Skin microbiota of first cousins affected by psoriasis and atopic dermatitis

This is the first study in which the skin microbiota of AD and psoriatic selected individuals subjected to the same lifestyle and environment factors has been compared. Indeed, we evaluated the skin microbiota of much selected subjects affected by psoriasis and AD, compared with the microbiota of a healthy related control. In particular, we analyzed samples from the area behind the left ear, evaluating the microbiota associated to this specific anatomical district. One of the main factor that seem to be involved in the development of allergic diseases is the mode of delivery; indeed, cesarean section has been observed to be associated with a moderately risk of allergic rhinitis, asthma and hospitalization for asthma [15]. One hypothesis concerns the composition of the gut microbiota, which is established early in childhood. Vaginal delivery leads to the first colonization of infant gut with maternal vaginal and fecal bacteria, while cesarean babies are deprived of this natural exposure and present a different gut microbiota [15]. The first steps of infant gut colonization play a pivotal role in normal tolerance induction, as well as in the development and homeostasis of the immune system. Therefore, cesarean delivery may lead to an increased susceptibility to atopic conditions. Interestingly, all subjects enrolled in the present study were born by vaginal delivery and no correlations with the development of AD and psoriasis can be suggested. However, significant differences have been detected in the abundance of several bacterial family in subjects enrolled in the study. Propionibacteriaceae, indeed, showed a different distribution among the three groups analyzed, as AD and healthy individuals had a larger abundance of aforementioned bacterial family and its major human species Propionibacterium acnes, if compared with the subject affected by psoriasis. P. acnes are dominant microorganisms in normal skin [16–19], and a decrease in the number of these microbes could be a reflection of disordered ecological niches that become inhospitable to these microorganisms, and probably play a pivotal role in the pathogenesis of psoriasis or could be involved in the disease worsening [17]. P. acnes could have a beneficial and protective role on the human organism, and in particular, at skin level, by mean of its immunomodulatory action in signaling human cells [18, 19]. It has been hypothesized that P. acnes could protect the human skin from the action of several pathogenic bacteria, and its decrease could lead to a reduction of the protective skin barrier [17]. However, to date it is not clear if the decrease observed in P. acnes abundance is a consequence of the inflammatory state of psoriasis, or if this reduction is involved in the pathogenesis of the aforementioned disease.

An increase in Streptococcaceae has been observed in psoriatic subject, confirming data of previous works, in which the presence of Streptococcus spp was linked to the pathogenesis of psoriasis [20, 21]. Streptococcaceae are highly relevant among the environmental factors that are involved in the development of psoriasis [21]. Different mechanisms, such as molecular mimicry, superantigens and the ability of streptococci for intracellular uptake and persistence in skin cells, may be involved in the pathogenesis of the disease. Furthermore, the skin microbiota associated to the subject with psoriasis showed a larger abundance of Rhodobacteraceae, in comparison to that of healthy and AD individual. Interestingly, a minor bacterial diversity has been observed in psoriatic sample, as Paracoccus was the predominant bacterial family detected. At the contrary, Rhodobacter and Haematobacter represented a significant part of the skin microbiota of AD and healthy subjects. Rhodobacter spp are able to produce a molecule, named lycogen, structurally similar to lycopene, which can acts as anti-inflammatory agent and as inhibitor of melanogenesis. This molecule is able to prevent the down-regulation of procollagen I and inhibit elevated production of NF?B, a transcription factor involved in cellular stress, which were elicited by UV-light exposure [22–24]. The absence of Rhodobacteraceae among the skin microbiota observed in psoriatic individual could be linked to the reduction of the physiological skin barrier integrity that is involved in the symptomatology and etiopathology of psoriasis.

Finally, our results did not underline a difference between the microbiota composition of AD individual and the healthy control, except for the higher frequency of occurrence of S. aureus in AD subject, even if a high abundance of Staphylococcaceae has been detected in both groups of individuals. Several evidences exist about the mainly role of S. aureus in the pathogenesis of AD [25–27]. In particular, the skin of AD subjects has been observed to be more frequently colonized by S. aureus if compared to that of healthy control. This microorganism is able to increase the skin inflammation by mean of specific toxins which act as superantigens and, as a consequence, they may induce monocytes and lymphocytes activation, increasing also the production of several pro-inflammatory cytokines [28, 29]. Interestingly, as the severity of AD lesions increased, also the load of S. aureus has been observed to become higher. Probably, the high abundance of S. aureus we detected in AD sample contributed to worsening the skin barrier damages, leading to the characteristic skin lesions that affected AD subject enrolled in the present study. Moreover, the pivotal role of S. aureus in AD was underlined by the low frequency of S. aureus in non-lesional skin sample of AD individual, compared to the lesional skin sample of the same subject. Interestingly, the microbiota composition of non-lesional skin belonging to AD and psoriatic individuals was very similar to the bacterial composition of sample from the healthy control. These findings suggested that the cutaneous dysbiosis we observed in psoriatic and AD subjects was directly linked to the skin damages that characterize psoriasis and AD. Moreover, bacteria belonging to Parococcus genera, which have been observed to be increased in psoriasis skin sample, seem to be involved in the formation of skin pustules and they may have a direct role in the maintenance and worsening of psoriatic skin lesions [30]. Cutaneous bacteria have already been observed to be directly involved in the pathogenesis of several skin diseases, in particular in psoriasis and AD, where patients show a significant difference between the microbiota composition of lesional skin and non-lesional skin [31]. S. aureus, for example, is thought to play a pivotal role in the pathogenesis of these diseases, being involved not only in the pathology onset, but also in its progression, leading to an exacerbation of inflammatory response [31]. Moreover, differences in bacterial composition often observed in different skin sites may be directly involved in the different severity of cutaneous lesions on specific skin areas.

Although, several contradictory data about the specific role of cutaneous microbiota exist due to different sampling techniques. Some studies analyze the microbiota composition using skin swabs, while others investigate the bacterial composition from the complete epidermis and dermis, leading to different results [31]. To date, there are no enough information about the specific role of the skin microbiota in cutaneous diseases, as it is not clear if the bacterial dysbiosis often associated to these dyseases is the leading cause or a consequence of the pathological status. Interestingly, several evidences underlined that also intestinal bacteria seem to be directly involved in the onset and in the maintenance of allergic diseases, suggesting the possibility of preventing or treating AD and psoriasis by influencing the intestinal microbiota. The gut dysbiosis, associated to disruption of intestinal barrier function, may lead to a significant increase in local and systemic inflammation that is often associated to allergic diseases [32, 33]. AD patients, in particular, showed several changes in the gut microbiota composition, as bifidobacteria were significantly lower in comparison to healthy subjects, while the number of staphylococci was significantly higher in AD individuals compared with controls. Consequently, a decrease of anti-inflammatory molecules due to the reduction of bifidobacteria and a parallel increase in pro-inflammatory molecules due to the proliferation of staphylococci in the intestinal environment, may lead to the worsening of inflammation status and symptomatology of allergic diseases [32].