Biology subjects

Nunn, T.

Publications and source records attributed to Nunn, T..

3 recordsLinked to original sources

bioRxiv2026

CFTR dysfunction in the intestinal epithelium is sufficient to promote pathogenic expansion of E. coli and enhanced barrier permeability in cystic fibrosis

Changes in the gut microbiome in cystic fibrosis (CF) are well characterized, yet their causes and downstream effects remain largely unknown. Well-documented alterations include reduced overall complexity (i.e. alpha diversity) of the gut microbiota and increased relative abundance of E. coli, which are associated with greater inflammation and shorter stature in infants. Previous results from our laboratory using a germ-free cystic fibrosis transmembrane conductance regulator (Cftr) mutant mouse model (CF mouse) demonstrated that the observed fecal microbiome dysbiosis is driven by mutated Cftr independent of factors such as diet or antibiotic treatment. We expand on these results in this report by using the defined 8-member community Altered Schaedler Flora (ASF) with and without E. coli, to show that E. coli is pathogenic in the context of the CF gut microbiome, resulting in increased intestinal permeability. We also show that Cftr deletion in intestinal epithelial cells alone, using a Villin-Cre targeted model, is sufficient to raise E. coli abundance in the fecal microbiome, increase intestinal permeability, and amplify the number of TH17 cells in the mesenteric lymph nodes. Together, our results demonstrate that the intestinal epithelium plays a dominant role in fecal microbiome alterations in CF and that the resultant dysbiosis contributes to CF pathogenesis.

microbiology↗

bioRxiv2024

Phylogenetic and functional diversity among Drosophila-associated metagenome-assembled genomes

Host-associated microbial communities can mediate interactions between their hosts and biotic and abiotic environments. While much work has been done to document how microbiomes vary across species and environments, much less is known about the functional consequences of this variation. Here, we test for functional variation among drosophilid-associated bacteria by conducting Oxford Nanopore long-read sequencing and generating metagenome-assembled genomes (MAGs) from six species of drosophilid fly collected in association with anthropogenic environments in North America, Europe, and Africa. Using phylogenetic analyses, we find that drosophilid flies harbor a diverse microbiome that includes core members closely related to the genera Gilliamella, Orbus, Entomomonas, Dysgonomonas, and others. Comparisons with publicly available bacterial genomes show that many of these genera are associated with phylogenetically diverse insect gut microbiomes. Using functional annotations and predicted secondary metabolite biosynthetic gene clusters, we show that MAGs belonging to different bacterial orders and genera vary in gene content and predicted functions including metabolic capacity and how they respond to environmental stressors. Our results provide evidence that wild drosophilid flies harbor phylogenetically and functionally diverse microbial communities. These findings highlight a need to quantify the abundance and function of insect-associated bacteria from the genera Gilliamella, Orbus, Entomomonas, and others on the performance of their insect hosts across diverse environments.

genomics↗

bioRxiv2022

Miltefosine attenuates inflammation, reduces atherosclerosis, and alters gut microbiota in hyperlipidemic mice.

Excess cholesterol induces foam cell formation, NLRP3 inflammasome activation, and IL-1{beta} release in atherosclerotic plaques. We have shown previously that Miltefosine increased cholesterol release and dampened NLRP3 inflammasome assembly in macrophages. Here, we show that Miltefosine reduced LPS-induced choline uptake by macrophages and attenuated NLRP3 inflammasome assembly in mice. Miltefosine-fed mice showed reduced plasma IL-1{beta} in a polymicrobial cecal slurry injection model of systemic inflammation. Miltefosine-fed mice showed increased reverse cholesterol transport from macrophages to plasma, liver, and feces. Hyperlipidemic apoE-/- mice fed with Miltefosine showed significantly reduced weight gain and markedly reduced atherosclerotic lesions vs. control mice. 16S rDNA sequencing and analysis showed alterations in the gut microbiota profile of Miltefosine-fed hyperlipidemic apoE-/- vs. control mice, with the most notable changes in Romboutsia and Bacteroidetes species. Taken together, these data indicate that Miltefosine causes pleiotropic effects on lipid metabolism, inflammasome activity, atherosclerosis, and the gut microbiota.

cell biology↗