Unique Gut Microbiome Signatures among Adult Patients with Moderate to Severe Atopic Dermatitis in Southern Chinese.

Imbalance of the immune system caused by alterations of the gut microbiome is considered to be a critical factor in the pathogenesis of infant eczema, but the exact role of the gut microbiome in adult atopic dermatitis (AD) patients remains to be clarified. To investigate the differences of the gut microbiome between adult AD patients and healthy individuals, stool samples of 234 adults, containing 104 AD patients and 130 healthy subjects, were collected for 16S rRNA gene amplicon. Altered structure and metabolic dysfunctions of the gut microbiome were identified in adult AD patients. Our results illustrated that the adult AD patients were more likely to have allergies, particularly non-food allergies. In addition, the gut microbiome composition of the AD and normal groups were considerably different. Moreover, Romboutsia and Clostridi-um_sensu_stricto_1 was enriched in the normal group, whereas Blautia, Butyricicoccus, Lachnoclostridium, Eubacterium_hallii_group, Erysi-pelatoclostridium, Megasphaera, Oscillibacter, and Flavonifractor dominated in the AD group. Additionally, purine nucleotide degradation pathways were significantly enriched in the AD group, and the enrichment of proteinogenic amino acid biosynthesis pathways was found in the normal group. This study provides insights into new therapeutic strategies targeting the gut microbiome for AD and evidence for the involvement of the gut-skin axis in AD patients.

A Novel E3 Probiotics Formula Restored Gut Dysbiosis and Remodelled Gut Microbial Network and Microbiome Dysbiosis Index (MDI) in Southern Chinese Adult Psoriasis Patients.

Psoriasis is a common chronic immune-mediated inflammatory skin disease with the association of various comorbidities. Despite the introduction of highly effective biologic therapies over the past few decades, the exact trigger for an immune reaction in psoriasis is unclear. With the majority of immune cells residing in the gut, the effect of gut microbiome dysbiosis goes beyond the gastrointestinal site and may exacerbate inflammation and regulate the immune system elsewhere, including but not limited to the skin via the gut-skin axis. In order to delineate the role of the gut microbiome in Southern Chinese psoriasis patients, we performed targeted 16S rRNA sequencing and comprehensive bioinformatic analysis to compare the gut microbiome profile of 58 psoriasis patients against 49 healthy local subjects presumably with similar lifestyles. Blautia wexlerae and Parabacteroides distasonis were found to be enriched in psoriasis patients and in some of the healthy subjects, respectively. Metabolic functional pathways were predicted to be differentially abundant, with a clear shift toward SCFA synthesis in healthy subjects. The alteration of the co-occurrence network was also evident in the psoriasis group. In addition, we also profiled the gut microbiome in 52 of the 58 recruited psoriasis patients after taking 8 weeks of an orally administrated novel E3 probiotics formula (with prebiotics, probiotics and postbiotics). The Dermatological Life Quality Index (p = 0.009) and Psoriasis Area and Severity Index (p < 0.001) were significantly improved after taking 8 weeks of probiotics with no adverse effect observed. We showed that probiotics could at least partly restore gut dysbiosis via the modulation of the gut microbiome. Here, we also report the potential application of a machine learning-derived gut dysbiosis index based on a quantitative PCR panel (AUC = 0.88) to monitor gut dysbiosis in psoriasis patients. To sum up, our study suggests the gut microbial landscape differed in psoriasis patients at the genera, species, functional and network levels. Additionally, the dysbiosis index could be a cost-effective and rapid tool to monitor probiotics use in psoriasis patients.

Baicalin ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice through modulating skin barrier function, gut microbiota and JAK/STAT pathway.

Baicalin has distinct therapeutic effects in various skin diseases animal models such as atopic dermatitis (AD) and psoriasis. In this study, we aimed to investigate the anti-atopic dermatitis (AD) effects of baicalin in 2,4-dinitrochlorobenzene (DNCB)-treated mice. Female BALB/c mice treated with DNCB to induce AD-like skin lesions and orally administrated with baicalin daily for 14 consecutive days. Baicalin significantly inhibited dorsal skin thickness and trans-epidermal water loss and epidermal thickness in dorsal skin. In addition, baicalin also significantly up-regulated the protein expressions of filaggrin, involucrin, and loricrin, but inhibited the inflammatory response and the activation of NF-κB and JAK/STAT pathways in the dorsal skin of the DNCB-treated mice. Furthermore, baicalin significantly restored the abundance of probiotics in the gut microbiota of the DNCB-treated mice. Pseudo germ-free (GF) DNCB-treated mice receiving fecal microbiota from baicalin donors reduced the dorsal skin thickness and skin EASI score, and inhibited the release of IgE, histamine, TNF-α and IL-4 in serum of mice. In summary, baicalin ameliorates AD-like skin lesions induced by DNCB in mice via regulation of the Th1/Th2 balance, improvement of skin barrier function and modulation of gut dysbiosis, and inhibition of inflammation through suppressing the activation of NF-κB and JAK/STAT pathways.

