sechenovSechenov Medical JournalСеченовский вестник2218-73322658-3348Сеченовский Университет10.47093/2218-7332.2024.15.1.4-19sechenov-1051Research ArticleCELL BIOLOGY, CYTOLOGY, HISTOLOGYКЛЕТОЧНАЯ БИОЛОГИЯ, ЦИТОЛОГИЯ, ГИСТОЛОГИЯProspects for microbiome modulation in autoimmune diseases: a literature reviewПерспективы модуляции микробиома при аутоиммунных заболеваниях: обзор литературыhttps://orcid.org/0000-0001-9429-6997ПешковаМ. А.PeshkovaM. A.

Пешкова Мария Алексеевна*, младший научный сотрудник Научного центра мирового уровня «Цифровой биодизайн и персонализированное здравоохранение»

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119048

Maria A. Peshkova, Researcher, World-Class Research Center «Digital Biodesign and Personalized Healthcare»

8/2, Trubetskaya str., Moscow, 119048

peshkova_m_a@staff.sechenov.ruhttps://orcid.org/0000-0002-9522-1142КорнеевА. А.KorneevA. A.

Корнеев Александр Александрович, лаборант Лаборатории синтеза полимеров медицинского назначения Института регенеративной медицины Научно-технологического парка биомедицины

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119048

Alexander A. Korneev, Laboratory technician, Laboratory of the Polymers Synthesis for Medical Applications, Institute for Regenerative Medicine of Biomedical Science & Technology Park

8/2, Trubetskaya str., Moscow, 119048

https://orcid.org/0000-0001-9428-8487КотеневаП. И.KotenevaP. I.

Котенева Полина Игоревна, лаборант Дизайн-центра «Биофабрика» Института регенеративной медицины Научно-технологического парка биомедицины 

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119048

Polina I. Koteneva, Laboratory technician, Design center «Biofactory», Institute for Regenerative Medicine of Biomedical Science & Technology Park

8/2, Trubetskaya str., Moscow, 119048

https://orcid.org/0000-0002-2665-4972КошелеваН. В.KoshelevaN.  V.

Кошелева Настасья Владимировна, канд. биол. наук, доцент, заведующая лабораторией клинических смартнанотехнологий Института регенеративной медицины Научно-технологического парка биомедицины

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119048

Nastasia V. Kosheleva, Cand. of Sci. (Biology), Associate Professor, Head of Laboratory of Clinical Smart Nanotechnologies, Institute for Regenerative Medicine of Biomedical Science & Technology Park

8/2, Trubetskaya str., Moscow, 119048

https://orcid.org/0000-0001-7773-2435ТимашевП. С.TimashevP. S.

Тимашев Петр Сергеевич, д-р хим. наук, профессор Научного центра мирового уровня «Цифровой биодизайн и персонализированное здравоохранение», научный руководитель Научно-технологического парка биомедицины; старший научный сотрудник химического факультета

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119048

Ленинские горы, д. 1, стр. 3, г. Москва, 119991

Peter S. Timashev, Dr. of Sci. (Chemistry), Professor, WorldClass Research Center «Digital Biodesign and Personalized Healthcare», Scientifi c Supervisor of Biomedical Science & Technology Park); Senior researcher, Chemistry Department

8/2, Trubetskaya str., Moscow, 119048

1/3, Leninskie Gory, Moscow, 119991

 

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России» (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian FederationФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России» (Сеченовский Университет); ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»РоссияSechenov First Moscow State Medical University (Sechenov University); Lomonosov Moscow State UniversityRussian Federation2024190420241514–19Copyright © Peshkova M.A., Korneev A.A., Koteneva P.I., Kosheleva N.V., Timashev P.S., 20242024Пешкова М.А., Корнеев А.А., Котенева П.И., Кошелева Н.В., Тимашев П.С.Peshkova M.A., Korneev A.A., Koteneva P.I., Kosheleva N.V., Timashev P.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sechenovmedj.com/jour/article/view/1051

Autoimmune diseases are characterized by dysregulation of immune responses and damage to healthy body tissues. Their complete cure remains elusive, and existing therapies are often accompanied by side effects. Recent studies have shown a signifi cant role of disturbances in the composition of the microbiome in the development of autoimmune reactions. Moreover, modulation of the microbiome through various therapeutic interventions represents a promising direction in the framework of complex therapy of the underlying disease. Extracellular vesicles, in particular exosomes, transport biologically active substances between cells, and a number of studies have shown their therapeutic effect in autoimmune diseases. However, the role of extracellular vesicles in modulating the microbiome remains poorly understood, and further research is needed to better understand their impact on the pathogenesis of autoimmune diseases and associated microbiome changes, as well as to develop new treatment strategies. The presented literature review, based on a study of English-language sources, examines the importance of the microbiota of different loci of the human body (intestines, skin, oral cavity) in the development of autoimmune diseases such as multiple sclerosis, psoriasis and Sjögren’s disease. The role of extracellular vesicles in modulating the microbiome during autoimmune diseases therapy is discussed.

Аутоиммунные заболевания (АИЗ) характеризуются дисрегуляцией иммунных реакций и поражением здоровых тканей организма. Их полное излечение остается труднодостижимым, а существующие методы терапии часто сопровождаются побочными эффектами. Последние исследования показали значимую роль нарушений состава микробиома в развитии аутоиммунных реакций; более того, модуляция микробиома посредством различных терапевтических вмешательств представляет собой перспективное направление в рамках комплексной терапии основного заболевания. Внеклеточные везикулы, в частности экзосомы, переносят биологически активные вещества между клетками, и в ряде работ был показан их лечебный эффект при АИЗ. Однако роль внеклеточных везикул в модуляции микробиома остается недостаточно изученной, поэтому для более глубокого понимания их влияния на патогенез АИЗ и связанных с ним изменений микробиома, а также для разработки новых стратегий лечения необходимы дальнейшие исследования. В представленном обзоре литературы на основании изучения англоязычных источников рассматривается значение микробиоты разных локусов организма человека (кишечника, кожи, ротовой полости) в развитии таких АИЗ, как рассеянный склероз, псориаз, болезнь Шёгрена. Обсуждается роль внеклеточных везикул в модуляции микробиома при терапии АИЗ.

