(1) Background: Chronic spontaneous urticaria (CSU) has been linked to the dysbiosis of the gut microbiota. Furthermore, various studies have highlighted the anti-inflammatory properties of short-chain fatty acids (SCFAs), whose production is primarily regulated by the gut microbiota. However, only a few studies have investigated the role of major SCFA producers, such as Lachnospiraceae, in skin inflammatory diseases. (2) Goal: This study aimed to compare the abundance of Lachnospiraceae between CSU patients and healthy controls (HCs). (3) Material and methods: In this case–control study, 16S rRNA sequencing was performed to compare the composition of the gut microbiome between 22 CSU patients and 23 HCs. (4) Results: Beta-diversity revealed significant clustering (p < 0.05) between the CSU patients and HCs. Alpha diversity in the CSU group was significantly decreased according to the Evenness index (p < 0.05). The linear discriminant analysis effect size (LEfSe) identified the significant depletion of the Lachnospiraceae family in CSU patients. (5) Conclusion: Our study revealed the dysbiosis of the gut microbiota in CSU patients, including decreased levels of Lachnospiraceae members, responsible for SCFA production, suggesting that SCFAs may contribute to immune dysfunction in the pathogenesis of CSU. We speculate that the modulation of SCFAs could serve as a prospective additional option in CSU treatment.

Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2–3% of the world’s population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity. The objective of this clinical study was to investigate the effect of GLP-1 receptor agonist semaglutide therapy on pro-inflammatory factors in the serum and the severity of the clinical picture of psoriasis in obese patients with type 2 diabetes mellitus (T2DM) on chronic metformin therapy. This randomized clinical study was conducted on 31 psoriatic patients with T2DM that were randomized into two groups: one that received semaglutide during the 12-week trial (n = 15), while the second was control (n = 16). The results demonstrated that the severity of the clinical picture of psoriasis, determined by the Psoriasis Area and Severity Index (PASI) score, was significantly better after the administration of semaglutide (the median baseline PASI score in patients treated with semaglutide was 21 (IQR = 19.8), while after 12 weeks of therapy the score was 10 (IQR = 6; p = 0.002). Also, the quality of life in the group of patients who received the drug, measured by the Dermatology Life Quality Index (DLQI), improved significantly after 3 months (a median baseline DLQI score in the semaglutide group was 14 (IQR = 5) at the beginning of the study, and after 12 weeks of treatment the median DLQI score was 4 (IQR = 4; p = 0.002)). The use of semaglutide led to a significant decrease in pro-inflammatory cytokines in the serum (IL6), as well as a significant decrease in CRP values (p < 0.05). A significant decrease in the body mass index (BMI) value in the semaglutide-treated group was also identified, as well as a significant decrease in the level of low-density cholesterol (LDL) (p < 0.05). In conclusion, semaglutide, based on its systemic anti-inflammatory characteristics, could contribute to the treatment of psoriatic obese patients with T2DM.