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McComb, E. J.

Publications and source records attributed to McComb, E. J..

2 recordsLinked to original sources
bioRxiv2022

Highly specialized carbohydrate metabolism capability in Bifidobacterium strain associated with intestinal barrier maturation in early preterm infants

"Leaky gut", or high intestinal barrier permeability, is common in preterm newborns. The role of microbiota in this process remains largely uncharacterized. We employed both short- and long-read sequencing of the 16S rRNA gene and metagenomes to characterize the intestinal microbiome of a longitudinal cohort of 113 preterm infants born between 240/7-326/7 weeks of gestation. Enabled by enhanced taxonomic resolution, we found significantly increased abundance of Bifidobacterium breve and a diet rich in mothers breastmilk to be associated with intestinal barrier maturation during the first week of life. We combined these factors using genome- resolved metagenomics and identified a highly specialized genetic capability of the Bifidobacterium strains to assimilate human milk oligosaccharides and host-derived glycoproteins. Our study proposed mechanistic roles of breastmilk feeding and intestinal microbial colonization in postnatal intestinal barrier maturation; these observations are critical towards advancing therapeutics to prevent and treat hyperpermeable gut- associated conditions, including necrotizing enterocolitis. IMPORTANCEDespite improvements in neonatal intensive care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality. "Leaky gut", or intestinal barrier immaturity with elevated intestinal permeability, is the proximate cause of susceptibility to NEC. Early detection and intervention to prevent leaky gut in "at-risk" preterm neonates is critical to lower the risk for potentially life-threatening complications like NEC. However, the complex interactions between the developing gut microbial community, nutrition, and intestinal barrier function, remain largely uncharacterized. In this study, we revealed the critical role of sufficient breastmilk feeding volume and specialized carbohydrate metabolism capability of Bifidobacterium in coordinated postnatal improvement of intestinal barrier. Determining the clinical and microbial biomarkers that drive the intestinal developmental disparity will inform early detection and novel therapeutic strategies to promote appropriate intestinal barrier maturation, prevent NEC and other adverse health conditions in preterm infants.

microbiology↗
bioRxiv2018

Ultra-high throughput multiplexing and sequencing of >500 bp amplicon regions on the Illumina HiSeq 2500 platform

Amplification, sequencing and analysis of the 16S rRNA gene affords characterization of microbial community composition. As this tool has become more popular and amplicon-sequencing applications have grown in the total number of samples, growth in sample multiplexing is becoming necessary while maintaining high sequence quality and sequencing depth. Here, modifications to the Illumina HiSeq 2500 platform are described which produce greater multiplexing capabilities and 300 bp paired-end reads of higher quality than produced by the current Illumina MiSeq platform. To improve the feasibility and flexibility of this method, a 2-Step PCR amplification protocol is also described that allows for targeting of different amplicon regions, thus improving amplification success from low bacterial bioburden samples.\n\nImportanceAmplicon sequencing has become a popular and widespread tool for surveying microbial communities. Lower overall costs associated with high throughput sequencing have made it a widely-adopted approach, especially for projects which necessitate sample multiplexing to eliminate batch effect and reduced time to acquire data. The method for amplicon sequencing on the Illumina HiSeq 2500 platform described here provides improved multiplexing capabilities while simultaneously producing greater quality sequence data and lower per sample cost relative to the Illumina MiSeq platform, without sacrificing amplicon length. To make this method more flexible to various amplicon targeted regions as well as improve amplification from low biomass samples, we also present and validate a 2-Step PCR library preparation method.

microbiology↗