Changes in the composition of intestinal microbiota and their association with cortisol, melatonin, tumor necrosis factor-α, and interleukin-17 levels in women with idiopathic recurrent miscarriage
- Authors: Gumenyuk L.N.1, Gavrilov M.V.2, Puchkina G.A.1, Asanova F.S.1, Medzhitova D.R.1, Bordyugov M.D.1, Tishchenko V.A.1, Rudeva K.A.1
-
Affiliations:
- V.I. Vernadsky Crimean Federal University
- GUTA Clinic LLC
- Issue: No 6 (2024)
- Pages: 37-45
- Section: Original Articles
- URL: https://journals.rcsi.science/0300-9092/article/view/260521
- DOI: https://doi.org/10.18565/aig.2024.34
- ID: 260521
Cite item
Abstract
Objective: This study aimed to evaluate changes in the taxonomic composition of the intestinal microbiota and examine their relationship with serum levels of cortisol, melatonin, tumor necrosis factor-α (TNF-α), and interleukin-17 (IL-17) in women with idiopathic recurrent miscarriage (IRM).
Materials and methods: This study included 55 women with IRM and 60 women with healthy pregnancies. The taxonomic composition of the gut microbiota and the serum concentrations of cortisol, melatonin, TNF-α, and IL-17 were analyzed.
Results: The study found that women with IRM exhibited changes in the taxonomic composition of intestinal microbiota, characterized by a significant decrease in α-diversity of the bacterial community (Chao1 index p=0.014) and a decrease in the abundance of Bifidobacterium (p<0.001), Lachnospira (p=0.032), Roseburia (p=0.003), and Coprococcus (p=0.012). Additionally, there was an increase in the abundance of Ruminococcus (p<0.001) and Klebsiella (p=0.002). Significant correlations were observed between cortisol levels and the presence of Lachnospira bacteria (r=-0.51; p=0.002) and between melatonin and the presence of Coprococcus bacteria (r=-0.49; p=0.012). Correlations were also identified between TNF-α and IL-17 concentrations and the Chao1 index (r=-0.51, p=0.002; r=-0.54, p=0.001, respectively), TNF-α and the abundance of Ruminococcus bacteria (r=0.51; p=0.002), and IL-17 and the abundance of Bifidobacterium (r=-0.52; p=0.001).
Conclusion: Potential modifications to the gut microbiota may have preventive and therapeutic implications in women with IRM.
Full Text
##article.viewOnOriginalSite##About the authors
Lesya N. Gumenyuk
V.I. Vernadsky Crimean Federal University
Author for correspondence.
Email: lesya_gymenyuk@mail.ru
ORCID iD: 0000-0003-2785-3882
Dr. Med. Sci., Professor at the Department of Psychiatry, Narcology, Psychotherapy with a course of general and medical psychology, S.I. Georgievsky Medical Institute
Russian Federation, SimferopolMikhail V. Gavrilov
GUTA Clinic LLC
Email: centr.gyn@yandex.ru
ORCID iD: 0000-0002-3957-2087
Head of Operational Gynecology
Russian Federation, MoscowGalina A. Puchkina
V.I. Vernadsky Crimean Federal University
Email: puchkina.g.a@mail.ru
ORCID iD: 0000-0002-8882-8317
Associate Professor at the Department of Obstetrics, Gynecology and Perinatology No. 1, S.I. Georgievsky Medical Institute
Russian Federation, SimferopolFeride S. Asanova
V.I. Vernadsky Crimean Federal University
Email: feride.asanova.01.01@mail.ru
ORCID iD: 0009-0003-3919-6485
Student at the S.I. Georgievsky Medical Institute
Russian Federation, SimferopolDiana R. Medzhitova
V.I. Vernadsky Crimean Federal University
Email: medzhitova9032001@mail.ru
ORCID iD: 0009-0008-8642-3851
Student at the S.I. Georgievsky Medical Institute
Russian Federation, SimferopolMaxim D. Bordyugov
V.I. Vernadsky Crimean Federal University
Email: maksjing4@mail.ru
ORCID iD: 0009-0002-4031-8649
Student at the S.I. Georgievsky Medical Institute
Russian Federation, SimferopolVladislav A. Tishchenko
V.I. Vernadsky Crimean Federal University
Email: lacebrra2016@gmail.com
ORCID iD: 0009-0003-3344-0766
Student at the S.I. Georgievsky Medical Institute
Russian Federation, SimferopolKsenia A. Rudeva
V.I. Vernadsky Crimean Federal University
Email: rudeva00@mail.ru
ORCID iD: 0009-0001-1857-1157
Student at the S.I. Georgievsky Medical Institute
Russian Federation, SimferopolReferences
- Lund M., Kamper-Jørgensen M., Nielsen H.S., Lidegaard Ø., Andersen A.-M.N., Christiansen O.B. Prognosis for live birth in women with recurrent miscarriage: what is the best measure of success? Obstet. Gynecol. 2012; 119(1): 37-43. https://dx.doi.org/10.1097/AOG.0b013e31823c0413.
