Palabras clave
microARNs
microbiota
permeabilidad intestinal
autoanticuerpos
Cómo citar
Resumen
Problema: El aumento de la infertilidad a nivel mundial no solo esta vinculado al aumento de la edad materna sino al impacto de factores ambientales que provocan cambios epigenéticos en el estado de salud de la mujer, y que tienen impacto en el origen de trastornos inflamatorios cuyo primer síntoma podria ser la infertilidad. Método de estudio: Se reclutó a un total de 301 mujeres con multiples fracasos de FIV-ET. Se analizo la expresión de microARNs especificos asociados a desbalances de la microbiota junto con marcadores en sangre y en saliva. Todas las pacientes mostraron desbalances al menos uno de los marcadores antes mencionados y decidieron seguir con su tratamiento habitual (n=23) o personalizar una suplementación alimentaria y de probioticos durante 75 días (n=278). La tasa de embarazo fue comparada entre ambos grupos luego de 180 días de busqueda de embarazo. Resultado(s): El 84% de las pacientes infértiles mostraron un aumento en al menos uno de estos microARNs. Teniendo en cuenta estos parámetros y los marcadores de sangre periférica y saliva, las pacientes fueron suplementadas con una combinación de dietas biomédicas, probióticos y nutracéuticos. La tasa de embarazo tras otro intento de FIV-ET fue del 75% para el grupo que personalizo la suplementación y del 30% para el grupo que no realizó la suplementación (*p<0.05). Conclusiones: Una suplementación dietaria adecuada según nuestra novedosa plataforma de diagnóstico de microARNs mejoró la tasa de embarazo de los pacientes con multiples fallas de FIV-ET.
Citas
Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018;62:2-10. doi:10.1016/j. clinbiochem.2018.03.012
Inhorn MC, Patrizio P. Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2014;21(4):411-426. doi:10.1093/humupd/dmv016
Sadegui MR. Unexplained Infertility, the Controversial Matter in Management of Infertile Couples - PubMed.; 2015. doi:10.1093/humupd/dmv016. Epub 2015 Mar 22. PMID: 25801630
Kåhrström CT, Pariente N, Weiss U. Intestinal microbiota in health and disease. Nature. 2016;535(7610):47. doi:10.1038/535047a
Dinan TG, Cryan JF. The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol Clin North Am. 2017;46(1):77-89. doi:10.1016/j.gtc.2016.09.007
Lynch S V., Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016;375(24):2369-2379. doi:10.1056/nejmra1600266
Fallucca F, Porrata C, Fallucca S, Pianesi M. Influence of diet on gut microbiota, inflammation and type 2 diabetes mellitus. First experience with macrobiotic Ma-Pi 2 diet. Diabetes Metab Res Rev. 2014;30(S1):48-54. doi:10.1002/dmrr.2518
Aagaard K, Riehle K, Ma J, et al. A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy. PLoS One. 2012;7(6). doi:10.1371/journal. pone.0036466
Boers SA, Jansen R, Hays JP. Understanding and overcoming the pitfalls and biases of next-generation sequencing (NGS) methods for use in the routine clinical microbiological diagnostic laboratory. Eur J Clin Microbiol Infect Dis. 2019;38(6):1059-1070. doi:10.1007/s10096-019-03520-3
Degruttola AK, Low D, Mizoguchi A, Mizoguchi E. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis. 2016;22(5):1137-1150. doi:10.1097/MIB.0000000000000750
Campisciano G, Florian F, D’Eustacchio A, et al. Subclinical alteration of the cervical–vaginal microbiome in women with idiopathic infertility. J Cell Physiol. 2017;232(7):1681-1688. doi:10.1002/jcp.25806
Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol. 2017;17(8):469-482. doi:10.1038/nri.2017.64
