Abstract
SummaryThe human microbiota plays a critical role in host health. Proper development of the infant microbiome is particularly important. Its dysbiosis leads to both short-term health issues and long-term disorders lasting into adulthood. A central way in which the microbiome interacts with the host is through the production of effector molecules, such as proteins and small molecules. Here, a metagenomic library constructed from 14 infant stool microbiomes is analyzed for the production of effectors that modulate three distinct host pathways: immune response (nuclear factor κB [NF-κB] activation), autophagy (LC3-B puncta formation), and redox potential (NADH:NAD ratio). We identify microbiome-encoded bioactive metabolites, including commendamide and hydrogen sulfide and their associated biosynthetic genes, as well as a previously uncharacterized autophagy-inducing operon from Klebsiella spp. This work extends our understanding of microbial effector molecules that are known to influence host pathways. Parallel functional screening of metagenomic libraries can be easily expanded to investigate additional host processes.
Highlights
Mounting evidence suggests that proper development of an infant’s gut microbiome is critical to the health of the developing child
Stool was collected from diapers, and microbial DNA was extracted using techniques previously established by our lab (Cohen et al, 2015; Brady, 2007). 16S rDNA sequences from individual metagenomic samples were amplified and sequenced to determine each microbiome’s taxonomic composition (Figure 1A; Table S1)
Samples were dominated by the Bacteroidetes and Firmicutes phyla, which is typical of most child and adult microbiome compositions in the Western world (Qin et al, 2010; Eckburg et al, 2005), individual infant stool metagenomes showed significant phyla-level variation in abundance
Summary
Mounting evidence suggests that proper development of an infant’s gut microbiome is critical to the health of the developing child. Mode of delivery (vaginal versus Cesarian), and feeding patterns (breastfeeding versus formula) are several factors that can cause dysbioses of the infant’s gut microbiome, which is often associated with disease in the infant host (Arrieta et al, 2014; Yang et al, 2016; Mohammadkhah et al, 2018). Adverse development of the infant gut microbiome is thought to affect health later in life. A recent study in mice has shown that increased prenatal maternal stress can result in long-lasting changes in the infant microbiome associated with anxiety-like behaviors later in life (Gur et al, 2019). Reduced alpha diversity in the gut microbiomes of one-year-old infants has been linked to changes in cognitive abilities one year later (Carlson et al, 2018). The far-reaching influence of the infant microbiome, as illustrated by these studies, makes it of particular interest among microbial communities
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