Interactions between host genotype and microbiota interact to regulate early pathologies associates with Inflammatory Bowel Disease (IBD)
This study from the Rawls lab investigates early subclinical stages of inflammatory bowel disease (IBD) in mice with a deletion of the IBD-associated transcription factor HNF4A in intestinal epithelial cells (IECs), revealing that they exhibit early signs of intestinal inflammation and microbiota changes starting at 4-5 weeks of age. The research shows that these phenotypes are dependent on the microbiota, with specific microbial changes, including an enrichment of Akkermansia muciniphila, occurring before the onset of full-blown colitis, highlighting the role of HNF4A in shaping the gut microbiome and preventing early inflammation.
Kelly, C., Jawahar, J., Davey, L., Everitt, J.I., Galanko, J.A., Anderson, C., Avendano, J.E., McCann, J.R., Sartor, R.B., Valdivia, R.H., and Rawls, J.F. (2023) Spontaneous episodic inflammation in the intestines of mice lacking HNF4A is driven by microbiota and associated with early-life microbiota alterations. mBio. 14(4):e0150423.
Host microbiomes shape response to viral and bacterial pathogens
The Kelly lab investigates how the early developing respiratory and gut microbiomes in children function in promoting resistance to various infectious human pathogens, including SARS-CoV-2 and Streptococcus pneumoniae.
Hurst JH, McCumber AW, Aquino JN, Rodriguez J, Heston SM, Lugo DJ, Rotta AT, Turner NA, Pfeiffer TS, Gurley TC, Moody MA, Denny TN, Rawls JF, Clark JS, Woods CW, Kelly MS. Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults. Clin Infect Dis. 2022 Aug 24;75(1):e928-e937. doi: 10.1093/cid/ciac184. PMID: 35247047; PMCID: PMC8903463.
Kelly MS, Plunkett C, Yu Y, Aquino JN, Patel SM, Hurst JH, Young RR, Smieja M, Steenhoff AP, Arscott-Mills T, Feemster KA, Boiditswe S, Leburu T, Mazhani T, Patel MZ, Rawls JF, Jawahar J, Shah SS, Polage CR, Cunningham CK, Seed PC. Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy. ISME J. 2022 Mar;16(3):655-665. doi: 10.1038/s41396-021-01108-4. Epub 2021 Sep 11. PMID: 34511605; PMCID: PMC8857224.
The Cancer Microbiome Reveals Which Bacteria Live in Tumors
Biomedical engineers at Duke University have devised an algorithm to remove contaminated microbial genetic information from The Cancer Genome Atlas (TCGA). With a clearer picture of the microbiota living in various organs in both healthy and cancerous states, researchers will now be able to find new biomarkers of disease and better understand how numerous cancers affect the human body. Read more
CITATION: The Cancer Microbiome Atlas: A Pan-Cancer Comparative Analysis to Distinguish Tissue-Resident Microbiota from Contaminants. Anders B. Dohlman, Diana Arguijo Mendoza, Shengli Ding, Michael Gao, Holly Dressman, Iliyan D. Iliev, Steven M. Lipkin, Xiling Shen. Cell Host & Microbe, 2021. DOI: 10.1016/j.chom.2020.12.001
Bass Connections Project: Smart Toilet - A Disruptive Technology to Improve Health and Wellness
Our daily excreta, feces and urine, are rich in latent data and a greatly under-utilized source for precision health monitoring. The Duke University Center for WaSH-AID (Water, Sanitation, Hygiene and Infectious Disease) is developing a device for the hands-off extraction and packaging of human excreta so that the sample can be used for diagnosis of wellness and disease. This Duke “Smart Toilet” is a novel platform with the potential to transform healthcare as a noninvasive source of individualized biological data that can be used for early disease detection, surveillance for infectious disease and continuous personalized health and wellness monitoring. This Bass Connections project will focus on the engineering development, quality control, refinement and business and regulatory strategy of the Duke Smart Toilet platform.
Early Infancy Gut Microbiota Predicts the Quality of Vaccine-Induced Antibody Responses in Rhesus Macaques
Dr. Sallie Permar and team are studying the emergence of a number of vaccine settings that commensal microbiota are linked to vaccine-elicited immune responses. We remain without a highly-effective HIV vaccine or novel strategies for pediatric HIV-1 prevention that move beyond ART-based therapy. The gut microbiota is most plastic during infancy, with the transition from a relatively sterile environment in utero to one of constant exposure to pathogenic and nonpathogenic microbial organisms. Currently the team is defining the relationship between the developing microbiota in infant rhesus monkeys and the immunologic response following HIV-1 vaccination. Review Poster
Pediatric Obesity Microbiome & Metabolism Study (POMMS)
Duke researchers are working to develop a biorepository resource that contains microbiome and metabolism-relevant samples from well-characterized adolescents with obesity undergoing different types of weight loss therapies. The team is broadly performing multiple types of microbiome analysis including marker gene, shotgun DNA, and transcript sequencing and performing targeted and untargeted metabolomics analyses. Visit the POMMS webiste
Bass Connections Project: Blue Devil Resistome (2017-2018)
Fourteen undergraduates, led by Dr. Lingchong You, are exploring and mapping the distribution of antibiotic resistant bacteria on Duke Campus. The team is evaluating the microbiome of Duke and how resistance spreads and fluctuates in the environment by collecting and analyzing environmental samples from a host of locations around Duke. Read about the Blue Devil Resistome Project
Microbes Control Action of Host Genes to Influence Health
Dr. John Rawls and team have shown that microbes can control the actions of their animal hosts by manipulating the molecular machinery of animal cells, triggering patterns of gene expression that consequently contribute to health and disease. The work, which was conducted in zebrafish and mice, could have implications for human inflammatory bowel diseases like Crohn’s disease and ulcerative colitis. Read more in Duke Today
Mapping the Genomic Atlas of Your Inner Fish Gut
Dr. John Rawls and team discovered a network of genes and genetic regulatory elements in the lining of the intestines that has stayed remarkably the same from fishes to humans. Many of these genes are linked to human illnesses, such as inflammatory bowel diseases, diabetes and obesity. Read more in Duke Today
Hematapoietic Stem Cell Transplantation and the Microbiome
Dr. Anthony Sung's laboratory has been actively involved in studying the microbiome. Disruptions in the microbiome have been associated with 9-fold increases in blood stream infections, 10-fold increases in graft-versus-host disease-related mortality, and 50% decreases in overall survival after hematopoietic stem cell transplantation. The goal of the study is to use murine models to evaluate strategies to manipulate the microbiome to improve stem cell transplant outcomes, with the goal of translating findings into phase 1 clinical trials. This work was presented at the 2017 Annual Meeting of the American Society of Hematology and supported by the Damon Runyon Cancer Research Foundation and Duke Cancer Institute.