экзосомымикробиота кишечникамикробиота кожимикробиота ротовой полостирассеянный склерозпсориазболезнь Шёгренаexosomesintestinal microbiotaskin microbiotaoral microbiotamultiple sclerosispsoriasisSjogren’s diseaseРабота выполнена при финансовой поддержке Министерства науки и высшего образования Российской Федерации в рамках Соглашения о предоставлении из федерального бюджета грантов в форме субсидий в соответствии с пунктом 4 статьи 78.1 Бюджетного кодекса Российской Федерации на обеспечение проведения научных исследований российскими научными организациями и (или) образовательными организациями высшего образования совместно с иностранными организациями научных исследований в рамках обеспечения реализации программы двух- и многостороннего научно-технологического взаимодействия № 075–15-2021–951 от 28 сентября 2021 г.The study was fi nancially supported by the Ministry of Science and Higher Education of the Russian Federation, under the Agreement on granting from the federal budget in the form of subsidies in accordance with paragraph 4 of Article 78.1 of the Budget Code of the Russian Federation to ensure the conduct of scientifi c research by Russian research organizations and (or) Educational organizations of higher education together with foreign research organizations in the framework of ensuring the implementation of the program of bilateral and multilateral scientifi c and technological cooperation No. 075–15-2021–951 dated September 28, 2021.ReferencesGuo H., Li L., Liu B., et al. Inappropriate treatment response to DMARDs: A pathway to diffi cult-to-treat rheumatoid arthritis. Int Immunopharmacol. 2023 Sep; 122: 110655. https://doi.org/10.1016/J.INTIMP.2023.110655. Epub 2023 Jul 21. PMID: 37481847Guo H., Li L., Liu B., et al. Inappropriate treatment response to DMARDs: A pathway to diffi cult-to-treat rheumatoid arthritis. Int Immunopharmacol. 2023 Sep; 122: 110655. https://doi.org/10.1016/J.INTIMP.2023.110655. Epub 2023 Jul 21. PMID: 37481847Laigle L., Chadli L., Moingeon P. Biomarker-driven development of new therapies for autoimmune diseases: current status and future promises. Expert Rev Clin Immunol. 2023 Mar; 19(3): 305–314. https://doi.org/10.1080/1744666X.2023.2172404. Epub 2023 Jan 27. PMID: 36680799Laigle L., Chadli L., Moingeon P. Biomarker-driven development of new therapies for autoimmune diseases: current status and future promises. Expert Rev Clin Immunol. 2023 Mar; 19(3): 305–314. https://doi.org/10.1080/1744666X.2023.2172404. Epub 2023 Jan 27. PMID: 36680799Vangoitsenhoven R., Cresci G.A.M. Role of microbiome and antibiotics in autoimmune diseases. Nutr Clin Pract. 2020 Jun; 35(3): 406–416. https://doi.org/10.1002/NCP.10489. Epub 2020 Apr 22. PMID: 32319703Vangoitsenhoven R., Cresci G.A.M. Role of microbiome and antibiotics in autoimmune diseases. Nutr Clin Pract. 2020 Jun; 35(3): 406–416. https://doi.org/10.1002/NCP.10489. Epub 2020 Apr 22. PMID: 32319703Rosser E.C., Mauri C. A clinical update on the signifi cance of the gut microbiota in systemic autoimmunity. J Autoimmun. 2016 Nov; 74: 85–93. https://doi.org/10.1016/J.JAUT.2016.06.009. Epub 2016 Jul 29. PMID: 27481556Rosser E.C., Mauri C. A clinical update on the signifi cance of the gut microbiota in systemic autoimmunity. J Autoimmun. 2016 Nov; 74: 85–93. https://doi.org/10.1016/J.JAUT.2016.06.009. Epub 2016 Jul 29. PMID: 27481556López P., De Paz B., Rodríguez-Carrio J., et al. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep. 2016 Apr 5; 6: 24072. https://doi.org/10.1038/SREP24072. PMID: 27044888; PMCID: PMC4820712López P., De Paz B., Rodríguez-Carrio J., et al. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep. 2016 Apr 5; 6: 24072. https://doi.org/10.1038/SREP24072. PMID: 27044888; PMCID: PMC4820712Needell J.C., Zipris D. The role of the intestinal microbiome in type 1 diabetes pathogenesis. Curr Diab Rep. 2016 Oct; 16(10): 89. https://doi.org/10.1007/S11892-016-0781-Z. PMID: 27523648Needell J.C., Zipris D. The role of the intestinal microbiome in type 1 diabetes pathogenesis. Curr Diab Rep. 2016 Oct; 16(10): 89. https://doi.org/10.1007/S11892-016-0781-Z. PMID: 27523648Jangi S., Gandhi R., Cox L.M., et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016 Jun 28; 7: 12015. https://doi.org/10.1038/NCOMMS12015. PMID: 27352007; PMCID: PMC4931233Jangi S., Gandhi R., Cox L.M., et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016 Jun 28; 7: 12015. https://doi.org/10.1038/NCOMMS12015. PMID: 27352007; PMCID: PMC4931233Chen J., Wright K., Davis J.M., et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 2016 Apr 21; 8(1): 43. https://doi.org/10.1186/S13073-016-0299-7. PMID: 27102666; PMCID: PMC4840970Chen J., Wright K., Davis J.M., et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 2016 Apr 21; 8(1): 43. https://doi.org/10.1186/S13073-016-0299-7. PMID: 27102666; PMCID: PMC4840970Coit P., Sawalha A.H. The human microbiome in rheumatic autoimmune diseases: A comprehensive review. Clin Immunol. 2016 Sep; 170: 70–79. https://doi.org/10.1016/J.CLIM.2016.07.026. Epub 2016 Aug 2. PMID: 27493014Coit P., Sawalha A.H. The human microbiome in rheumatic autoimmune diseases: A comprehensive review. Clin Immunol. 2016 Sep; 170: 70–79. https://doi.org/10.1016/J.CLIM.2016.07.026. Epub 2016 Aug 2. PMID: 27493014Wang W.M., Jin H.Z. Skin microbiome: an actor in the pathogenesis of psoriasis. Chin Med J (Engl). 2018 Jan 5; 131(1): 95–98. https://doi.org/10.4103/0366-6999.221269. PMID: 29271387; PMCID: PMC5754965Wang W.M., Jin H.Z. Skin microbiome: an actor in the pathogenesis of psoriasis. Chin Med J (Engl). 2018 Jan 5; 131(1): 95–98. https://doi.org/10.4103/0366-6999.221269. PMID: 29271387; PMCID: PMC5754965Olejniczak-Staruch I., Ciążyńska M., Sobolewska-Sztychny D., et al. Alterations of the skin and gut microbiome in psoriasis and psoriatic arthritis. Int J Mol Sci. 2021 Apr 13; 22(8): 3998. https://doi.org/10.3390/ijms22083998. PMID: 33924414; PMCID: PMC8069836Olejniczak-Staruch I., Ciążyńska M., Sobolewska-Sztychny D., et al. Alterations of the skin and gut microbiome in psoriasis and psoriatic arthritis. Int J Mol Sci. 2021 Apr 13; 22(8): 3998. https://doi.org/10.3390/ijms22083998. PMID: 33924414; PMCID: PMC8069836Nikitakis N.G., Papaioannou W., Sakkas L.I., et al. The autoimmunity–oral microbiome connection. Oral Dis. 2017 Oct; 23(7): 828–839. https://doi.org/10.1111/ODI.12589. Epub 2016 Nov 24. PMID: 27717092Nikitakis N.G., Papaioannou W., Sakkas L.I., et al. The autoimmunity–oral microbiome connection. Oral Dis. 2017 Oct; 23(7): 828–839. https://doi.org/10.1111/ODI.12589. Epub 2016 Nov 24. PMID: 27717092Li K., Wei S., Hu L., et al. Protection of fecal microbiota transplantation in a mouse model of multiple sclerosis. Mediators Infl amm. 2020 Aug 5; 2020: 2058272. https://doi.org/10.1155/2020/2058272. PMID: 32831634; PMCID: PMC7426773Li K., Wei S., Hu L., et al. Protection of fecal microbiota transplantation in a mouse model of multiple sclerosis. Mediators Infl amm. 2020 Aug 5; 2020: 2058272. https://doi.org/10.1155/2020/2058272. PMID: 32831634; PMCID: PMC7426773Engen P.A., Zaferiou A., Rasmussen H., et al. Single-arm, nonrandomized, time series, single-subject study of fecal microbiota transplantation in multiple sclerosis. Front Neurol. 2020 Sep 8; 11: 978. https://doi.org/10.3389/fneur.2020.00978. PMID: 33013647; PMCID: PMC7506051Engen P.A., Zaferiou A., Rasmussen H., et al. Single-arm, nonrandomized, time series, single-subject study of fecal microbiota transplantation in multiple sclerosis. Front Neurol. 2020 Sep 8; 11: 978. https://doi.org/10.3389/fneur.2020.00978. PMID: 33013647; PMCID: PMC7506051Vijayashankar M., Raghunath N. Pustular psoriasis responding to probiotics – a new insight. Our Dermatology Online. 2012; 3: 326–329. https://doi.org/10.7241/OURD.20124.71Vijayashankar M., Raghunath N. Pustular psoriasis responding to probiotics – a new insight. Our Dermatology Online. 2012; 3: 326–329. https://doi.org/10.7241/OURD.20124.71Choy C.T., Chan U.K., Siu P.L.K., et al. A novel E3 probiotics formula restored gut dysbiosis and remodelled gut microbial network and microbiome dysbiosis index (MDI) in Southern Chinese adult psoriasis patients. Int J Mol Sci. 2023 Mar 31; 24(7): 6571. https://doi.org/10.3390/ijms24076571. PMID: 37047542; PMCID: PMC10094986Choy C.T., Chan U.K., Siu P.L.K., et al. A novel E3 probiotics formula restored gut dysbiosis and remodelled gut microbial network and microbiome dysbiosis index (MDI) in Southern Chinese adult psoriasis patients. Int J Mol Sci. 2023 Mar 31; 24(7): 6571. https://doi.org/10.3390/ijms24076571. PMID: 37047542; PMCID: PMC10094986Herrala M., Turunen S., Hanhineva K., et al. Low-dose doxycycline treatment normalizes levels of some salivary metabolites associated with oral microbiota in patients with primary sjögren’s syndrome. Metabolites. 2021 Sep 3; 11(9): 595. https://doi.org/10.3390/metabo11090595. PMID: 34564411; PMCID: PMC8470364Herrala M., Turunen S., Hanhineva K., et al. Low-dose doxycycline treatment normalizes levels of some salivary metabolites associated with oral microbiota in patients with primary sjögren’s syndrome. Metabolites. 2021 Sep 3; 11(9): 595. https://doi.org/10.3390/metabo11090595. PMID: 34564411; PMCID: PMC8470364Secher T., Kassem S., Benamar M., et al. Oral administration of the probiotic strain Escherichia coli Nissle 1917 reduces susceptibility to neuroinfl ammation and repairs experimental autoimmune encephalomyelitis-induced intestinal barrier dysfunction. Front Immunol. 