OBJECTIVE: To investigate the potential mechanisms of sepsis pathogenesis in intensive care unit (ICU), with a specific focus on the role of skin microbiota, and to evaluate the causal relationships between skin microbiota and ICU sepsis using Mendelian randomization (MR). METHODS: A two-sample MR analysis was performed using skin microbiota genome-wide association study (GWAS) summary data from German population cohorts as exposures, combined with ICU sepsis susceptibility and 28-day mortality GWAS summary data from the IEU OpenGWAS database as outcomes. The primary causal effect estimates were generated using the inverse variance weighted (IVW) method, supplemented by validation through MR-Egger and weighted median approaches. Heterogeneity and pleiotropy tests, along with sensitivity analyses, were conducted to evaluate the robustness of the results. RESULTS: Regarding risk of ICU sepsis, IVW analysis showed that order Pseudomonadales [odds ratio (OR) = 0.93, 95% confidence interval (95%CI) was 0.88-0.98], family Flavobacteriaceae (OR = 0.93, 95%CI was 0.90-0.96), and genus Acinetobacter (OR = 0.96, 95%CI was 0.93-0.99) were significantly negatively correlated with the risk of ICU sepsis (all P < 0.05). There was a significant positive correlation between the risk of ICU sepsis and the presence of β-Proteobacteria (OR = 1.05, 95%CI was 1.00-1.11) and Actinobacteria (OR = 1.05, 95%CI was 1.00-1.11), both P < 0.05. Regarding 28-day mortality of ICU sepsis, IVW analysis showed that phylum Bacteroidetes (OR = 0.92, 95%CI was 0.86-0.99), family Streptococcaceae (OR = 0.92, 95%CI was 0.85-0.98), family Flavobacteriaceae (OR = 0.90, 95%CI was 0.83-0.97), genus Streptococcus (OR = 0.92, 95%CI was 0.86-0.99), ASV016 [Enhydrobacter] (OR = 0.92, 95%CI was 0.87-0.98), and ASV042 [Acinetobacter] (OR = 0.92, 95%CI was 0.88-0.97) were significantly negatively correlated with the 28-day mortality of ICU sepsis (all P < 0.05); family Moraxellaceae (OR = 1.09, 95%CI was 1.00-1.18) and ASV008 [Staphylococcus] (OR = 1.08, 95%CI was 1.03-1.14) was significantly positively correlated with the 28-day mortality of ICU sepsis (both P < 0.05). Sensitivity analysis and MR-PRESSO showed no heterogeneity, pleiotropy, or horizontal pleiotropy between skin microbiota and ICU sepsis risk and 28-day mortality rate. Analysis of confounding factors showed that single nucleotide polymorphisms (SNPs) associated with relevant skin bacteria could independently and causally affect the risk of ICU sepsis or ICU sepsis related mortality rate, independent of other confounding factors. The Steiger test results indicated that the established causal relationship was not due to reverse causality. CONCLUSIONS Skin microbiota composition may influence both sepsis susceptibility and 28-day mortality in ICU settings. Family Flavobacteriaceae demonstrated protective effects against sepsis onset and mortality. These findings provide new perspectives for early detection and management strategies.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Mendelian Randomization Analysis ; Microbiota ; Skin/microbiology* ; Genome-Wide Association Study ; Risk Factors ; Skin Microbiome

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.
Humans ; Medicine, Chinese Traditional ; Gastrointestinal Tract ; Skin Diseases/drug therapy* ; Gastrointestinal Microbiome

PURPOSE: Alterations in the intestinal microbiota in early life affects the development of atopic dermatitis (AD) in humans. This study aimed to further investigate the effects of gut dysbiosis in early life in an ovalbumin (OVA)-induced mouse model of AD. METHODS: The AD mouse model was developed by serial OVA sensitization and mice were treated with an antibiotic cocktail in their drinking water for 2 weeks before primary sensitization. Probiotics (Lactobacillus rhamnosus, 1 × 10⁹ CFU) or 100 µL of fresh fecal supernatant were orally administered daily from 1 week before the first sensitization until the end of the study. RESULTS: The AD mice which received antibiotics had significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. Total systemic immunoglobulin E production and skin interleukin (IL) 4 levels were significantly increased in the antibiotic-treated mice compared to the other groups. Antibiotic treatment also increased the levels of IL17 and group 3 innate lymphoid cells (ILC3) in the gut and significantly suppressed the production of short-chain fatty acids (SCFAs) and decreased the number FOXP3⁺ cells. CONCLUSIONS: Our results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4⁺IL17⁺/CD4⁺FOXP3⁺ regulatory T cells and ILC3s.
Animals ; Anti-Bacterial Agents ; Cytokines ; Dermatitis, Atopic ; Drinking Water ; Dysbiosis ; Fatty Acids ; Fatty Acids, Volatile ; Feces ; Gastrointestinal Microbiome ; Humans ; Immunoglobulin E ; Immunoglobulins ; Interleukins ; Intestines ; Lymphocytes ; Mice ; Microbiota ; Ovalbumin ; Ovum ; Phenotype ; Probiotics ; Skin ; T-Lymphocytes, Regulatory ; Water

