Alterations of circulating free fatty acids in patients with pemphigus vulgaris

Free fatty acids (FFA) have gained research interest owing to their functions in both local and systemic immune regulation. Changes in the serum levels of anti-inflammatory short chain fatty acids (SCFA), primarily derived from the gut microbiota, and pro-inflammatory medium (MCFA) and long (LCFA) chain fatty acids, derived from either the gut microbiota or the diet, have been associated with autoimmunity. Circulating FFA were retrospectively analysed by a gas chromatography-mass spectrometry method in the serum of 18 patients with pemphigus vulgaris (PV) at the baseline and 6 months (n = 10) after immunosuppressive treatments, and 18 healthy controls (HC). Circulating FFA were correlated with the Pemphigus Disease Area Index (PDAI) and serum concentrations of interferon-gamma (IFN-γ), Interleukin (IL)-17A, IL-5, IL-10 and IL-21. Principal Component analysis computed on FFA abundances revealed significant differences in the profile of SCFA (p = 0,012), MCFA (p = 0.00015) and LCFA (p = 0,035) between PV patients and HC, which were not significantly changed by immunosuppressive treatments. PV patients showed a significantly lower serum concentration of propionic (p < 0.0005) and butyric (p < 0.0005) acids, SCFA with anti-inflammatory functions, while hexanoic (p < 0.0005) and hexadecanoic (p = 0.0006) acids, pro-inflammatory MCFA and LCFA respectively, were over-represented. Treatments induced a significant decrease of hexanoic (p = 0.035) and a further increase of hexadecanoic (p = 0.046) acids. Positive correlations emerged between IFN-γ and acetic acid (Rho = 0.60), IFN-γ and hexanoic acid (Rho = 0.46), IL-5 and both hexadecanoic acid (Rho = 0.50) and octadecanoic acid (Rho = 0.53), butyric acid and PDAI (Rho = 0.53). PV was associated with a remarked imbalance of circulating FFA compared to HC. The serum alterations of SCFA, MCFA, and LCFA may contribute to promoting inflammation in PV. Deeper insights into the immunomodulatory functions of these molecules may pave the way for personalized dietary interventions in PV patients.

[1]  Miao Yang,et al.  Alterations of fecal microbiome and metabolome in pemphigus patients. , 2023, Journal of autoimmunity.

[2]  Lina Sun,et al.  T cells in health and disease , 2023, Signal transduction and targeted therapy.

[3]  M. Manetti,et al.  The differential crosstalk of the skin-gut microbiome axis as a new emerging actor in systemic sclerosis. , 2023, Rheumatology.

[4]  Y. Zhang,et al.  Association of gut microbiome and metabolites with onset and treatment response of patients with pemphigus vulgaris , 2023, Frontiers in Immunology.

[5]  A. Romano,et al.  Microbiota Alterations in Patients with Mucous Membrane Pemphigoid and Pemphigus Vulgaris: A Systematic Review , 2023, Applied Sciences.

[6]  A. Mosig,et al.  Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections , 2023, Open Biology.

[7]  Shukla Das,et al.  A Snapshot of T Cell Subset Cytokines in Pemphigus Vulgaris: A Cross-Sectional Study , 2022, Cureus.

[8]  A. Amedei,et al.  Crohn’s disease recurrence updates: first surgery vs. surgical relapse patients display different profiles of ileal microbiota and systemic microbial-associated inflammatory factors , 2022, Frontiers in Immunology.

[9]  K. Valeš,et al.  Metabolomics of Cerebrospinal Fluid in Multiple Sclerosis Compared With Healthy Controls: A Pilot Study , 2022, Frontiers in Neurology.

[10]  M. Agostini,et al.  A method for assessing plasma free fatty acids from C2 to C18 and its application for the early detection of colorectal cancer. , 2022, Journal of Pharmaceutical and Biomedical Analysis.

[11]  H. Kaneto,et al.  Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation , 2022, International journal of molecular sciences.

[12]  R. Berni Canani,et al.  Potential Clinical Applications of the Postbiotic Butyrate in Human Skin Diseases , 2022, Molecules.

[13]  Cen Guo,et al.  Gut-brain axis: Focus on gut metabolites short-chain fatty acids , 2022, World journal of clinical cases.

[14]  Enno Schmidt,et al.  Mucous membrane pemphigoid. , 2022, Autoimmunity reviews.

[15]  S. Shetty,et al.  Effect of medium chain fatty acid in human health and disease , 2021, Journal of Functional Foods.