2017 Sep 14; 8: 1096. https://doi.org/10.3389/fimmu.2017.01096. PMID: 28959254; PMCID: PMC5603654Secher T., Kassem S., Benamar M., et al. Oral administration of the probiotic strain Escherichia coli Nissle 1917 reduces susceptibility to neuroinfl ammation and repairs experimental autoimmune encephalomyelitis-induced intestinal barrier dysfunction. Front Immunol. 2017 Sep 14; 8: 1096. https://doi.org/10.3389/fimmu.2017.01096. PMID: 28959254; PMCID: PMC5603654Lavasani S., Dzhambazov B., Nouri M., et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010 Feb 2; 5(2): e9009. https://doi.org/10.1371/JOURNAL.PONE.0009009. PMID: 20126401; PMCID: PMC2814855Lavasani S., Dzhambazov B., Nouri M., et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010 Feb 2; 5(2): e9009. https://doi.org/10.1371/JOURNAL.PONE.0009009. PMID: 20126401; PMCID: PMC2814855Salehipour Z., Haghmorad D., Sankian M., et al. Bifi dobacterium animalis in combination with human origin of Lactobacillus plantarum ameliorate neuroinfl ammation in experimental model of multiple sclerosis by altering CD4+ T cell subset balance. Biomed Pharmacother. 2017 Nov; 95: 1535–1548. https://doi.org/10.1016/J.BIOPHA.2017.08.117. Epub 2017 Sep 22. PMID: 28946394Salehipour Z., Haghmorad D., Sankian M., et al. Bifi dobacterium animalis in combination with human origin of Lactobacillus plantarum ameliorate neuroinfl ammation in experimental model of multiple sclerosis by altering CD4+ T cell subset balance. Biomed Pharmacother. 2017 Nov; 95: 1535–1548. https://doi.org/10.1016/J.BIOPHA.2017.08.117. Epub 2017 Sep 22. PMID: 28946394He B., Hoang T.K., Tian X., et al. Lactobacillus reuteri reduces the severity of experimental autoimmune encephalomyelitis in mice by modulating gut microbiota. Front Immunol. 2019 Mar 7; 10: 385. https://doi.org/10.3389/FIMMU.2019.00385. PMID: 30899262; PMCID: PMC6416370He B., Hoang T.K., Tian X., et al. Lactobacillus reuteri reduces the severity of experimental autoimmune encephalomyelitis in mice by modulating gut microbiota. Front Immunol. 2019 Mar 7; 10: 385. https://doi.org/10.3389/FIMMU.2019.00385. PMID: 30899262; PMCID: PMC6416370Zhao Q., Yu J., Zhou H., et al. Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism. Sig Transduct Target Ther. 2023 Jan 30; 8(1): 40. https://doi.org/10.1038/s41392-022-01219-0. PMID: 36710269; PMCID: PMC9884668Zhao Q., Yu J., Zhou H., et al. Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism. Sig Transduct Target Ther. 2023 Jan 30; 8(1): 40. https://doi.org/10.1038/s41392-022-01219-0. PMID: 36710269; PMCID: PMC9884668Lu W., Deng Y., Fang Z., et al. Potential role of probiotics in ameliorating psoriasis by modulating gut microbiota in imiquimod-induced psoriasis-like mice. Nutrients. 2021 Jun 11; 13(6): 2010. https://doi.org/10.3390/NU13062010. PMID: 34207960; PMCID: PMC8230682Lu W., Deng Y., Fang Z., et al. Potential role of probiotics in ameliorating psoriasis by modulating gut microbiota in imiquimod-induced psoriasis-like mice. Nutrients. 2021 Jun 11; 13(6): 2010. https://doi.org/10.3390/NU13062010. PMID: 34207960; PMCID: PMC8230682Chen Y.H., Wu C.S., Chao Y.H., et al. Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasislike mice. J food drug Anal. 2017 Jul; 25(3): 559–566. https://doi.org/10.1016/J.JFDA.2016.06.003. Epub 2016 Aug 5. PMID: 28911642; PMCID: PMC9328808Chen Y.H., Wu C.S., Chao Y.H., et al. Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasislike mice. J food drug Anal. 2017 Jul; 25(3): 559–566. https://doi.org/10.1016/J.JFDA.2016.06.003. Epub 2016 Aug 5. PMID: 28911642; PMCID: PMC9328808Rather I.A., Bajpai V.K., Huh Y.S., et al. Probiotic lactobacillus sakei proBio-65 extract ameliorates the severity of imiquimod induced psoriasis-like skin infl ammation in a mouse model. Front Microbiol. 2018 May 17; 9: 1021. https://doi.org/10.3389/fmicb.2018.01021. PMID: 29867905; PMCID: PMC5968580Rather I.A., Bajpai V.K., Huh Y.S., et al. Probiotic lactobacillus sakei proBio-65 extract ameliorates the severity of imiquimod induced psoriasis-like skin infl ammation in a mouse model. Front Microbiol. 2018 May 17; 9: 1021. https://doi.org/10.3389/fmicb.2018.01021. PMID: 29867905; PMCID: PMC5968580Akers J.C., Gonda D., Kim R., et al. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol. 2013 May; 113(1): 1–11. https://doi.org/10.1007/s11060-013-1084-8. Epub 2013 Mar 2. PMID: 23456661; PMCID: PMC5533094Akers J.C., Gonda D., Kim R., et al. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol. 2013 May; 113(1): 1–11. https://doi.org/10.1007/s11060-013-1084-8. Epub 2013 Mar 2. PMID: 23456661; PMCID: PMC5533094Zhang J., Buller B.A., Zhang Z.G., et al. Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinfl ammation in the demyelinating central nervous system. Exp Neurol. 2022 Jan; 347: 113895. https://doi.org/10.1016/J.EXPNEUROL.2021.113895. Epub 2021 Oct 13. PMID: 34653510Zhang J., Buller B.A., Zhang Z.G., et al. Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinfl ammation in the demyelinating central nervous system. Exp Neurol. 2022 Jan; 347: 113895. https://doi.org/10.1016/J.EXPNEUROL.2021.113895. Epub 2021 Oct 13. PMID: 34653510Riazifar M., Mohammadi M.R., Pone E.J., et al. Stem cellderived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano. 2019 Jun 25; 13(6): 6670–6688. https://doi.org/10.1021/acsnano.9b01004. Epub 2019 May 29. PMID: 31117376; PMCID: PMC6880946Riazifar M., Mohammadi M.R., Pone E.J., et al. Stem cellderived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano. 2019 Jun 25; 13(6): 6670–6688. https://doi.org/10.1021/acsnano.9b01004. Epub 2019 May 29. PMID: 31117376; PMCID: PMC6880946Kimura K. Regulatory T cells in multiple sclerosis. Clin Exp Neuroimmunol. 2020 Aug; 11: 148–155. https://doi.org/10.1111/CEN3.12591Kimura K. Regulatory T cells in multiple sclerosis. Clin Exp Neuroimmunol. 2020 Aug; 11: 148–155. https://doi.org/10.1111/CEN3.12591Zhang B., Lai R.C., Sim WK., et al. Topical application of mesenchymal stem cell exosomes alleviates the imiquimod induced psoriasis-like infl ammation. Int J Mol Sci. 2021 Jan 13; 22(2): 720. https://doi.org/10.3390/IJMS22020720. PMID: 33450859; PMCID: PMC7828312Zhang B., Lai R.C., Sim WK., et al. Topical application of mesenchymal stem cell exosomes alleviates the imiquimod induced psoriasis-like infl ammation. Int J Mol Sci. 2021 Jan 13; 22(2): 720. https://doi.org/10.3390/IJMS22020720. PMID: 33450859; PMCID: PMC7828312Zhang Y., Yan J., Li Z., et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate psoriasis-like skin infl ammation. J Interferon Cytokine Res. 2022 Jan; 42(1): 8–18. https://doi.org/10.1089/JIR.2021.0146. PMID: 35041513Zhang Y., Yan J., Li Z., et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate psoriasis-like skin infl ammation. J Interferon Cytokine Res. 2022 Jan; 42(1): 8–18. https://doi.org/10.1089/JIR.2021.0146. PMID: 35041513Rodrigues S.C., Cardoso R.M.S., Freire P.C., et al. Immunomodulatory properties of umbilical cord blood-derived small extracellular vesicles and their therapeutic potential for infl ammatory skin disorders. Int J Mol Sci. 2021 Sep 10; 22(18): 9797. https://doi.org/10.3390/IJMS22189797. PMID: 34575956; PMCID: PMC8468428Rodrigues S.C., Cardoso R.M.S., Freire P.C., et al. Immunomodulatory properties of umbilical cord blood-derived small extracellular vesicles and their therapeutic potential for infl ammatory skin disorders. Int J Mol Sci. 2021 Sep 10; 22(18): 9797. https://doi.org/10.3390/IJMS22189797. PMID: 34575956; PMCID: PMC8468428Xing Y., Li B., He J., et al. Labial gland mesenchymal stem cell derived exosomes-mediated miRNA-125b attenuates experimental Sjogren’s syndrome by targeting PRDM1 and suppressing plasma cells. Front Immunol. 2022 Apr 4; 13: 871096. https://doi.org/10.3389/fimmu.2022.871096. PMID: 35444638; PMCID: PMC9014006Xing Y., Li B., He J., et al. Labial gland mesenchymal stem cell derived exosomes-mediated miRNA-125b attenuates experimental Sjogren’s syndrome by targeting PRDM1 and suppressing plasma cells. Front Immunol. 2022 Apr 4; 13: 871096. https://doi.org/10.3389/fimmu.2022.871096. PMID: 35444638; PMCID: PMC9014006Zhao Q., Bae E.H., Zhang Y., et al. Inhibitory effects of extracellular vesicles from iPS-cell-derived mesenchymal stem cells on the onset of sialadenitis in Sjögren’s syndrome are mediated by immunomodulatory splenocytes and improved by inhibiting miR125b. Int J Mol Sci. 2023 Mar 9 ; 24(6): 5258. https://doi.org/10.3390/ijms24065258 PMID: 36982329; PMCID: PMC10049013Zhao Q., Bae E.H., Zhang Y., et al. Inhibitory effects of extracellular vesicles from iPS-cell-derived mesenchymal stem cells on the onset of sialadenitis in Sjögren’s syndrome are mediated by immunomodulatory splenocytes and improved by inhibiting miR125b. Int J Mol Sci. 2023 Mar 9 ; 24(6): 5258. https://doi.org/10.3390/ijms24065258 PMID: 36982329; PMCID: PMC10049013Tong L., Zhang S., Liu Q., et al. Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis. Sci Adv. 2023 Apr 14; 9(15): eade5041. https://doi.org/10.1126/SCIADV.ADE5041. Epub 2023 Apr 12. PMID: 37043568; PMCID: PMC10096581Tong L., Zhang S., Liu Q., et al. Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis. Sci Adv. 2023 Apr 14; 9(15): eade5041. https://doi.org/10.1126/SCIADV.ADE5041. Epub 2023 Apr 12. PMID: 37043568; PMCID: PMC10096581Yang L., Wang T., Zhang X., et al. Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-infl ammation and restoring gut dysbiosis. BMC Cardiovasc Disord. 