
Nita H. Salzman, MD, PhD
Professor, Pediatrics and Microbiology & Immunology; Director, Medical Scientist Training Program; Founding Director, Center for Microbiome Research
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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BATF is Required for Treg Homeostasis and Stability to Prevent Autoimmune Pathology.
(Khatun A, Wu X, Qi F, Gai K, Kharel A, Kudek MR, Fraser L, Ceicko A, Kasmani MY, Majnik A, Burns R, Chen YG, Salzman N, Taparowsky EJ, Fang D, Williams CB, Cui W.) Adv Sci (Weinh). 2023 Aug 16:e2206692 PMID: 37587835 SCOPUS ID: 2-s2.0-85168114370 08/17/2023
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Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape.
(Fung C, Fraser LM, Barrón GM, Gologorsky MB, Atkinson SN, Gerrick ER, Hayward M, Ziegelbauer J, Li JA, Nico KF, Tyner MDW, DeSchepper LB, Pan A, Salzman NH, Howitt MR.) Proc Natl Acad Sci U S A. 2023 Jun 06;120(23):e2216908120 PMID: 37253002 PMCID: PMC10266004 SCOPUS ID: 2-s2.0-85160593821 05/30/2023
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(Bora G, Atkinson SN, Pan A, Sood M, Salzman N, Karrento K.) J Dig Dis. 2023 May;24(5):348-358 PMID: 37448237 SCOPUS ID: 2-s2.0-85167367088 07/14/2023
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Gut microbiota and metabolites drive chronic sickle cell disease pain.
(Sadler KE, Atkinson SN, Ehlers VL, Waltz TB, Hayward M, Rodríguez García DM, Salzman NH, Stucky CL, Brandow AM.) bioRxiv. 2023 Apr 28 PMID: 37163080 PMCID: PMC10168372 05/10/2023
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Body Mass Index and Gut Microbiome: A Cluster-Randomized, Controlled, Pilot Feasibility Study.
(Frenn M, Salzman N, Lam V, Holtz M, Moosreiner A, Garnier-Villarreal M.) Child Obes. 2023 Feb 02 PMID: 36730730 SCOPUS ID: 2-s2.0-85163663740 02/03/2023
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Group 3 innate lymphoid cells require BATF to regulate gut homeostasis in mice.
(Wu X, Khatun A, Kasmani MY, Chen Y, Zheng S, Atkinson S, Nguyen C, Burns R, Taparowsky EJ, Salzman NH, Hand TW, Cui W.) J Exp Med. 2022 Nov 07;219(11) PMID: 36048018 PMCID: PMC9440727 SCOPUS ID: 2-s2.0-85137136864 09/02/2022
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(Zenga J, Atkinson S, Yen T, Massey B, Stadler M, Bruening J, Peppard W, Reuben M, Hayward M, Mesich B, Buchan B, Ledeboer N, Sanchez JL, Fraser R, Lin CW, Holtz ML, Awan M, Wong SJ, Puram SV, Salzman N.) EBioMedicine. 2022 Jul;81:104099 PMID: 35671624 PMCID: PMC9168040 SCOPUS ID: 2-s2.0-85131428877 06/08/2022
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(Cabrera SM, Coren AT, Pant T, Ciecko AE, Jia S, Roethle MF, Simpson PM, Atkinson SN, Salzman NH, Chen YG, Hessner MJ.) Sci Rep. 2022 Feb 28;12(1):3306 PMID: 35228584 PMCID: PMC8885673 SCOPUS ID: 2-s2.0-85125563972 03/02/2022
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(Sargin P, Roethle MF, Jia S, Pant T, Ciecko AE, Atkinson SN, Salzman NH, Teng RJ, Chen YG, Cabrera SM, Hessner MJ.) Gut Microbes. 2022;14(1):2136467 PMID: 36261888 PMCID: PMC9586621 SCOPUS ID: 2-s2.0-85140364986 10/21/2022
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Skin inflammation activates intestinal stromal fibroblasts and promotes colitis.
(Dokoshi T, Seidman JS, Cavagnero KJ, Li F, Liggins MC, Taylor BC, Olvera J, Knight R, Chang JT, Salzman NH, Gallo RL.) J Clin Invest. 2021 Nov 01;131(21) PMID: 34720087 PMCID: PMC8553570 SCOPUS ID: 2-s2.0-85118499787 11/02/2021
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(Salzman NH, Schwimmer JB.) Curr Opin Endocr Metab Res. 2021 Aug;19:22-29 PMID: 34222711 PMCID: PMC8248528 07/06/2021
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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 SCOPUS ID: 2-s2.0-85101105180 02/19/2021