Microbiome: Role in Inflammatory Skin Diseases

Figures & data

Figure 1 Crosstalk between the skin and the microbiome under conditions of pathogenic bacteria.

Figure 2 Flow diagram of study selection.

Table 1 Characterization of the Skin Microbiota in ISDs.Note: ↑, Increase; ↓, Decrease

Disease	Microbial Alterations		Immune Dysregulation	Refs
ATOPIC DERMATITIS(AD)	↑Staphylococcus epidermidis ↑Staphylococcus hemolysis ↑Staphylococcus spp. ↑Staphylococcus aureus	↓Cutibacterium spp. ↓Streptococcus spp. ↓Corynebacterium spp. ↓Propionibacterium acnes ↓Acinetobacter ↓Corynebacterium ↓Proteus	↓AMP ↑IL-4,↑IL-5, ↑IL-13,↑IL-31, ↑IL-1,↑IL-12, ↑IL-22, ↑IL-6, ↑IL-8, ↑IgE, ↑TSLP, ↑TNF-α,	[22–27]
SEBORRHEIC DERMATITIS(SD)	↑Staphylococcus spp. ↑Staphylococcus epidermidis ↑Streptococcus spp. ↑Pseudomonas spp. ↑Acinetobacter ↑Malassezia ↑Mycococcus, ↑Candida ↑Filamentous fungus spores	↓Cutibacterium spp.	↑IL-1α,↑IL-1β, ↑IL-2, ↑IL-8, ↑IL-10,↑IL-12, ↑TNF-α, ↑IFN-γ	[28–32]
ROSACEA	↑Corynebacterium kropp ↑Gordonia ↑Geobacillus	↓Cutibacterium acnes ↓Acinetobacter ↓Roseomonas spp.	↑IL–10, ↑AMPs	[33]
PSORIASIS	↑Firmicutes ↑Streptococcus spp. ↑Prevotella ↑Staphylococcus spp. ↑Staphylococcus aureus ↑Staphylococcus pettenkoferi ↑Staphylococcus sciuri ↑Corynebacterium kroppenstedii ↑Corynebacterium simulans ↑Neisseria spp. ↑Finegoldia spp.	↓Actinobacteria ↓Gordoniaceae ↓Staphylococcus epidermidis ↓Cutibacterium spp. ↓Staphylococcus spp. ↓Cutibacterium acnes ↓Cutibacterium granulosum ↓Burkholderia spp. ↓Lactobacilli	↑IL-1, ↑IL-6, ↑ IL-8,↑IL17, ↑IL-12, ↑IL-23, ↑IL-22, ↑TNF- α, ↑IFN- α, ↑TGF-b, ↑iNOS,↑HSP70,	[34–37]
ACNE	↑Firmicutes ↑Proteobacteria ↑Staphylococcus spp.	↓Actinobacteria ↓Cutibacterium spp. ↓Cutibacterium acnes ↓Cutibacterium granulosu	↑IL-12, ↑IL-23, ↑TNF- α, ↑IFN- α	[38,39]
DIAPER DERMATITIS (DD)	↑Enterococcus ↑Erwinia ↑Pseudomonas ↑Staphylococcus aureus	↓Clostridium ↓Actinomyces ↓Staphylococcus epidermidis,	↑IL-1,↑IL-8, ↑TNF- α	[40,41]
MALASSEZIA FOLLICULITIS (MF)	↑ Malassezia. sympodialis ↑ Malassezia.Restricta ↑ Malassezia. furfu	-	↑IL –1α,↑IL-4, ↑IL-6, ↑IL-8, ↑IL-10, ↑IL-12 ↑TNF-α,	[42–44]

Table 2 Role of Staphylococcal SAgs and Candida Albicans in Inflammatory Skin Diseases

Microorganism	Virulence Factors	Possible role in AD	Possible role in Psoriasis		Possible role in DD	Refs
Staphylococcus aureus	α-toxin	Keratinocyte membrane damage / lysis that erodes epidermal barrier integrity				[220,221]
	d-Toxin	Stimulates mast cell degranulation and synergizes with IgE to induce allergic skin inflammation				[222]
	Protein A	Proinflammatory. Binds to TNFR-1 on keratinocytes				[223,224]
	Clumping factor B	Adherence of the stratum corneum to corneocytes promotes colonization by S. aureus				[225]
	Protease	Facilitate dissolution of the stratum corneum				[226]
	Phenol-soluble Modulins (PSM)	Stimulates keratinocyte production of Il-36, IL-17A, and Th17 inflammation, triggering AD associated skin pro-inflammatory responses.		/	/	[227,228]
	Staphylococcal SAgs (SEA, SEB, SEC, TSST-1)	Triggers B cell expansion of keratinocytes, APC mediated T cell activation, mast cell degranulation. Causes superantigen responses to produce IL-1, TNF-α Etc. proinflammatory factors. Induces local erythema and dermatitis.Sometimes causes disease flare.		DCs are stimulated to release IL-12 and IL-23, differentiate into Th17 cell populations, and produce pro-inflammatory mediators, such as IL-17, TNF- α, IFN- α And IL-22.	SEAcauses skin redness and damage to DD like skin lesions and may contribute to low-grade fever	[1,70,71]
Candida albicans	Phospholipase	Associated with membrane damage, adhesion, and penetration of host cells. Hydrolyzes one or more ester linkages in glycerophospholipids. Resulting in cell lysis.				[83]
	Aspartyl proteases	Enhances the ability of an organism to colonize and penetrate host tissues as well as to evade the host immune system.				[84,85]
	Biomembrane	Evasion of host immune mechanisms, resistance to antifungal therapy.				[82]
	Candidalysin	Disruption of the epithelial membrane by embedding, permeabilizing, and creating holes leads to weakening of the cytoplasmic contents.				[86,87]
	Candida specific antibodies	High levels of IgE	High levels of IgA		/	[93,183]
	Protein compounds of C. albicans	Proteins 27, 37, 43, 46, 125, and 175 kDa, which stimulate the ad immune system and immunoglobulin response.	/		/	[91]

