Data from three randomized controlled trials included in this study showed that taking an oral probiotic can significantly improve clinical conditions. Three studies reported on inflammation-related indicators as well. Two of the studies found a decrease in IL-6 levels, and three found a reduction in CRP levels.
Clinical improvement
Clinical improvement in psoriasis patients can be measured using the PASI score. For 12 weeks, Navarro et al. (2019) found that probiotics containing a mixture of three bacterial strains (Bifidobacterium longum, Bifidobacterium lactis, and Lactobacillus rhamnosus) had a higher proportion of PASI 75 than placebo group [12]. The same thing happened in a study by Moludi with probiotics containing a mixture of four bacterial strains (Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium lactis, and Bifidobacterium langue) for 8 weeks [9, 13]. The meta-analysis of the studies that evaluated PASI 75 revealed a statistically significant value, indicating that the administration of this oral probiotic has a positive effect on patient clinical improvement.
Two studies included in the meta-analysis by Zeng et al. (2021) also demonstrated that the probiotic group developed PASI faster than the placebo group. However, the statistical results of the meta-analysis showed insignificant results [7]. A meta-analysis of probiotics in other skin diseases (in this case, atopic dermatitis), discovered that probiotics improve atopic dermatitis clinical manifestations by suppressing the Th2 and increasing the Th1 response [8, 14, 15].
Inflammatory biomarker
Inflammatory biomarkers assessed in this meta-analysis were IL-6 and CRP levels. IL-6 is a pro-inflammatory cytokine, whereas CRP is an acute phase protein produced by hepatocytes and adipocytes in response to peripheral pro-inflammatory cytokines elevation [11]. As a result, these two biomarkers are linked. Groeger et al. (2013) found that using one strain of probiotic bacteria (Bifidobacterium infantis) for 8 weeks resulted in a 34% decrease in CRP levels in the probiotic group after the intervention. There was a 2% increase in CRP levels in the placebo group. The serum levels of IL-6 in the probiotic and placebo groups decreased by 3% and 5% respectively, after the intervention [11]. Moludi et al. (2021) discovered a 1.55 mg/L decrease in CRP levels in the probiotic group (P < 0.05), compared to 0.49 mg/dL in the placebo group (P = 0.13). IL-6 levels were also reduced in the probiotic group by 4.04 mg/L (P < 0.05) and by 1.5 mg/L in the placebo group (P = 0.093) [13]. Moludi et al. (2022) found a decrease in CRP levels of 1.67 mg/L (P < 0.05) in the probiotic group and 0.70 mg/L (P = 0.111) in the placebo group [9]. Based on the findings of this meta-analysis, oral probiotics were found to be significantly more effective than placebo in lowering levels of inflammatory markers (particularly IL-6 and CRP). When IL-6 was suppressed, Th17 activity was also reduced. According to one study, probiotics increase Th1 function while decreasing Th2 and Th17 function [8]. Th17 plays a role in psoriasis exacerbations [16].
The human microbiota is a group of commensal and pathogenic living microorganisms (bacteria, viruses, fungi, or archaea) that are found in the human body. Meanwhile, the microbiome refers to the collective microbiota and their “theater of activity” which includes structural elements, metabolites, molecules, and environmental conditions. The theory suggests there are around 10–100 trillion microbiomes in the human body [17–19]. Through its interactions with the host, specifically the innate and adaptive immune systems, the microbiome plays an important role in maintaining immune homeostasis. The dysbiosis of the microbiome can disrupt communication between the microbiome and the host, resulting in an immune system imbalance [6, 20, 21].
Many studies have recently been conducted on the relationship between the gut microbiome and skin diseases. This is based on the concept of the gut-brain-skin axis, which was first proposed in 1930 by Stokes and Pillsbury but could not be adequately proven due to limitations at the time. The study concept at the time was that bacterial products could affect the pathogenesis of various skin conditions [22]. When the skin is in a state of homeostasis, it can perform its functions effectively, – such as protection, temperature regulation, water retention, and so on [23]. Many studies have now established a bidirectional link between gut microbiome dysbiosis and skin homeostasis disruptions, which lead to a variety of skin disorders [24].
The gut-skin axis describes the relationship between gut and skin conditions. Although the exact mechanism is still unknown, the immunological and endocrine systems are most likely involved [6]. Existing theory suggests that short-chain fatty acids particularly butyrate- are fermentation products derived from undigested polysaccharides by the gut microbiome (e.g., Bacteroides, Bifidobacterium, Cutibacterium, and Lactobacillus) could suppress immune responses by increasing intestinal permeability; inhibiting inflammatory cell proliferation, migration, and adhesion, and inhibiting pro-inflammatory cytokine production [16, 22–24]. According to several studies, people with chronic skin diseases have higher levels of gut bacterial DNA in their blood, which contributes to the inflammatory response. Similarly, the gut microbiota metabolites can enter the circulatory system, accumulate in the skin, and disrupt skin homeostasis. Although this has no direct effect on the immune system, it can reduce the protective barrier of the skin and make it more prone to inflammation [6, 23].
Another theory suggests that the gut microbiota also produces neurotransmitters such as norepinephrine, serotonin, and acetylcholine. This causes enteroendocrine cells to release hormones, causing systemic inflammation as well as skin damage. For example, increased serotonin levels can cause an itch-scratch response, which is associated with atopic dermatitis; and increased acetylcholine and norepinephrine levels can promote sebum production, which increases acne manifestation [6, 24].
The development of psoriasis is also thought to be linked to gut barrier disruption and dysbiosis of the gut microbiome [16, 20]. When the gut barrier is compromised, bacteria and their metabolites can move throughout the body, exacerbating systemic inflammation in psoriasis. Then, pattern recognition receptors, such as Toll-Like receptors, identify the lipopolysaccharide (LPS) that is released by gram-negative bacteria. TLRs recognize microbe components and then activate antibacterial and inflammatory innate immune responses. After TLR activation, the intracellular transcription factors (NF-κB and interferon I) as well as pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) are secreted. Furthermore, IL-1β and IL-6 stimulate Th17 cell differentiation, exacerbating the inflammatory response in psoriasis [16].
Several studies have found differences in the gut microbiome between healthy and psoriasis patients, though the findings in each study may be contradictory [20]. Most of the studies stated that Bifidobacterium performs an important role as an anti-inflammatory agent in skin diseases, including psoriasis [20]. Several studies have shown a decrease in Bacteroidetes in people with psoriasis [24–27], while others have shown an increase in Bacteroidetes in psoriatic people compared to healthy people [20]. Several studies have found that the most abundant microbiome in psoriasis is Firmicutes [24, 26, 27]. According to some studies, Akkermansia and Faecalibacterium levels are elevated in psoriasis patients [25]. However, other studies have shown that Akkermansia and Faecalibacterium are diminished in psoriasis patients [20, 28–30].
The link between gut dysbiosis and skin disease suggests that modulating the gut microbiome could be used to treat skin diseases such as psoriasis. Oral probiotic administration is one method for modulating the gut microbiome [6, 31]. Oral probiotics are living microorganisms found in supplements or specific foods that provide health benefits to the host when administered in appropriate doses. Lactobacilli and Bifidobacteria are the most commonly utilized bacteria as oral probiotics [6, 32]. Several studies [9, 11–13] have found that people who receive oral probiotic therapy have improved clinical outcomes and inflammatory biomarkers.