Environmental factors, especially microbiota, modify genetic susceptibility to many chronic diseases. The NGRRC provides an essential resource for local, regional, national and international multidisciplinary investigators to explore the hypothess that commensal bacteria strongly influence physiologic processes in normal hosts and pathogenic inflammatory, metabolic and neoplastic responses in genetically susceptible hosts. This unit provides a resource for broadly based NIH-funded investigators to examine physiologic and pathophysiologic differences in germ-free (sterile) vs. gnotobiotic (known life, selectively colonized) vs. specific pathogen-free mice of different genetic backgrounds, to explore the functional alterations of normal vs. dysbiotic bacterial communities in murine models and human diseases, and to define the functional relevance of bacterial genes. The microbiota can be precisely manipulated by colonizing germ-free rodents with single or multiple commensal or pathogenic bacterial, viral or fungal species using isogenic wild type or genetically engineered bacterial strains. In addition, fecal transplants can be performed from murine models or human donors.
Specific aims : 1. Provide germ-free or selectively colonized wild type and mutant mice or their tissues and cells to NIH-funded investigators. 2. Derive additional GF genetically engineered mouse strains for NIH-funded investigators. 3. Support pilot studies for investigators with novel hypotheses to generate preliminary data for NIH grant applications. 4. Train personnel to develop gnotobiotic facilities in other institutions, 5. Develop innovative techniques to improve our gnotobiotic resource. We provide a unique and essential resource for a multidisciplinary group of NIH-funded investigators to study the physiologic and pathophysiologic function of normal and dysbiotic commensal bacteria, with particular emphasis on gene/environmental interactions in genetically altered mice (transgenic, knockout or spontaneously mutated) with altered physiology and disease phenotypes. In the past 4 years of funding, the NGRRC provided 8930 gnotobiotic mice to 73 investigators in 46 institutions. 62 funded and 11 submitted NIH grants (in 6 Institutes) by 52 investigators depend on gnotobiotic mice from the NGRRC.

Public Health Relevance

Altered microbiota composition (dysbiosis) is associated with a number of inflammatory (IBD, NASH, atherosclerosis), metabolic (diabetes, metabolic syndrome), neoplastic (colon cancer) and even behavioral (depression, autism) disorders. However the functional consequences of these compositional changes and the role of individual bacterial species remain unknown. Selective colonization of gnotobiotic mice with native or genetically engineered bacterial species or defined consortia can determine bacterial function, host/microbial and microbial/microbial interactions.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Material Resource Grants (P40)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (45))
Program Officer
Mirochnitchenko, Oleg
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Internal Medicine/Medicine
Schools of Medicine
Chapel Hill
United States
Zip Code
Harley, Isaac T W; Stankiewicz, Traci E; Giles, Daniel A et al. (2014) IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology 59:1830-9
Arthur, Janelle C; Gharaibeh, Raad Z; Mühlbauer, Marcus et al. (2014) Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer. Nat Commun 5:4724
Ooi, Jot Hui; Waddell, Amanda; Lin, Yang-Ding et al. (2014) Dominant effects of the diet on the microbiome and the local and systemic immune response in mice. PLoS One 9:e86366
Camp, J Gray; Frank, Christopher L; Lickwar, Colin R et al. (2014) Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape. Genome Res 24:1504-16
Oh, Jason Z; Ravindran, Rajesh; Chassaing, Benoit et al. (2014) TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41:478-92
Lindenstrauss, Angela G; Ehrmann, Matthias A; Behr, Jürgen et al. (2014) Transcriptome analysis of Enterococcus faecalis toward its adaption to surviving in the mouse intestinal tract. Arch Microbiol 196:423-33
Shanahan, Michael T; Carroll, Ian M; Grossniklaus, Emily et al. (2014) Mouse Paneth cell antimicrobial function is independent of Nod2. Gut 63:903-10
Maharshak, Nitsan; Packey, Christopher D; Ellermann, Melissa et al. (2013) Altered enteric microbiota ecology in interleukin 10-deficient mice during development and progression of intestinal inflammation. Gut Microbes 4:316-24
Tchaptchet, Sandrine; Fan, Ting-Jia; Goeser, Laura et al. (2013) Inflammation-induced acid tolerance genes gadAB in luminal commensal Escherichia coli attenuate experimental colitis. Infect Immun 81:3662-71