- Abu-Heija A. Thrombophilia and recurrent pregnancy loss: Is heparin still the drug of choice? Sultan Qaboos Univ. Med. J. 2014; 14(1): e26-36. https:// dx.doi.org/10.12816/0003333.
- Mor G., Aldo P., Alvero A.B. The unique immunological and microbial aspects of pregnancy. Nat. Rev. Immunol. 2017; 17(8): 469-82. https:// dx.doi.org/10.1038/nri.2017.64.
- Saifi B., Rezaee S.A., Tajik N., Ahmadpour M.E., Ashrafi M., Vakili R. et al. Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. Reprod. Biomed. Online. 2014; 29(4): 481-9. https://dx.doi.org/10.1016/j.rbmo.2014.06.008.
- Shaarawy M., Nagui A.R. Enhanced expression of cytokines may play a fundamental role in the mechanisms of immunologically mediated recurrent spontaneous abortion. Acta Obstet. Gynecol. Scand. 1997; 76(3): 205-11. https://dx.doi.org/10.3109/00016349709048142.
- Azizieh F.Y., Raghupathy R.G. Tumor necrosis factor-α and pregnancy complications: a prospective study. Med. Princ. Pract. 2015; 24(2): 165-70. https://dx.doi.org/10.1159/000369363.
- Sha J., Liu F., Zhai J., Liu X., Zhang Q., Zhang B. Alteration of Th17 and Foxp3+ regulatory T cells in patients with unexplained recurrent spontaneous abortion before and after the therapy of hCG combined with immunoglobulin. Exp. Ther. Med. 2017; 14(2): 1114-8. https://dx.doi.org/10.3892/etm.2017.4574.
- McCarthy R., Jungheim E.S., Fay J.C., Bates K., Herzog E.D., England S.K. Riding the rhythm of melatonin through pregnancy to deliver on t.ime. Front. Endocrinol. (Lausanne). 2019; 13(10): 616. https://dx.doi.org/10.3389/fendo.2019.00616.
- Palmer K.T., Bonzini M., Harris E.C., Linaker C., Bonde J.P. Work activities and risk of prematurity, low birth weight and pre-eclampsia: an updated review with meta-analysis. Occup. Environ. Med. 2013; 70(4): 213-2. https:// dx.doi.org/10.1136/oemed-2012-101032.
- Sandyk R., Anastasiadis P.G., Anninos P.A., Tsagas N. The pineal gland and spontaneous abortions: Implications for therapy with melatonin and magnetic field. Int. J. Neurosci. 1992; 62(3-4): 243-50. https:// dx.doi.org/10.3109/00207459108999775.
- Jin M, Li D., Ji .R., Liu W., Xu X., Feng X. Changes in gut microorganism in patients with positive immune antibody-associated recurrent abortion. Biomed. Res. Int. 2020; 2020: 4673250. https://dx.doi.org/10.1155/2020/ 4673250.
- Cui Y., Zou L., Ye Q., Li D., Wu H., He L. Gut microbiota composition and functional prediction in recurrent spontaneous abortion. Research Square; 2021. https://dx.doi.org/10.21203/rs.3.rs-906730/v1.
- Liu Y., Chen H., Feng L., Zhang J. Interactions between gut microbiota and metabolites modulate cytokine network imbalances in women with unexplained miscarriage. NPJ Biofilms Microbiomes. 2021; 7(1): 24. https://dx.doi.org/10.1038/s41522-021-00199-3.
- Быкова С.В., Сабельникова Е.А., Парфенов А.И., Гудкова Р.Б., Крумс Л.М., Чикунова Б.З. Репродуктивные расстройства у женщин с целиакией. Влияние этиотропной терапии. Экспериментальная и клиническая гастроэнтерология. 2011; 3: 12-8. [Bykova S.V., Sabelnikova E.A., Parfenov A.I., Gudkova R.B., Krums L.M., Chikunova B.Z. Reproductive disorders in women with celiac disease. Impact of etiotropic therapy. Experimental and Clinical Gastroenterology. 2011; (3): 12-8. (in Russian)].
- Bender Atik R., Christiansen O.B., Elson J., Kolte A.M., Lewis S., Middeldorp S. et al.; ESHRE Guideline Group on RPL. ESHRE guideline: recurrent pregnancy loss.:an update in 2022. Hum. Reprod. Open. 2023; 2023(1): hoad002. https://dx.doi.org/10.1093/hropen/hoad002.
