{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T01:11:39Z","timestamp":1780708299072,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Emerging research underscores the substantial link between gut flora and various inflammatory skin diseases. We hypothesize that there exists a complex gut\u2013skin axis, possibly affecting the progression of conditions such as eczema, acne, psoriasis, and rosacea. However, the precise nature of the causal connection between gut flora and skin diseases remains unestablished. In this study, we started by compiling summary data from genome-wide association studies (GWAS) featuring 211 unique gut microbiota and four types of skin conditions. We scrutinized these data across different taxonomic strata. Subsequently, we leveraged Mendelian randomization (MR) to ascertain if there is a causal link between gut microbiota and these skin conditions. We also performed a bidirectional MR analysis to identify the causality\u2019s direction. By utilizing Mendelian randomization, we identified 26 causal connections between the gut microbiome and four recognized inflammatory skin conditions, including 9 positive and 17 negative causal directions. Additional sensitivity analyses of these results revealed no evidence of pleiotropy or heterogeneity. Our MR analysis suggests a causal connection between gut microbiota and skin diseases, potentially providing groundbreaking perspectives for future mechanistic and clinical studies on microbiota-affected skin conditions.<\/jats:p>","DOI":"10.3390\/microorganisms11102586","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T05:43:28Z","timestamp":1697694208000},"page":"2586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Exploring the Association between Gut Microbiota and Inflammatory Skin Diseases: A Two-Sample Mendelian Randomization Analysis"],"prefix":"10.3390","volume":"11","author":[{"given":"Junhao","family":"Long","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglan","family":"Gu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Child Health, Department of Nephrology, Children\u2019s Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juexi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, Central China Normal University, Wuhan 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1001\/jamadermatol.2016.5538","article-title":"Global Skin Disease Morbidity and Mortality: An Update from the Global Burden of Disease Study 2013","volume":"153","author":"Karimkhani","year":"2017","journal-title":"JAMA Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Salem, I., Ramser, A., Isham, N., and Ghannoum, M.A. (2018). The Gut Microbiome as a Major Regulator of the Gut-Skin Axis. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01459"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2096995","DOI":"10.1080\/19490976.2022.2096995","article-title":"Impact of gut microbiome on skin health: Gut-skin axis observed through the lenses of therapeutics and skin diseases","volume":"14","author":"Mahmud","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1136\/gut.52.10.1442","article-title":"Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E1 and E2 production by intestinal myofibroblasts","volume":"52","author":"Willemsen","year":"2003","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Samuelson, D.R., Welsh, D.A., and Shellito, J.E. (2015). Regulation of lung immunity and host defense by the intestinal microbiota. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.01085"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s40257-019-00467-1","article-title":"The Microbiome and Atopic Dermatitis: A Review","volume":"20","author":"Pothmann","year":"2019","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lee, Y.B., Byun, E.J., and Kim, H.S. (2019). Potential Role of the Microbiome in Acne: A Comprehensive Review. J. Clin. Med., 8.","DOI":"10.3390\/jcm8070987"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s13671-017-0178-5","article-title":"The Role of the Skin and Gut Microbiome in Psoriatic Disease","volume":"6","author":"Yan","year":"2017","journal-title":"Curr. Dermatol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.jfma.2020.04.034","article-title":"An altered fecal microbial profiling in rosacea patients compared to matched controls","volume":"120","author":"Chen","year":"2020","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1093\/rheumatology\/keaa506","article-title":"Circulating adiponectin levels and systemic lupus erythematosus: A two-sample Mendelian randomization study","volume":"60","author":"Dan","year":"2020","journal-title":"Rheumatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41588-020-00763-1","article-title":"Large-scale association analyses identify host factors influencing human gut microbiome composition","volume":"53","author":"Kurilshikov","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian Randomization Analysis with Multiple Genetic Variants Using Summarized Data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet. Epidemiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1002\/sim.6835","article-title":"Combining information on multiple instrumental variables in Mendelian randomization: Comparison of allele score and summarized data methods","volume":"35","author":"Burgess","year":"2016","journal-title":"Stat. Med."},{"key":"ref_18","first-page":"67","article-title":"Using Mendelian randomisation to assess causality in observational studies","volume":"22","author":"Pagoni","year":"2019","journal-title":"BMJ Ment. Health"},{"key":"ref_19","first-page":"2681","article-title":"Invited Commentary: Detecting Individual and Global Horizontal Pleiotropy in Mendelian Randomization\u2014A Job for the Humble Heterogeneity Statistic?","volume":"187","author":"Bowden","year":"2018","journal-title":"Am. