Projects_laboratory_m

Metagenomic predictors of childhood obesity, cross-talk with maternal microflora

Project goal: The purpose of this project: To determine metagenomic mediators and the role of the maternal microbiome in childhood obesity.
Project description: Overweight and obesity are a global problem and a challenge for the public health system around the world. In 2020, the proportion of obese people worldwide accounted for 30%, which is about three times higher than in 2010. According to Chang Chen et al., 2018, in 2014 there were 38.9 million overweight pregnant women worldwide and 14.6 million obese pregnant women. Maternal obesity affects fertility disorders, miscarriages, fetal abnormalities, and various long-term adverse effects on the child. At a later age, children born to overweight mothers are more likely to suffer from obesity and cardiometabolic diseases themselves. In Kazakhstan, overweight was found in 30.6% and 28.1% of women in 2012 and 2013, respectively. In recent years, a hypothesis has been formed that the gut microflora can be identified as a new factor of maternal obesity and related risks in offspring. This is confirmed by the difference in the microflora in the cohort of children born to overweight mothers from children born to mothers with normal body weight.
Project facilitators:
PI: Samat Kozhakhmetov
Madiyar Nurgaziyev
Nurislam Mukhanbetzhanov
Zharkyn Jarmukhanov
Zarina Meiirmanova
Arailym Duisebayeva
Project partners:
Astana Medical University
Realisation period:
2023-2025
Expected results: The study will include children and their mothers, at least 200 samples and metadata will be collected: Obese group 50/50 children/mothers with obesity; Control group: 50/50 children/mothers with normal weight. The relationship between the maternal metagenomic profile and the metagenomic profile of children is determined. The relationship between maternal metagenome-specific obesity and childhood obesity will be studied. The collected sample bank, metagenomic and clinical data itself will be one of the important results of this study. Also, the data collected during research activities, pre-encoded, will be deposited in an open database of scientific and technical information. The results of the study will contribute to the expansion of the international knowledge base and the subsequent development of personalized treatment approaches. It should be noted that the project will be in line with the project implemented in our organization to track the trajectory of the development of the gut microflora of children up to adolescence and its logical continuation. Long-term follow-up (up to 15 years) of the study participants will also be conducted to obtain updated information about the state of health and biodiversity, as well as the profile of the microbiome. This approach can then hypothetically reveal a link between perinatal covariates and long-term outcomes and hypothesize an intervention to modulate this microflora as an approach to improving health. An additional result beyond the scope of the research results will be the training of young specialists and volunteer students in microbiome and metagenomic analysis methods, ranging from DNA isolation to bioinformatic analysis methods.
Methodology: The study includes children of both sexes born in 2023 from mothers with obesity and normal weight, excluding children with congenital pathologies. Recruitment is conducted through parent surveys with informed consent and assignment of alphanumeric codes for confidentiality. Fecal samples are self-collected using DNA/RNA Shield tubes. Children are observed at least once every 3 months, with height and weight assessment. Samples are stored at -80°C, DNA is extracted using ZymoBIOMICS kit. Metagenomic shotgun sequencing is performed on Illumina NovaSeq 6000 platform. Data analysis is conducted using bioBakery, MetaPhlAn 4.0, HUMAnN 3.0, and inStrain. Statistical analysis includes diversity indices calculation, use of DESeq2, edgeR, and LEfSe. The study was approved by the Ethics Committee of Nazarbayev University (No.05-2022 dated 10/21/2022), sequencing results will be deposited in the SRA database.
Contacts: Samat Kozhakhmetov, Email: skozhakhmetov@nu.edu.kz