2022 Feb 17; 22(1): 61. https://doi.org/10.1186/S12872-022-02508-W. PMID: 35172728; PMCID: PMC8851843Yang L., Wang T., Zhang X., et al. Exosomes derived from human placental mesenchymal stem cells ameliorate myocardial infarction via anti-infl ammation and restoring gut dysbiosis. BMC Cardiovasc Disord. 2022 Feb 17; 22(1): 61. https://doi.org/10.1186/S12872-022-02508-W. PMID: 35172728; PMCID: PMC8851843Barros C.P., Guimarães J.T., Esmerino E.A., et al. Paraprobiotics and postbiotics: concepts and potential applications in dairy products. Curr Opin Food Sci. 2020; 32: 1–8. https://doi.org/10.1016/J.COFS.2019.12.003Barros C.P., Guimarães J.T., Esmerino E.A., et al. Paraprobiotics and postbiotics: concepts and potential applications in dairy products. Curr Opin Food Sci. 2020; 32: 1–8. https://doi.org/10.1016/J.COFS.2019.12.003González-Lozano E., García-García J., Gálvez J., et al. Novel horizons in postbiotics: Lactobacillaceae extracellular vesicles and their applications in health and disease. Nutrients. 2022 Dec 13; 14(24): 5296. https://doi.org/10.3390/NU14245296. PMID: 36558455; PMCID: PMC9782203González-Lozano E., García-García J., Gálvez J., et al. Novel horizons in postbiotics: Lactobacillaceae extracellular vesicles and their applications in health and disease. Nutrients. 2022 Dec 13; 14(24): 5296. https://doi.org/10.3390/NU14245296. PMID: 36558455; PMCID: PMC9782203Hao H., Zhang X., Tong L., et al. Effect of extracellular vesicles derived from lactobacillus plantarum Q7 on gut microbiota and ulcerative colitis in mice. Front Immunol. 2021 Dec 2; 12: 777147. https://doi.org/10.3389/FIMMU.2021.777147. PMID: 34925349; PMCID: PMC8674835Hao H., Zhang X., Tong L., et al. Effect of extracellular vesicles derived from lactobacillus plantarum Q7 on gut microbiota and ulcerative colitis in mice. Front Immunol. 2021 Dec 2; 12: 777147. https://doi.org/10.3389/FIMMU.2021.777147. PMID: 34925349; PMCID: PMC8674835Du C., Wang K., Zhao Y., et al. Supplementation with milk-derived extracellular vesicles shapes the gut microbiota and regulates the transcriptomic landscape in experimental colitis. Nutrients. 2022 Apr 26; 14(9): 1808. https://doi.org/10.3390/NU14091808. PMID: 35565775; PMCID: PMC9104790Du C., Wang K., Zhao Y., et al. Supplementation with milk-derived extracellular vesicles shapes the gut microbiota and regulates the transcriptomic landscape in experimental colitis. Nutrients. 2022 Apr 26; 14(9): 1808. https://doi.org/10.3390/NU14091808. PMID: 35565775; PMCID: PMC9104790Shaban A.M., Raslan M., Sharawi Z.W., et al. Antibacterial, antifungal, and anticancer effects of camel milk exosomes: an in vitro study. Vet Sci. 2023 Feb 6; 10(2): 124. https://doi.org/10.3390/VETSCI10020124. PMID: 36851428; PMCID: PMC9963947Shaban A.M., Raslan M., Sharawi Z.W., et al. Antibacterial, antifungal, and anticancer effects of camel milk exosomes: an in vitro study. Vet Sci. 2023 Feb 6; 10(2): 124. https://doi.org/10.3390/VETSCI10020124. PMID: 36851428; PMCID: PMC9963947Wajda D.A., Sosnoff J.J. Cognitive-motor interference in multiple sclerosis: a systematic review of evidence, correlates, and consequences. Biomed Res Int. 2015; 2015: 720856. https://doi.org/10.1155/2015/720856. Epub 2015 Mar 9. PMID: 25839039; PMCID: PMC4369906Wajda D.A., Sosnoff J.J. Cognitive-motor interference in multiple sclerosis: a systematic review of evidence, correlates, and consequences. Biomed Res Int. 2015; 2015: 720856. https://doi.org/10.1155/2015/720856. Epub 2015 Mar 9. PMID: 25839039; PMCID: PMC4369906Rutsch A., Kantsjö J.B., Ronchi F. The gut-brain axis: how microbiota and host infl ammasome infl uence brain physiology and pathology. Front Immunol. 2020 Dec 10; 11: 604179. https://doi.org/10.3389/FIMMU.2020.604179. PMID: 33362788; PMCID: PMC7758428Rutsch A., Kantsjö J.B., Ronchi F. The gut-brain axis: how microbiota and host infl ammasome infl uence brain physiology and pathology. Front Immunol. 2020 Dec 10; 11: 604179. https://doi.org/10.3389/FIMMU.2020.604179. PMID: 33362788; PMCID: PMC7758428Dyńka D., Kowalcze K., Paziewska A. The role of ketogenic diet in the treatment of neurological diseases. Nutrients. 2022 Nov 24; 14(23): 5003. https://doi.org/10.3390/NU14235003. PMID: 36501033; PMCID: PMC9739023Dyńka D., Kowalcze K., Paziewska A. The role of ketogenic diet in the treatment of neurological diseases. Nutrients. 2022 Nov 24; 14(23): 5003. https://doi.org/10.3390/NU14235003. PMID: 36501033; PMCID: PMC9739023Mora P., Chapouly C. Astrogliosis in multiple sclerosis and neuroinfl ammation: what role for the notch pathway? Front Immunol. 2023 Oct 23; 14: 1254586. https://doi.org/10.3389/FIMMU.2023.1254586. PMID: 37936690; PMCID: PMC10627009Mora P., Chapouly C. Astrogliosis in multiple sclerosis and neuroinfl ammation: what role for the notch pathway? Front Immunol. 2023 Oct 23; 14: 1254586. https://doi.org/10.3389/FIMMU.2023.1254586. PMID: 37936690; PMCID: PMC10627009Schauf M., Chinthapatla H., Dimri S., et al. Economic burden of multiple sclerosis in the United States: A systematic literature review. J Manag care Spec Pharm. 2023 Dec; 29(12): 1354-1368. https://doi.org/10.18553/JMCP.2023.23039. Epub 2023 Nov 17. PMID: 37976077; PMCID: PMC10776266Schauf M., Chinthapatla H., Dimri S., et al. Economic burden of multiple sclerosis in the United States: A systematic literature review. J Manag care Spec Pharm. 2023 Dec; 29(12): 1354-1368. https://doi.org/10.18553/JMCP.2023.23039. Epub 2023 Nov 17. PMID: 37976077; PMCID: PMC10776266Hauser S.L., Cree B.A.C. Treatment of multiple sclerosis: a review. Am J Med. 2020 Dec; 133(12): 1380-1390.e2. https://doi.org/10.1016/J.AMJMED.2020.05.049. Epub 2020 Jul 17. PMID: 32682869; PMCID: PMC7704606Hauser S.L., Cree B.A.C. Treatment of multiple sclerosis: a review. Am J Med. 2020 Dec; 133(12): 1380-1390.e2. https://doi.org/10.1016/J.AMJMED.2020.05.049. Epub 2020 Jul 17. PMID: 32682869; PMCID: PMC7704606Baecher-Allan C., Kaskow B.J., Weiner H.L. Multiple sclerosis: mechanisms and immunotherapy. Neuron. 2018 Feb 21; 97(4): 742–768. https://doi.org/10.1016/J.NEURON.2018.01.021. PMID: 29470968Baecher-Allan C., Kaskow B.J., Weiner H.L. Multiple sclerosis: mechanisms and immunotherapy. Neuron. 2018 Feb 21; 97(4): 742–768. https://doi.org/10.1016/J.NEURON.2018.01.021. PMID: 29470968Prajeeth C.K., Dittrich-Breiholz O., Talbot S.R., et al. IFN-γ producing Th1 cells induce different transcriptional profi les in microglia and astrocytes. Front Cell Neurosci. 2018 Oct 10; 12: 352. https://doi.org/10.3389/fncel.2018.00352. PMID: 30364000; PMCID: PMC6191492Prajeeth C.K., Dittrich-Breiholz O., Talbot S.R., et al. IFN-γ producing Th1 cells induce different transcriptional profi les in microglia and astrocytes. Front Cell Neurosci. 2018 Oct 10; 12: 352. https://doi.org/10.3389/fncel.2018.00352. PMID: 30364000; PMCID: PMC6191492Chen J., Liu X., Zhong Y. Interleukin-17A: The Key cytokine in neurodegenerative diseases. Front Aging Neurosci. 2020 Sep 29; 12: 566922. https://doi.org/10.3389/fnagi.2020.566922. PMID: 33132897; PMCID: PMC7550684Chen J., Liu X., Zhong Y. Interleukin-17A: The Key cytokine in neurodegenerative diseases. Front Aging Neurosci. 2020 Sep 29; 12: 566922. https://doi.org/10.3389/fnagi.2020.566922. PMID: 33132897; PMCID: PMC7550684Yu A., Duan H., Zhang T., et al. IL-17A promotes microglial activation and neuroinfl ammation in mouse models of intracerebral haemorrhage. Mol Immunol. 2016 May; 73: 151–157. https://doi.org/10.1016/J.MOLIMM.2016.04.003. Epub 2016 Apr 22. PMID: 27107665Yu A., Duan H., Zhang T., et al. IL-17A promotes microglial activation and neuroinfl ammation in mouse models of intracerebral haemorrhage. Mol Immunol. 2016 May; 73: 151–157. https://doi.org/10.1016/J.MOLIMM.2016.04.003. Epub 2016 Apr 22. PMID: 27107665Huppert J., Closhen D., Croxford A., et al. Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J. 2010 Apr; 24(4): 1023–1034. https://doi.org/10.1096/FJ.09-141978. Epub 2009 Nov 25. PMID: 19940258Huppert J., Closhen D., Croxford A., et al. Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J. 2010 Apr; 24(4): 1023–1034. https://doi.org/10.1096/FJ.09-141978. Epub 2009 Nov 25. PMID: 19940258Alvarez J.I., Cayrol R., Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta – Mol Basis Dis. 2011 Feb; 1812(2): 252–264. https://doi.org/10.1016/J.BBADIS.2010.06.017. Epub 2010 Jul 7. PMID: 20619340Alvarez J.I., Cayrol R., Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta – Mol Basis Dis. 2011 Feb; 1812(2): 252–264. https://doi.org/10.1016/J.BBADIS.2010.06.017. Epub 2010 Jul 7. PMID: 20619340Fraussen J., de Bock L., Somers V. B cells and antibodies in progressive multiple sclerosis: Contribution to neurodegeneration and progression. Autoimmun Rev. 2016 Sep; 15(9): 896–899. https://doi.org/10.1016/J.AUTREV.2016.07.008. Epub 2016 Jul 7. PMID: 27396817Fraussen J., de Bock L., Somers V. B cells and antibodies in progressive multiple sclerosis: Contribution to neurodegeneration and progression. Autoimmun Rev. 2016 Sep; 15(9): 896–899. https://doi.org/10.1016/J.AUTREV.2016.07.008. Epub 2016 Jul 7. PMID: 27396817Holloman J.P., Axtell R.C., Monson N.L., et al. The role of B Cells in primary progressive multiple sclerosis. Front Neurol. 2021 Jun 7; 12: 680581. https://doi.org/10.3389/FNEUR.2021.680581. PMID: 34163430; PMCID: PMC8215437Holloman J.P., Axtell R.C., Monson N.L., et al. The role of B Cells in primary progressive multiple sclerosis. Front Neurol. 