**2.1 Skin microbiota in psoriasis**

Several studies reported the characteristic features of microbiota in psoriatic skin (**Table 2**). Significant differences were observed between psoriatic lesion and control skin, but the changes were different in each study. Gao et al. [19] and Chang et al. [14] reported an increase in lesional skin diversity compared to nonlesional and control. In contrast, subsequent studies by Fahlen et al. [18] found wider range of Shannon index values in the control suggesting that the trend of decrease in lesional psoriasis microbiome diversity is consistent with the findings by Alexseyenko et al. [17] who observed a decrease in the diversity and significantly lower Shannon index in lesional skin. Consistent with previous studies, Tett et al. [16] found that psoriatic plaques at the ear are characterized by a significant decrease in microbial diversity. When beta diversity was analyzed to describe heterogeneity of microbial community, Fahlen et al. [18] reported a lower beta diversity in psoriasis compared to control, while Alexseyenko et al. [17] found that beta diversity was the highest in lesional skin, followed by unaffected skin, and the lowest in healthy skin. In line with the study by Tett et al. [16], which reported that ear lesions revealed higher beta diversity, Loeshe et al. [12] and Chang et al. [14] also reported a higher beta diversity at dry skin sites in psoriasis. At the phylum level, most skin bacterial composition fall into four major phyla: *Actinobacteria*, *Firmicutes*, *Bacteroidetes*, and *Proteobacteria*. Within these phyla, the three most abundant genera are: *Propionibacterium*, *Corynebacterium*, and *Staphylococcus*. From the studies of Gao et al. [19], Fahlen et al. [18], and Langan et al. [10], it has been revealed that at the phylum level, compared to healthy skin, psoriatic skin was associated with an increase in the relative abundance of *Firmicutes* but a decrease for *Actinobacteria*, which is partially consistent with Alexseyenko et al. [17] who identified psoriatic lesion as cutaneo type 2, which was dominated by *Firmicutes* and *Actinobacteria*. In contrast, *Firmicutes* were lower in the studies by Loeshe et al. [12], Assarsson et al. [13], and Drago et al. [15]. *Proteobacteria* showed inconsistent abundance, lower in lesional skin as observed by Gao et al. [19] whereas Fahlen et al. [18] observed an increase, and Drago et al. [15] reported that *Proteobacteria* and *Bacteroidetes* were the dominant microbiota in psoriasis lesion. At the genus

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*Skin and Gut Microbiota in Psoriasis: A Systematic Review*

**Population Result**

23 Pso, 20 C Pso L

At the phylum level: **↑** *Firmicutes*, **↓***Actinobacteria* At the genus level:

*Propionibacterium*

Pso NL

associated with Pso L

**↑***Prevotella*, *Staphylococcus*, **↓***Anaerococcus* and

*Prevotella* and *Staphylococcus* significantly

*Actinobacteria*-to-*Firmicutes* ratio, partially

Biological therapies demonstrated the largest impact on the ratio of *Actinobacteria* to *Firmicutes Corynebacterium*, *Staphylococcus*, significantly

**↑** *Streptococcus* regardless of the sampling site **↑** *Brevibacterium* richness and evenness in in the elbow lesions, compared to back lesions **↓***Propionibacterium* PsoL, PsoNL compared C in

Alpha diversity and bacterial taxa from skin swab,

At the phylum level: **↑***Actinobacteria* in leg, scalp, and trunk lesions **↓***Firmicutes* in scalp and trunk

At the species level: **↑***Bacilli***↓***Propionibacterium* 

*Streptococcus* colonization of skin does not correlate with severity in lesional and non-lesional skin

Significant change in abundance from baseline in

No difference diversity in Pso L vs. Pso NL except

Pso L microbiota was not converging with Pso NL

Microbiota diverged further between Pso L and Pso

*Anaerococcus*, *Peptoniphilus*, *Gardnerella*, *Prevotella*,

scraping, and biopsy are comparable

At the genus level: **↓***Caulobacteraceae*, *Corynebacterium* leg lesions

89 Pso Pso L and Pso NL respond similarly to ustekinumab

**↑***Anaerococcus*, *Propionibacterium*

reversible during treatment

correlated with PASI scores

Pso L and Pso NL

elbow lesions Remark

114 Pso Beta diversity: Pso L > Pso NL Pso L

lesions

*acnes* in scalp lesions

as treatment progressed

**↓***Firmicutes Staphylococcus*

**↓***Firmicutes*, *Staphylococcus*, *Finegoldia*,

**↓***Pseudomonas* in treatment responders

NL across body sites

all body sites

**↑** in trunk

Pso L

*Clostridium* Pso NL **↓***Firmicutes*

26 Pso Pso L

Pso L

34 Pso, 25 C Beta diversity: no significant differences between

*DOI: http://dx.doi.org/10.5772/intechopen.92686*

**ratings of the quality**

Prospective systemic treatment/2

Crosssectional/4

Crosssectional/4

Longitudinal RCT/1

Crosssectional/4

Longitudinal Narrowband UVB/2

Crosssectional/4

**Study Study design/**

Langan et al. [10] (2019)

