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Background and aimsBirth mode and other early life factors affect a newborn's microbial colonization with potential long-term health effects. Individual variations in early life gut microbiota development, especially their effects on the functional repertoire of microbiota, are still poorly characterized. This study aims to provide new insights into the gut microbiome developmental trajectories during the first year of life.MethodsOur study comprised 78 term infants sampled at 3 weeks, 3 months, 6 months, and 12 months (n = 280 total samples), and their mothers were sampled in late pregnancy (n = 50). Fecal DNA was subjected to shotgun metagenomic sequencing. Infant samples were studied for taxonomic and functional maturation, and maternal microbiota was used as a reference. Hierarchical clustering on taxonomic profiles was used to identify the main microbiota developmental trajectories in the infants, and their associations with perinatal and postnatal factors were assessed.ResultsIn line with previous studies, infant microbiota composition showed increased alpha diversity and decreased beta diversity by age, converging toward an adult-like profile. However, we did not observe an increase in functional alpha diversity, which was stable and comparable with the mother samples throughout all the sampling points. Using a de novo clustering approach, two main infant microbiota clusters driven by Bacteroidaceae and Clostridiaceae emerged at each time point. The clusters were associated with birth mode and their functions differed mainly in terms of biosynthetic and carbohydrate degradation pathways, some of which consistently differed between the clusters for all the time points. The longitudinal analysis indicated three main microbiota developmental trajectories, with the majority of the infants retaining their characteristic cluster until 1 year. As many as 40% of vaginally delivered infants were grouped with infants delivered by C-section due to their clear and persistent depletion in Bacteroides. Intrapartum antibiotics, any perinatal or postnatal factors, maternal microbiota composition, or other maternal factors did not explain the depletion in Bacteroides in the subset of vaginally born infants.ConclusionOur study provides an enhanced understanding of the compositional and functional early life gut microbiota trajectories, opening avenues for investigating elusive causes that influence non-typical microbiota development.

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Biogeographic variations in the gut microbiota reflect host and environmental factors delineating human populations, and are pivotal to understand global patterns of host-microbiota interactions in health and prevalent lifestyle-related diseases, such as type 2 diabetes mellitus (T2D). Pakistani adults, having an exceptionally high prevalence of T2D, are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by 16S ribosomal RNA gene amplicon sequencing and qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis. Overall, urbanized Pakistanis’ gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.