbiome community structure and function with gut health and host nutritional status. This registration is for the the Toronto cohort of the study, which will focus on refugee and young adult obstetric clinics in Toronto, a population of specific relevance to undernutrition. This cohort is expected to yield insights into the influence of eukaryotic microbes that are often viewed as asymptomatic. The target demographic of the study is young mothers, 28 years of age and younger, in the Toronto and Greater Toronto Area. The investigators have identified this younger demographic due to the lack of knowledge on the microbiome of young women, and their vulnerability to undernutrition. A second complementary cohort will be based in the Matiari district of Pakistan. This project will yield unprecedented insights into the relationships between prokaryotic and eukaryotic microbes in the gut and their associations with maternal health and birth outcomes. The central hypothesis of the study is that alterations of the microbiota in the maternal gut (dysbiosis) exacerbated by nutritional status or pathogen exposure during pregnancy, impacts weight gain because of impaired nutrient absorption, leading to corresponding negative birth outcomes. The study will be a prospective, longitudinal, observational study to investigate the impact and relationship between prokaryotic and eukaryotic microbes in the gut and their association with maternal health and birth outcomes among young women, 28 years of age and younger in the Toronto and Greater Toronto Area. The study will aim to recruit 400 women into two groups based on BMI at time of recruitment (Normal BMI will be defined as between 20 and 24.9 kg/m2 and Low BMI will be defined as less than 20 kg/m2). With a goal of having 200 participants within the normal BMI group and 200 participants within the low BMI group. Although this is the recruitment aim, in the event that the investigators are unable to recruit 200 women with a low BMI, more women will be recruited that fall within the normal BMI range. The study will follow women and their infants over the course of their pregnancy and for a year post-partum, collecting stool, rectal and blood samples, nutritional information, heath assessments, anthropometric measurements and empowerment metrics at different time points.

主要结局

次要结局

• Infant growth: weight(within 24 hours of birth, 3 months, 6 months and 12 months)
• Anthropometrics: Maternal triceps skinfold thickness(8-20 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum)
• Maternal blood biomarkers(8-20 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum)
• Infant sex(Determined at delivery)
• Infant morbidity(3 months, 6 months and 12 months)
• Reported maternal medication use(8-20 weeks post-conception, 30-34 weeks post-conception, within 24 hours of delivery, 3-months post-partum, 6 months post-partum and 12 months post-partum)
• Preterm birth(Within 24 hours of birth)
• Stillbirth(Within 24 hours of birth)
• Birth size: head circumference(within 24 hours of birth)
• Infant Stool biomarkers: Calprotectin, Lipocalin and Claudin 15(3 months and 12 months)
• Anthropometrics: Maternal middle upper arm circumference(8-20 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum,and 12 months post-partum)
• Infant blood biomarkers(12 months)
• Maternal morbidity(8-20 weeks post-conception, 30-34 weeks post-conception, 3 months post-partum, 6 months post-partum and 12 months post-partum)
• Infant growth: mid upper arm circumference(within 24 hours of birth, 3 months, 6 months and 12 months)
• Reported Infant medication use(within 24 hours of birth, 3 months, 6 months and 12 months)
• Self-efficacy(3 months post-partum and 12 months post partum)
• Anthropometrics: Maternal BMI(8-20 weeks post-conception, 30-34 weeks post-conception, delivery, 3-months post-partum, 6 months post-partum and 12 months post-partum)
• Anthropometrics: Maternal height(8-20 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post partum)
• Anthropometrics: Maternal weight(8-20 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum)
• Infant growth: head circumference(within 24 hours of birth, 3 months, 6 months and 12 months)
• Breast feeding: amount and initiation of complementary feeding(within 24 hours of birth, 3 months, 6 months and 12 months)
• Dietary diversity(8-20 weeks post conception, 30-34 weeks post conception, 3 months post-partum and 12 months post partum)
• Household annual food insecurity(3 months post-partum and 12 months post-partum)
• Perceived decision making(3 months post-partum and 12 months post partum)
• Perceived social support(3 months post-partum and 12 months post partum)
• Infant growth: length(within 24 hours of birth, 3 months, 6 months and 12 months)
• Infant growth: triceps skinfold thickness(within 24 hours of birth, 3 months, 6 months and 12 months)
• Infant Gestational age(8-20 weeks post conception)
• Maternal dietary intake(8-20 weeks post conception, 30-34 weeks post conception and 12 months post partum)
• Maternal demographics(8-20 weeks post-conception)
• Food insecurity(8-20 weeks post conception, 3 months post partum and 12 months post partum)
• Small for gestational age(Within 24 hours of birth)
• Maternal stool biomarkers: Calprotectin, Lipocalin and Claudin 15(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Maternal: incidence of pathobionts(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Infant: incidence of pathobionts(3 months and 12 months)
• Infant: gut bacterial profile as measured through 16S rDNA sequence surveys(3 and 12 months post partum)
• Infant: microbiome taxonomic alpha and beta diversity(3 months and 12 months)
• Perceived parental stress(3 months post-partum and 12 months post partum)
• Birth size: length(within 24 hours of birth)
• Birth size: weight(within 24 hours of birth)
• Infant dietary intake: NutricheQ Questionnaire(12 months)
• Large for gestational age(Within 24 hours of birth)
• Delivery assessment(within 24 hours of birth)
• Maternal gut bacteria profile as measured through 16S rDNA sequence surveys(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Infant: blood metallomics profile as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25)(12 months)
• Birth defects(within 24 hours of birth)
• Maternal: metabolomic profile of stool (metabolites involved in central metabolism as analysed by Mass Spectrometry)(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Infant eukaryotic microbiome profile as measured through 18S and ITS rDNA sequence surveys(3 months and 12 months)
• Maternal: microbiome taxonomic alpha and beta diversity(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Maternal: blood metallomics profile as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25)(8-20 weeks post conception, 30-34 weeks post conception, and 12 months post partum)
• Maternal metabolic pathway expression profile as measured through whole microbiome RNASeq (metatranscriptomics)(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Maternal eukaryotic microbiome profile as measured through 18S and ITS rDNA sequence surveys(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Maternal bacterial gene expression profile as measured through whole microbiome RNASeq (metatranscriptomics)(8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
• Maternal age(Documented at 8-20 weeks post-conception)