
Nita H. Salzman, MD, PhD
Professor, Pediatrics and Microbiology & Immunology; Director, Center for Microbiome Research; Associate Director, Medical Scientist Training Program; CRI Research Unit Leader for Infection, Inflammation and Immunology Research Unit; Director, GI Clinical Laboratory
Contact Information
General Interests
Education
Research Interests
The intestinal microbiota is a complex and primarily bacterial ecosystem that lives in a symbiotic relationship with its host. When maintained in a homeostatic relationship with the host, the microbiota carries out numerous critical functions for the host, related to nutrition, metabolism, immune maturation and host protection, and in this context becomes part of the host barrier to infection. The host immune system interacts with the intestinal microbiota, ultimately establishing and maintaining a homeostatic relationship with this vast ecosystem. Disruptions in either the host barrier or the microbial ecosystem can lead to homeostatic collapse and the development of intestinal inflammation in both animal models and in human disease.
Our laboratory is engaged in both basic and translational studies to investigate the innate mucosal immunology of the GI tract, with a focus on host-microbiome interactions and innate barriers to bacterial infection. Antimicrobial peptides (AMPs) are essential components of the host barrier. These are peptides with broad-spectrum antibiotic activity against bacteria, fungi, and viruses, but have been shown to have diverse additional roles both related and unrelated to host defense. Epithelial cells and circulating immune cells endogenously produce these peptides, as do bacteria. One of our primary interests is to understand the multifaceted in vivo roles of intestinal AMPs. Our work has focused primarily on enteric alpha-defensins, produced in Paneth cells localized to the small intestinal crypts. Previous work in our lab demonstrated that Paneth cell defensins have an important role in protecting the mammalian host from enteric bacterial pathogen infection. Recent work from our laboratory has shown that Paneth cell defensins are essential regulators of the composition of the intestinal microbiota, and can modulate mucosal immune responsiveness through their regulation of the microbiota.
Recently, we have translated our findings to the study of Paneth cell antimicrobial peptides (AMPs) in pediatric Crohn’s disease (CD). CD, one of the subtypes of inflammatory bowel diseases manifests with chronic intestinal inflammation and is associated with abnormal bacterial growth at mucosal surfaces (dysbiosis). Several genetic mutations that have been associated with increased risk for the development of CD have also been associated with Paneth cell dysfunction. As part of the Crohn’s and Colitis Foundation of America (CCFA) Microbiome Consortium, we are investigating the relationship between Paneth cell dysfunction and dysbiosis in pediatric CD patients.
A second translational study focuses on the role of the microbiome in the development and progression of pediatric non-alcoholic fatty liver disease (NAFLD). NAFLD is associated with obesity and metabolic syndrome and its prevalence has increased in parallel to the prevalence of obesity and type-2 diabetes. The development of NAFLD, its different phenotypes, and the heterogeneity of disease progression are not completely understood. Recent evidence suggests that there is an association between intestinal microbial colonization (the intestinal microbiome) and obesity in humans and in animal models. In addition, there is evidence of abnormalities of bacterial colonization, and intestinal bacterial product induced inflammation associated with NAFLD and progression to NASH. This study investigates the composition of the intestinal microbiome in pediatric patients with obesity and obesity plus NAFLD, to determine the relationship between alterations in the intestinal microbiome, immune activation, and the development of NAFLD.
We have recently begun to investigate the basic mechanisms of bacterial colonization of the GI tract, using Enterococcus faecalis as a model organism. E. faecalis is a common commensal of the mammalian gut, but also an opportunistic pathogen, which is currently an important cause of infection in hospitalized patients. We have developed a novel system to colonize mice with marked laboratory strains of E. faecalis and are using this system to explore both bacterial-host and bacterial-microbiome interactions in the native mouse GI tract, to understand the important host and bacterial determinants essential for colonization and permissive/protective for systemic infection.