Stehlikova et al. [11] (2019)

Loesche et al. [12] (2018) Remark: study did not include healthy control

Assarsson et al. [13] (2018) Remark: study did not include healthy controls


*Skin and Gut Microbiota in Psoriasis: A Systematic Review DOI: http://dx.doi.org/10.5772/intechopen.92686*

*Human Microbiome*

**2. Psoriasis and microbiota**

mass spectrometry (MALDI-TOF) (**Table 1**).

**2.1 Skin microbiota in psoriasis**

Additionally, it has been known that several microorganisms contribute to psoriasis exacerbation alterations in the innate and adaptive immune processes [9]. The increasing evidence here suggests that the microbiota may play a critical role in psoriasis pathogenesis. This systematic review aims to elucidate the correlation between the microbiome and psoriasis pathogenesis, and the microbiota modula-

The initial search revealed a total of 629 studies of which 501 studies were excluded based on their title and abstract. The full texts were reviewed, and a further 116 studies were excluded. An additional four studies from the reference lists of already included studies were included in the systematic review. In total, 16 studies were included in this systematic review; 10 studies investigated the skin microbiome, of which 6 studies were cross-sectional and 4 studies were prospective study. Six studies investigated the gut microbiome, including five cross-sectional studies and one prospective study. The most commonly used method was 16S r RNA (skin swab, biopsies, curette); Langan et al. [10] used traditional culture combined with

Several studies reported the characteristic features of microbiota in psoriatic skin (**Table 2**). Significant differences were observed between psoriatic lesion and control skin, but the changes were different in each study. Gao et al. [19] and Chang et al. [14] reported an increase in lesional skin diversity compared to nonlesional and control. In contrast, subsequent studies by Fahlen et al. [18] found wider range of Shannon index values in the control suggesting that the trend of decrease in lesional psoriasis microbiome diversity is consistent with the findings by Alexseyenko et al. [17] who observed a decrease in the diversity and significantly lower Shannon index in lesional skin. Consistent with previous studies, Tett et al. [16] found that psoriatic plaques at the ear are characterized by a significant decrease in microbial diversity. When beta diversity was analyzed to describe heterogeneity of microbial community, Fahlen et al. [18] reported a lower beta diversity in psoriasis compared to control, while Alexseyenko et al. [17] found that beta diversity was the highest in lesional skin, followed by unaffected skin, and the lowest in healthy skin. In line with the study by Tett et al. [16], which reported that ear lesions revealed higher beta diversity, Loeshe et al. [12] and Chang et al. [14] also reported a higher beta diversity at dry skin sites in psoriasis. At the phylum level, most skin bacterial composition fall into four major phyla: *Actinobacteria*, *Firmicutes*, *Bacteroidetes*, and *Proteobacteria*. Within these phyla, the three most abundant genera are: *Propionibacterium*, *Corynebacterium*, and *Staphylococcus*. From the studies of Gao et al. [19], Fahlen et al. [18], and Langan et al. [10], it has been revealed that at the phylum level, compared to healthy skin, psoriatic skin was associated with an increase in the relative abundance of *Firmicutes* but a decrease for *Actinobacteria*, which is partially consistent with Alexseyenko et al. [17] who identified psoriatic lesion as cutaneo type 2, which was dominated by *Firmicutes* and *Actinobacteria*. In contrast, *Firmicutes* were lower in the studies by Loeshe et al. [12], Assarsson et al. [13], and Drago et al. [15]. *Proteobacteria* showed inconsistent abundance, lower in lesional skin as observed by Gao et al. [19] whereas Fahlen et al. [18] observed an increase, and Drago et al. [15] reported that *Proteobacteria* and *Bacteroidetes* were the dominant microbiota in psoriasis lesion. At the genus

tion that may lead to possible therapeutic interventions.

**68**


**71**

better defines the microbiome.