A Novel Multi-Strain E3 Probiotic Formula Improved the Gastrointestinal Symptoms and Quality of Life in Chinese Psoriasis Patients.

Psoriasis is a chronic immune-mediated inflammatory disease affecting the skin and other systems. Gastrointestinal disease was found to be correlated with psoriasis in previous studies and it can significantly affect the quality of life of psoriasis patients. Despite the importance of the gut microbiome in gut and skin health having already been demonstrated in many research studies, the potential effect of probiotics on GI comorbidities in psoriasis patients is unclear. To investigate the effects of probiotics on functional GI comorbidities including irritable bowel syndrome, functional constipation, and functional diarrhea in psoriasis patients, we conducted a targeted 16S rRNA sequencing and comprehensive bioinformatic analysis among southern Chinese patients to compare the gut microbiome profiles of 45 psoriasis patients over an 8-week course of novel oral probiotics. All the participants were stratified into responders and non-responders according to their improvement in GI comorbidities, which were based on their Bristol Stool Form Scale (BSFS) scores after intervention. The Dermatological Life Quality Index (DLQI) score revealed a significant improvement in quality of life within the responder group (DLQI: mean 10.4 at week 0 vs. mean 15.9 at week 8, p = 0.0366). The proportion of psoriasis patients without GI comorbidity manifestation at week 8 was significantly higher than that at week 0 (week 0: Normal 53.33%, Constipation/Diarrhea 46.67%; week 8: Normal 75.56%, Constipation/Diarrhea 24.44%, p = 0.0467). In addition, a significant difference in the gut microbiome composition between the responders and non-responders was observed according to alpha and beta diversities. Differential abundance analysis revealed that the psoriasis patients exhibited (1) an elevated relative abundance of Lactobacillus acidophilus, Parabacteroides distasonis, and Ruminococcus bromii and (2) a reduced relative abundance of Oscillibacter, Bacteroides vulgatus, Escherichia sp., and Biophila wadsworthia after the 8-week intervention. The responders also exhibited a higher relative abundance of Fusicatenibacter saccharivorans when compared to the non-responders. In summary, our study discovers the potential clinical improvement effects of the novel probiotic formula in improving GI comorbidities and quality of life in psoriasis patients. We also revealed the different gut microbiome composition as well as the gut microbial signatures in the patients who responded to probiotics. These findings could provide insight into the use of probiotics in the management of psoriasis symptoms.

Improvements in Gut Microbiome Composition Predict the Clinical Efficacy of a Novel Synbiotics Formula in Children with Mild to Moderate Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a significant association with various type-2 inflammation-related comorbidities. Ongoing research suggests the crucial involvement of gut microbiome, especially in childhood onset AD, and hence, probiotics have emerged as a potential non-steroid-based therapeutics option to complement existing AD management plans. In order to delineate the impact of probiotics in the gut microbiome of pediatric AD patients from southern China, targeted 16S rRNA sequencing and thorough bioinformatic analysis were performed to analyze the gut microbiome profiles of 24 AD children after taking an orally administered novel synbiotics formula with triple prebiotics for 8 weeks. A notable improvement in Eczema Area and Severity Index (EASI) (p = 0.008) was observed after taking an 8-week course of probiotics, with no adverse effects observed. The relative abundances of key microbial drivers including Bacteroides fragilis and Lactobacillus acidophilus were significantly increased at week 8. We also found that the positive responsiveness towards an 8-week course of probiotics was associated with improvements in the gut microbiome profile with a higher relative abundance of probiotic species. Over-represented functional abundance pathways related to vitamin B synthesis and peptidoglycan recycling may imply the underlying mechanism. In summary, our study suggests how the gut microbial landscape shifts upon probiotic supplementation in AD children, and provides preliminary evidence to support targeted probiotic supplementation for the management of childhood AD.

Novel Multi-Strain E3 Probiotic Formulation Improved Mental Health Symptoms and Sleep Quality in Hong Kong Chinese.