Table 3 Role of Malassezia in Inflammatory Skin Diseases

Diseases	Possible Role of Malassezia in Inflammatory Skin Diseases.	Refs
AD	Lipases and phospholipases are produced that release unsaturated free fatty acids from sebum to initiate inflammatory responses.	[77]
	Keratinocytes are stimulated to produce inflammatory cytokines (such as IL-4, IL-6, IL-8, and TNF- α), Induces IgE mediated mast cell degranulation, and the release of leukotrienes,	[80]
SD	Stimulates IL-8 secretion and inhibits IL-1 secretion. Lipases and phospholipases are produced that release unsaturated free fatty acids from sebum to initiate inflammatory responses. Generation of tryptophan metabolites like indole derivatives (indole-3-formaldehyde) triggers SD immune response.	[229]
		[230]
Ance	Lipases and phospholipases are produced that release unsaturated free fatty acids from sebum to initiate inflammatory responses.	[149]
	Abnormal keratinization affecting the hair follicle duct, chemotactic for polymorphonuclear neutrophils and promoting the secretion of proinflammatory cytokines by keratinocytes and monocytes.	[148]
Psoriasis	Upregulation of TNF-α, IL-1, IL-6, IL-8, and IL-12.	[173]
	Lipases and phospholipases are produced that release unsaturated free fatty acids from sebum to initiate inflammatory responses.	[171]
	Upregulated expression of heat shock protein 70 (HSP70).Involved in the innate immune response leading to NF- κ B activation, with release of pro-inflammatory cytokines. Upregulates CD4 + and CD8 + T cell responses, and modulates adaptive immune responses.	[172]
MF	Lipases and phospholipases are produced that release unsaturated free fatty acids from sebum to initiate inflammatory responses. Upregulation of IL- α, IL-6, IL-8, IL-12, TNF-α and the anti-inflammatory cytokines IL-4 and IL-10	[199]

Table 4 Abbreviations

Abbreviation	Full Name
AD	Atopic dermatitis
AhR	Aryl-hydrocarbon receptor
AMP	Antimicrobial peptides
AMPS	Antimicrobial peptides
APCs	Antigen-presenting cells
C. albicans	Candida albicans
CAP18	Cathelicidin antimicrobial peptide 18
CGRP	Calcitonin gene-related peptide
CLFA	Clumping factors A
CLFB	Clumping factors B
CLR	C-type lectin receptor
CONS	Coagulase-negative staphylococci
cPLA2	Cytosolic PLA2
CRISPR/Cas	CRISPR-associated proteins system
CXCL8	C-X-C motif ligand 8
DC	Dendritic cell
DCs	Dendritic cells
DD	Diaper Dermatitis
DF	Dandruff
ESAT-6	Early secretory antigenic 6
FDP	Filaggrin degradation products
FFA	Free fatty acid
FNBP	Fibronectin binding protein
HBD	Humanβ- defensin
HBD-2	Humanβ-defensin 2
HBD-3	Humanβ-defensin 3
HLA	Human leukocyte antigen
HSP70	heat shock protein 70
IFN-γ	Interferon-gamma
IL	Interleukin
IL-23	Interleukin-23
iNOS	Inducible nitric oxide synthase
irak4	Interleukin-1 receptor-associated kinase 4
ISDA	Iron-regulated surface determinant protein A
ISDs	Inflammatory skin diseases
KC	Keratinocytes
LPC	Lysophosphatidylcholines
LTA	Lipoteichoic acid
MF	Malassezia folliculitis
M. globosa	Malassezia. globosa
M. furfur	Malassezia. furfur
M. restricta	Malassezia. restricta
M. sympodialis	Malassezia. sympodialis
MMP-9	Matrix metallo proteinase-9
MPAKs	Mitogen-activated protein kinase
MyD88	Myeloid differentiation primary response 88
NFAT	Activated T cells
NF-κB	Nuclear factor κ B
NOD	Nucleotide-binding oligomerization domain
OMN	Omiganan
P. acnes	Propionibacterium acnes
PLA2	Phospholipase A2
PSM-γ	Phenol solubility regulating protein-γ
PSM-δ	Phenol solubility regulating protein-δ
Roxp	Radical oxygenase
RT2	Ribotype 2
RT4	Ribotype 4
RT5	Ribotype 5
SAgs	Staphylococcus aureus superantigens
S. aureus	Staphylococcus aureus
SCFAs	Short-chain fatty acids
SD	Seborrheic dermatitis
SE	Staphylococcal enterotoxins
SEA	Staphylococcal enterotoxin A
SEB	Staphylococcal enterotoxin B
SEC	Staphylococcal enterotoxin C
SPL	Sphingolipids
S. Alvi	Snodgrassella alvi
S. Epidermidis	Staphylococcus epidermidis
TARC	Thymus and activation of cytokines
TRAF6	TNFR-associated factor 6
TEWL	Transepidermal water loss
TGF-β	Transforming growth factor-beta
TLR	Toll-like receptor
TNF	Tumor necrosis factor
TSLP	Thymic stromal lymphopoietin
TSST	Toxic shock syndrome toxin

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