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Sources of Gut Microbiota Variation in a Large Longitudinal Finnish Infant Cohort
40 Pages Posted: 6 Apr 2023More...
Background: Although the infant gut microbiota has been extensively studied, comprehensive assessment on the microbiota covariates including technical variables has not been performed in large infant cohorts.
Methods:We studied the effect of 109 variables on the 16S rRNA gene amplicon-based gut microbiota profiles of infants sampled longitudinally over the first two years of life in the Finnish HELMi birth cohort. Spot faecal samples from both parents were included for intra-family analyses, totalling to 7660 samples from 985 families that were evaluated for beta-diversity patterns using permutational multivariate analysis on Bray-Curtis distances, and differential abundance testing and alpha-diversity for variables of interest. We also assessed the effect of different taxonomic levels and distance methods.
Findings: In time point-specific models, the largest effect sizes, up to 6%, were seen for the DNA extraction batch, delivery mode and related perinatal exposures, defecation frequency and parity/siblings. Variables of gastrointestinal function were continuously important during the first two years, reflecting changes in e.g., feeding habits. The effect of parity/siblings on infant microbiota was modified by birth mode and exposure to intrapartum antibiotics, exemplifying the tight interlinkage of perinatal factors relevant for infant microbiota research. In total, up to 19% of the biological microbiota variation in the infant gut could be explained. Our results highlight the need to interpret variance partitioning results in the context of each cohort’s characteristics and homogeneity.
Interpretation: Our study provides a comprehensive report of key covariates of infant gut microbiota composition across the two first years of life in a homogenous cohort. The study highlights possible important future research areas and confounding factors to be considered.
Funding: This research was supported by Business Finland, Academy of Finland, Foundation of Nutrition Research and University of Helsinki.
Declaration of Interest: The authors declare no competing interests.
Ethical Approval: The cohort study was approved by The Hospital District of Helsinki and Uusimaa and performed in accordance with the principles of the Helsinki Declaration. Parents signed an informed consent at enrollment.
Keywords: Infant gut microbiota, variance partitioning, PERMANOVA, beta-diversity, birth cohort
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