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Background & Aims: IgA exerts its primary function at mucosal surfaces, where it binds microbial antigens to regulate bacterial growth and epithelial attachment. One third of individuals with IgA deficiency (IgAD) suffers from recurrent mucosal infections, possibly related to an altered microbiota. We aimed to delineate the impact of IgAD and the IgA-autoantibody status on the composition and functional capacity of the gut microbiota., Methods: We performed a paired, lifestyle-balanced analysis of the effect of IgA on the gut microbiota composition and functionality based on fecal samples from individuals with IgAD and IgA-sufficient household members (n = 100), involving quantitative shotgun metagenomics, species-centric functional annotation of gut bacteria, and strain-level analyses. We supplemented the data set with 32 individuals with IgAD and examined the influence of IgA-autoantibody status on the composition and functionality of the gut microbiota., Results: The gut microbiota of individuals with IgAD exhibited decreased richness and diversity and was enriched for bacterial species encoding pathogen-related functions including multidrug and antimicrobial peptide resistance, virulence factors, and type III and VI secretion systems. These functional changes were largely attributed to Escherichia coli but were independent of E coli strain variations and most prominent in individuals with IgAD with IgA-specific autoreactive antibodies., Conclusions: The microbiota of individuals with IgAD is enriched for species holding increased proinflammatory potential, thereby potentially decreasing the resistance to gut barrier-perturbing events. This phenotype is especially pronounced in individuals with IgAD with IgA-specific autoreactive antibodies, thus warranting a screening for IgA-specific autoreactive antibodies in IgAD to identify patients with IgAD with increased risk for gastrointestinal implications., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Environmental surveillance is a critical tool for combatting public health threats represented by the global COVID-19 pandemic and the continuous increase of antibiotic resistance in pathogens. With its power to detect entire microbial communities, metagenomics-based methods stand out in addressing the need. However, several hurdles remain to be overcome in order to generate actionable interpretations from metagenomic sequencing data for infection prevention. Conceptually and technically, we focus on viability assessment, taxonomic resolution, and quantitative metagenomics, and discuss their current advancements, necessary precautions and directions to further development. We highlight the importance of building solid conceptual frameworks and identifying rational limits to facilitate the application of techniques. We also propose the usage of internal standards as a promising approach to overcome analytical bottlenecks introduced by low biomass samples and the inherent lack of quantitation in metagenomics. Taken together, we hope this perspective will contribute to bringing accurate and consistent metagenomics-based environmental surveillance to the ground., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shen, McFarland, Young, Hayden and Hartmann.)

The human gut microbiome can now be characterized in unprecedented detail by an approach based on high-throughput sequencing of total stool DNA, that we name quantitative metagenomics. Central to the approach is a catalog that lists all the genes of intestinal microbes that are known - 9.9 millions, identified by the analysis of 1267 stool samples. Beyond the gene list, genetic units that carry them begun to be known; many of these correspond to bacterial species that were never isolated and cultured yet. Quantitative metagenomics allows developing powerful algorithms to diagnose a disease, monitor patients and identify individuals at risk to progress towards a disease. This lays ground for developing new approaches to better restore and even preserve the health by modulation of the altered microbiome, which contributes to promote or aggravate a disease., (Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.)