2021 Jun 7; 12: 680581. https://doi.org/10.3389/FNEUR.2021.680581. PMID: 34163430; PMCID: PMC8215437Ochoa-Reparaz J., Magori K., Kasper L.H. The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis. Ann Transl Med. 2017 Mar; 5(6): 145. https://doi.org/10.21037/ATM.2017.01.18. PMID: 28462225; PMCID: PMC5395488Ochoa-Reparaz J., Magori K., Kasper L.H. The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis. Ann Transl Med. 2017 Mar; 5(6): 145. https://doi.org/10.21037/ATM.2017.01.18. PMID: 28462225; PMCID: PMC5395488Gandy K.A.O., Zhang J., Nagarkatti P., et al. The role of gut microbiota in shaping the relapse-remitting and chronicprogressive forms of multiple sclerosis in mouse models. Sci Rep. 2019 May 6; 9(1): 6923. https://doi.org/10.1038/S41598-019-43356-7. PMID: 31061496; PMCID: PMC6502871Gandy K.A.O., Zhang J., Nagarkatti P., et al. The role of gut microbiota in shaping the relapse-remitting and chronicprogressive forms of multiple sclerosis in mouse models. Sci Rep. 2019 May 6; 9(1): 6923. https://doi.org/10.1038/S41598-019-43356-7. PMID: 31061496; PMCID: PMC6502871Parodi B., Kerlero de Rosbo N. The gut-brain axis in multiple sclerosis. Is Its dysfunction a pathological trigger or a consequence of the disease? Front Immunol. 2021 Sep 21; 12: 718220. https://doi.org/10.3389/FIMMU.2021.718220. PMID: 34621267; PMCID: PMC8490747Parodi B., Kerlero de Rosbo N. The gut-brain axis in multiple sclerosis. Is Its dysfunction a pathological trigger or a consequence of the disease? Front Immunol. 2021 Sep 21; 12: 718220. https://doi.org/10.3389/FIMMU.2021.718220. PMID: 34621267; PMCID: PMC8490747Miyake S., Kim S., Suda W., et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015 Sep 14; 10(9): e0137429. https://doi.org/10.1371/JOURNAL.PONE.0137429. PMID: 26367776; PMCID: PMC4569432Miyake S., Kim S., Suda W., et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015 Sep 14; 10(9): e0137429. https://doi.org/10.1371/JOURNAL.PONE.0137429. PMID: 26367776; PMCID: PMC4569432Yadav M., Ali S., Shrode R.L., et al. Multiple sclerosis patients have an altered gut mycobiome and increased fungal to bacterial richness. PLoS One. 022 Apr 26; 17(4): e0264556. https://doi.org/10.1371/JOURNAL.PONE.0264556. PMID: 35472144; PMCID: PMC9041819Yadav M., Ali S., Shrode R.L., et al. Multiple sclerosis patients have an altered gut mycobiome and increased fungal to bacterial richness. PLoS One. 022 Apr 26; 17(4): e0264556. https://doi.org/10.1371/JOURNAL.PONE.0264556. PMID: 35472144; PMCID: PMC9041819Chen J., Chia N., Kalari K.R., et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep. 2016 Jun 27; 6: 28484. https://doi.org/10.1038/SREP28484. PMID: 27346372; PMCID: PMC4921909Chen J., Chia N., Kalari K.R., et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep. 2016 Jun 27; 6: 28484. https://doi.org/10.1038/SREP28484. PMID: 27346372; PMCID: PMC4921909Nouri M., Bredberg A., Weström B., et al. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS One. 2014 Sep 3; 9(9): e106335. https://doi.org/10.1371/JOURNAL.PONE.0106335. PMID: 25184418; PMCID: PMC4153638Nouri M., Bredberg A., Weström B., et al. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS One. 2014 Sep 3; 9(9): e106335. https://doi.org/10.1371/JOURNAL.PONE.0106335. PMID: 25184418; PMCID: PMC4153638Buscarinu M.C., Cerasoli B., Annibali V., et al. Altered intestinal permeability in patients with relapsing-remitting multiple sclerosis: A pilot study. Mult Scler. 2017 Mar; 23(3): 442–446. https://doi.org/10.1177/1352458516652498. Epub 2016 Jul 11. PMID: 27270497Buscarinu M.C., Cerasoli B., Annibali V., et al. Altered intestinal permeability in patients with relapsing-remitting multiple sclerosis: A pilot study. Mult Scler. 2017 Mar; 23(3): 442–446. https://doi.org/10.1177/1352458516652498. Epub 2016 Jul 11. PMID: 27270497Kinashi Y., Hase K. Partners in leaky gut syndrome: intestinal dysbiosis and autoimmunity. Front Immunol. 2021 Apr 22; 12: 673708. https://doi.org/10.3389/FIMMU.2021.673708. PMID: 33968085; PMCID: PMC8100306Kinashi Y., Hase K. Partners in leaky gut syndrome: intestinal dysbiosis and autoimmunity. Front Immunol. 2021 Apr 22; 12: 673708. https://doi.org/10.3389/FIMMU.2021.673708. PMID: 33968085; PMCID: PMC8100306Pellegrino A., Coppola G., Santopaolo F., et al. Role of Akkermansia in human diseases: from causation to therapeutic properties. Nutrients. 2023 Apr 8; 15(8): 1815. https://doi.org/10.3390/NU15081815. PMID: 37111034; PMCID: PMC10142179Pellegrino A., Coppola G., Santopaolo F., et al. Role of Akkermansia in human diseases: from causation to therapeutic properties. Nutrients. 2023 Apr 8; 15(8): 1815. https://doi.org/10.3390/NU15081815. PMID: 37111034; PMCID: PMC10142179Derrien M., Van Baarlen P., Hooiveld G., et al. Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol. 2011 Aug 1; 2: 166. https://doi.org/10.3389/FMICB.2011.00166. PMID: 21904534; PMCID: PMC3153965Derrien M., Van Baarlen P., Hooiveld G., et al. Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front Microbiol. 2011 Aug 1; 2: 166. https://doi.org/10.3389/FMICB.2011.00166. PMID: 21904534; PMCID: PMC3153965Wu N., Li X., Ma H., et al. The role of the gut microbiota and fecal microbiota transplantation in neuroimmune diseases. Front Neurol. 2023 Feb 1; 14: 1108738. https://doi.org/10.3389/FNEUR.2023.1108738. PMID: 36816570; PMCID: PMC9929158Wu N., Li X., Ma H., et al. The role of the gut microbiota and fecal microbiota transplantation in neuroimmune diseases. Front Neurol. 2023 Feb 1; 14: 1108738. https://doi.org/10.3389/FNEUR.2023.1108738. PMID: 36816570; PMCID: PMC9929158Braniste V., Al-Asmakh M., Kowal C., et al. The gut microbiota infl uences blood-brain barrier permeability in mice. Sci Transl Med. 2014 Nov 19; 6(263): 263ra158. https://doi.org/10.1126/SCITRANSLMED.3009759. PMID: 25411471; PMCID: PMC4396848Braniste V., Al-Asmakh M., Kowal C., et al. The gut microbiota infl uences blood-brain barrier permeability in mice. Sci Transl Med. 2014 Nov 19; 6(263): 263ra158. https://doi.org/10.1126/SCITRANSLMED.3009759. PMID: 25411471; PMCID: PMC4396848Venkatesh M., Mukherjee S., Wang H., et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and toll-like receptor 4. Immunity. 2014 Aug 21; 41(2): 296–310. https://doi.org/10.1016/J.IMMUNI.2014.06.014. Epub 2014 Jul 24. PMID: 25065623; PMCID: PMC4142105Venkatesh M., Mukherjee S., Wang H., et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and toll-like receptor 4. Immunity. 2014 Aug 21; 41(2): 296–310. https://doi.org/10.1016/J.IMMUNI.2014.06.014. Epub 2014 Jul 24. PMID: 25065623; PMCID: PMC4142105Scott S.A., Fu J., Chang P.V. Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor. Proc Natl Acad Sci USA. 2020 Aug 11; 117(32): 19376–19387. https://doi.org/10.1073/pnas.2000047117. Epub 2020 Jul 27. PMID: 32719140; PMCID: PMC7431026Scott S.A., Fu J., Chang P.V. Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor. Proc Natl Acad Sci USA. 2020 Aug 11; 117(32): 19376–19387. https://doi.org/10.1073/pnas.2000047117. Epub 2020 Jul 27. PMID: 32719140; PMCID: PMC7431026Singh R., Chandrashekharappa S., Bodduluri S.R., et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun. 2019 Jan 9; 10(1): 89. https://doi.org/10.1038/S41467-018-07859-7. PMID: 30626868; PMCID: PMC6327034Singh R., Chandrashekharappa S., Bodduluri S.R., et al. Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway. Nat Commun. 2019 Jan 9; 10(1): 89. https://doi.org/10.1038/S41467-018-07859-7. PMID: 30626868; PMCID: PMC6327034Rothhammer V., Mascanfroni I.D., Bunse L., et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and CNS infl ammation via the aryl hydrocarbon receptor. Nat Med. 2016 Jun; 22(6): 586–597. https://doi.org/10.1038/NM.4106. Epub 2016 May 9. PMID: 27158906; PMCID: PMC4899206Rothhammer V., Mascanfroni I.D., Bunse L., et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and CNS infl ammation via the aryl hydrocarbon receptor. Nat Med. 2016 Jun; 22(6): 586–597. https://doi.org/10.1038/NM.4106. Epub 2016 May 9. PMID: 27158906; PMCID: PMC4899206Ochoa-Repáraz J., Mielcarz D.W., Wang Y., et al. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010 Sep; 3(5): 487–495. https://doi.org/10.1038/MI.2010.29. Epub 2010 Jun 9. PMID: 20531465Ochoa-Repáraz J., Mielcarz D.W., Wang Y., et al. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010 Sep; 3(5): 487–495. https://doi.org/10.1038/MI.2010.29. Epub 2010 Jun 9. PMID: 20531465Hoban A.E., Stilling R.M., Ryan F.J., et al. Regulation of prefrontal cortex myelination by the microbiota. Transl Psychiatry. 2016 Apr 5; 6(4): e774. https://doi.org/10.1038/TP.2016.42. PMID: 27045844; PMCID: PMC4872400Hoban A.E., Stilling R.M., Ryan F.J., et al. Regulation of prefrontal cortex myelination by the microbiota. Transl Psychiatry. 2016 Apr 5; 6(4): e774. https://doi.org/10.1038/TP.2016.42. PMID: 27045844; PMCID: PMC4872400Berer K., Gerdes L.A., Cekanaviciute E., et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 2017 Oct 3; 114(40): 10719–10724. https://doi.org/10.1073/pnas.1711233114. Epub 2017 Sep 11. PMID: 28893994; PMCID: PMC5635914Berer K., Gerdes L.A., Cekanaviciute E., et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 2017 Oct 3; 114(40): 10719–10724. https://doi.org/10.1073/pnas.1711233114. Epub 2017 Sep 11. PMID: 28893994; PMCID: PMC5635914Cekanaviciute E., Yoo B.B., Runia T.F., et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci USA. 2017 Oct 3; 114(40): 10713–10718. https://doi.org/10.1073/pnas.1711235114. Epub 2017 Sep 11. PMID: 28893978; PMCID: PMC5635915Cekanaviciute E., Yoo B.B., Runia T.F., et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci USA. 2017 Oct 3; 114(40): 10713–10718. https://doi.org/10.1073/pnas.1711235114. Epub 2017 Sep 11. PMID: 28893978; PMCID: PMC5635915Montgomery T.L., Künstner A., Kennedy J.J., et al. Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity. Proc Natl Acad Sci U S A. 2020 Nov 3; 117(44): 27516–27527. https://doi.org/10.1073/pnas.2002817117. Epub 2020 Oct 19. PMID: 33077601; PMCID: PMC7959502Montgomery T.L., Künstner A., Kennedy J.J., et al. Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity. Proc Natl Acad Sci U S A. 2020 Nov 3; 117(44): 27516–27527. https://doi.org/10.1073/pnas.2002817117. Epub 2020 Oct 19. PMID: 33077601; PMCID: PMC7959502Miyauchi E., Kim S.W., Suda W., et al. Gut microorganisms act together to exacerbate infl ammation in spinal cords. Nature. 2020 Sep; 585(7823): 102–106. https://doi.org/10.1038/S41586-020-2634-9. Epub 2020 Aug 26. PMID: 32848245Miyauchi E., Kim S.W., Suda W., et al. Gut microorganisms act together to exacerbate infl ammation in spinal cords. Nature. 2020 Sep; 585(7823): 102–106. https://doi.org/10.1038/S41586-020-2634-9. Epub 2020 Aug 26. PMID: 32848245Zhang H., Yang Z., Tang K., et al. Stigmatization in patients with psoriasis: a mini review. Front Immunol. 2021 Nov 15; 12: 715839. https://doi.org/10.3389/FIMMU.2021.715839. PMID: 34867945; PMCID: PMC8634029Zhang H., Yang Z., Tang K., et al. Stigmatization in patients with psoriasis: a mini review. Front Immunol. 2021 Nov 15; 12: 715839. https://doi.org/10.3389/FIMMU.2021.715839. PMID: 34867945; PMCID: PMC8634029Jankowiak B., Krajewska-Kułak E., Jakoniuk M., et al. Stigmatization among patients with plaque psoriasis. J Clin Med. 2023 Oct 9; 12(19): 6425. https://doi.org/10.3390/JCM12196425. PMID: 37835068; PMCID: PMC10573936Jankowiak B., Krajewska-Kułak E., Jakoniuk M., et al. Stigmatization among patients with plaque psoriasis. J Clin Med. 2023 Oct 9; 12(19): 6425. https://doi.org/10.3390/JCM12196425. PMID: 37835068; PMCID: PMC10573936Zhou X., Chen Y., Cui L., et al. Advances in the pathogenesis of psoriasis: from keratinocyte perspective. Cell Death Dis. 2022 Jan 24; 13(1): 81. https://doi.org/10.1038/S41419-022-04523-3. PMID: 35075118; PMCID: PMC8786887Zhou X., Chen Y., Cui L., et al. Advances in the pathogenesis of psoriasis: from keratinocyte perspective. Cell Death Dis. 2022 Jan 24; 13(1): 81. https://doi.org/10.1038/S41419-022-04523-3. PMID: 35075118; PMCID: PMC8786887Goodman W.A., Levine A.D., Massari J.V., et al. IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells. J Immunol. 2009 Sep 1; 183(5): 3170–3176. https://doi.org/10.4049/JIMMUNOL.0803721. Epub 2009 Jul 31. PMID: 19648274; PMCID: PMC2903207Goodman W.A., Levine A.D., Massari J.V., et al. IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells. J Immunol. 2009 Sep 1; 183(5): 3170–3176. https://doi.org/10.4049/JIMMUNOL.0803721. Epub 2009 Jul 31. PMID: 19648274; PMCID: PMC2903207Yang L., Li B., Dang E., et al. Impaired function of regulatory T cells in patients with psoriasis is mediated by phosphorylation of STAT3. J Dermatol Sci. 2016 Feb; 81(2): 85–92. https://doi.org/10.1016/J.JDERMSCI.2015.11.007. Epub 2015 Nov 17. PMID: 26627723Yang L., Li B., Dang E., et al. Impaired function of regulatory T cells in patients with psoriasis is mediated by phosphorylation of STAT3. J Dermatol Sci. 2016 Feb; 81(2): 85–92. https://doi.org/10.1016/J.JDERMSCI.2015.11.007. Epub 2015 Nov 17. PMID: 26627723Harris T.J., Grosso J.F., Yen H.-R., et al. Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17dependent autoimmunity. J Immunol. 2007 Oct 1; 179(7): 4313–4317. https://doi.org/10.4049/JIMMUNOL.179.7.4313. PMID: 17878325Harris T.J., Grosso J.F., Yen H.-R., et al. Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17dependent autoimmunity. J Immunol. 2007 Oct 1; 179(7): 4313–4317. https://doi.org/10.4049/JIMMUNOL.179.7.4313. PMID: 17878325Chen Z., Laurence A., Kanno Y., et al. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA. 2006 May 23; 103(21): 8137–8142. https://doi.org/10.1073/PNAS.0600666103. Epub 2006 May 12. PMID: 16698929; PMCID: PMC1459629Chen Z., Laurence A., Kanno Y., et al. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci USA. 2006 May 23; 103(21): 8137–8142. https://doi.org/10.1073/PNAS.0600666103. Epub 2006 May 12. PMID: 16698929; PMCID: PMC1459629Gao Z., Tseng C.H., Strober B.E., et al. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS One. 2008 Jul 23; 3(7): e2719. https://doi.org/10.1371/JOURNAL.PONE.0002719. PMID: 18648509; PMCID: PMC2447873Gao Z., Tseng C.H., Strober B.E., et al. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS One. 2008 Jul 23; 3(7): e2719. https://doi.org/10.1371/JOURNAL.PONE.0002719. PMID: 18648509; PMCID: PMC2447873Fahlén A., Engstrand L., Baker B.S., et al. Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch Dermatol Res. 2012 Jan; 304(1): 15–22. https://doi.org/10.1007/S00403-011-1189-X. Epub 2011 Nov 8. PMID: 22065152Fahlén A., Engstrand L., Baker B.S., et al. Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch Dermatol Res. 2012 Jan; 304(1): 15–22. https://doi.org/10.1007/S00403-011-1189-X. Epub 2011 Nov 8. PMID: 22065152Boix-Amorós A., Badri M.H., Manasson J., et al. Alterations in the cutaneous microbiome of patients with psoriasis and psoriatic arthritis reveal similarities between non-lesional and lesional skin. Ann Rheum Dis. 2023 Apr; 82(4): 507–514. https://doi.org/10.1136/ARD-2022-223389. Epub 2022 Dec 12. PMID: 36600182Boix-Amorós A., Badri M.H., Manasson J., et al. Alterations in the cutaneous microbiome of patients with psoriasis and psoriatic arthritis reveal similarities between non-lesional and lesional skin. Ann Rheum Dis. 2023 Apr; 82(4): 507–514. https://doi.org/10.1136/ARD-2022-223389. Epub 2022 Dec 12. PMID: 36600182Assarsson M., Söderman J., Dienus O., et al. Signifi cant differences in the bacterial microbiome of the pharynx and skin in patients with psoriasis compared with healthy controls. Acta Derm Venereol. 2020 Sep 30; 100(16): adv00273. https://doi.org/10.2340/00015555-3619. PMID: 32852562; PMCID: PMC9234991Assarsson M., Söderman J., Dienus O., et al. Signifi cant differences in the bacterial microbiome of the pharynx and skin in patients with psoriasis compared with healthy controls. Acta Derm Venereol. 2020 Sep 30; 100(16): adv00273. https://doi.org/10.2340/00015555-3619. PMID: 32852562; PMCID: PMC9234991Assarsson M., Duvetorp A., Dienus O., et al. Signifi cant changes in the skin microbiome in patients with chronic plaque psoriasis after treatment with narrowband ultraviolet B. Acta Derm Venereol. 2018 Apr 16; 98(4): 428–436. https://doi.org/10.2340/00015555-2859. PMID: 29199351Assarsson M., Duvetorp A., Dienus O., et al. Signifi cant changes in the skin microbiome in patients with chronic plaque psoriasis after treatment with narrowband ultraviolet B. Acta Derm Venereol. 2018 Apr 16; 98(4): 428–436. https://doi.org/10.2340/00015555-2859. PMID: 29199351Alekseyenko A.V., Perez-Perez G.I., Souza A. De, et al. Community differentiation of the cutaneous microbiota in psoriasis. Microbiome. 2013 Dec 23; 1(1): 31. https://doi.org/10.1186/2049-2618-1-31. PMID: 24451201; PMCID: PMC4177411Alekseyenko A.V., Perez-Perez G.I., Souza A. De, et al. Community differentiation of the cutaneous microbiota in psoriasis. Microbiome. 2013 Dec 23; 1(1): 31. https://doi.org/10.1186/2049-2618-1-31. PMID: 24451201; PMCID: PMC4177411Rungjang A., Meephansan J., Payungporn S., et al. Skin microbiota profi les from tape stripping and skin biopsy samples of patients with psoriasis treated with narrowband ultraviolet B. Clin Cosmet Investig Dermatol. 2022 Aug 30; 15: 1767–1778. https://doi.org/10.2147/CCID.S374871. PMID: 36065340; PMCID: PMC9440725Rungjang A., Meephansan J., Payungporn S., et al. Skin microbiota profi les from tape stripping and skin biopsy samples of patients with psoriasis treated with narrowband ultraviolet B. Clin Cosmet Investig Dermatol. 2022 Aug 30; 15: 1767–1778. https://doi.org/10.2147/CCID.S374871. PMID: 36065340; PMCID: PMC9440725Aslan Kayıran M., Sahin E., Koçoğlu E., et al. Is cutaneous microbiota a player in disease pathogenesis? Comparison of cutaneous microbiota in psoriasis and seborrheic dermatitis with scalp involvement. Indian J Dermatol Venereol Leprol. 2022 NovDec; 88(6): 738–748. https://doi.org/10.25259/IJDVL_323_21. PMID: 35389020Aslan Kayıran M., Sahin E., Koçoğlu E., et al. Is cutaneous microbiota a player in disease pathogenesis? Comparison of cutaneous microbiota in psoriasis and seborrheic dermatitis with scalp involvement. Indian J Dermatol Venereol Leprol. 2022 NovDec; 88(6): 738–748. https://doi.org/10.25259/IJDVL_323_21. PMID: 35389020Loesche M.A., Farahi K., Capone K., et al. Longitudinal study of the psoriasis-associated skin microbiome during therapy with Ustekinumab in a randomized phase 3b clinical trial. J Invest Dermatol. 2018 Sep; 138(9): 1973–1981. https://doi.org/10.1016/jjid.2018.03.1501. Epub 2018 Mar 17. PMID: 29559344Loesche M.A., Farahi K., Capone K., et al. Longitudinal study of the psoriasis-associated skin microbiome during therapy with Ustekinumab in a randomized phase 3b clinical trial. J Invest Dermatol. 2018 Sep; 138(9): 1973–1981. https://doi.org/10.1016/jjid.2018.03.1501. Epub 2018 Mar 17. PMID: 29559344Grice E.A., Kong H.H., Conlan S., et al. Topographical and temporal diversity of the human skin microbiome. Science. 2009 May 29; 324(5931): 1190–1192. https://doi.org/10.1126/SCIENCE.1171700. PMID: 19478181; PMCID: PMC2805064Grice E.A., Kong H.H., Conlan S., et al. Topographical and temporal diversity of the human skin microbiome. Science. 