Mental health issues have emerged as a significant concern in public health, given their association with physical and psychological comorbidities and the resultant socioeconomic burdens. Recent studies have highlighted the interplay between gut microbes and brain functions through the gut-brain axis. To investigate this further, we conducted a targeted 16S rRNA sequencing and comprehensive bioinformatic analysis among Southern Chinese individuals to explore the role of the gut microbiome in depression, anxiety, and sleep disturbance. We analyzed the differences in the gut microbiome profile of 68 participants with sleep disturbance and mood symptoms before and after an 8-week course of a novel oral E3 multi-strain probiotics formula. The results revealed a significant improvement in subjective sleep quality (PSQI: mean 8.79 at baseline vs. 7.10 at week 8, p < 0.001), depressive symptoms (PHQ9: mean 6.17 at baseline vs. 4.76 at week 8, p < 0.001), and anxious symptoms (GAD7: mean 4.90 at baseline vs. 3.76 at week 8, p < 0.001). Additionally, there were notable differences in beta diversity (weighted UniFrac; p = 0.045) and increased Firmicutes/Bacteroidetes (F/B) ratio (p = 4 × 10-4) were observed in the gut microbiome analysis. Furthermore, the relative abundance of Bifidobacterium bifidum (p < 0.001), Lactobacillus acidophilus (p < 0.001), Lactobacillus helveticus (p < 0.001) and Lactobacillus plantarum (p < 0.001) were significantly increased after the 8-week probiotic supplementation. Our study suggests that the gut microbial landscape varies between responders and non-responders at multiple levels, including genera, species, functional, and network interaction. Notably, the use of probiotics in populations with depressive or anxious symptoms and poor sleeping quality remodeled the gut microbiome and demonstrated improved mood and sleep quality.

Pimecrolimus for the Treatment of Atopic Dermatitis in Infants: An Asian Perspective.

Atopic dermatitis (AD) is a common chronic, multisystem inflammatory skin disease in pediatric patients. There has been an increase in the incidence of AD in the pediatric population of the Asia-Pacific region. Studies have shown that genetic, epigenetic, environmental and cultural factors may lead to differences in the clinical manifestation and prevalence of AD between races. Early treatment of AD is necessary to prevent the atopic march leading to comorbidities such as asthma and allergic rhinitis. Topical corticosteroids (TCS) are used as first-line therapy for the treatment of AD, but their long-term usage poses a risk to the patient's health. Pimecrolimus (1%) is a topical calcineurin inhibitor (TCI) that is indicated for the treatment of mild to moderate AD. Pimecrolimus has no apparent increase in adverse events compared to TCS, and it causes less of a burning sensation than tacrolimus. The safety and efficacy of pimecrolimus has been established through various clinical trials; yet, in many Asian countries, the use of pimecrolimus in infants is still restricted due to safety concerns. Based on the available evidence, the expert panel recommends pimecrolimus in infants between 3 months and 2 years of age in the Asian population.

Anti-atopic dermatitis effect of a modified Huang-Lian-Jie-Du decoction and its active fraction on 2,4-dinitrobenzene and MC903-induced mouse models.

BACKGROUND: Huang-Lian-Jie-Du Decoction is a traditional Chinese medicine formula which has long been used to treat inflammatory skin disease including AD. However, Gardeniae Fructus, a component herb of HLJDD, has noticeable toxicity in liver and kidney. We therefore replaced Gardeniae Fructus with Dictamni Cortex with a hope to derive at a modified HLJDD (MHLJDD) with better safety profile. PURPOSE: The present study aimed to develop MHLJDD and identify its active fraction as innovative therapeutic agents for AD using 2,4-dinitrobenzene (DNCB) and calcipotriol (MC903)-sensitized mouse models of AD. METHODS: MHLJDD and the combination of the 1-butanol-soluble-fraction and the water-soluble-fraction (MHLJDD-F) were given intragastrically to the DNCB-induced mice and MC903-induced mice for two weeks. The body weight, dorsal skin/ear thickness and severity of AD symptoms of the mice were measured throughout the study. Scratching behaviors were observed after drug treatment. The blood and dorsal skin/ear tissues of mice were harvested for histopathological examination and biochemical analyses. RESULTS: The results revealed that DNCB- and MC903-induced AD symptoms, including skin thickening, dryness, erythema and excoriations, in the dorsal skin and ears were significantly alleviated in the MHLJDD and MHLJDD-F-treated mice. Ceramides content and protein expressions of filaggrin and loricrin were also up-regulated after treatment with MHLJDD and MHLJDD-F. In addition, skin inflammation induced by DNCB and MC903 were markedly suppressed in the MHLJDD and MHLJDD-F-treated mice, and the action mechanisms involve suppression of the release of inflammatory cytokines, as well as downregulation of the activation of NF-κB and MAPKs pathways. Besides, MHLJDD and MHLJDD-F could reverse the abundance of gut microbiota induced by DNCB in mice. CONCLUSIONS: MHLJDD and MHLJDD-F could markedly relieve AD-like symptoms induced by DNCB and MC903 in mice through, at least in part, improving the epidermal barrier function and inhibiting skin inflammation via suppressing the activation of NF-κB and MAPKs pathways and regulation of the gut microflora dysbiosis. This study reported for the first time that MHLJDD and its active fraction could be used as innovative therapeutic agents for AD.

