Biology subjects

Cope, E. K.

Publications and source records attributed to Cope, E. K..

4 recordsLinked to original sources

bioRxiv2026

Bacteroides fragilis modulates gut microbiome community composition, frontal cortex gene expression, and fecal and frontal cortex metabolites in a mouse model of Alzheimers disease pathologies

Alzheimers disease (AD) is a neurodegenerative disease and the leading cause of dementia among elderly. Gut microbiome alterations precede pathogenesis and may affect disease outcomes. We evaluated the role of Bacteroides fragilis in triple transgenic mice modeling AD pathologies (3xTg-AD) and wild-type controls (WT). Subsets of 3xTg-AD and WT mice were longitudinally treated with B. fragilis or sterile vehicle control for five consecutive days at 8 weeks of age and then monthly up to 52-56 weeks. Fecal samples were collected fortnightly from 8 through 52-56 weeks of age. Mice were sacrificed at 8 (baseline), 24 (amyloid-{beta} plaques modeled), and 52-56 (amyloid-{beta} plaques and neurofibrillary tangles modeled) weeks of age. Expression of genes involved in neuroinflammation and neurotransmission were quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Fecal bacterial microbiota were assessed by sequencing the V4 region of the 16S rRNA gene, and microbiome sequence data were analyzed using QIIME 2. Frontal cortex and fecal metabolomes were evaluated using LC-MS/MS. We observed that B. fragilis colonized the gut microbiota of 3xTg-AD mice earlier and more consistently than WT mice. 3xTg-AD mice treated with B. fragilis demonstrate lower gene expression of GFAP, SLC1A3, and FOXO3 in the frontal cortex. Consistent with this finding, treatment with B. fragilis restores levels of amino acid derivatives and neurotransmitters in 3xTg-AD mice to resemble levels in WT mice. These results highlight the role of the gut microbiome in AD-associated neuroinflammation and neurotransmission and the need for future studies to elucidate the mechanisms underlying these changes. ImportancePrevious studies in animals modeling Alzheimers disease pathologies and humans living with Alzheimers disease demonstrate shifts in the gut microbial community composition prior to and concomitant with pathological onset. The bacterial genus, Bacteroides, is commonly found differentially abundant in these studies but its effects on disease outcomes are poorly understood. In this study, we explore the effects of chronic exposure to Bacteroides fragilis in triple transgenic mice modeling Alzheimers disease pathologies and healthy, wild-type controls. We observed changes in microbial community composition in mice modeling Alzheimers disease when treated with B. fragilis, and associated changes in neuroinflammation, biomarkers of neurotransmission, and the brain metabolome. Taken together, these results suggest that Bacteroides fragilis exerts neuromodulatory effects that may be beneficial in Alzheimers disease.

microbiology↗

bioRxiv2022

IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function

Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which are largely attributed to the effects of IL-13 on common epithelial cell types (mucus secretory and ciliated cells). The role of rare cells in airway T2 inflammation is less clear, though tuft cells have been shown to be critical in the initiation of T2 immunity in the intestine. Using bulk and single cell RNA sequencing of airway epithelium and mouse modeling, we find that IL-13 expands and programs airway tuft cells towards eicosanoid metabolism, and that tuft cell deficiency leads to a reduction in airway prostaglandin E2 (PGE2) concentration. Allergic airway epithelia bear a signature of prostaglandin E2 activation, and PGE2 activation leads to CFTR-dependent ion and fluid secretion and accelerated mucociliary transport. Together these data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.

immunology↗

bioRxiv2020

Soluble corn fiber reduces ovalbumin-induced sinonasal inflammation via the gut microbiota-airway axis

Asthma is a chronic airway inflammatory disease that affects approximately 300 million people worldwide, causing a substantial healthcare burden. Although there is a large degree of heterogeneity in the inflammatory response of asthmatics, a subset of patients are characterized by type-2 inflammation, which is in part mediated by TH2 cells in both the upper and lower airways. Asthma prevalence is increased in low-socioeconomic-status populations, where disparities in health behavior exist, including a shift toward a western diet characterized by low dietary fiber. Gut microbes metabolize fiber into short chain fatty acids that can reduce type-2 inflammation in peripheral organs, such as the airways. We hypothesized that soluble fiber can reduce ovalbumin (OVA)-induced upper airway inflammation in the context of the unified airway hypothesis, in mice maintained on ingredient-matched western (WD) and control diets (CD) through production of short chain fatty acids. Our results show that soluble fiber reduces IL-4 and IL-13 gene expression (p<0.05, Mann Whitney) in the sinonasal cavity of CD-fed mice, but this effect was lost in WD-fed mice. This loss of protection in WD-fed mice parallels compositional changes of the cecal and fecal microbiota. Mice fed a soluble fiber supplement while being maintained on a WD had altered microbial communities characterized by lower abundance of fiber fermentering bacteria. This work can be used to develop effective microbiome-based therapeutics as a low-cost method to reduce asthma morbidity. IMPORTANCEPrevious research has supported that western-style diets, typically high-fat and low-fiber, are associated with changes in the gut microbiome and increased inflammation. Western diets are accessible and prominent in low-socioeconomic-status populations, where asthma rates are highest; however, there has yet to be a low-cost asthma therapeutic. For the first time, we investigated whether supplementation with a physiologically relevant quantity of soluble corn fiber can reduce allergic airway inflammation. Our study supports that soluble corn fiber supplementation is associated with compositional shifts of the gut microbiota and reduced airway inflammation, promoting the use of fiber as a low-cost microbiome modifying therapy to reduce asthma-associated inflammation. However, soluble corn fiber in conjunction with a western diet resulted in an alternate gut microbiome composition and loss of protection against allergic airway inflammation. These findings further support the importance of the gut microbiota in host health.

microbiology↗

bioRxiv2020

Environmental Exposures Influence Nasal Microbiome Composition in a Longitudinal Study of Division I Collegiate Athletes

BackgroundThe anterior nares host a complex microbial community that contributes to upper airway health. Although the bacterial composition of the nasal passages have been well characterized in healthy and diseased cohorts, the role of prolonged environmental exposures and exercise in shaping the nasal microbiome in healthy adults is poorly understood. In this study, we longitudinally sampled female collegiate Division I athletes from two teams experiencing a similar athletic season and exercise regimen but vastly different environmental exposures (Swim/Dive and Basketball). Using 16S rRNA gene sequencing, we evaluated the longitudinal dynamics of the nasal microbiome pre-, during-, and at the end of the athletic season. ResultsThe nasal microbiota of the Swim/Dive and Basketball teams were distinct from each other at each time point sampled, driven by either low abundance (Jaccard, PERMANOVA p<0.05) or high-abundance changes in composition (Bray-Curtis, PERMANOVA p<0.05). The rate of change of microbial communities were greater in the Swim/Dive team compared to the Basketball team characterized by an increase in Staphylococcus in Swim/Dive and a decrease in Corynebacterium in both teams over time. ConclusionsThis is the first study that has evaluated the nasal microbiome in athletes. We obtained longitudinal nasal swabs from two gender-matched teams with similar age distributions (18-22 years old) over a 6 month period. Differences in the microbiota between teams and over time indicate that chlorine exposure, and potentially athletic training, induced changes in the nasal microbiome.

microbiology↗