*2.2.1 Probiotics in the treatment of skin and oral mucosa dysbiosis*

The skin represents another system where an immense variegation of microbiota environment can be found. Skin diseases caused by disturbances at the level of local microbiota that also showed to have strict connection with gut dysbiosis are quite exhaustive in explaining these malevolence patterns. Psoriatic lesions show a very specific histopathological conformation which present highly infiltrated immune cells like the CD3<sup>+</sup> T cells and dendritic cells (DCs). Psoriasis showed to have a genetic family trait prevalent in twins; researchers have spotted 36 genetic loci associated with PS susceptibility 1 (*PSORS1*) locus on chromosome 6p21.3 [82, 83]. Data confirmed that most of them are directly involved in the overexpression of those genes that regulate part of pro-inflammatory innate immune responses such as the NFkB activation and interleukin (IL)-23 signaling pathway. Intriguingly a 2018 study performed on mice proved the use of two specific probiotic *Lactobacillus* strains, the *L*. *salivarius* L305 and *L. rhamnosus* L307, in alleviating the clinical symptoms of psoriasis through inhibiting the aggressive effect of pro-inflammatory cytokines and interleukins like TNF-α, IL-1β, IL-6, IL-17, and IL-22 and promoting the anti-inflammatory/modulatory activity of IL-4 and IL-10 [84].

In oral dysbiosis, we are facing a similar inflammatory arrangement; oral diseases manifest with high-grade inflammatory patterns that spread from the gums to the adjacent structures gradually destroying the supporting tissues of the teeth, both ligaments and alveolar bones, causing early loss. Similarly to psoriasis in periodontitis, we may encounter multifactorial condition due to a combination of genetic variants triggered by the initial subgingival dysbiosis and then become highly susceptible to wider disease progression [85].

The gram-negative bacteria such as *Porphyromonas gingivalis*, *Tannerella forsythia*, and *Aggregatibacter actinomycetemcomitans* are be able to migrate into the system either down to the heart, lungs, and sex apparatus or are capable to enter into the brain via the bloodstream or via infected periodontal sites. Histopathological analysis has confirmed these bacteria almost everywhere in atheromatous plaques, the vagina, amniotic fluid, rheumatoid arthritis bioptic samples, and brain plaques typical of neurodegenerative diseases AD, PD, and MS [86–90].

As can be seen from published studies, different strains of probiotics have been used for the treatment of periodontitis. *Lactobacillus* strains are the commonest used in the majority of high-grade inflammatory disease. The use of *L. salivarius* in combination with *L. rhamnosus* and *B. subtilis* together with *L. reuteri* and *L. brevis* probiotics has shown the most promising results. High-positive results were also obtained by Laleman and colleagues in using *Streptococcus oralis* KJ3, *Streptococcus uberis* KJ2, and *Streptococcus ratti* JH145 [91, 92].

Therefore an associated altered gut microbiota may lead to chronic gut dysbiosis and propagation of systemic injuries that involve cells, tissues, system, and the intrinsic dysfunction of the regenerative mechanism.