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.3389\/fimmu.2018.01905","article-title":"Lactobacillus sakei WIKIM30 Ameliorates Atopic Dermatitis-Like Skin Lesions by Inducing Regulatory T Cells and Altering Gut Microbiota Structure in Mice","volume":"9","author":"Kwon","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1099\/ijs.0.2008\/000810-0","article-title":"Dialister succinatiphilus sp. nov. and Barnesiella intestinihominis sp. nov., isolated from human faeces","volume":"58","author":"Morotomi","year":"2008","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"660","DOI":"10.5551\/jat.RV17006","article-title":"Are Short Chain Fatty Acids in Gut Microbiota Defensive Players for Inflammation and Atherosclerosis?","volume":"24","author":"Ohira","year":"2017","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7437","DOI":"10.1007\/s00253-020-10749-y","article-title":"Lactobacillus salivarius LI01 encapsulated in alginate-pectin microgels ameliorates d-galactosamine-induced acute liver injury in rats","volume":"104","author":"Zhuge","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, M., Yang, L., Zhao, L., Bai, F., and Liu, X. (2022). Comparison of Intestinal Microbes in Noninfectious Anterior Scleritis Patients with and Without Rheumatoid Arthritis. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.925929"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1757-4749-3-1","article-title":"Acne vulgaris, probiotics and the gut-brain-skin axis-back to the future?","volume":"3","author":"Bowe","year":"2011","journal-title":"Gut Pathog."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1007\/s13555-021-00552-6","article-title":"Updated Treatment for Acne: Targeted Therapy Based on Pathogenesis","volume":"11","author":"Kurokawa","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_28","first-page":"371","article-title":"Concentration of selected cytokines in serum of patients with acne rosacea","volume":"65","author":"Salamon","year":"2008","journal-title":"Przegl. Lek."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1848158","DOI":"10.1080\/19490976.2020.1848158","article-title":"Gut Bacteroides species in health and disease","volume":"13","author":"Zafar","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1046\/j.1365-2249.2002.01921.x","article-title":"Nuclear factor-kappa B activation pathway in intestinal epithelial cells is a major regulator of chemokine gene expression and neutrophil migration induced by Bacteroides fragilis enterotoxin","volume":"130","author":"Kim","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1097\/MIB.0000000000000972","article-title":"A Single Species of Clostridium Subcluster XIVa Decreased in Ulcerative Colitis Patients","volume":"22","author":"Takeshita","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/j.1365-2133.2009.09420.x","article-title":"Interleukin-10 secretion from CD14+ peripheral blood mononuclear cells is downregulated in patients with acne vulgaris","volume":"162","author":"Caillon","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3920\/BM2016.0089","article-title":"Supplementation with Lactobacillus rhamnosus SP1 normalises skin expression of genes implicated in insulin signalling and improves adult acne","volume":"7","author":"Fabbrocini","year":"2016","journal-title":"Benef. Microbes"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sikora, M., Stec, A., Chrabaszcz, M., Knot, A., Waskiel-Burnat, A., Rakowska, A., Olszewska, M., and Rudnicka, L. (2020). Gut Microbiome in Psoriasis: An Updated Review. Pathogens, 9.","DOI":"10.3390\/pathogens9060463"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1111\/exd.13786","article-title":"Intestinal microbiota profiling and predicted metabolic dysregulation in psoriasis patients","volume":"27","author":"Chen","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1005115","DOI":"10.3389\/fimmu.2022.1005115","article-title":"The imbalance between Type 17 T-cells and regulatory immune cell subsets in psoriasis vulgaris","volume":"13","author":"Kim","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, F., Liu, Q., Wu, H., Tang, T., Zhao, T., and Li, Z. (2022). The dysbiosis gut microbiota induces the alternation of metabolism and imbalance of Th17\/Treg in OSA patients. Arch. Microbiol., 204.","DOI":"10.1007\/s00203-022-02825-w"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1111\/j.1365-2672.2007.03322.x","article-title":"Understanding the effects of diet on bacterial metabolism in the large intestine","volume":"102","author":"Louis","year":"2007","journal-title":"J. Appl. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1073\/pnas.1322269111","article-title":"The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition","volume":"111","author":"Chang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jid.2020.04.031","article-title":"Induction of Regulatory T Cells and Correction of Cytokine Disbalance by Short-Chain Fatty Acids: Implications for Psoriasis Therapy","volume":"141","author":"Schwarz","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1038\/ismej.2014.63","article-title":"Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men","volume":"8","author":"Salonen","year":"2014","journal-title":"ISME J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chiodini, R.J., Dowd, S.E., Chamberlin, W.M., Galandiuk, S., Davis, B., and Glassing, A. (2015). Microbial Population Differentials between Mucosal and Submucosal Intestinal Tissues in Advanced Crohn\u2019s Disease of the Ileum. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134382"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jaad.2017.07.055","article-title":"Evidence-based update on rosacea comorbidities and their common physiologic pathways","volume":"78","author":"Holmes","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"746923","DOI":"10.3389\/fphar.2021.746923","article-title":"An Integrated Gut Microbiota and Network Pharmacology Study on Fuzi-Lizhong Pill for Treating Diarrhea-Predominant Irritable Bowel Syndrome","volume":"12","author":"Zhen","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/exd.13143","article-title":"Integrative concepts of rosacea pathophysiology, clinical presentation and new therapeutics","volume":"26","author":"Holmes","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13545","DOI":"10.1038\/s41598-023-40549-z","article-title":"A comparative study using response surface methodology and artificial neural network towards optimized production of melanin by Aureobasidium pullulans AKW","volume":"13","author":"Saber","year":"2023","journal-title":"Sci. Rep."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/10\/2586\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:09:35Z","timestamp":1760130575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/10\/2586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,19]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["microorganisms11102586"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11102586","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,19]]}}}