Fasano A, Shea-Donohue T. Mechanisms of disease: The role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005;2(9):416-422. doi:10.1038/ncpgasthep0259
Arvonen M, Berntson L, Pokka T, Karttunen TJ, Vähäsalo P, Stoll ML. Gut microbiota-host interactions and juvenile idiopathic arthritis. Pediatr Rheumatol. 2016;14(1). doi:10.1186/s12969-016-0104-6
Fahlén A, Engstrand L, Baker BS, Powles A, Fry L. Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch Dermatol Res. 2012;304(1):15-22. doi:10.1007/s00403-011-1189-x
Hold GL, Smith M, Grange C, Watt ER, El-Omar EM, Mukhopadhya I. Role of the gut microbiota in inflammatory bowel disease pathogenesis: What have we learnt in the past 10 years? World J Gastroenterol. 2014;20(5):1192-1210. doi:10.3748/wjg.v20.i5.1192
Huipeng W, Lifeng G, Chuang G, Jiaying Z, Yuankun C. The differences in colonic mucosal microbiota between normal individual and colon cancer patients by polymerase chain reaction-denaturing gradient gel electrophoresis. J Clin Gastroenterol. 2014;48(2):138-144. doi:10.1097/MCG.0b013e3182a26719
Maes M, Kubera M, Leuni J-C. The gut-brain barrier in major depression: Intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. Published online
Pärtty A, Kalliomäki M, Wacklin P, Salminen S, Isolauri E. A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: A randomized trial. Pediatr Res. 2015;77(6):823-828. doi:10.1038/pr.2015.51
Peterson DA, Frank DN, Pace NR, Gordon JI. Metagenomic Approaches for Defining the Pathogenesis of Inflammatory Bowel Diseases. Cell Host Microbe. 2008;3(6):417-427. doi:10.1016/j.chom.2008.05.001
Jeon MK. Intestinal barrier: Molecular pathways and modifiers. World J Gastrointest Pathophysiol. 2013;4(4):94. doi:10.4291/wjgp.v4.i4.94
Catanzaro JR, Strauss JD, Bielecka A, et al. IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM. Sci Rep. 2019;9(1). doi:10.1038/s41598-019-49923-2
Gulyaeva LF, Kushlinskiy NE. Regulatory mechanisms of microRNA expression. J Transl Med. 2016;14(1). doi:10.1186/s12967-016-0893-x
Mortha A, Chudnovskiy A, Hashimoto D, et al. Microbiota- dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science (80- ). 2014;343(6178). doi:10.1126/science.1249288
Curtale G, Rubino M, Locati M. MicroRNAs as molecular switches in macrophage activation. Front Immunol. 2019;10(MAR). doi:10.3389/fimmu.2019.00799
Vojdani A. For the assessment of intestinal permeability, size matters. Altern Ther Health Med. 2013;19(1):12-24. Accessed January 12, 2021. https://pubmed.ncbi.nlm.nih. gov/23341423/
Gleicher N, El-Roeiy A. The reproductive autoimmune failure syndrome. Am J Obstet Gynecol. 1988;159(1):223-227. doi:10.1016/0002-9378(88)90525-X
Laschke MW, Menger MD. The gut microbiota: A puppet master in the pathogenesis of endometriosis? Am J Obstet Gynecol. 2016;215(1):68.e1-68.e4. doi:10.1016/j.ajog.2016.02.036
De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019;195(1):74-85. doi:10.1111/cei.13158
Yu LCH. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis. J Biomed Sci. 2018;25(1). doi:10.1186/s12929-018-0483-8
Flores R, Shi J, Fuhrman B, et al. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: A cross-sectional study. J Transl Med. 2012;10(1). doi:10.1186/1479-5876-10-253
Zeng B, Lai Z, Sun L, et al. Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study. Res Microbiol. 2019;170(1):43-52. doi:10.1016/j.resmic.2018.09.002
Yurtdaş G, Akdevelioğlu Y. A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota. J Am Coll Nutr. 2020;39(4):371-382. doi:10.1080/07315724.2019.1657515
