Victoria von Goetze

German Rheumatism Research Centre

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Hyun‐Dong Chang

German Rheumatism Research Centre

Lisa Budzinski

Technische Universität Berlin

Pawel Durek

German Rheumatism Research Centre

Kevin Heiking

German Rheumatism Research Centre

Britta Siegmund

Charité - Universitätsmedizin Berlin

Mir‐Farzin Mashreghi

German Rheumatism Research Centre

Andreas Radbruch

German Rheumatism Research Centre

René Riedel

Universität Hamburg

A. J. Beller

German Rheumatism Research Centre

AA Kruglov

Federal Medical-Biological Agency

Cooperative Institutions

German Rheumatism Research Centre

Leibniz Association

Charité - Universitätsmedizin Berlin

Humboldt-Universität zu Berlin

Ludwig-Maximilians-Universität München

Institute of Immunology

Freie Universität Berlin

German Centre for Cardiovascular Research

Universität Hamburg

Berlin-Brandenburger Centrum für Regenerative Therapien

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Specific microbiota enhances intestinal IgA levels by inducing TGF‐β in T follicular helper cells of Peyer's patches in mice

European Journal of Immunology (2020)

Alexander Beller Andrey Kruglov Pawel Durek Victoria von Goetze Katharina Werner

Abstract In humans and mice, mucosal immune responses are dominated by IgA antibodies and the cytokine TGF‐β, suppressing unwanted immune reactions but also targeting Ig class switching to IgA. It had been suggested that eosinophils promote the generation and maintenance of mucosal IgA‐expressing plasma cells. Here, we demonstrate that not eosinophils, but specific bacteria determine mucosal IgA production. Co‐housing of eosinophil‐deficient mice with mice having high intestinal IgA levels, as well as the intentional microbiota transfer induces TGF‐β expression in intestinal T follicular helper cells, thereby promoting IgA class switching in Peyer's patches, enhancing IgA + plasma cell numbers in the small intestinal lamina propria and levels of mucosal IgA. We show that bacteria highly enriched for the genus Anaeroplasma are sufficient to induce these changes and enhance IgA levels when adoptively transferred. Thus, specific members of the intestinal microbiota and not the microbiota as such regulate gut homeostasis, by promoting the expression of immune‐regulatory TGF‐β and of mucosal IgA.

Immunoglobulin A

Peyer's patch

Lamina propria

10.1002/eji.201948474

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Citations (62)

P104 Anaeroplasma, a potential anti-inflammatory probiotic for the treatment of chronic intestinal inflammation

Annals of the Rheumatic Diseases (2019)

A. J. Beller AA Kruglov Pawel Durek Victoria von Goetze Uwe Reuter

Career situation of first and presenting author

Post-doctoral fellow.

Introduction

The human intestine is colonized with billions of microorganisms, which form the gut microbiota, consisting of up to 1000 different bacterial species. Recent studies have implicated the intestinal microbiota in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjögren's syndrome. Yet, we still lack the knowledge which bacteria of the gut microbiota induce, promote or inhibit chronic inflammatory inflammation.

Objectives

The aim of our work is to identify members of the intestinal microbiota with pro- or anti-inflammatory properties for targeted and therapeutic manipulation of the microbiota in chronic inflammatory diseases.

Methods

We have developed high-resolution microbiota flow cytometry which allows us to analyze the microbiota on a single cell level. This provides a non-invasive, fast and efficient diagnostic tool to visualize dramatic changes of microbiota composition in inflammatory diseases, fast and efficiently, and isolate distinct bacteria for functional and molecular analyses.

Results

We have identified bacteria belonging to the genus Anaeroplasma, which enhances the levels of mucosal IgA. Adoptive transfer of Anaeroplasma increases the numbers of IgA+ germinal center B cells in the Peyer's patches and of IgA-secreting plasma cells in the lamina propria of the small intestine leading to significantly enhanced mucosal IgA levels. Anaeroplasma controls IgA expression presumably its ability to induce expression of the regulatory cytokine TGF-β in T cells, as we show here.

Conclusions

The anti-inflammatory properties of Anaeroplasma to induce the anti-inflammatory cytokine TGF-β, thereby also strengthening the intestinal barrier by enhancing mucosal IgA, qualify Anaeroplasma as potent probiotic for the prevention and treatment of chronic inflammation.

Disclosure of Interest

None declared.

10.1136/annrheumdis-2018-ewrr2019.92

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Citations (20)

Author response for "Single-cell phenotyping of bacteria combined with deep sequencing for improved contextualization of microbiome analyses"

Lisa Budzinski Victoria von Goetze Hyun‐Dong Chang

Contextualization

10.1002/eji.202250337/v4/response1

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Single‐cell phenotyping of bacteria combined with deep sequencing for improved contextualization of microbiome analyses

European Journal of Immunology (2023)

Lisa Budzinski Victoria von Goetze Hyun‐Dong Chang

Great effort was made to characterize the bacterial communities inhabiting the human body as a factor in disease, resulting in the realization that a wide spectrum of diseases is associated with an altered composition of the microbiome. However, the identification of disease-relevant bacteria has been hindered by the high cross-sectional diversity of individual microbiomes, and in most cases, it remains unclear whether the observed alterations are cause or consequence of disease. Hence, innovative analysis approaches are required that enable inquiries of the microbiome beyond mere taxonomic cataloging. This review highlights the utility of microbiota flow cytometry, a single-cell analysis platform to directly interrogate cellular interactions, cell conditions, and crosstalk with the host's immune system within the microbiome to take into consideration the role of microbes as critical interaction partners of the host and the spectrum of microbiome alterations, beyond compositional changes. In conjunction with advanced sequencing approaches it could reveal the genetic potential of target bacteria and advance our understanding of taxonomic diversity and gene usage in the context of the microenvironment. Single-cell bacterial phenotyping has the potential to change our perspective on the human microbiome and empower microbiome research for the development of microbiome-based therapy approaches and personalized medicine.

Human Microbiome Project

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10.1002/eji.202250337

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Citations (3)

Author response for "Single-cell phenotyping of bacteria combined with deep sequencing for improved contextualization of microbiome analyses"

Lisa Budzinski Victoria von Goetze Hyun‐Dong Chang

Contextualization

10.1002/eji.202250337/v3/response1

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