Publications
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(Hofeld BC, Puppala VK, Tyagi S, Ahn KW, Anger A, Jia S, Salzman NH, Hessner MJ, Widlansky ME.) Sci Rep. 2021 Feb 17;11(1):3972 PMID: 33597583 PMCID: PMC7889883 02/19/2021
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(Bajaj JS, Salzman N, Acharya C, Takei H, Kakiyama G, Fagan A, White MB, Gavis EA, Holtz ML, Hayward M, Nittono H, Hylemon PB, Cox IJ, Williams R, Taylor-Robinson SD, Sterling RK, Matherly SC, Fuchs M, Lee H, Puri P, Stravitz RT, Sanyal AJ, Ajayi L, Le Guennec A, Atkinson RA, Siddiqui MS, Luketic V, Pandak WM, Sikaroodi M, Gillevet PM.) JCI Insight. 2019 12 19;4(24) PMID: 31751317 PMCID: PMC6975263 11/22/2019
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(Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, Fagan A, Hayward M, Holtz ML, Matherly S, Lee H, Osman M, Siddiqui MS, Fuchs M, Puri P, Sikaroodi M, Gillevet PM.) Hepatology. 2019 11;70(5):1690-1703 PMID: 31038755 PMCID: PMC6819208 05/01/2019
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(Schwimmer JB, Johnson JS, Angeles JE, Behling C, Belt PH, Borecki I, Bross C, Durelle J, Goyal NP, Hamilton G, Holtz ML, Lavine JE, Mitreva M, Newton KP, Pan A, Simpson PM, Sirlin CB, Sodergren E, Tyagi R, Yates KP, Weinstock GM, Salzman NH.) Gastroenterology. 2019 10;157(4):1109-1122 PMID: 31255652 PMCID: PMC6756995 SCOPUS ID: 2-s2.0-85072272749 07/01/2019
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Longitudinal changes in the gut microbiome of infants on total parenteral nutrition.
(Dahlgren AF, Pan A, Lam V, Gouthro KC, Simpson PM, Salzman NH, Nghiem-Rao TH.) Pediatr Res. 2019 07;86(1):107-114 PMID: 30965357 PMCID: PMC6594895 SCOPUS ID: 2-s2.0-85064441222 04/10/2019
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Challenges in IBD Research: Preclinical Human IBD Mechanisms.
(Pizarro TT, Stappenbeck TS, Rieder F, Rosen MJ, Colombel JF, Donowitz M, Towne J, Mazmanian SK, Faith JJ, Hodin RA, Garrett WS, Fichera A, Poritz LS, Cortes CJ, Shtraizent N, Honig G, Snapper SB, Hurtado-Lorenzo A, Salzman NH, Chang EB.) Inflamm Bowel Dis. 2019 05 16;25(Suppl 2):S5-S12 PMID: 31095706 SCOPUS ID: 2-s2.0-85066863698 05/17/2019
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Sortase-Dependent Proteins Promote Gastrointestinal Colonization by Enterococci.
(Banla LI, Pickrum AM, Hayward M, Kristich CJ, Salzman NH.) Infect Immun. 2019 03;87(5) PMID: 30804098 PMCID: PMC6479037 SCOPUS ID: 2-s2.0-85065021405 02/26/2019
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Colonization of the mammalian intestinal tract by enterococci.
(Banla LI, Salzman NH, Kristich CJ.) Curr Opin Microbiol. 2019 02;47:26-31 PMID: 30439685 PMCID: PMC6511500 SCOPUS ID: 2-s2.0-85056238106 11/16/2018
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(Chakraborty R, Lam V, Kommineni S, Stromich J, Hayward M, Kristich CJ, Salzman NH.) Infect Immun. 2018 12;86(12) PMID: 30224553 PMCID: PMC6246901 SCOPUS ID: 2-s2.0-85056802367 09/19/2018
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(Malik M, Suboc TM, Tyagi S, Salzman N, Wang J, Ying R, Tanner MJ, Kakarla M, Baker JE, Widlansky ME.) Circ Res. 2018 10 12;123(9):1091-1102 PMID: 30355158 PMCID: PMC6205737 SCOPUS ID: 2-s2.0-85055600525 10/26/2018
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(Geldart KG, Kommineni S, Forbes M, Hayward M, Dunny GM, Salzman NH, Kaznessis YN.) Bioeng Transl Med. 2018 Sep;3(3):197-208 PMID: 30377660 PMCID: PMC6195901 11/01/2018
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(Grayson MH, Camarda LE, Hussain SA, Zemple SJ, Hayward M, Lam V, Hunter DA, Santoro JL, Rohlfing M, Cheung DS, Salzman NH.) Front Immunol. 2018;9:1587 PMID: 30042764 PMCID: PMC6048222 07/26/2018