**2.2 Gut microbiota in psoriasis**

*Human Microbiome*

**Phylum level**

**Genus level**

**72**

**Table 2.**

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

Increased *S. aureus,* decreased *P. acne* Gao et al. [19]

**Finding By** Alpha diversity Increased Gao et al. [19], Chang et al. [14]

*Firmicutes* Increased *Firmicutes* Gao et al. [19], Fahlen et al. [18],

*Actinobacteria* Decreased *Actinobacteria* Gao et al. [19], Fahlen et al. [18],

*Streptococcus* Increased *Streptococcus* Gao et al. [19], Fahlen et al. [18],

*Staphylococcus* Increased *Staphylococcus* Gao et al. [19], Tett et al. [16]

*Propionibacterium* Lower *Propionibacterium* Gao et al. [19], Fahlen et al. [18],

No correlation Loeshe et al. [12]

Decreased *Staphylococcus* Fahlen et al. [18]

Beta diversity Lower Fahlen et al. [18]

*Proteobacteria* Decreased *Proteobacteria* Gao et al. [19]

Gram positives Increased relative abundance of combined

*Streptococcus*

disease

*Summary of skin microbiota findings in psoriasis.*

Gram positives: *Corynebacterium*, *Propionibacterium*, *Staphylococcus*, and

*Corynebacterium* and *Staphylococcus* were significantly correlated with PASI scores

Site-specific microbiota without related

Decreased Fahlen et al. [18], Alexseyenko et al.

Highe Alexseyenko et al. [17], Tett et al. [16],

Decreased *Firmicutes* Loeshe et al. [12], Assarsson et al.

Increased *Proteobacteria* Fahlen et al. [18], Drago et al. [15]

Increased *Firmicutes* and *Actinobacteria* Alexseyenko et al. [17]

[17], Tett et al. [16]

Langan et al. [10]

Langan et al. [10]

[13], Drago et al. [15]

Loeshe et al. [12], Chang et al. [14]

Alexseyenko et al. [17], Stehlikova et al. [11], Drago et al. [15]

Drago et al. [15], Stehlikova et al.

[11], Loeshe et al. [12]

Alexseyenko et al. [17]

Langan et al. [10]

Tett et al. [16]

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 the induction of psoriasis [37].

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


**75**

**2.3 Skin mycobiota**

*Gut microbiota in patients with psoriasis.*

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

**ratings of the quality**

gut and skin into the bloodstream may take place in psoriasis, and be responsible for

**Population Result**

Case control/4 45Pso 45C ↑*Firmicutes/Bacteroidetes* ratio

At the phylum level: **↓***Firmicutes, Clostridiales, Verrucomicrobiales* ↑ *Bacteroidetes in* PsA vs. Pso **↓***Actinobacteria* in Pso vs. C At the genus level:

vs. C

Pso vs. C

correlated with PASI **↓***Actinobacteria*

**↓***Coprococcus* spp. in Pso and PsA

**↓***Akkermansia, Ruminococcus, Pseudobutyrivibrio* in PsA vs. C **↓***Parabacteroides, Coprobacillus* in

Cross-sectional/4 15Pso, 16PsA 17C Diversity: Pso, PsA < C

An investigation by Findley et al. suggests that fungal diversity is increased in psoriatic lesions, compared to healthy skin sites. Furthermore the skin of psoriatic patients, at the genus level, is dominant with Malassezia [43]. Whereas the study by Takemoto et al. found that psoriatic skin revealed higher diversity and decreased relative abundance of Malassezia, which is still the most abundant phylum compared to controls. Moreover, the ratio of *M. globosa* to *M. restricta* is lower in psoriatic lesions [44]. Stehlikova et al. [11] found no significant difference in alpha and beta diversity and a significant increase in abundance of *M. restricta* in back lesions and *M. sympodialis* in the elbow lesions. Conversely, however, Paulino et al. showed that psoriatic lesions on the back, in decreasing order of abundance, are predominated by *M. restricta*, followed by *M. globosa* and *M. sympodialis*, respectively. Paulino et al. concluded that there was no significant difference between the fungal compositions of psoriatic and healthy skin [45]. Furthermore, Paulino et al. also showed there was no consistent variation between psoriasis and healthy controls [46] as *M. furfur* was found only in the skin of psoriasis participants in the study by

driving the chronic, systemic inflammatory nature of the disease [42].