Efficacy and safety of modified Xiao-Feng Powder in the treatment of chronic urticaria: protocol of a randomized double-blind placebo-controlled study.

BACKGROUND: Chronic Urticaria (CU), a common skin disorder known as Yin Zhen in Chinese medicine, is characterized by recurrent, pruritic, pink-to-red edematous lesions and wheals on the skin. Xiao-Feng Powder (XFP, meaning Wind-Dispersing Powder), is reported to be one of the most frequently used Chinese herbal formulae for CU. In this study, we aim to investigate the effectiveness and safety of modified Xiao-Feng Powder (mXFP) for the treatment of CU. METHODS: In this randomised double-blind placebo-controlled clinical trial, 58 subjects identified as having mild to severe urticaria (Urticaria activity score greater than 10) will be recruited and randomised into two groups to receive antihistamine Bilastine with either mXFP or placebo for 12 weeks, followed by post treatment visits at week 16. The primary outcome measure is the change of weekly urticaria activity score (UAS7) at week 12. Secondary outcome measures include the Urticaria Control Test (UCT), Visual Analog Scale of Itch Severity (VAS), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), Angioedema Activity Score (AAS), immunoglobulin E (IgE) test, gut microbiota test and use of antihistamines during study period. The trial will be conducted at three Chinese medicine clinics in Hong Kong. EXPECTED OUTCOMES: The results of this study will establish robust clinical evidence about the efficacy and safety of mXFP in the treatment of CU. A specific feature of this trial is that it is a integrative medicine trial with subjects being allowed to take the Western and Chinese medicine together for the treatment. Trial registration This is registered on ClinicalTrials.gov, ID: NCT04967092. Register date: July 19, 2021. https://clinicaltrials.gov/ct2/show/NCT04967092 .

Effect of a Novel E3 Probiotics Formula on the Gut Microbiome in Atopic Dermatitis Patients: A Pilot Study.

Atopic dermatitis (AD) has been shown to be closely related to gut dysbiosis mediated through the gut−skin axis, and thus the gut microbiome has recently been explored as a potential therapeutic target for the treatment of AD. Contrasting and varying efficacy have been reported since then. In order to investigate the determining factor of probiotics responsiveness in individuals with AD, we initiated the analysis of 41 AD patients with varying disease severity in Hong Kong, whereas the severity was assessed by Eczema Area and Severity Index (EASI) by board certified dermatologist. 16S rRNA sequencing on the fecal samples from AD patients were performed to obtain the metagenomics profile at baseline and after 8 weeks of oral administration of a novel E3 probiotics formula (including prebiotics, probiotics and postbiotics). While EASI of the participants were significantly lower after the probiotics treatment (p < 0.001, paired Wilcoxon signed rank), subjects with mild AD were found to be more likely to respond to the probiotics treatment. Species richness among responders regardless of disease severity were significantly increased (p < 0.001, paired Wilcoxon signed rank). Responders exhibited (1) elevated relative abundance of Clostridium, Fecalibacterium, Lactobacillus, Romboutsia, and Streptococcus, (2) reduced relative abundance of Collinsella, Bifidobacterium, Fusicatenibacter, and Escherichia-Shigella amid orally-intake probiotics identified using the machine learning algorithm and (3) gut microbiome composition and structure resembling healthy subjects after probiotics treatment. Here, we presented the gut microbiome dynamics in AD patients after the administration of the E3 probiotics formula and delineated the unique gut microbiome signatures in individuals with AD who were responding to the probiotics. These findings could guide the future development of probiotics use for AD management.