*Skin and Gut Microbiota in Psoriasis: A Systematic Review*

level, *Streptococcus* were higher in lesional skin by Gao et al. [19], Fahlen et al. [18], Alexseyenko et al. [17], Stehlikova et al. [11], and Drago et al. [15] while Loeshe et al. [12] found no correlation between psoriasis lesional and unaffected skin. *Staphylococcus* were detected more frequently in the lesion by Gao et al. [19] and Tett et al. [16] opposite to Fahlen et al. [18] who found that *Staphylococcus* were increased in abundance in healthy controls. Lower abundance of *Propionibacterium* in lesional skin was reported by Gao et al. [19], Fahlen et al. [18], Drago et al. [15], Stehlikova et al. [11], and Loeshe et al. [12], which is in contrast to Alexseyenko et al. [17] who reported an increase in the relative abundance of combined Gram positives such as *Corynebacterium*, *Propionibacterium*, *Staphylococcus*, and *Streptococcus*. In the subsequent study by Langan et al. [10], the presence of *Corynebacterium* and *Staphylococcus* was found to be significantly correlated with PASI scores while *Anaerococcus* and *Propionibacterium* were associated with nonlesional skin. These are consistent with the reports by Gao et al. [19] and Chang et al. [14] that at species level lesional skin psoriasis had an increased level of *S. aureus* but a decreased level of *P. acne*. On the other hand, study on the importance of site-specific microbiota without related disease reported that at the species level the most abundant bacteria were *S. epidermidis* and *P. acne* irrespective of disease status and hence suggested that an underlying subject-specific microbial signature

*Pso—Psoriasis, C—Control, Pso L—Psoriasis lesional skin, Pso NL—Psoriasis non-lesional skin.*

**Population Result**

10 Pso, 12 C Alpha diversity: no difference observed when using

At the phylum level: ↓ *Actinobacteria*, ↑ *Proteobacteria* in trunk lesions At the phylum level:

↓ *Propionibacterium* in all sites, ↓*Staphylococcus* ↑*Streptococcus/Propionibacterium* ratio

At the phylum level: ↑ *Firmicutes*, ↓ *Actinobacteria,* 

At genus level: ↓ *Propionibacterium*, ↑ *Streptococcus*

the Shannon index Beta diversity: Pso L < C

6 Pso, 6 C Alpha diversity: Pso L > Pso NL, C Beta diversity: Pso L > C

*Proteobacteria*

At the species level: ↓ *P. acne*, ↓ Anaerobic species

Pso L

There is a challenge to identify the explicit features of healthy or psoriasis microbiomes. Investigations of such a complex system of bacteria, fungi, and viruses are difficult and there is also high variation between samples. The composition of these communities of microorganisms depends on skin characteristics, such as sebaceous gland concentration, moisture content, topography, and temperature, as well as on host genetics and exogenous environmental factors [20]. Thus, the skin microbiome is biogeographically specific for each body site [21]. Demographic differences, such as gender, age, place of residence, living with animals, hygiene habits, occupation, and ethnicity also influence the composition of the skin microbiome [22]. The underlying disease and/or disease severity may also have an effect on the microbiome diversity or alterations in microbial communities due to disease states.

*DOI: http://dx.doi.org/10.5772/intechopen.92686*

**ratings of the quality**

Crosssectional/4

Crosssectional/4

*Skin microbiota in patients with psoriasis.*

**Study Study design/**

Fahlen et al. [18] (2012)

Gao et al. [19] (2008)

**Table 1.**


*Skin and Gut Microbiota in Psoriasis: A Systematic Review DOI: http://dx.doi.org/10.5772/intechopen.92686*

#### **Table 1.**

*Human Microbiome*

Chang et al. [14] (2018)

Drago et al. [15] (2016)

Tett et al. [16] (2017) Remark: study did not include healthy control

Alekseyenko et al. [17] (2013)

**Study Study design/**

**ratings of the quality**

Crosssectional/4

Crosssectional/4

Crosssectional/4

Crosssectional/4

Longitudinal 12 weeks, 36 weeks after systemic treatment/1

**Population Result**

3 adult first cousins— 1 AD, 1 Pso, 1 C (same lifestyle and environmental factors)

28 Pso, 26 C Alpha diversity: Pso L > Pso NL > C

Psol L

sites

Pso NL **↑***S. sciuri* C

Pso L

Pso L

Pso L

*Firmicutes*) At the genus level:

*Schlegelella*. At the species level: *Acidobacteria*, *Schlegelella*

C:

Pso L

AD and C At the family level

**↑** Beta diversity in all dry skin sites

**↑***S. aureus* and *S. pettenkoferi*

**↑***P. acnes*, *P. granulosum*

At the phylum level

compare to AD and C

Pso compare to AD and C.