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

Jagielski et al. [47] compared to healthy controls and atopic dermatitis.

comparisons and results in incompatible outcomes (**Table 4**).

So far, no specific patterns of microbiota in psoriatic patients have been identi-

The difficulty to establish such precise features, although a plethora of published studies have attempted to do so, is due to the lack of standardized protocols. Differences in sample collection and processing, sequencing methods, and analysis procedures between studies may impact the study results [48], and can confound

**2.4 Factors affecting microbiota study**

fied (**Tables 1** and **3**).

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

**Study Study design/**

Scher et al. [23] (2015)

Masallat et al. [24] (2016)

**Table 3.**


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

#### **Table 3.**

*Human Microbiome*

Shapiro et al. [27] (2019)

Tan et al. [28] (2018)

Codoner et al. [25] (2018) Remark: study did not include healthy control

Chen et al. [29] (2018)

**Study Study design/**

**ratings of the quality**

**Population Result**

Cross-sectional/4 24 Pso 22 C Alpha diversity, beta diversity: no

Cross-sectional/4 14 Pso 14C Pso L

Cross-sectional/4 52Pso compared with

Patients receiving systemic treatment (DMARDs or biologics drugs BioSysDrug) subgroup analyses /2

project

a cohort of over 300 healthy individuals extracted from the human microbiome

Cross-sectional/4 32Pso 64 C Diversity: no significant difference

significant differences At the phylum level: ↑*Firmicutes,* 

↓*Bacteroidetes, Proteobacteria* At the species level:

↑*Ruminococcus gnavus, Doreaformici generans* and *Collinsella aerofaciens, Prevotella copri* and *Parabacteroides* 

*Actinobacteria*

*distasonis*

*citroniae*

*Faecalibacterium*

between Pso and C

**↓***Bacteroidetes*

*Megasphaera*

*Lachnospiraceae*

among Pso and C

receiving BioSysDrug

20 Pso **↓**the species *Prevotella stercorea*,

Enterotype 2 (predominance of *Prevotella*) tended to experience more frequent bacterial translocation and higher inflammatory status **↓***Bacteroides*, ↑*Akkermansia*,

At the phylum level: ↑*Firmicutes*,

At the genus level: ↑ *Ruminococcus,* 

At the family level: **↓***Bacteroidaceae, Prevotellaceae* ↑ *Ruminococcaceae,* 

Other covariates: sex, disease activity assessed by PASI score, phototherapy, arthritis, as well as diet, alcohol, smoking, coffee, tea, and habit of exercise, did not significantly affect the abundance profile of intestinal microbiota

belonging to *Prevotellaceae*, of the phylum *Bacteroidetes*, in patients

Pso: ↑Beta diversity

At the phylum level: **↓***Verrucomicrobia, Tenericutes* At the class level: **↓***Mollicutes,* 

*Verrucomicrobiae* At the order level: **↓***Verrucomicrobiales*, RF39 At the family level: **↓***Verrucomicrobiaceae*, S24–7 At the genus level: ↑*Bacteroidaceae*, *Enterococcaceae*, **↓***Akkermansia* At the species level: **↓***Akkermansia muciniphila*, ↑*Clostridium* 

**74**

*Gut microbiota in patients with psoriasis.*

gut and skin into the bloodstream may take place in psoriasis, and be responsible for driving the chronic, systemic inflammatory nature of the disease [42].

#### **2.3 Skin mycobiota**

An investigation by Findley et al. suggests that fungal diversity is increased in psoriatic lesions, compared to healthy skin sites. Furthermore the skin of psoriatic patients, at the genus level, is dominant with Malassezia [43]. Whereas the study by Takemoto et al. found that psoriatic skin revealed higher diversity and decreased relative abundance of Malassezia, which is still the most abundant phylum compared to controls. Moreover, the ratio of *M. globosa* to *M. restricta* is lower in psoriatic lesions [44]. Stehlikova et al. [11] found no significant difference in alpha and beta diversity and a significant increase in abundance of *M. restricta* in back lesions and *M. sympodialis* in the elbow lesions. Conversely, however, Paulino et al. showed that psoriatic lesions on the back, in decreasing order of abundance, are predominated by *M. restricta*, followed by *M. globosa* and *M. sympodialis*, respectively. Paulino et al. concluded that there was no significant difference between the fungal compositions of psoriatic and healthy skin [45]. Furthermore, Paulino et al. also showed there was no consistent variation between psoriasis and healthy controls [46] as *M. furfur* was found only in the skin of psoriasis participants in the study by Jagielski et al. [47] compared to healthy controls and atopic dermatitis.

