A5071925690- Clostridium difficile and Clostridium perfringens research
- Child Nutrition and Water Access
- Infant Nutrition and Health
- Microscopic Colitis
- Child Nutrition and Feeding Issues
- Pediatric health and respiratory diseases
- Parasitic Infections and Diagnostics
- Amoebic Infections and Treatments
- Viral gastroenteritis research and epidemiology
- Gut microbiota and health
- Eosinophilic Esophagitis
- Pancreatitis Pathology and Treatment
- Birth, Development, and Health
- Diet and metabolism studies
- Congenital Diaphragmatic Hernia Studies
- Immune Cell Function and Interaction
- Medical and Biological Ozone Research
- Food Security and Health in Diverse Populations
- Neonatal Respiratory Health Research
- IL-33, ST2, and ILC Pathways
- Helicobacter pylori-related gastroenterology studies
- Immune responses and vaccinations
University of Virginia
2014-2024
Washington University in St. Louis
2019-2023
University of Virginia Health System
2014-2019
Center for Global Health
2016
Malnutrition and dietary repair Childhood malnutrition is accompanied by growth stunting immaturity of the gut microbiota. Even after therapeutic intervention with standard commercial complementary foods, children may fail to thrive. Gehrig et al. Raman monitored metabolic parameters in healthy Bangladeshi those recovering from severe acute malnutrition. The authors investigated interactions between diet, microbiota development, recovery. Diets were then designed using pig mouse models nudge...
Disrupted development of the gut microbiota is a contributing cause childhood malnutrition.
Highlights•IL-25 is suppressed during human and murine Clostridium difficile infection (CDI)•Restoration of IL-25 reduces mortality morbidity CDI•Depletion or genetic deletion eosinophils negates IL-25-mediated protection•IL-25-induced eosinophilia maintains integrity the intestinal barrier CDISummaryClostridium (CDI) most common cause hospital-acquired in United States. Host susceptibility severity are influenced by disruption microbiota immune response. However, how regulate responses to...
Abstract Clostridium difficile ( C. ) incidence has tripled over the past 15 years and is attributed to emergence of hypervirulent strains. While it clear that toxins cause damaging colonic inflammation, immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an target upregulated in response . We demonstrate prevents -associated mortality epithelial disruption independently bacterial burden or toxin expression....
There is an emerging paradigm that the human microbiome central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica major cause amebic diarrhea developing countries. It colonizes colon lumen close proximity gut microbiota. Interestingly, not all individuals are equally susceptible E. Therefore, as microbiota highly variable within individuals, we sought determine if component could regulate susceptibility In studies utilizing murine model,...
Undernutrition in children is a pressing global health problem, manifested part by impaired linear growth (stunting). Current nutritional interventions have been largely ineffective overcoming stunting, emphasizing the need to obtain better understanding of its underlying causes. Treating Bangladeshi with severe acute malnutrition therapeutic foods reduced plasma levels biomarker osteoclastic activity without affecting biomarkers osteoblastic or improving their stunting. To characterize...
ABSTRACT Clostridium difficile is the most common hospital-acquired pathogen, causing antibiotic-associated diarrhea in over 250,000 patients annually United States. Disease primarily mediated by toxins A and B, which induce potent proinflammatory signaling host cells can activate an ASC-containing inflammasome. Recent findings suggest that intensity of response to infection correlates with disease severity. Our lab has identified cytokine interleukin-23 (IL-23) as a pathogenic mediator...
Linear growth stunting due to undernutrition affects 20% of children under the age five with far-reaching consequences, including increased susceptibility infection and altered cognitive development. Current nutritional interventions are largely ineffective in rescuing linear growth. A significant proportion originates utero; however, mechanisms by which maternal is transmitted between generations remain poorly characterized. Here we employed a gnotobiotic murine model intergenerational...
Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using murine model C. parvum oocyst challenge that recapitulates clinical features cryptosporidiosis during malnutrition, we interrogated the effect protein malnutrition (PM) on primary and secondary responses to challenge, tested differential ability mucosal priming strategies overcome PM-induced susceptibility. We determined while PM fundamentally alters systemic immune Cryptosporidium, with (106...
ABSTRACT Intestinal segmented filamentous bacteria (SFB) protect from ameba infection, and protection is transferable with bone marrow dendritic cells (BMDCs). SFB cause an increase in serum amyloid A (SAA), suggesting that SAA might mediate SFB's effects on BMDCs. Here we further explored the role of SFB-mediated protection. Transient gut colonization or administration alone transiently increased H3K27 histone demethylase Jmjd3, persistently Csf2ra expression granulocyte monocyte precursors...
ABSTRACT Clostridium difficile is a major, life-threatening hospital-acquired pathogen that causes mild to severe colitis in infected individuals. The tissue destruction and inflammation which characterize C. infection (CDI) are primarily due the Rho-glucosylating toxins A B. These cause epithelial cell death induce robust inflammatory signaling by activating transcription factor NF-κB, leading chemokine cytokine secretion. also activate inflammasome complex, leads secretion of pyrogenic...
The parasite Entamoeba histolytica is a cause of diarrhea in infants low-income countries. Previously, it was shown that tumor necrosis factor alpha (TNF-α) production associated with increased risk E. children. Interleukin-25 (IL-25) cytokine produced by intestinal epithelial cells has role maintenance gut barrier function and inhibition TNF-α production. IL-25 expression decreased humans the mouse model amebic colitis. Repletion blocked infection disruption mice, eosinophils, suppressed...
Aging is associated with low bone and lean mass as well alterations in the gut microbiota (GM). In this study, we determined whether reduced relative observed old mice could be transferred to healthy young by GM transplantation (GMT). from (21-month-old) adult (5-month-old) donors was used colonize germ-free (GF) three separate studies involving still growing 5- or 11-week-old recipients 17-week-old minimal growth. The of recipient similar that donors, demonstrating successful GMT. did not...
Childhood undernutrition is a major global health challenge with devastating lifelong consequences. Linear growth stunting due to has been linked poor outcomes, and mothers who experience in childhood are more likely give birth stunted children later life. Based on these findings, we hypothesized that intergenerational colonization of mice microbiota from human donors may recapitulate certain immune changes observed this disorder.
Introduction: Post-thrombotic syndrome (PTS) is the most common sequelae of deep vein thrombosis (DVT), manifested as venous insufficiency in up to 50% patients. Unfortunately, none existing therapies, including anticoagulants and thrombolytics, have shown definitive effects for PTS, presenting a vital unmet clinical need. Akkermansia Muciniphila (AKK) , gut commensal anaerobic bacterium, has been recognized with pleiotropic benefits wide range diseases cardiometabolic disorders. However,...
Abstract Clostridium difficile infection (CDI) occurs when the microbiota has been disrupted, stressing beneficial role of commensal bacteria. The ability to contribute protection historically linked induction host factors such as bile acids and out competing pathogen for nutrients space. influence modulate immune response dictate CDI outcome remains unexplored. Here, we show that IL-25, a cytokine regulated by microbiota, is suppressed in intestine during humans mice. Administration IL-25...
Childhood undernutrition is a major global health challenge with devastating lifelong consequences. Linear growth stunting due to has been linked poor outcomes, and mothers who experience are more likely give birth stunted children. Murine models that capture the intergenerational multifactorial nature of critical understanding underlying biology this disorder. Here we report gnotobiotic mouse model using microbiota from human infants healthy or trajectories. Intergenerational transmission...