2009 May 29; 324(5931): 1190–1192. https://doi.org/10.1126/SCIENCE.1171700. PMID: 19478181; PMCID: PMC2805064Zákostelská Z., Málková J., Klimešová K., et al. Intestinal microbiota promotes psoriasis-like skin infl ammation by enhancing Th17 response. PLoS One. 2016 Jul 19; 11(7): e0159539. https://doi.org/10.1371/JOURNAL.PONE.0159539. PMID: 27434104; PMCID: PMC4951142Zákostelská Z., Málková J., Klimešová K., et al. Intestinal microbiota promotes psoriasis-like skin infl ammation by enhancing Th17 response. PLoS One. 2016 Jul 19; 11(7): e0159539. https://doi.org/10.1371/JOURNAL.PONE.0159539. PMID: 27434104; PMCID: PMC4951142França K. Topical probiotics in dermatological therapy and skincare: a concise review. Dermatol Ther (Heidelb). 2021 Feb; 11(1): 71–77. https://doi.org/10.1007/S13555-020-00476-7. Epub 2020 Dec 19. PMID: 33340341; PMCID: PMC7859136França K. Topical probiotics in dermatological therapy and skincare: a concise review. Dermatol Ther (Heidelb). 2021 Feb; 11(1): 71–77. https://doi.org/10.1007/S13555-020-00476-7. Epub 2020 Dec 19. PMID: 33340341; PMCID: PMC7859136Habeebuddin M., Karnati R.K., Shiroorkar P.N., et al. Topical probiotics: more than a skin deep. Pharmaceutics. 2022 Mar 3; 14(3): 557. https://doi.org/10.3390/PHARMACEUTICS14030557. PMID: 35335933; PMCID: PMC8955881Habeebuddin M., Karnati R.K., Shiroorkar P.N., et al. Topical probiotics: more than a skin deep. Pharmaceutics. 2022 Mar 3; 14(3): 557. https://doi.org/10.3390/PHARMACEUTICS14030557. PMID: 35335933; PMCID: PMC8955881Leung D.Y.M., Travers J.B., Giorno R., et al. Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis. J Clin Invest. 1995 Nov; 96(5): 2106–2112. https://doi.org/10.1172/JCI118263. PMID: 7593594; PMCID: PMC185858Leung D.Y.M., Travers J.B., Giorno R., et al. Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis. J Clin Invest. 1995 Nov; 96(5): 2106–2112. https://doi.org/10.1172/JCI118263. PMID: 7593594; PMCID: PMC185858Valdimarsson H., Baker B.S., Jónsdóttir I., et al. Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens? Immunol Today. 1995 Mar; 16(3): 145–149. https://doi.org/10.1016/0167-5699(95)80132-4. PMID: 7718088Valdimarsson H., Baker B.S., Jónsdóttir I., et al. Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens? Immunol Today. 1995 Mar; 16(3): 145–149. https://doi.org/10.1016/0167-5699(95)80132-4. PMID: 7718088Rendon A., Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019 Mar 23; 20(6): 1475. https://doi.org/10.3390/ijms20061475. PMID: 30909615; PMCID: PMC6471628Rendon A., Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019 Mar 23; 20(6): 1475. https://doi.org/10.3390/ijms20061475. PMID: 30909615; PMCID: PMC6471628Hsu D.K., Fung M.A., Chen H.-L. Role of skin and gut microbiota in the pathogenesis of psoriasis, an infl ammatory skin disease. Med Microecol. 2020 June; 4: 100016. https://doi.org/10.1016/j.medmic.2020.100016Hsu D.K., Fung M.A., Chen H.-L. Role of skin and gut microbiota in the pathogenesis of psoriasis, an infl ammatory skin disease. Med Microecol. 2020 June; 4: 100016. https://doi.org/10.1016/j.medmic.2020.100016Kim H., Cho S.K., Kim H.W., et al. The prevalence of Sjögren’s syndrome in rheumatoid arthritis patients and their clinical features. J Korean Med Sci. 2020 Nov 23; 35(45): e369. https://doi.org/10.3346/JKMS.2020.35.E369. PMID: 33230982; PMCID: PMC7683240Kim H., Cho S.K., Kim H.W., et al. The prevalence of Sjögren’s syndrome in rheumatoid arthritis patients and their clinical features. J Korean Med Sci. 2020 Nov 23; 35(45): e369. https://doi.org/10.3346/JKMS.2020.35.E369. PMID: 33230982; PMCID: PMC7683240Xu J., Chen C., Yin J., et al. Lactate-induced mtDNA accumulation activates cGAS-STING signaling and the infl ammatory response in Sjögren’s syndrome. Int J Med Sci. 2023 Aug 15; 20(10): 1256– 1271. https://doi.org/10.7150/IJMS.83801. PMID: 37786436; PMCID: PMC10542019Xu J., Chen C., Yin J., et al. Lactate-induced mtDNA accumulation activates cGAS-STING signaling and the infl ammatory response in Sjögren’s syndrome. Int J Med Sci. 2023 Aug 15; 20(10): 1256– 1271. https://doi.org/10.7150/IJMS.83801. PMID: 37786436; PMCID: PMC10542019Zhan Q., Zhang J., Lin Y., et al. Pathogenesis and treatment of Sjogren’s syndrome: Review and update. Front Immunol. 2023 Feb 2; 14: 1127417. https://doi.org/10.3389/fimmu.2023.1127417. PMID: 36817420; PMCID: PMC9932901Zhan Q., Zhang J., Lin Y., et al. Pathogenesis and treatment of Sjogren’s syndrome: Review and update. Front Immunol. 2023 Feb 2; 14: 1127417. https://doi.org/10.3389/fimmu.2023.1127417. PMID: 36817420; PMCID: PMC9932901Szymula A., Rosenthal J., Szczerba B.M., et al. T cell epitope mimicry between Sjögren’s syndrome Antigen A (SSA)/ Ro60 and oral, gut, skin and vaginal bacteria. Clin Immunol. 2014 May-Jun; 152(1–2): 1–9. https://doi.org/10.1016/J.CLIM.2014.02.004. Epub 2014 Feb 19. PMID: 24576620; PMCID: PMC4004658Szymula A., Rosenthal J., Szczerba B.M., et al. T cell epitope mimicry between Sjögren’s syndrome Antigen A (SSA)/ Ro60 and oral, gut, skin and vaginal bacteria. Clin Immunol. 2014 May-Jun; 152(1–2): 1–9. https://doi.org/10.1016/J.CLIM.2014.02.004. Epub 2014 Feb 19. PMID: 24576620; PMCID: PMC4004658Bellando-Randone S., Russo E., Venerito V., et al. Exploring the oral microbiome in rheumatic diseases, state of art and future prospective in personalized medicine with an AI approach. J Pers Med. 2021 Jun 30; 11(7): 625. https://doi.org/10.3390/JPM11070625. PMID: 34209167; PMCID: PMC8306274Bellando-Randone S., Russo E., Venerito V., et al. Exploring the oral microbiome in rheumatic diseases, state of art and future prospective in personalized medicine with an AI approach. J Pers Med. 2021 Jun 30; 11(7): 625. https://doi.org/10.3390/JPM11070625. PMID: 34209167; PMCID: PMC8306274Lee J., Alam J., Choi E., et al. Association of a dysbiotic oral microbiota with the development of focal lymphocytic sialadenitis in IκB-ζ-defi cient mice. NPJ Biofi lms Microbiomes. 2020 Oct 30; 6(1): 49. https://doi.org/10.1038/S41522-020-00158-4. PMID: 33127905; PMCID: PMC7599236Lee J., Alam J., Choi E., et al. Association of a dysbiotic oral microbiota with the development of focal lymphocytic sialadenitis in IκB-ζ-defi cient mice. NPJ Biofi lms Microbiomes. 2020 Oct 30; 6(1): 49. https://doi.org/10.1038/S41522-020-00158-4. PMID: 33127905; PMCID: PMC7599236van der Meulen T.A., Harmsen H.J.M., Bootsma H., et al. Dysbiosis of the buccal mucosa microbiome in primary Sjögren’s syndrome patients. Rheumatology (Oxford). 2018 Dec 1; 57(12): 2225–2234. https://doi.org/10.1093/RHEUMATOLOGY/KEY215. PMID: 30060225van der Meulen T.A., Harmsen H.J.M., Bootsma H., et al. Dysbiosis of the buccal mucosa microbiome in primary Sjögren’s syndrome patients. Rheumatology (Oxford). 2018 Dec 1; 57(12): 2225–2234. https://doi.org/10.1093/RHEUMATOLOGY/KEY215. PMID: 30060225Rusthen S., Kristoffersen A.K., Young A., et al. Dysbiotic salivary microbiota in dry mouth and primary Sjögren’s syndrome patients. PLoS One. 2019 Jun 18; 14(6): e0218319. https://doi.org/10.1371/JOURNAL.PONE.0218319. PMID: 31211815; PMCID: PMC6581286Rusthen S., Kristoffersen A.K., Young A., et al. Dysbiotic salivary microbiota in dry mouth and primary Sjögren’s syndrome patients. PLoS One. 2019 Jun 18; 14(6): e0218319. https://doi.org/10.1371/JOURNAL.PONE.0218319. PMID: 31211815; PMCID: PMC6581286Zhou Z., Ling G., Ding N., et al. Molecular analysis of oral microfl ora in patients with primary Sjögren’s syndrome by using high-throughput sequencing. PeerJ. 2018 Sep 28; 6: e5649. https://doi.org/10.7717/PEERJ.5649. PMID: 30280027; PMCID: PMC6166617Zhou Z., Ling G., Ding N., et al. Molecular analysis of oral microfl ora in patients with primary Sjögren’s syndrome by using high-throughput sequencing. PeerJ. 2018 Sep 28; 6: e5649. https://doi.org/10.7717/PEERJ.5649. PMID: 30280027; PMCID: PMC6166617Siddiqui H., Chen T., Aliko A., et al. Microbiological and bioinformatics analysis of primary Sjogren’s syndrome patients with normal salivation. J Oral Microbiol. 2016 Oct 20; 8: 31119. https://doi.org/10.3402/JOM.V8.31119. PMID: 27770517; PMCID: PMC5075221Siddiqui H., Chen T., Aliko A., et al. Microbiological and bioinformatics analysis of primary Sjogren’s syndrome patients with normal salivation. J Oral Microbiol. 2016 Oct 20; 8: 31119. https://doi.org/10.3402/JOM.V8.31119. PMID: 27770517; PMCID: PMC5075221Wang X., Pang K., Wang J., et al. Microbiota dysbiosis in primary Sjögren’s syndrome and the ameliorative effect of hydroxychloroquine. Cell Rep. 2022 Sep 13; 40(11): 111352. https://doi.org/10.1016/J.CELREP.2022.111352. PMID: 36103827Wang X., Pang K., Wang J., et al. Microbiota dysbiosis in primary Sjögren’s syndrome and the ameliorative effect of hydroxychloroquine. Cell Rep. 2022 Sep 13; 40(11): 111352. https://doi.org/10.1016/J.CELREP.2022.111352. PMID: 36103827Alam J., Lee A., Lee J., et al. Dysbiotic oral microbiota and infected salivary glands in Sjögren’s syndrome. PLoS One. 2020 Mar 24; 15(3): e0230667. https://doi.org/10.1371/JOURNAL.PONE.0230667. PMID: 32208441; PMCID: PMC7092996Alam J., Lee A., Lee J., et al. Dysbiotic oral microbiota and infected salivary glands in Sjögren’s syndrome. PLoS One. 2020 Mar 24; 15(3): e0230667. https://doi.org/10.1371/JOURNAL.PONE.0230667. PMID: 32208441; PMCID: PMC7092996Zhou F., Paz H.A., Sadri M., et al. Nutrient Sensing, nutrition, and metabolism: dietary bovine milk exosomes elicit changes in bacterial communities in C57BL/6 mice. Am J Physiol – Gastrointest Liver Physiol. 