The human gastrointesfinal tract is populated with as many as 100 trillion bacteria that provide their host with dietary metabolites and protecfion against pathogens. Increasing evidence indicates appropriate intesfinal microbiota colonization during early stages of life is important for preventing immune-mediated diseases later in life. A key question is: How does the early intestinal microbiota provide these long-term benefits? Evidence is emerging that the human gut microbiota participates in the creation of epigenetic marks, thereby impacfing long-term gene regulafion with consequences for health. The intesfinal microbiota has also been implicated in obesity, a chronic inflammatory condifion now associated with eariy life events affecfing assembly of the gut microbiota, including cesarean secfions, anfibiofics, and formula feeding. These observafions suggest that disrupfion of the early gut microbiota may lead to metabolic deficiencies later in life through epigenetic mechanisms;however, the specific microbiotaregulated targets that influence the obese phenotype are currently unknown. Dr. Ramer-Tait will test the hypothesis that the lack of symbiotic microbiota during eariy development precipitates regulation of proinflammatory T cell phenotype genes via epigenetic mechanisms, with long-term consequences for metabolic health. She will combine gnotobiofic mouse models with high-throughput sequencing technologies to study the interacfions among the microbiota, the immune system, and the epigenome in the context of obesity. During her project. Dr. Ramer-Tait will employ her extensive training in immunology, microbiology, and gnotobiofic mouse models of inflammatory diseases. Her COBRE mentors include a well-respected molecular microbial ecologist with expertise in high throughput sequence analyses and a bioinformatician with vast expertise in analysis of large data sets derived from genome sequencing projects. This project will advance the thematic focus of the associated proposed Nebraska Center for the Prevention of Obesity Disease through Dietary Molecules by providing critical information about how the gut microbiota regulates the host immune system and precipitates metabolic diseases. By understanding these host-microbial relafionships, we can strategically design novel dietary interventions to control obesity by modulafing the intesfinal microbiota.

Public Health Relevance

Appreciation is growing for the role of non-dietary, environmental factors in obesity, including eariy-life events that impact intesfinal microbes and regulate the host epigenome. However, specific microbiotaregulated targets that influence the obese phenotype are currently unknown. This project will elucidate the interacfions among the microbiota, immune system, and epigenome in the context of obesity to facilitate future development of dietary strategies that modulate gut bacteria to prevent disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM104320-01A1
Application #
8662976
Study Section
Special Emphasis Panel (ZGM1-TWD-C (C1))
Project Start
Project End
Budget Start
2014-08-05
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$226,500
Indirect Cost
$76,500
Name
University of Nebraska Lincoln
Department
Type
DUNS #
555456995
City
Lincoln
State
NE
Country
United States
Zip Code
68583
Zhang, Hanyuan; Vieira Resende E Silva, Bruno; Cui, Juan (2018) miRDis: a Web tool for endogenous and exogenous microRNA discovery based on deep-sequencing data analysis. Brief Bioinform 19:415-424
Leiferman, Amy; Shu, Jiang; Grove, Ryan et al. (2018) A diet defined by its content of bovine milk exosomes and their RNA cargos has moderate effects on gene expression, amino acid profiles and grip strength in skeletal muscle in C57BL/6 mice. J Nutr Biochem 59:123-128
Okla, Meshail; Zaher, Walid; Alfayez, Musaad et al. (2018) Inhibitory Effects of Toll-Like Receptor 4, NLRP3 Inflammasome, and Interleukin-1? on White Adipocyte Browning. Inflammation 41:626-642
Chakrabarti, Subhadeep; Guha, Snigdha; Majumder, Kaustav (2018) Food-Derived Bioactive Peptides in Human Health: Challenges and Opportunities. Nutrients 10:
Kittana, Hatem; Quintero-Villegas, Maria I; Bindels, Laure B et al. (2018) Galactooligosaccharide supplementation provides protection against Citrobacter rodentium-induced colitis without limiting pathogen burden. Microbiology 164:154-162
Neilsen, Beth K; Chakraborty, Binita; McCall, Jamie L et al. (2018) WDR5 supports colon cancer cells by promoting methylation of H3K4 and suppressing DNA damage. BMC Cancer 18:673
Kuss, Mitchell; Kim, Jiyoung; Qi, Dianjun et al. (2018) Effects of tunable, 3D-bioprinted hydrogels on human brown adipocyte behavior and metabolic function. Acta Biomater 71:486-495
Yates, Dustin T; Petersen, Jessica L; Schmidt, Ty B et al. (2018) ASAS-SSR Triennnial Reproduction Symposium: Looking Back and Moving Forward-How Reproductive Physiology has Evolved: Fetal origins of impaired muscle growth and metabolic dysfunction: Lessons from the heat-stressed pregnant ewe. J Anim Sci 96:2987-3002
Natarajan, Sathish Kumar; Ibdah, Jamal A (2018) Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy. Int J Mol Sci 19:
Camara Teixeira, Daniel; Cordonier, Elizabeth L; Wijeratne, Subhashinee S K et al. (2018) A cell death assay for assessing the mitochondrial targeting of proteins. J Nutr Biochem 56:48-54

Showing the most recent 10 out of 68 publications