28 Pso Alpha diversity: Pso L < Pso NL in ear lesions

At the phylum level: *Actinobacteria* and *Firmicutes*.

At the genus level: *Staphylococcus* At the species level:

75 Pso, 124 C Alpha diversity: Pso L < Pso NL and C

At the phylum level:

Beta diversity: Pso L > Pso NL > C.

compare to AD, C.

**↑** Alpha diversity at dry skin sites, with a trend at the sebaceous (scalp) site, and no increase at moist

**↓** *Firmicutes*, **↑** *Proteobacteria* in Pso L compare to

**↓***Staphylococcaceae*, *Propionibacteriaceae* in Pso L

At the species level: **↓** *Propionibacterium* acnes in

(richness did not correlate with PASI score) Beta diversity: Pso L > Pso NL in ear lesions

**↓** *S. aureus* in Pso L < C < AD, no difference in Psp NL

*S. epidermidis*, *P. acnes*, S*. caprae*/*capitis*, and *M. luteus*

Cutaneotype 2 (dominated by *Actinobacteria*,

*Acidobacteria* positively correlated with PASI

Cutaneotype 1 (dominated by *Proteobacteria*)

between the lesion and unaffected groups, or

**↑**Relative abundance of *Corynebacterium*, *Propionibacterium*, *Staphylococcus* and *Streptococcus*

**↓** *Cupriavidus, Flavisolibacter*

longitudinally within groups

17 Pso, 15 c No statistically significant difference was observed

**↑** combined relative abundance of *Corynebacterium*, *Propionibacterium*, *Staphylococcus*, *Streptococcus* **↓***Cupriavidus, Flavisolibacter*, *Methylobacterium*,

**↑** *Streptococcaceae*, *Rhodobacteraceae*, *Campylobacteraceae*, *Moraxellaceae* in Pso L

**70**

*Skin microbiota in patients with psoriasis.*

level, *Streptococcus* were higher in lesional skin by Gao et al. [19], Fahlen et al. [18], Alexseyenko et al. [17], Stehlikova et al. [11], and Drago et al. [15] while Loeshe et al. [12] found no correlation between psoriasis lesional and unaffected skin. *Staphylococcus* were detected more frequently in the lesion by Gao et al. [19] and Tett et al. [16] opposite to Fahlen et al. [18] who found that *Staphylococcus* were increased in abundance in healthy controls. Lower abundance of *Propionibacterium* in lesional skin was reported by Gao et al. [19], Fahlen et al. [18], Drago et al. [15], Stehlikova et al. [11], and Loeshe et al. [12], which is in contrast to Alexseyenko et al. [17] who reported an increase in the relative abundance of combined Gram positives such as *Corynebacterium*, *Propionibacterium*, *Staphylococcus*, and *Streptococcus*. In the subsequent study by Langan et al. [10], the presence of *Corynebacterium* and *Staphylococcus* was found to be significantly correlated with PASI scores while *Anaerococcus* and *Propionibacterium* were associated with nonlesional skin. These are consistent with the reports by Gao et al. [19] and Chang et al. [14] that at species level lesional skin psoriasis had an increased level of *S. aureus* but a decreased level of *P. acne*. On the other hand, study on the importance of site-specific microbiota without related disease reported that at the species level the most abundant bacteria were *S. epidermidis* and *P. acne* irrespective of disease status and hence suggested that an underlying subject-specific microbial signature better defines the microbiome.

There is a challenge to identify the explicit features of healthy or psoriasis microbiomes. Investigations of such a complex system of bacteria, fungi, and viruses are difficult and there is also high variation between samples. The composition of these communities of microorganisms depends on skin characteristics, such as sebaceous gland concentration, moisture content, topography, and temperature, as well as on host genetics and exogenous environmental factors [20]. Thus, the skin microbiome is biogeographically specific for each body site [21]. Demographic differences, such as gender, age, place of residence, living with animals, hygiene habits, occupation, and ethnicity also influence the composition of the skin microbiome [22]. The underlying disease and/or disease severity may also have an effect on the microbiome diversity or alterations in microbial communities due to disease states.