MA A, L O, MI P, et al. Potential biomarkers of infertility associated with microbiome imbalances. Am J Reprod Immunol. Published online 2021. doi:10.1111/AJI.13438
Zhang L, Zhang F, He DK, Fan XM, Shen J. MicroRNA-21 is upregulated during intestinal barrier dysfunction induced by ischemia reperfusion. Kaohsiung J Med Sci. 2018;34(10):556-563. doi:10.1016/j.kjms.2018.05.006
Zhang L, Shen J, Cheng J, Fan X. MicroRNA-21 regulates intestinal epithelial tight junction permeability. Cell Biochem Funct. 2015;33(4):235-240. doi:10.1002/cbf.3109
Nakata K, Sugi Y, Narabayashi H, et al. Commensal Microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4. J Biol Chem. 2017;292(37):15426-15433. doi:10.1074/jbc.M117.788596
Shi C, Liang Y, Yang J, et al. MicroRNA-21 Knockout Improve the Survival Rate in DSS Induced Fatal Colitis through Protectingagainst Inflammation and Tissue Injury. PLoS One.2013;8(6). doi:10.1371/journal.pone.0066814
Shi C, Yang Y, Xia Y, et al. Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer. Gut. 2016;65(9):1470-1481. doi:10.1136/gutjnl-2014-308455
Jiang W, Li X. Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy. Mol Diagnosis Ther. 2015;19(3):141-158. doi:10.1007/s40291-015-0142-7
Xu WD, Pan HF, Li JH, Ye DQ. MicroRNA-21 with therapeutic potential in bl Sci. 2016;17(6). doi:10.3390/ijms17060864
Wang Z, Brandt S, Medeiros A, et al. MicroRNA 21 Is a homeostatic regulator of macrophage polarization and prevents prostaglandin e2 -mediated M2 generation. PLoS One. 2015;10(2). doi:10.1371/journal.pone.0115855
Croston TL, Lemons AR, Beezhold DH, Green BJ. MicroRNA regulation of host immune responses following fungal exposure. Front Immunol. 2018;9(FEB). doi:10.3389/fimmu. 2018.00170
Abdul-Maksoud RS, Sediq AM, Kattaia AAA, et al. Serum miR-210 and miR-155 expression levels as novel biomarkers for rheumatoid arthritis diagnosis. Br J Biomed Sci. 2017;74(4):209-213. doi:10.1080/09674845.2017.1343545
Bala S, Csak T, Saha B, et al. The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis. J Hepatol. 2016;64(6):1378-1387. doi:10.1016/j.jhep.2016.01.035
Saare M, Rekker K, Laisk-Podar T, et al. Challenges in endometriosis miRNA studies — From tissue heterogeneity to disease specific miRNAs. Biochim Biophys Acta - Mol Basis Dis. 2017;1863(9):2282-2292. doi:10.1016/j.bbadis.2017.06.018
Nisenblat V, Sharkey DJ, Wang Z, et al. Plasma miRNAs display limited potential as diagnostic tools for endometriosis. J Clin Endocrinol Metab. 2019;104(6):1999-2022. doi:10.1210/jc.2018-01464
Rotelli MT, Di Lena M, Cavallini A, et al. Fecal microRNA profile in patients with colorectal carcinoma before and after curative surgery. Int J Colorectal Dis. 2015;30(7):891-898. doi:10.1007/s00384-015-2248-0
Kulnigg-Dabsch S. Autoimmungastritis. Wiener Medizinische Wochenschrift. 2016;166(13-14):424-430. doi:10.1007/s10354-016-0515-5
Rodriguez-Castro KI, Franceschi M, Noto A, et al. Clinical manifestations of chronic atrophic gastritis. Acta Biomed. 2018;89(8-S):88-92. doi:10.23750/abm.v89i8-S.7921
Belizário JE, Faintuch J, Garay-Malpartida M. New frontiers for treatment of metabolic diseases. Mediators Inflamm. 2018;2018. doi:10.1155/2018/2037838
Kalinkovich A, Gabdulina G, Livshits G. Autoimmunity, inflammation, and dysbiosis mutually govern the transition from the preclinical to the clinical stage of rheumatoid arthritis. Immunol Res. 2018;66(6):696-709. doi:10.1007/s12026-018-9048-x
Vojdani A, Vojdani E, Herbert M, Kharrazian D. Correlation between antibodies to bacterial lipopolysaccharides and barrier proteins in sera positive for asca and anca. Int J Mol Sci. 2020;21(4). doi:10.3390/ijms21041381