The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility

Xiaolin Liu; Nina van Beek; Aleksa Cepic; Nadia A. Andreani; Cecilia J. Chung; 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; Kaisa Tasanen-Määttä; Snejina Vassileva; Detlef Zillikens; Christian D. Sadik; Enno Schmidt; Saleh Ibrahim; John F. Baines

doi:10.3389/fimmu.2023.1212551

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility

Xiaolin Liu, Nina van Beek, Aleksa Cepic, Nadia A. Andreani, Cecilia J. Chung, 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 LinnenmannLaura Huilaja, Kaisa Tasanen-Määttä, Snejina Vassileva, Detlef Zillikens, Christian D. Sadik, Enno Schmidt^*, Saleh Ibrahim^*, John F. Baines^*

^*Corresponding author for this work

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.

Original language	English
Article number	1212551
Journal	Frontiers in Immunology
Volume	14
Pages (from-to)	1212551
ISSN	1664-3224
DOIs	https://doi.org/10.3389/fimmu.2023.1212551
Publication status	Published - 10.2023

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Centers: Center for Research on Inflammation of the Skin (CRIS)

DFG Research Classification Scheme

2.21-05 Immunology
2.22-19 Dermatology
2.22-22 Clinical Immunology and Allergology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3389/fimmu.2023.1212551

Cite this

Liu, X., van Beek, N., Cepic, A., Andreani, N. A., Chung, C. J., Hermes, B. M., Yilmaz, K., Benoit, S., Drenovska, K., Gerdes, S., Gläser, R., Goebeler, M., Günther, C., von Georg, A., Hammers, C. M., Holtsche, M. M., Hübner, F., Kiritsi, D., Schauer, F., ... Baines, J. F. (2023). The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility. Frontiers in Immunology, 14, 1212551. Article 1212551. https://doi.org/10.3389/fimmu.2023.1212551

@article{18a39af568b1456aa121b5913210135c,

title = "The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility",

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.",

author = "Xiaolin Liu and {van Beek}, Nina and Aleksa Cepic and Andreani, {Nadia A.} and Chung, {Cecilia J.} and Hermes, {Britt M.} and Kaan Yilmaz and Sandrine Benoit and Kossara Drenovska and Sascha Gerdes and Regine Gl{\"a}ser and Matthias Goebeler and Claudia G{\"u}nther and {von Georg}, Anabelle and Hammers, {Christoph M.} and Holtsche, {Maike M.} and Franziska H{\"u}bner and Dimitra Kiritsi and Franziska Schauer and Beke Linnenmann and Laura Huilaja and Kaisa Tasanen-M{\"a}{\"a}tt{\"a} and Snejina Vassileva and Detlef Zillikens and Sadik, {Christian D.} and Enno Schmidt and Saleh Ibrahim and Baines, {John F.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Liu, van Beek, Cepic, Andreani, Chung, Hermes, Yilmaz, Benoit, Drenovska, Gerdes, Gl{\"a}ser, Goebeler, G{\"u}nther, von Georg, Hammers, Holtsche, H{\"u}bner, Kiritsi, Schauer, Linnenmann, Huilaja, Tasanen-M{\"a}{\"a}tt{\"a}, Vassileva, Zillikens, Sadik, Schmidt, Ibrahim and Baines.",

year = "2023",

month = oct,

doi = "10.3389/fimmu.2023.1212551",

language = "English",

volume = "14",

pages = "1212551",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media",

}

Liu, X, van Beek, N, Cepic, A, Andreani, NA, Chung, CJ, Hermes, BM, Yilmaz, K, Benoit, S, Drenovska, K, Gerdes, S, Gläser, R, Goebeler, M, Günther, C, von Georg, A, Hammers, CM , Holtsche, MM, Hübner, F, Kiritsi, D, Schauer, F, Linnenmann, B, Huilaja, L, Tasanen-Määttä, K, Vassileva, S, Zillikens, D, Sadik, CD , Schmidt, E , Ibrahim, S & Baines, JF 2023, 'The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility', Frontiers in Immunology, vol. 14, 1212551, pp. 1212551. https://doi.org/10.3389/fimmu.2023.1212551

TY - JOUR

T1 - The gut microbiome in bullous pemphigoid

T2 - implications of the gut-skin axis for disease susceptibility

AU - Liu, Xiaolin

AU - van Beek, Nina

AU - Cepic, Aleksa

AU - Andreani, Nadia A.

AU - Chung, Cecilia J.

AU - Hermes, Britt M.

AU - Yilmaz, Kaan

AU - Benoit, Sandrine

AU - Drenovska, Kossara

AU - Gerdes, Sascha

AU - Gläser, Regine

AU - Goebeler, Matthias

AU - Günther, Claudia

AU - von Georg, Anabelle

AU - Hammers, Christoph M.

AU - Holtsche, Maike M.

AU - Hübner, Franziska

AU - Kiritsi, Dimitra

AU - Schauer, Franziska

AU - Linnenmann, Beke

AU - Huilaja, Laura

AU - Tasanen-Määttä, Kaisa

AU - Vassileva, Snejina

AU - Zillikens, Detlef

AU - Sadik, Christian D.

AU - Schmidt, Enno

AU - Ibrahim, Saleh

AU - Baines, John F.

N1 - Publisher Copyright: Copyright © 2023 Liu, van Beek, Cepic, Andreani, Chung, Hermes, Yilmaz, Benoit, Drenovska, Gerdes, Gläser, Goebeler, Günther, von Georg, Hammers, Holtsche, Hübner, Kiritsi, Schauer, Linnenmann, Huilaja, Tasanen-Määttä, Vassileva, Zillikens, Sadik, Schmidt, Ibrahim and Baines.

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85177668987&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/4ee4f6fc-697f-3791-af51-de98a90ad9b6/

U2 - 10.3389/fimmu.2023.1212551

DO - 10.3389/fimmu.2023.1212551

M3 - Journal articles

C2 - 38022583

AN - SCOPUS:85177668987

SN - 1664-3224

VL - 14

SP - 1212551

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1212551

ER -

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Cite this

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

CRC 1526, PANTAU: Pathomechanisms of Antibody-mediated Autoimmunity

Cite this