#### **Table 2.**

*Summary of skin microbiota findings in psoriasis.*

Moreover, microbiome diversities differ between studies; however, the more recent studies demonstrate decreased alpha diversity with increased beta diversity in psoriasis. Also, there are data that demonstrate a trend toward a changing microbial composition in psoriasis-affected skin. *Propionibacterium* is known as a protective commensal bacterium that is related with SCFA and propionate production, which regulates immune function. The decrease in the relative abundance of this microorganism in psoriasis may be related to the course of disease. In most studies, *Staphylococcus* are dominant in psoriatic skin, as species such as *S. aureus* proposed pathogenic Th17 activation while S*. epidermidis* appear to modulate immune and barrier functions. Interestingly, a study by Tett et al. [16] reported

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*Skin and Gut Microbiota in Psoriasis: A Systematic Review*

*S. epidermidis* strains contain known virulence-related genes that are predominate in psoriasis-affected skin. Therefore, a future study at the species and the strain

The fecal sample study by Scher et al. [23] revealed that gut microbiome in skin psoriasis and psoriatic arthritis had a decrease in alpha diversity compared to control, and *Actinobacteria* had a decrease in relative abundance at the phylum level. This is in line with Masallat et al. [24] who found that the relative abundance of *Actinobacteria* was reduced in psoriasis versus healthy controls with a negative correlation of PASI score whereas the ratio of *Firmicutes* to *Bacteroidetes* was positively correlated with PASI score. This is consistent with Codoner et al. [25] who found a lower abundance of *Bacteroides* at the genus level and characterized core microbiome of psoriasis by an increase in *Feacalibacterium* but a decrease in *Bacteroides* spp. The abundance of *Akkermansia*, *Ruminococcus*, and *Pseudobutyrivibrio* was found to be lower in psoriatic arthritis compared to controls by Scher et al. [23]. Eppinga et al. [26] found that the abundance of *Faecalibacterium prausnitzii* was reduced in psoriasis with a significant increase in the relative abundance of *Escherichia coli* (**Table 3**). The gut is considered as a major immune organ, with gut-associated lymphoid tissue (GALT) being the most complex immune compartment [30]. It is well known that change in the microbe composition may promote both health and disease [31]. Intestinal dysbiosis has been implicated in the etiology of various diseases [32], such as Crohn's disease and obesity [33, 34]. Moreover, there is strong evidence that indicates intestinal dysbiosis is clinically relevant to psoriasis [35, 36]. The importance of the gut-skin axis in the pathogenesis of psoriasis has recently been documented in humans, as well as in animal models of psoriasis [9, 37]. A study by Tan et al. identified that the signature of gut microbiota and its function are significantly altered in the gut of patients with psoriasis [28]. Intestinal and skin microbiota directly regulate imiquimod-induced skin inflammation (IISI), and emphasizes the importance of microbiota in the pathogenesis of psoriasis [38]. A study by Zákostelská et al. has shown that exposure of mice to antibiotics inhibited

To identify bacterial pathways, which may be involved in the pathogenesis of psoriasis, it should be highlighted that SCFAs potentially regulate the generation and function of Th17 cells [39]. Moreover, in psoriasis the loss or depletion of *Faecalibacterium prausnitzii*, a major source of the protective SCFAs in the gut, may be associated with disease development [26]. In psoriatic arthritis, decreased *Akkermansia* and *Ruminococcus*, which are protective bacteria that regulate the intestinal barrier that produces SCFA, may be related with disease severity. Gut dysbiosis markedly reduced butyrate production, which inhibits NF-ĸβ, an inflammation pathway that impacts gut epithelial integrity and consequential cross-talk between gut proteins, bacteria, and the innate and humoral immune systems [27]. Alterations in the pathways involved in LPS function were also observed in psoriasis patients. Additionally, LPS is also thought to be involved in gut inflammation and has been linked to the pathogenesis of insulin resistance and diabetes mellitus [40], which has been epidemiologically associated with psoriasis. A decrease in *Bacteroides*, which are known to play an immunomodulatory role in the gut through the production of polysaccharide A that induces regulatory T cells, may result in an altered immune response [41]. Whereas a decrease in *Actinobacteria*, a phylum that includes the Bifidobacterium species that have been shown to reduce intestinal inflammation, suppresses autoimmunity, and induces regulatory T cell expression. There are also several studies that have shown how bacterial translocation from the

*DOI: http://dx.doi.org/10.5772/intechopen.92686*

level may provide more information.

**2.2 Gut microbiota in psoriasis**

the induction of psoriasis [37].

*S. epidermidis* strains contain known virulence-related genes that are predominate in psoriasis-affected skin. Therefore, a future study at the species and the strain level may provide more information.