Efficacy and action mechanisms of a Chinese herbal formula on experimental models of atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a skin inflammatory disease characterized by erythema, eruption, lichenification and pruritus. Shi Zhen Formula (SZF), an empirical Chinese herbal preparation, has clinical efficacy in relieving the symptoms of AD patients. However, the underlying molecular mechanisms of SZF remained unclear. AIM OF THE STUDY: We aimed to investigate the anti-AD effects of SZF and elucidate its underlying molecular mechanisms using in vitro and in vivo models of AD. MATERIALS AND METHODS: High-performance liquid chromatography analysis was performed for quality control of SZF extract. The anti-inflammatory effect of SZF was investigated through evaluating the levels of nitric oxide (NO), chemokines and pro-inflammatory cytokines in the lipopolysaccharide (LPS) stimulated RAW264.7 cells. AD-like skin lesions in female BALB/c mice were induced by 2,4-dinitrochlorobenzene (DNCB). SZF (3.15, 6.30 and 9.45 g/kg) and dexamethasone (5 mg/kg) were administered by gavage daily for 15 consecutive days. The body weight, skin thickness, skin dermatitis severity and scratching behaviors were recorded throughout the study. Histological analysis, reverse transcription-quantitative polymerase chain reaction (RT-PCR), western blot (WB) and ELISA analysis were used to illuminate the molecular targets associated with the anti-AD effects of SZF. RESULTS: SZF markedly decreased the epidermal thickening and infiltration of mast cells in the ears and dorsal skin of the 2,4-dinitrochlorobenzene (DNCB)-treated mice. SZF not only suppressed the levels of immunoglobulin E (IgE), histamine, thymic stromal lymphopoietin (TSLP) and IL-4 in the serum but also suppressed the over-production of IL-4 and IL-6 and gene expressions of IL-4, IL-13, IL-31 and TSLP in the dorsal skin. Moreover, SZF improved epidermal barrier by increasing the protein expressions of filaggrin, involucrin and loricrin and inhibited the activation of NF-κB p65 pathway in the dorsal skin of the DNCB-treated mice. CONCLUSION: SZF alleviates DNCB induced AD-like skin lesions in mice through regulating Th1/Th2 balance, improving epidermal barrier and inhibiting skin inflammation. Our research findings provide scientific footing on the use of this Chinese herbal formula for the treatment of AD.

Kawasaki disease in siblings and a review of drug treatment.

We have managed two anonymized siblings with Kawasaki disease (KD). The occurrence of KD in the elder brother alerted us to the occurrence of incomplete KD in the younger brother. Both siblings were treated with intravenous immunoglobulin and a high dose of dipyridamole with resolution of the coronary artery aneurysm. Dipyridamole was used instead of aspirin because both siblings were glucose-6-phosphate dehydrogenase deficient for which aspirin was contraindicated. To prevent damage to the coronary arteries, treatment should be started as soon as the diagnosis is made. There have been a lot of advances in medical therapy in recent years, which are reviewed together with conventional proven therapy for KD. Early diagnosis and prompt treatment are important to achieve optimal treatment outcome in KD. Family history of KD among siblings enables clinicians for an earlier diagnosis so as to prevent the disease complications particularly in patients with incomplete features.

Warts (non-genital).

INTRODUCTION: Warts are caused by the human papillomavirus (HPV), of which there are over 100 types. HPV probably infects the skin via areas of minimal trauma. Risk factors include use of communal showers, occupational handling of meat, and immunosuppression. In immunocompetent people, warts are harmless and resolve as a result of natural immunity within months or years. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for warts (non-genital)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 17 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic, review we present information relating to the effectiveness and safety of the following interventions: intralesional bleomycin; intralesional candida antigen; contact immunotherapy; cryotherapy; duct tape occlusion; photodynamic treatment; pulsed dye laser; surgical procedures; and topical salicylic acid.

Warts (non-genital).

INTRODUCTION: Warts are caused by the human papillomavirus (HPV), of which there are over 100 types, which probably infects the skin via areas of minimal trauma. Risk factors include use of communal showers, occupational handling of meat, and immunosuppression. In immunocompetent people, warts are harmless and resolve as a result of natural immunity within months or years. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for warts (non-genital)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic, review we present information relating to the effectiveness and safety of the following interventions: intralesional bleomycin; cimetidine; contact immunotherapy; cryotherapy; duct tape occlusion; formaldehyde, glutaraldehyde; homeopathy; photodynamic treatment; pulsed dye laser; surgical procedures; topical salicylic acid; and zinc sulphate.