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Background: While early life exposures such as mode of birth, breastfeeding, and antibiotic use are established regulators of microbiome composition in early childhood, recent research suggests that the social environment may also exert influence. Two recent studies in adults demonstrated associations between socioeconomic factors and microbiome composition. This study expands on this prior work by examining the association between family socioeconomic status (SES) and host genetics with microbiome composition in infants and children. Methods: Family SES was used to predict a latent variable representing six genera abundances generated from whole-genome shotgun sequencing. A polygenic score derived from a microbiome genome-wide association study was included to control for potential genetic associations. Associations between family SES and microbiome diversity were assessed. Results: Anaerostipes, Bacteroides, Eubacterium, Faecalibacterium, and Lachnospiraceae spp. significantly loaded onto a latent factor, which was significantly predicted by SES (p &lt, 0.05) but not the polygenic score (p &gt, 0.05). Our results indicate that SES did not predict alpha diversity but did predict beta diversity (p &lt, 0.001). Conclusions: Our results demonstrate that modifiable environmental factors influence gut microbiome composition at an early age. These results are important as our understanding of gut microbiome influences on health continue to expand.

Summary Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting >6,500 metagenomes, we obtained >1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (>10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations., Graphical Abstract, Highlights • P. copri is not a monotypic species but composed of four distinct clades • The P. copri complex is more prevalent in populations with non-Westernized lifestyles • P. copri clades are frequently co-present within non-Westernized individuals • Ancient stool samples suggest Westernization leads to P. copri underrepresentation, Tett et al. find that the intestinal microbe Prevotella copri encompasses four distinct clades constituting the P. copri complex. The complex is prevalent in non-Westernized populations where co-presence of all clades is commonly observed within individuals. Analysis of ancient stool samples supports Westernization as contributing to reduced P. copri prevalence.

The NOD-like receptors (NLRs) were among the first innate immune receptors discovered, yet a clear understanding of the basic principles underlying their mechanisms of action is lacking. Two recent studies provide important cell biological insights into the subcellular sites of NOD1- and NOD2-dependent signaling.