[16]  R. Eming,et al.  Human desmocollin 3-specific IgG antibodies are pathogenic in a humanized HLA-class II transgenic mouse model of pemphigus. , 2021, The Journal of investigative dermatology.

[17]  Yi Qiu,et al.  Effects of short-chain fatty acids in inhibiting HDAC and activating p38 MAPK are critical for promoting B10 cell generation and function , 2021, Cell Death & Disease.

[18]  G. Wallace,et al.  Behçet’s Disease—Do Microbiomes and Genetics Collaborate in Pathogenesis? , 2021, Frontiers in Immunology.

[19]  A. Oturai,et al.  Serum Short-Chain Fatty Acids and Associations With Inflammation in Newly Diagnosed Patients With Multiple Sclerosis and Healthy Controls , 2021, Frontiers in Immunology.

[20]  Chang H. Kim.  Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids , 2021, Cellular & Molecular Immunology.

[21]  N. Gasaly,et al.  Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases , 2021, International journal of molecular sciences.

[22]  F. Stingo,et al.  Free Fatty Acids Signature in Human Intestinal Disorders: Significant Association between Butyric Acid and Celiac Disease , 2021, Nutrients.

[23]  R. Bergman,et al.  Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV) , 2020, Journal of the European Academy of Dermatology and Venereology : JEADV.

[24]  S. Turroni,et al.  Alterations in Circulating Fatty Acid Are Associated With Gut Microbiota Dysbiosis and Inflammation in Multiple Sclerosis , 2020, Frontiers in Immunology.

[25]  E. Elinav,et al.  Interaction between microbiota and immunity in health and disease , 2020, Cell Research.

[26]  A. Amedei,et al.  Not just 'immunity': how the microbiota can reshape our approach to cancer immunotherapy. , 2020, Immunotherapy.

[27]  D. Calina,et al.  Targeted Metabolomic Analysis of Serum Fatty Acids for the Prediction of Autoimmune Diseases , 2019, Front. Mol. Biosci..

[28]  Karolina Bajdak-Rusinek,et al.  The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms , 2019, Inflammation Research.

[29]  X. Xiong,et al.  The imbalance of gut microbiota and its correlation with plasma inflammatory cytokines in pemphigus vulgaris patients , 2019, Scandinavian journal of immunology.

[30]  R. Eming,et al.  Pemphigus: Current and Future Therapeutic Strategies , 2019, Front. Immunol..

[31]  A. Amedei,et al.  I’ve Gut A Feeling: Microbiota Impacting the Conceptual and Experimental Perspectives of Personalized Medicine , 2018, International journal of molecular sciences.

[32]  A. Sinha,et al.  Autoantibody Signaling in Pemphigus Vulgaris: Development of an Integrated Model , 2018, Front. Immunol..

[33]  M. Blüher,et al.  Free fatty acids sensitize dendritic cells to amplify TH1/TH17‐immune responses , 2016, European journal of immunology.

[34]  Y. Bhutia,et al.  Short, but Smart: SCFAs Train T Cells in the Gut to Fight Autoimmunity in the Brain. , 2015, Immunity.

[35]  R. Gold,et al.  Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. , 2015, Immunity.

[36]  Z. Ruan,et al.  Stearic acid induces proinflammatory cytokine production partly through activation of lactate-HIF1α pathway in chondrocytes , 2015, Scientific Reports.

[37]  G. Dryden,et al.  Relationship between gut microbiota and development of T cell associated disease , 2014, FEBS letters.

[38]  A. Jehle,et al.  Free Fatty Acids and Their Metabolism Affect Function and Survival of Podocytes , 2014, Front. Endocrinol..

[39]  A. Rudensky,et al.  Metabolites produced by commensal bacteria promote peripheral regulatory T cell generation , 2013, Nature.

[40]  Jie Zheng,et al.  The imbalance of Th17 and regulatory T cells in pemphigus patients. , 2013, European journal of dermatology : EJD.

[41]  C. Sadasivan,et al.  Anti‐Inflammatory Property of n‐Hexadecanoic Acid: Structural Evidence and Kinetic Assessment , 2012, Chemical biology & drug design.

[42]  H. Ashrafian,et al.  Understanding the role of gut microbiome-host metabolic signal disruption in health and disease. , 2011, Trends in microbiology.

[43]  M. Veldhoen,et al.  Th17 T cells: linking innate and adaptive immunity. , 2007, Seminars in immunology.