Balanoposthitis is a common inflammatory skin disease that mostly affects uncircumcised males. The diagnostic criteria for this relatively common condition, remain vague and depend mainly on clinical manifestations and exclusion of overt infection, along with specific inflammatory and neoplastic skin diseases. The main purpose of histopathological examination is to confirm the special type of balanoposthitis such as circinate balanitis and plasma cell balanitis, and to exclude pre-malignant conditions. When accompanied by persistent erythematous lesions involving the balanopreputial sac in uncircumcised patients, infiltration of lymphocytes, histiocytes, and plasma cells can be seen in upper part of the chorion.
The cutaneous microbiome can be influenced by physio-barrier integrity, inflammation, antimicrobial peptides, and even lipids, as reported in atopic dermatitis[16, 17]. The thin epithelium of prepuce and glans penis have similarities to other parts of the skin, except that there was no hair follicle or eccrine sweat gland exist on glans penis, penis crown, and preputial mucosa. The BP enrolled in the present study showed a higher rate of the redundant prepuce (26 cases but 1), higher incidences of STIs, and tended to use condom during sexual behavior. Indeed, bacteria enriched in BP were influenced by these factors, like Genus Phyllobacterium, Prevotella bivia, and Staphylococcus warneri.
In the present study, we profile the bacterial diversity and richness in BP by using a high throughput 16 s rRNA sequencing and to compare the physio-barrier status between BP and HC and score their inflammation severity by designing a scoring algorithm for balanoposthitis. To the best of our knowledge, this is the first report to assess the skin microbiome as related to balanoposthitis and skin physical barrier in the glans penis.
In regard to physio-barrier status, we found that both BP and HCRP similarly had increased TEWL and skin hydration, which maintained a higher level of water content and exudation compared to HCNP. The high pH value, as well as a higher level of water content in BP, may favor the growth of certain bacteria, like that of the optimal pH of 7.5 for Staphylococcus aureus. It has been reported that cutaneous pH is influenced by filaggrin degradation, fatty acid content, sodium-hydrogen exchanger (NHE1) activation, melanosome release. In the present study, we found that there was no difference in pH between healthy subjects with normal or redundant prepuce.
We could not find significant difference in Alpha or Beta diversity between BP and HC, in general. We confirmed the previous finding that there was a significant difference in Beta diversity between HCNP and HCRP, suggesting that the prepuce could not be a neglected niche for local anatomical environment. Noting that there was a significant difference in Beta diversity between BP and HCRP, we postulate that inflammatory status is more prevailing to determine the Beta diversity. Specifically, we found the observed species decreased with higher severity scores of BP, similar findings were reported in atopic dermatitis that Eczema Area and Severity Index negatively correlated with the observed species.
By LEfSe analysis, we found that Staphylococcus warneri and Prevotella bivia were two balanoposthitis-associated species, which were more abundant in patients with more disease severity. Staphylococcus warneri is a coagulase-negative pathogen capable of producing several virulent factors, such that factors with ability to adhere and invade human epithelial cells, to form biofilm via ica-independent mechanisms, and to destroy cells by extracellular toxins. Moreover, Staphylococcus warneri has been shown to be involved in spontaneous abortion in cattle and humans. Whether BP was associated with spontaneous abortion is an interesting topic to investigate. Prevotella bivia was reported as a cause of bacterial vaginosis, through its capacity to alter barrier properties and induction of epithelial cell activation in the vagina. We postulated that Prevotella bivia is pathogenic to BP. As Genus Prevotella could be found in the urethra and bladder, retrogradation of Prevotella bivia in BP could not be ignored.