Biology subjects

Yung, R.

Publications and source records attributed to Yung, R..

3 recordsLinked to original sources

bioRxiv2026

High-fat diet rewires gut host-microbiota relationship to derive worse outcomes following Clostridioides difficile infection

AbstractClostridioides difficile is a leading cause of hospital-acquired enteric infections, with outcomes ranging from mild diarrhea to life-threatening pseudomembranous colitis and death. Dietary modulations can influence the course of antibiotic-induced C. difficile infection (CDI), and high-fat diets are associated with increased mortality. Here, we profiled host innate immune cells, cecal microbial composition, and the host transcriptome of normal diet (ND) and high-fat diet (HFD)-fed C57BL/6 male and female mice following experimental CDI during the acute and recovery phases. HFD-fed male mice exhibited delayed disease onset but increased mortality following CDI. During acute infection, HFD-fed males showed increased monocyte infiltration and expansion of CD103CD11b- and CD103-CD11b dendritic cell subsets; transcriptomic modules were enriched for antigen presentation and signatures consistent with T cell activation, coincident with enrichment of Escherichia and Lactococcus. In contrast, during recovery, HFD-fed males and females displayed sustained neutrophil and monocyte infiltration, depletion of eosinophils (prominent in males), tissue-resident Tim4/CD206 macrophage subsets and ILC3s, increased expression of Tlr4 and endothelial activation markers, downregulation of metabolic pathways, and failure to restore cecal microbial diversity. Collectively, these data indicate that high-fat feeding disrupts resolution programs after CDI and promotes progression to severe disease, with the most pronounced susceptibility in males.

microbiology↗

bioRxiv2025

Single-cell RNA sequencing identifies accumulation of Fcgr2b+ virtual memory like CD8 T cells with cytotoxic and inflammatory potential in aged mouse white adipose tissue

Aging and obesity are associated with pro-inflammatory changes in adipose tissue. Overlapping mechanisms, such as the infiltration of inflammatory macrophages and T cells into visceral adipose tissue, have been implicated in contributing inflammation. However, a comparative analysis from both states is needed to identify distinct regulatory targets. Here, we performed single-cell RNA sequencing of stromal vascular fractions (SVF) isolated from gonadal white adipose tissue (gWAT) of young mice fed either a normal or a high-fat diet, and aged mice fed a normal diet. Our analysis revealed that physiological aging, compared to high-fat diet induced obesity, was associated with accumulation of phenotypically distinct CD8 T cells resembling virtual memory (VM) CD8 T cells. These cells expressed high levels of Cd44, Sell, Il7r, Il2rb, lacked Itga4, and exhibited elevated Fcgr2b expression which was associated with pseudotime differentiation trajectories. Flow cytometry confirmed an age-associated increase in Fcgr2b+CD49d- VM like CD8 T cells in gWAT. Notably, these Fcgr2b-expressing cells exhibited a cytotoxic profile, and expressed granzyme M. Functional analysis using recombinant granzyme M revealed its potential in inducing inflammation in mouse fibroblasts and macrophages. Together, our study has identified Fcgr2b+CD49d- VM-like CD8 T cells in the adipose tissue of aged mice with regulatory, cytotoxic and inflammatory potential.

immunology↗

bioRxiv2019

Outbreak of murine infection with Clostridium difficile associated with the administration of a pre- and peri-natal methyl-donor diet

Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and peri-natal methyl-donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to a Clostridium difficile strain of ribotype 027 we term 16N203. C. difficile infection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, the C. difficile outbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, presence of C. difficile bacteria in fecal/colonic culture, and detection of C. difficile toxins. F1 mice from parents fed the methyl-supplementation diet also had significantly reduced survival (p<0.0001) than F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak of C. difficile in association with a pre- and perinatal methyl-donor diet suggest the important role diet may play in host defense and CDI risk factors.\n\nImportanceClostridium difficile infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of antibiotics of animals to establish disease. The outbreak we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated to a pre- and peri-natal methyl-supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.

epidemiology↗