#### **2.4 Factors affecting microbiota study**

So far, no specific patterns of microbiota in psoriatic patients have been identified (**Tables 1** and **3**).

The difficulty to establish such precise features, although a plethora of published studies have attempted to do so, is due to the lack of standardized protocols. Differences in sample collection and processing, sequencing methods, and analysis procedures between studies may impact the study results [48], and can confound comparisons and results in incompatible outcomes (**Table 4**).


**Table 4.**

*Summary of gut microbiota findings in psoriasis.*

Different factors that may affect microbiome study


Sequencing methods, analysis procedures, and techniques for studying the microbiome:

	- Several studies suggested that primers for V1V3 and V3V4 hypervariable regions were described to sufficiently cover the skin bacterial diversity [20].

**77**

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

V3V4 region compared to the V1V2 region [11].

○ Statnikov et al. concluded that using 16S rRNA data from the V3–V5 locus leads to accurate and statistically significant molecular signatures, whereas

○ The latter study by Stehlikova et al. observed that variable regions of the V3V4 region capture a wider microbial diversity than the V1V2 region, where observed and estimated richness was significantly higher when using the

• Whole-genome shotgun metagenomics offers the most comprehensive and robust data; however, as a result of its high cost, only a few shotgun metagenomic studies have been conducted on the microbiota associated with the skin, such as the Human Microbiome Project [54]. We found very few studies on

Several studies reveal that psoriasis treatment changes the gut and skin micro-

biome, such as the correlation between psoriasis systemic treatment and the *Actinobacteria*-to-*Firmicutes* ratio. Biological therapies demonstrated the largest impact [10] during ustekinumab treatment; the composition of microbiota diverged further between lesional and non-lesional skin, across body sites, which could be due to the regression of lesions that returns the skin to more normal environments and increases the body site-specific niches [12]. Secukinumab (anti-IL17) therapy is associated with distinct and more profound gut microbiome shifts than ustekinumab therapy (anti-IL 12/23), in patients with psoriasis by increasing the relative abundance of *Proteobacteria* and decreases in *Bacteroidetes* and *Firmicutes* [55]. Burns et al. demonstrates that UVR has profound qualitative and quantitative influences on the composition of the skin microbiome by an increase in the phylum Cyanobacteria and a decrease in the family Lactobacillaceae and Pseudomonadaceae [56]. This suggests that skin microbiome alterations after UVB treatment could be related to treatment and treatment responses [13]. Thus, it may be implied that the

modulation of the gut and skin microbiota can improve disease condition.

The use of orally administered antibiotics, prebiotics, probiotics, and most recently, fecal transplantation [57] also appears to improve the disease condition

significant improvement at 12 weeks in the patient with psoriasis [60].

• Pro- and prebiotics are commonly used to modulate the microbiome by promoting the growth of specific species. Three studies using three distinct probiotic species affecting distinct pathways of the pathomechanism of psoriasis [61, 62] have all shown improvement in the course of the disease. The probiotics resulted in the improvement of epithelial barrier function, increased production of TNF-alpha by epithelial cells, and regulated activation of the NF-ĸβ pathway [63]. An issue with probiotic supplementation is

• Antibiotic treatment of psoriasis can alter the bowel flora toward normality, and therapy might include the use of appropriate antibiotics to reduce susceptible microbes while permitting others to flourish [58]. Saxena and Dogra reported that administration of benzathine penicillin in psoriasis vulgaris patients showed a significant improvement [59] and administration of azithromycin revealed a

Therapeutic modalities that target the shifting microbiota:

and may be a practical prospect as a therapeutic avenue.

data from the V1–V3 locus carry a limited diagnostic signal [53].

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

psoriasis microbiome.

**2.5 Therapeutic implements**