The commensal microbiota contributes to the maintenance of immune homeostasis in the human body. Autoimmunity can be aggravated or alleviated by the microbiota, which affects both innate and adaptive immune cells. Many studies have demonstrated the role of gut dysbiosis, the alteration of the gut microbiome, in the development and progression of numerous autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue and is characterized by skin and lung fibrosis, as well as injuries in small arteries. Recent studies have shown variable degrees of dysbiosis in SSc patients and the effect of probiotics on these patients, providing evidence for the potential link between microbiota and SSc. However, further research is needed to elucidate the key microorganisms and the mechanisms through which they affect the pathoimmunological process of SSc. This review summarizes the current knowledge regarding the association between microbiota and SSc, and discusses the changing perspectives and potential therapy strategies based on the microbiota and its products.
Arteries ; Autoimmune Diseases ; Autoimmunity ; Connective Tissue ; Dysbiosis ; Fibrosis ; Gastrointestinal Microbiome ; Homeostasis ; Human Body ; Humans ; Lung ; Microbiota ; Probiotics ; Scleroderma, Systemic ; Skin

Atopic dermatitis (AD) is a representative allergic disease that is accompanied with high disease prevalence and considerable socioeconomic burden. While the pathophysiology is largely unknown, the role of microbes in health and diseases has drawn attention. The development of metagenomics that is a recent advance in analyzing microbiome has enabled us to research how microbiome impacts the development and aggravation of AD. Skin microbiome and intestinal microbiome are assumed to affect the AD. Research has shown a difference in skin and intestinal microbial composition between AD patients and normal controls. Based on the findings of microbial impacts on the AD, efforts to use probiotics for the treatment or prevention of AD have been made. However, further research is needed until the firm conclusion is reached.
Dermatitis ; Dermatitis, Atopic* ; Gastrointestinal Microbiome ; Humans ; Metagenomics ; Microbiota* ; Prevalence ; Probiotics ; Skin

The microbiome, which has been defined as ‘the ecological community of commensal, symbiotic and pathogenic microorganisms that share our body space, may be distinguished from the microbiota as it includes the collective genomes. An increasing level of evidence reveals that the human microbiome plays a major role in health. For this reason, it is often referred to as the ‘forgotten organ.’ All surfaces of the human body that are exposed to the environment are colonized, including skin, respiratory system, urogenital tract and gastrointestinal (GI) tract, totaling at least 100 trillion microbial cells. The known roles of the GI microbiome include metabolic functions, synthesis functions, and immune roles. Recent studies indicate that the human gut microbiome plays a significant role in health and disease. Dysbiosis, defined as a pathological imbalance in a microbial community, is becoming increasingly appreciated as a ‘central environmental factor’ that is both associated with complex phenotypes and affected by host genetics, diet, and antibiotic use. More recently, a link has been established between the dysmetabolism of bile acids (BAs) in the gut and the gut-liver axis, and this relationship with the microbiome has been highlighted. This review summarizes the microbiome of the hepatobiliary system and how microbiome is related to diseases of the liver and biliary tract.
Bile Acids and Salts ; Biliary Tract ; Biota ; Colon ; Diet ; Dysbiosis ; Gallbladder ; Gastrointestinal Microbiome ; Genetics ; Genome ; Human Body ; Humans ; Liver ; Microbiota* ; Pancreas ; Phenotype ; Respiratory System ; Skin

The microbiome is vital for immune system development and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the skin and the gut have recently been linked to alterations in immune responses and to the development of skin diseases, such as atopic dermatitis (AD). In this review, we summarize the recent findings on the gut and skin microbiome, highlighting the roles of major commensals in modulating skin and systemic immunity in AD. Although our understanding of the gut-skin axis is only beginning, emerging evidence indicates that the gut and skin microbiome could be manipulated to treat AD.
Dermatitis, Atopic* ; Dysbiosis ; Gastrointestinal Microbiome ; Homeostasis ; Immune System ; Microbiota* ; Skin ; Skin Diseases

During the second half of the 2000s, the significant impact of human microbiome on human diseases and health conditions was found. Since the Human Microbiome Project, many microbiome studies have been reported in domestic and international references. Gastrointestinal tract microbiome has been most investigated so far, and the association with illness has been demonstrated in many diseases. Recently, the range of study was extended to multiple human organs, such as the respiratory tract, skin, and urogenital tract. Given the scale and speed of research and development in recent years, the role of microbiome in many diseases would be established before long. In this review, we aimed to summarize the current status of microbiome studies in Korea and foreign countries with an emphasis on respiratory tract microbiome. The main concept and analytical methods for microbiome research, associations of microbiome and diseases, and research projects on Korean microbiome are reviewed.
Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans* ; Korea* ; Metagenomics ; Microbiota* ; Pulmonary Ventilation ; Respiratory System ; Skin