Autoimmune disorders involving the connective tissue have complex pathogenetic origins and diverse clinical manifestations. Systemic sclerosis (or scleroderma) has the highest cause specific mortality of all of the connective tissue diseases, and the majority of patients with systemic sclerosis suffer from serious gastrointestinal tract symptoms. While the cause of gastrointestinal tract dysfunction in systemic sclerosis is unknown, Dr. Elizabeth Volkmann, a Rheumatologist at UCLA who specializes in the care of patients with systemic sclerosis, has recently teamed up with Dr. Jonathan Braun, Chair of Pathology and Laboratory Medicine, to discover whether patients with systemic sclerosis have alterations in their intestinal microbiota.
Current Research Projects
Working with a team of gastroenterologists at UCLA, which includes Dr. Bennett Roth, Dr. Terri Getzug and Dr. Jeffrey Conklin, the UCLA Scleroderma Microbiome Initiative, also seeks to determine whether certain microbial species contribute to the gastrointestinal phenotype in systemic sclerosis. Dr. Volkmann’s group has recently demonstrated that patients with systemic sclerosis have increased pathobiont (invasive, pro-inflammatory) microbial genera and decreased commensal (normal, healthy) microbial genera compared with healthy control patients. In addition, this group found that systemic sclerosis patients with lower levels of Bacteroides fragilis (a commensal bacterial species) had more severe gastrointestinal symptoms compared with patients with higher levels of this species. The UCLA Scleroderma Microbiome Initiative continues to explore the intricate interactions among the microbiome, metabolome, and proteome in systemic sclerosis, with the hopes of identifying novel therapeutic targets for this devastating autoimmune condition.
Unique Microbial Signature Identified in Systemic Sclerosis
Medscape (June 12, 2015)
First gut microbiota alterations described in systemic sclerosis patients
PM360 (June 11, 2015)
Jonathan Braun, MD, PhD
Chair and Professor, Pathology and Laboratory Medicine; Molecular & Medical Pharmacology, UCLA
View Bio Address UCLA MRL Building, 4525 MC: 173216 Los Angeles CA 90095 workPhone: (310) 794-7953workFax: (310) 267-4486workfaxEmail: firstname.lastname@example.orgINTERNETWebsite: UCLA Pathology & Laboratory Medicine
Dr. Jonathan Braun is Professor and Chair of Pathology and Laboratory Medicine, and Professor of Molecular and Medical Pharmacology at the David Geffen School of Medicine, and Chair of Pathology and Laboratory Medicine. A distinguished pathologist and mucosal immunologist , his 30 year career has been devoted to mucosal host-microbial interaction and the immune cell biology of chronic inflammatory disease (IBD and HIV) and lymphoma pathogenesis. With a long-standing commitment to inflammatory bowel disease, in recent years he has focused on the relationship of the intestinal microbiome and function to human genetic disease variation in IBD disease pathogenesis, penetrance, and phenotype. He has innovated in the detection and bioinformatics analysis of microbiome, metabolites, and peptides, through participation in the NIDDK IBD Genetics Consortium and NIH HMP2 projects, and as PI of the CCFA Microbiome Initiative.
Relevant Recent Publications
- Tong M, McHardy I, Ruegger P, Goudarzi M, Kashyap PC, Haritunians T, Li X, Graeber TG, Schwager E, Huttenhower C, Fornace AJ Jr, Sonnenburg JL, McGovern DP, Borneman J, Braun J. Reprograming of gut microbiome energy metabolism by the FUT2 Crohn’s disease risk polymorphism. ISME J. 2014 Nov;8(11):2193-206. doi: 10.1038/ismej.2014.64. PMID: 24781901
- McHardy IH, Goudarzi M, Tong M, Ruegger PM, Schwager E, Weger JR, Graeber TG, Sonnenburg JL, Horvath S, Huttenhower C, McGovern DP, Fornace AJ Jr, Borneman J, Braun J. Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships. Microbiome. 2013 Jun 5;1(1):17. doi: 10.1186/2049-2618-1-17. PMCID: 3971612
- McHardy IH, Li X, Tong M, Ruegger P, Jacobs J, Borneman J, Anton P, Braun J. HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota. Microbiome. 2013 Oct 12;1(1):26. doi: 10.1186/2049-2618-1-26. PMID: 24451087
Active Funding in Microbiome-Related Research
|Funding Agency/Grant Number:||NIH U54 DK102557|
|Title:||“Characterizing the gut microbial community for diagnosis and therapy of IBD”|
|Goals:||To identify the relationship of microbial composition, microbial genes, and their metabolite and peptide products in the intestinal mucosa of IBD patients|
|Funding Agency/Grant Number:||CCFA Microbiome Consortium/323814 Crohn’s and Colitis Foundation of America|
|Title:||“Establishing Mechanistically Validated Targets and Lead Molecules for Microbiome-based Therapy in IBD”|
|Goals:||To mechanistically validate candidate microbiota and their products that determine IBD disease state and activity; to identify lead molecules for targeting these validated candidates; and, to expand the prospective candidates via longitudinal multi’omic human analyses.|
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Elizabeth Volkmann, MD, MS
Clinical Instructor, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at UCLA
Dr. Elizabeth Volkmann is a Clinical instructor in the Department of Medicine, Division of Rheumatology at UCLA. She is the Founder and Director of the Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Integrative Clinic Program at UCLA. She received her medical degree from UCLA David Geffen School of Medicine, and subsequently completed her residency in Internal Medicine and fellowships in Rheumatology and Medical Education at UCLA. During her fellowship, she participated in the Specialty Training and Advanced Research (STAR) Program and earned her Master of Science degree in Clinical Research.
Her clinical and research expertise is in systemic sclerosis (scleroderma), a rare and disabling autoimmune disease that affects gastrointestinal function in the majority of patients. She is currently the principal investigator of an innovative study to characterize the gastrointestinal tract microbiome in patients with systemic sclerosis. This study aims to investigate the hypothesis that the systemic sclerosis disease state is associated with altered colonic microbial composition at the human mucosal-luminal interface, and to determine whether certain microbial genera contribute to symptoms of gastrointestinal tract dysfunction in patients with systemic sclerosis. If affirmed, such genera could provide specific targets for intervention to avert or treat this important clinical dimension of systemic sclerosis.
Recent Relevant Publications/Presentations:
- Volkmann ER, Chang, Y-L, Barroso N, et al. Systemic sclerosis is associated with a unique colonic microbial consortium. Annals Rheumatic Diseases 2015;74:151.
- Volkmann ER. Systemic sclerosis is associated with a unique colonic microbial consortium. Oral Presentation at the European League Against Rheumatism Annual Congress, 2015. Rome, Italy.
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