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Biology subjects

Lin, D. L.

Publications and source records attributed to Lin, D. L..

3 recordsLinked to original sources

Salivary microbiome diversity is associated with oralhealth and disease

The oral microbiome is a complex community of bacteria, fungi, and viruses that inhabit the oral cavity. Microbes of the oral microbiome are implicated in health and disease. We collected 220 unstimulated saliva samples from patients with periodontal disease and varying degrees of dental caries, as well as from subjects with no signs of oral disease. Metagenomic analysis of saliva revealed significantly higher abundance of periodontal pathogens in people with gum disease, and significantly higher abundance of cariogenic species in people with dental caries. We also found that salivary microbiome diversity was significantly higher in people with periodontal disease, but not in those with only caries. Furthermore, oral microbiome diversity is affected by oral hygiene habits such as flossing frequency, but not brushing frequency. Clustering and differential analysis allowed us to identify specific commensal species, such as Prevotella pallens and Veillonella atypica, which are significantly higher in patients without oral disease. Clustering further suggested that oral microbiome diversity may contribute to disease risk. These results suggest that oral hygiene behaviors influence the oral microbiome, and modulation of the oral microbiome could prevent or reduce the incidence and severity of oral disease.

microbiology↗

Neonatal gut-microbiome-derived 12,13 DiHOME impedes tolerance and promotes childhood atopy and asthma

Neonates at risk of childhood atopy and asthma are characterized by gut microbiome perturbation and fecal enrichment of 12,13 DiHOME(1); however, the underlying mechanism and source of this metabolite remain poorly understood. Here we show that 12,13 DiHOME treatment of human dendritic cells altered peroxisome proliferator-activated receptor {gamma} regulated gene expression and decreased immune tolerance. In mice, 12,13 DiHOME treatment prior to airway challenge exacerbated pulmonary inflammation and decreased lung regulatory T cells. Neonatal fecal metagenomic sequencing revealed putative bacterial sources of 12,13 DiHOME. In our cohort, three bacterial genes and their product, 12,13 DiHOME, are associated with increased odds of childhood atopy or asthma, suggesting that early-life gut-microbiome risk factors may shape immune tolerance and identify high-risk neonates years in advance of clinical symptoms.\n\nOne Sentence SummaryEarly-life gut-microbiome risk factors may shape immune tolerance and identify neonates at high-risk of disease.

microbiology↗

Dengue virus hijacks a noncanonical oxidoreductase function of a cellular oligosaccharyltransferase complex

Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide CRISPR screen to identify host dependency factors required for DENV propagation, and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation. However, the OST subunit MAGT1, which associates with STT3B, is also required for DENV propagation. MAGT1 expression requires STT3B, and a catalytically inactive STT3B also rescues MAGT1 expression, supporting the hypothesis that STT3B serves to stabilize MAGT1 in the context of DENV infection. We found that the oxidoreductase CxxC active site motif of MAGT1 was necessary for DENV propagation as cells expressing an AxxA MAGT1 mutant were unable to support DENV infection.\n\nInterestingly, cells expressing single-cysteine CxxA or AxxC mutants of MAGT1 were able to support DENV propagation. Utilizing the engineered peroxidase APEX2, we demonstrate the close proximity between MAGT1 and NS1 or NS4B during DENV infection. These results reveal that the oxidoreductase activity of the STT3B-containing OST is necessary for DENV infection, which may guide the development of antivirals targeting DENV.

microbiology↗