Frontiers in Immunology (Nov 2023)
The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility
- Xiaolin Liu,
- Xiaolin Liu,
- Nina van Beek,
- Aleksa Cepic,
- Aleksa Cepic,
- Nadia A. Andreani,
- Nadia A. Andreani,
- Cecilia J. Chung,
- Cecilia J. Chung,
- Britt M. Hermes,
- Britt M. Hermes,
- Kaan Yilmaz,
- Sandrine Benoit,
- Kossara Drenovska,
- Sascha Gerdes,
- Regine Gläser,
- Matthias Goebeler,
- Claudia Günther,
- Anabelle von Georg,
- Christoph M. Hammers,
- Maike M. Holtsche,
- Franziska Hübner,
- Dimitra Kiritsi,
- Franziska Schauer,
- Beke Linnenmann,
- Laura Huilaja,
- Laura Huilaja,
- Kaisa Tasanen-Määttä,
- Kaisa Tasanen-Määttä,
- Snejina Vassileva,
- Detlef Zillikens,
- Detlef Zillikens,
- Christian D. Sadik,
- Christian D. Sadik,
- Enno Schmidt,
- Enno Schmidt,
- Enno Schmidt,
- Saleh Ibrahim,
- Saleh Ibrahim,
- John F. Baines,
- John F. Baines
Affiliations
- Xiaolin Liu
- Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany
- Xiaolin Liu
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
- Nina van Beek
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Aleksa Cepic
- Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany
- Aleksa Cepic
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
- Nadia A. Andreani
- Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany
- Nadia A. Andreani
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
- Cecilia J. Chung
- Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany
- Cecilia J. Chung
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
- Britt M. Hermes
- Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany
- Britt M. Hermes
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
- Kaan Yilmaz
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Sandrine Benoit
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
- Kossara Drenovska
- Department of Dermatology and Venereology, Medical University-Sofia, Sofia, Bulgaria
- Sascha Gerdes
- Department of Dermatology, Venereology and Allergology, University of Kiel, Kiel, Germany
- Regine Gläser
- Department of Dermatology, Venereology and Allergology, University of Kiel, Kiel, Germany
- Matthias Goebeler
- Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany
- Claudia Günther
- Department of Dermatology, University Hospital, Technische Universität (TU) Dresden, Dresden, Germany
- Anabelle von Georg
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Christoph M. Hammers
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Maike M. Holtsche
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Franziska Hübner
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Dimitra Kiritsi
- Department of Dermatology, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
- Franziska Schauer
- Department of Dermatology, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
- Beke Linnenmann
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Laura Huilaja
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Laura Huilaja
- 0Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
- Kaisa Tasanen-Määttä
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Kaisa Tasanen-Määttä
- 0Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
- Snejina Vassileva
- Department of Dermatology and Venereology, Medical University-Sofia, Sofia, Bulgaria
- Detlef Zillikens
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Detlef Zillikens
- 1Center for Research on Inflammation of the Skin (CRIS), University of Lübeck, Lübeck, Germany
- Christian D. Sadik
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Christian D. Sadik
- 1Center for Research on Inflammation of the Skin (CRIS), University of Lübeck, Lübeck, Germany
- Enno Schmidt
- Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, Germany
- Enno Schmidt
- 1Center for Research on Inflammation of the Skin (CRIS), University of Lübeck, Lübeck, Germany
- Enno Schmidt
- 2Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Saleh Ibrahim
- 2Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany
- Saleh Ibrahim
- 3College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
- John F. Baines
- Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany
- John F. Baines
- Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
- DOI
- https://doi.org/10.3389/fimmu.2023.1212551
- Journal volume & issue
-
Vol. 14
Abstract
Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects the elderly. An altered skin microbiota in BP was recently revealed. Accumulating evidence points toward a link between the gut microbiota and skin diseases; however, the gut microbiota composition of BP patients remains largely underexplored, with only one pilot study to date, with a very limited sample size and no functional profiling of gut microbiota. To thoroughly investigate the composition and function of the gut microbiota in BP patients, and explore possible links between skin conditions and gut microbiota, we here investigated the gut microbiota of 66 patients (81.8% firstly diagnosed) suffering from BP and 66 age-, sex-, and study center-matched controls (CL) with non-inflammatory skin diseases (132 total participants), using 16S rRNA gene and shotgun sequencing data. Decreased alpha-diversity and an overall altered gut microbial community is observed in BP patients. Similar trends are observed in subclassifications of BP patients, including first diagnoses and relapsed cases. Furthermore, we observe a set of BP disease-associated gut microbial features, including reduced Faecalibacterium prausnitzii and greater abundance of pathways related to gamma-aminobutyric acid (GABA) metabolism in BP patients. Interestingly, F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and psoriasis patients. Moreover, GABA plays multiple roles in maintaining skin health, including the inhibition of itching by acting as a neurotransmitter, attenuating skin lesions by balancing Th1 and Th2 levels, and maintaining skin elasticity by increasing the expression of type I collagen. These findings thus suggest that gut microbiota alterations present in BP may play a role in the disease, and certain key microbes and functions may contribute to the link between gut dysbiosis and BP disease activity. Further studies to investigate the underlying mechanisms of the gut-skin interaction are thus clearly warranted, which could aid in the development of potential therapeutic interventions.
Keywords
