Biology subjects

Youngblut, N.

Publications and source records attributed to Youngblut, N..

4 recordsLinked to original sources

bioRxiv2025

Flagellin in the human gut microbiome is a diet-adjustable adjuvant for vaccination

The intestinal microbiota is thought to modulate immune responsiveness to vaccines. Human studies on this topic, however, have yielded inconsistent results1,2. We hypothesized that the microbiome would influence innate immune responses, and thus vaccine reactogenicity, more directly than vaccine immunogenicity. To test this, we established the {micro}HEAT (Microbial-Human Ecology And Temperature) study, which longitudinally profiled the fecal microbiota, oral body temperature and serum antibody responses of 171 healthy adults (18-40 years old) before and after vaccination for SARS-CoV-2. Increased temperature after vaccination ({Delta}T) was associated with habitual diet and with baseline metabolic and immune markers. The microbiomes of {Delta}T-high ({Delta}Thi) participants were characterized by high expression of flagellin and an overabundance of the flagellated bacterium Waltera. Fecal samples from {Delta}Thi participants induced more inflammation in human cells and stronger post-vaccine temperature responses in mice compared to {Delta}Tlo samples, suggesting a causal role for the microbiome. Moreover, Waltera flagellin replicated the inflammatory phenotypes in vitro and was modulable via a dietary additive. Overall, these data suggest that flagellin from the gut microbiome stimulates innate immunity and vaccine reactogenicity, and that this axis can be manipulated via diet. These findings have implications for improving human vaccine tolerance and immunogenicity.

microbiology↗

bioRxiv2021

Struo2: efficient metagenome profiling database construction for ever-expanding microbial genome datasets

Mapping metagenome reads to reference databases is the standard approach for assessing microbial taxonomic and functional diversity from metagenomic data. However, public reference databases often lack recently generated genomic data such as metagenome-assembled genomes (MAGs), which can limit the sensitivity of read-mapping approaches. We previously developed the Struo pipeline in order to provide a straight-forward method for constructing custom databases; however, the pipeline does not scale well with the ever-increasing number of publicly available microbial genomes. Moreover, the pipeline does not allow for efficient database updating as new data are generated. To address these issues, we developed Struo2, which is >3.5-fold faster than Struo at database generation and can also efficiently update existing databases. We also provide custom Kraken2, Bracken, and HUMAnN3 databases that can be easily updated with new genomes and/or individual gene sequences. Struo2 enables feasible database generation for continually increasing large-scale genomic datasets. AvailabilityO_LIStruo2: https://github.com/leylabmpi/Struo2 C_LIO_LIPre-built databases: http://ftp.tue.mpg.de/ebio/projects/struo2/ C_LIO_LIUtility tools: https://github.com/nick-youngblut/gtdb_to_taxdump C_LI

bioinformatics↗

bioRxiv2019

GeNet: Deep Representations for Metagenomics

We introduce GeNet, a method for shotgun metagenomic classification from raw DNA sequences that exploits the known hierarchical structure between labels for training. We provide a comparison with state-of-the-art methods Kraken and Centrifuge on datasets obtained from several sequencing technologies, in which dataset shift occurs. We show that GeNet obtains competitive precision and good recall, with orders of magnitude less memory requirements. Moreover, we show that a linear model trained on top of representations learned by GeNet achieves recall comparable to state-of-the-art methods on the aforementioned datasets, and achieves over 90% accuracy in a challenging pathogen detection problem. This provides evidence of the usefulness of the representations learned by GeNet for downstream biological tasks.

bioinformatics↗

bioRxiv2019

The virome in adult monozygotic twins with concordant or discordant gut microbiomes

The virome is one of the most variable components of the human gut microbiome. Within twin-pairs, viromes have been shown to be similar for infants but not for adults, indicating that as twins age and their environments and microbiomes diverge, so do their viromes. The degree to which the microbiome drives the viromes vast diversity is unclear. Here, we examined the relationship between microbiome diversity and virome diversity in 21 adult monozygotic twin pairs selected for high or low microbiome concordance. Viromes derived from virus-like particles were unique to each subject, dominated by Caudovirales and Microviridae, and exhibited a small core that included crAssphage. Microbiome-discordant twins had more dissimilar viromes compared to microbiome-concordant twins, and the richer the microbiomes, the richer the viromes. These patterns were driven by the bacteriophages, not eukaryotic viruses. These observations support a strong role of the microbiome in patterning the virome.

microbiology↗