2019 Nov 1; 317(5): G618–G624. https://doi.org/10.1152/AJPGI.00160.2019. Epub 2019 Sep 11. PMID: 31509432; PMCID: PMC6879888Zhou F., Paz H.A., Sadri M., et al. Nutrient Sensing, nutrition, and metabolism: dietary bovine milk exosomes elicit changes in bacterial communities in C57BL/6 mice. Am J Physiol – Gastrointest Liver Physiol. 2019 Nov 1; 317(5): G618–G624. https://doi.org/10.1152/AJPGI.00160.2019. Epub 2019 Sep 11. PMID: 31509432; PMCID: PMC6879888Rastogi S., Singh A. Gut microbiome and human health: exploring how the probiotic genus Lactobacillus modulate immune responses. Front Pharmacol. 2022 Oct 24; 13: 1042189. https://doi.org/10.3389/fphar.2022.1042189. PMID: 36353491; PMCID: PMC9638459Rastogi S., Singh A. Gut microbiome and human health: exploring how the probiotic genus Lactobacillus modulate immune responses. Front Pharmacol. 2022 Oct 24; 13: 1042189. https://doi.org/10.3389/fphar.2022.1042189. PMID: 36353491; PMCID: PMC9638459Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research. Appl Environ Microbiol. 2008 Aug; 74(16): 4985–4996. https://doi.org/10.1128/AEM.00753-08. Epub 2008 Jun 6. PMID: 18539818; PMCID: PMC2519286Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research. Appl Environ Microbiol. 2008 Aug; 74(16): 4985–4996. https://doi.org/10.1128/AEM.00753-08. Epub 2008 Jun 6. PMID: 18539818; PMCID: PMC2519286Dempsey E., Corr S.C. Lactobacillus spp. for gastrointestinal health: current and future perspectives. Front Immunol. 2022 Apr 6; 13: 840245. https://doi.org/10.3389/FIMMU.2022.840245. PMID: 35464397; PMCID: PMC9019120Dempsey E., Corr S.C. Lactobacillus spp. for gastrointestinal health: current and future perspectives. Front Immunol. 2022 Apr 6; 13: 840245. https://doi.org/10.3389/FIMMU.2022.840245. PMID: 35464397; PMCID: PMC9019120De Almeida C.V., Antiga E., Lulli M. Oral and topical probiotics and postbiotics in skincare and dermatological therapy: a concise review. Microorganisms. 2023 May 27; 11(6): 1420. https://doi.org/10.3390/MICROORGANISMS11061420. PMID: 37374920; PMCID: PMC10301930De Almeida C.V., Antiga E., Lulli M. Oral and topical probiotics and postbiotics in skincare and dermatological therapy: a concise review. Microorganisms. 2023 May 27; 11(6): 1420. https://doi.org/10.3390/MICROORGANISMS11061420. PMID: 37374920; PMCID: PMC10301930Gelmetti C., Rigoni C., Cantù A.M., et al. Topical prebiotics/ postbiotics and PRURISCORE validation in atopic dermatitis. International study of 396 patients. J Dermatolog Treat. 2023 Dec; 34(1): 2131703. https://doi.org/10.1080/09546634.2022.2131703. Epub 2022 Oct 17. PMID: 36205596Gelmetti C., Rigoni C., Cantù A.M., et al. Topical prebiotics/ postbiotics and PRURISCORE validation in atopic dermatitis. International study of 396 patients. J Dermatolog Treat. 2023 Dec; 34(1): 2131703. https://doi.org/10.1080/09546634.2022.2131703. Epub 2022 Oct 17. PMID: 36205596Knackstedt R., Knackstedt T., Gatherwright J. The role of topical probiotics in skin conditions: A systematic review of animal and human studies and implications for future therapies. Exp Dermatol. 2020 Jan; 29(1): 15–21. https://doi.org/10.1111/EXD.14032. Epub 2019 Sep 18. PMID: 31494971Knackstedt R., Knackstedt T., Gatherwright J. The role of topical probiotics in skin conditions: A systematic review of animal and human studies and implications for future therapies. Exp Dermatol. 2020 Jan; 29(1): 15–21. https://doi.org/10.1111/EXD.14032. Epub 2019 Sep 18. PMID: 31494971Hussey G.S., Molina C.P., Cramer M.C., et al. Lipidomics and RNA sequencing reveal a novel subpopulation of nanovesicle within extracellular matrix biomaterials. Sci Adv. 2020 Mar 20; 6(12): eaay4361. https://doi.org/10.1126/SCIADV.AAY4361. PMID: 32219161; PMCID: PMC7083606Hussey G.S., Molina C.P., Cramer M.C., et al. Lipidomics and RNA sequencing reveal a novel subpopulation of nanovesicle within extracellular matrix biomaterials. Sci Adv. 2020 Mar 20; 6(12): eaay4361. https://doi.org/10.1126/SCIADV.AAY4361. PMID: 32219161; PMCID: PMC7083606Manzaneque-López M.C., Sánchez-López C.M., Pérez-Bermúdez P., et al. Dietary-derived exosome-like nanoparticles as bacterial modulators: beyond microRNAs. Nutrients. 2023 Mar 3; 15(5): 1265. https://doi.org/10.3390/NU15051265. PMID: 36904264; PMCID: PMC10005434Manzaneque-López M.C., Sánchez-López C.M., Pérez-Bermúdez P., et al. Dietary-derived exosome-like nanoparticles as bacterial modulators: beyond microRNAs. Nutrients. 2023 Mar 3; 15(5): 1265. https://doi.org/10.3390/NU15051265. PMID: 36904264; PMCID: PMC10005434Skowron K., Bauza-Kaszewska J., Kraszewska Z., et al. Human skin microbiome: impact of intrinsic and extrinsic factors on skin microbiota. Microorganisms. 2021 Mar 5; 9(3): 543. https://doi.org/10.3390/MICROORGANISMS9030543. PMID: 33808031; PMCID: PMC7998121Skowron K., Bauza-Kaszewska J., Kraszewska Z., et al. Human skin microbiome: impact of intrinsic and extrinsic factors on skin microbiota. Microorganisms. 2021 Mar 5; 9(3): 543. https://doi.org/10.3390/MICROORGANISMS9030543. PMID: 33808031; PMCID: PMC7998121Quan C., Chen X.Y., Li X., et al. Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium. J Am Acad Dermatol. 2020 Apr; 82(4): 955–961. https://doi.org/10.1016/J.JAAD.2019.06.024. Epub 2019 Jun 19. PMID: 31228520Quan C., Chen X.Y., Li X., et al. Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium. J Am Acad Dermatol. 2020 Apr; 82(4): 955–961. https://doi.org/10.1016/J.JAAD.2019.06.024. Epub 2019 Jun 19. PMID: 31228520Cros M.P., Mir-Pedrol J., Toloza L., et al. New insights into the role of Cutibacterium acnes-derived extracellular vesicles in infl ammatory skin disorders. Sci Rep. 2023 Sep 25; 13(1): 16058. https://10.1038/S41598-023-43354-W. PMID: 37749255; PMCID: PMC10520063Cros M.P., Mir-Pedrol J., Toloza L., et al. New insights into the role of Cutibacterium acnes-derived extracellular vesicles in infl ammatory skin disorders. Sci Rep. 2023 Sep 25; 13(1): 16058. https://10.1038/S41598-023-43354-W. PMID: 37749255; PMCID: PMC10520063Jo C.S., Myung C.H., Yoon Y.C., et al. The effect of lactobacillus plantarum extracellular vesicles from Korean women in their 20s on skin aging. Curr Issues Mol Biol. 2022 Jan 21;44(2):526–540. https://doi.org/10.3390/CIMB44020036. PMID: 35723322; PMCID: PMC8928950Jo C.S., Myung C.H., Yoon Y.C., et al. The effect of lactobacillus plantarum extracellular vesicles from Korean women in their 20s on skin aging. Curr Issues Mol Biol. 2022 Jan 21;44(2):526–540. https://doi.org/10.3390/CIMB44020036. PMID: 35723322; PMCID: PMC8928950Zhou H., Tan X., Chen G., et al. Extracellular vesicles of commensal skin microbiota alleviate cutaneous infl ammation in atopic dermatitis mouse model by re-establishing skin homeostasis. J Invest Dermatol. 2023 Mar 11: S0022-202X(23)00169-0. https://doi.org/10.1016/J.JID.2023.02.023. Epub ahead of print. PMID: 36907322Zhou H., Tan X., Chen G., et al. Extracellular vesicles of commensal skin microbiota alleviate cutaneous infl ammation in atopic dermatitis mouse model by re-establishing skin homeostasis. J Invest Dermatol. 2023 Mar 11: S0022-202X(23)00169-0. https://doi.org/10.1016/J.JID.2023.02.023. Epub ahead of print. PMID: 36907322Kim M.H., Choi S.J., Choi H., et al. Lactobacillus plantarumderived extracellular vesicles protect atopic dermatitis induced by Staphylococcus aureus-derived extracellular vesicles. Allergy Asthma Immunol Res. 2018 Sep; 10(5): 516–532. https://doi.org/10.4168/AAIR.2018.10.5.516. PMID: 30088371; PMCID: PMC6082821Kim M.H., Choi S.J., Choi H., et al. Lactobacillus plantarumderived extracellular vesicles protect atopic dermatitis induced by Staphylococcus aureus-derived extracellular vesicles. Allergy Asthma Immunol Res. 2018 Sep; 10(5): 516–532. https://doi.org/10.4168/AAIR.2018.10.5.516. PMID: 30088371; PMCID: PMC6082821Rebelo M.B., Oliveira C.S., Tavaria F.K. Novel strategies for preventing dysbiosis in the oral cavity. Front Biosci. 2023 Oct 16; 15(4): 23. https://doi.org/10.31083/j.fbe1504023. PMID: 38163934Rebelo M.B., Oliveira C.S., Tavaria F.K. Novel strategies for preventing dysbiosis in the oral cavity. Front Biosci. 2023 Oct 16; 15(4): 23. https://doi.org/10.31083/j.fbe1504023. PMID: 38163934Zhang Y., Ding Y., Guo Q. Probiotic species in the management of periodontal diseases: an overview. Front Cell Infect Microbiol. 2022 Mar 25; 12: 806463. https://doi.org/10.3389/FCIMB.2022.806463. PMID: 35402306; PMCID: PMC8990095Zhang Y., Ding Y., Guo Q. Probiotic species in the management of periodontal diseases: an overview. Front Cell Infect Microbiol. 2022 Mar 25; 12: 806463. https://doi.org/10.3389/FCIMB.2022.806463. PMID: 35402306; PMCID: PMC8990095Bizzini B., Pizzo G., Scapagnini G., et al. Probiotics and oral health. Curr Pharm Des. 2012; 18(34): 5522–5531. https://doi.org/10.2174/138161212803307473. PMID: 22632388Bizzini B., Pizzo G., Scapagnini G., et al. Probiotics and oral health. Curr Pharm Des. 2012; 18(34): 5522–5531. https://doi.org/10.2174/138161212803307473. PMID: 22632388Abikshyeet P., Mishra P., Bhuyan L., et al. Probiotics: dawn of a new era in dental caries management. J Pharm Bioallied Sci. 2022 Jul; 14(Suppl 1): S34–S38. https://doi.org/10.4103/JPBS.JPBS_801_21. Epub 2022 Jul 13. PMID: 36110745; PMCID: PMC9469361Abikshyeet P., Mishra P., Bhuyan L., et al. Probiotics: dawn of a new era in dental caries management. J Pharm Bioallied Sci. 2022 Jul; 14(Suppl 1): S34–S38. https://doi.org/10.4103/JPBS.JPBS_801_21. Epub 2022 Jul 13. PMID: 36110745; PMCID: PMC9469361

The authors declare that there are no conflicts of interest present.