- Mitra S., Förster-Fromme K., Damms-Machado A., Scheurenbrand T., Biskup S., Huson D.H., Bischoff S.C. Analysis of the intestinal microbiota using SOLiD 16S rRNA gene sequencing and SOLiD shotgun sequencing. BMC Genomics. 2013;14(Suppl. 5): S16. https://dx.doi.org/10.1186/1471-2164-14-S5-S16.
- Caporaso J.G., Kuczynski J., Stombaugh J., Bittinger K., Bushman F.D., Costello E.K. et al. QIIME allows analysis of high-throughput community sequencing data. Nat. Methods. 2010; 7(5): 335-6. https://dx.doi.org/10.1038/nmeth.f.303.
- DeSantis T.Z., Hugenholtz P., Larsen N., Rojas M., Brodie E.L., Keller K. et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 2006; 72(7): 5069-72. https://dx.doi.org/10.1128/AEM.03006-05.
- Ritari J., Salojärvi J., Lahti L., de Vos W.M. Improved taxonomic assignment of human intestinal 16S rRNA sequences by a dedicated reference database. BMC Genomics. 2015; 16: 1056. https://dx.doi.org/10.1186/ s12864-015-2265-y.
- Guang Y., Shen X., Tan Y., Tang S., Chen J., Zhang L. et al. Systematic analysis of microbiota in pregnant Chinese women and its association with miscarriage. Ann. Transl. Med. 2022; 10(20): 1099. https://dx.doi.org/10.21037/ atm-22-4115.
- Vinolo M.A.R., Rodrigues H.G., Nachbar R.T., Curi R. Regulation of Inflammation by short chain fatty acids. Nutrients. 2011; 3(10): 858-76. https://dx.doi.org/10.3390/nu3100858.
- Zhang Q., Hu W.M., Deng Y.L., Wan J.J., Wang Y.J, Jin P. Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing's syndrome. Front. Endocrinol. (Lausanne). 2023; 13: 1095438. https://dx.doi.org/10.3389/fendo.2022.1095438.
- Michels N., Van de Wiele T., Fouhy F., O'Mahony S., Clarke G., Keane J. Gut microbiome patterns depending on children's psychosocial stress: Reports versus biomarkers. Brain Behav. Immun. 2019; 80: 751-762. https://dx.doi.org/10.1016/j.bbi.2019.05.024.
- van de Wouw M., Boehme M., Lyte J.M., Wiley N., Strain C., O'Sullivan O. et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J. Physiol. 2018; 596(20): 4923-44. https://dx.doi.org/10.1113/JP276431.
- Поросюк М.В., Клементьев Д.Д., Ходов Н.А., Гуменюк Л.Н., Эсатова Э.С., Середа Е.В. и др. Изменения микробиоты кишечника у больных ювенильным идиопатическим артритом. Вестник РГМУ. 2022; 6: 13-9. [Porosyuk M.V., Klementiev D.D., Hodov N.A., Gumenyuk L.N., Esatova E.S., Sereda E.V. et al. Gut microbiota alterations in patients with juvenile idiopathic arthritis. Bulletin of RSMU. 2022; (6): 13-9. (in Russian)]. https:// dx.doi.org/10.24075/brsmu.2022.060.
- Huang X., Qiu Y., Gao Y., Zhou R., Hu Q., He Z. et al. Gut microbiota mediate melatonin signalling in association with type 2 diabetes. Diabetologia. 2022; 65(10): 1627-41. https://dx.doi.org/10.1007/s00125-022-05747-w.
- Henke M.T., Kenny D.J., Cassilly C.D., Vlamakis H., Xavier R.J., Clardy J. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide. Proc. Natl. Acad. Sci. USA. 2019; 116(26): 12672-7. https://dx.doi.org/10.1073/ pnas.1904099116.
- Miao T., Yu Y., Sun J., Ma A., Yu J., Cui M. et al. Decrease in abundance of bacteria of the genus Bifidobacterium in gut microbiota may be related to pre-eclampsia progression in women from East China. Food Nutr. Res. 2021; 65. https://dx.doi.org/10.29219/fnr.v65.5781.
- Vatanen T., Kostic A.D., d'Hennezel E., Siljander H., Franzosa E.A., Yassour M. et al.; DIABIMMUNE Study Group. Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell. 2016; 165(4): 842-53. https://dx.doi.org/10.1016/j.cell.2016.04.007.
- Henrick B.M., Chew S., Casaburi G., Brown H.K., Frese S.A., Zhou Y. et al. Colonization by B. infantis EVC001 modulates enteric inflammation in exclusively breastfed infants. Pediatr. Res. 2019; 86(6): 749-57. https://dx.doi.org/10.1038/s41390-019-0533-2.
Supplementary files
![](/img/style/loading.gif)