Title : Effects of lipopolysaccharide on the maintenance of skin homeostasis and improvement of skin problems including atopic dermatitis
Abstract:
The skin is directly exposed to the environment, and its homeostasis seems to be maintained by a crosstalk between the skin resident bacteria and environmental bacteria. Kasahara et al. reported that many bacteria that are found in forests and farms live on the skin of people with good skin condition (30th IFSCC congress). Additionally, Gueniche et al. reported that a solution of Viteoscilla filiformis isolated from a hotspring is effective in improving atopic dermatitis (AD). Moreover, the balance of resident bacteria on the skin differs between patients with AD and healthy individuals. Myles et al. reported that symptoms improved when Roseomonas mucosa collected from the skin of healthy individuals was transplanted onto the skin of patients with AD.
Interestingly, although Gram-positive bacteria are overwhelmingly present as the skin resident bacteria, Gram-negative bacteria, such as Roseomonas and Viteoscilla, are effective in improving AD. Gram-negative bacteria are characterized by having lipopolysaccharides (LPS) with a strong innate immune-activating ability in the cell membrane. LPS have long been known to cause sepsis when present in the blood. However, LPS are abundant in the intestines and environment, and their effect is completely different when present in blood compared to their effect on oral and dermal ingestion. As Bufe et al. reported that the exposure of LPS during early childhood and the onset of allergy are inversely correlated, it is thought that oral and percutaneous LPS ingestion is safe and has a positive role in maintaining the homeostasis of the body.
Therefore, we randomly assigned a moisturizing cream containing Pantoea agglomerans LPS and a placebo cream to 25 patients with mild AD, and evaluated the disease transition under a double-blind protocol. Evaluation was carried out using the eczema area and severity index (EASI) score by a dermatologist and self-evaluation using the visual analog scale on itching and skin condition. As a result, no statistically significant difference was noted in the EASI score, but self-evaluation on itching and skin condition showed a statistically higher improvement rate in patients using LPS cream.
In the skin, not only typical immune cells but also keratinocytes express receptors for LPS (toll-like receptor 4). When keratinocytes were stimulated with LPS, no expression of inflammatory cytokines was noted; however, the promotion of autophagy involved in turnover, the augmentation of filaggrin, which is a barrier function protein, and the induction of β-defensin (in vivo antibacterial substance) were observed. When Langerhans cells were stimulated with LPS, no expression of inflammatory cytokines was noted; however, the expression of inflammatory chemokine thymus and activation-regulated chemokine decreased. Treg cells activated by LPS affect neutrophils, which leads to inflammation in suppressive direction. Taken together, LPS, which is a component of Gram-negative bacteria, contributes to the maintenance of the skin homeostasis, and it may be effective as a part of the routine skin care of patients with mild AD.
