akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2024.547akusherstvo-2284Research ArticleОRIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИMaternal gut microbiome and its impact on developing idiopathic late fetal growth retardationСостояние материнского кишечного микробиома и его влияние на развитие синдрома идиопатической поздней задержки роста плодаhttps://orcid.org/0000-0002-2006-0110ЖелезоваМ. Е.ZhelezovaM. E.

Железова Мария Евгеньевна, д.м.н., проф.

420012 Казань, ул. Карла Маркса, д. 74

Maria E. Zhelezova, MD, Dr Sci Med, Prof.

74 Karl Marks Str., Kazan 420012

https://orcid.org/0000-0003-2242-216XБектурБ. К.BekturB. К.

Бектур Бегимай кызы

420110 Казань, ул. Братьев Касимовых, д. 40а

Begimai Bektur kyzy, MD.

40a Brothers Kasimov Str., Kazan 420110

bekturbegimai@gmail.comhttps://orcid.org/0000-0003-0999-4374МальцеваЛ. И.MaltsevaL. I.

Мальцева Лариса Ивановна, д.м.н., проф

Казань 420015, ул. Бутлерова, д. 36

Larisa I. Maltseva, MD, Dr Sci Med, Prof.

36 Butlerova Str., Kazan 420015

https://orcid.org/0000-0002-9119-559XШариповаР. И.SharipovaR. I.

Шарипова Резеда Ильнуровна, к.м.н.

420012 Казань, ул. Карла Маркса, д. 74

Rezeda I. Sharipova, MD, PhD

74 Karl Marks Str., Kazan 420012

https://orcid.org/0009-0007-6668-0554ШакирзяноваД. Б.ShakirzyanovaD. B.

Шакирзянова Дана Булатовна

420012 Казань, ул. Карла Маркса, д. 74

Dana B. Shakirzyanova

74 Karl Marks Str., Kazan 420012

ФГАОУ ВО «Казанский (Приволжский) федеральный университет»РоссияKazan (Volga Region) Federal UniversityRussian FederationООО «Клиника Нуриевых»РоссияNuriev Clinic LLCRussian FederationКазанская государственная медицинская академия – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияKazan State Medical Academy – Branch of the Russian Medical Academy of Continuing Professional Education, Health Ministry of Russian FederationRussian Federation202410012025186788799Copyright © Zhelezova M.E., Bektur B.К., Maltseva L.I., Sharipova R.I., Shakirzyanova D.B., 20252025Железова М.Е., Бектур Б.К., Мальцева Л.И., Шарипова Р.И., Шакирзянова Д.Б.Zhelezova M.E., Bektur B.К., Maltseva L.I., Sharipova R.I., Shakirzyanova D.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/2284Aim

Aim: to analyze a rectal microbiome composition in pregnant women and assess its potential impact on developing of idiopathic late fetal growth retardation (FGR) syndrome.

Materials and Methods

Materials and Methods. We analyzed a course of pregnancy and labour in 80 pregnant women: main group consisted of 40 pregnant women with FGR, control group – of 40 healthy pregnant women. The analysis of the intestinal microbiota in 53 pregnant women (25 pregnant women with late FGR and 28 healthy pregnant women) was carried out by using nitrogenous base sequencing in the 16S ribosomal RNA (rRNA) genes.

Results

Results. Analyses of the gut microbiome composition in pregnant women in study groups revealed significant differences particularly showing a 1.0 % increase in the proportion of Clostridiales Ruminococcaceae Oscillospira that correlated with a 331.7 g increase in neonatal weight gain; a 1.0 % increase in the level of Coriobacteriales Coriobacteriaceae Collinsella was associated with a 476.2 g decrease in neonatal weight gain. The Firmicutes/Bacteroides ratio was 2,0 and 3.6 in main and control group (p = 0.02), respectively, which may suggest about a microbiological dysbiosis with putative pathophysiological outcomes. A significant association between elevated leucocyte counts (in the absence of other manifestations of inflammatory processes) and the probability of FGR development was found. A white blood cell count ≥ 11.05×109/L predicted the risk of FGR with a sensitivity of 60.6 % and a specificity of 79.2 %. Also, erythrocyte sedimentation rate level of ≥ 41.5 mm/hour was associated with increased FGR risk, demonstrating a sensitivity of 85.7 % and specificity of 70.6 %.

Conclusion

Conclusion. It can be concluded that gut dysbiosis may play a role in development of late idiopathic FGR. A negative correlation between a decreased Firmicutes/Bacteroides ratio as well as higher Actinobacteria proportion and fetal birth weight was found.

Цель

Цель: изучить состав микробиома прямой кишки беременных и оценить его возможное влияние на развитие синдрома идиопатической поздней задержки роста плода (ЗРП).

Материалы и методы

Материалы и методы. Проведен анализ течения беременности и родов 80 беременных. Основную группу составили 40 беременных с ЗРП, контрольную группу – 40 здоровых беременных. Анализ микробиоты кишечника у 53 беременных (25 беременных с поздней ЗРП и 28 здоровых беременных) проведен с использованием секвенирования азотистых оснований в генах 16S рибосомальной РНК (рРНК).

Результаты

Результаты. Анализ микробиомного состава кишечника беременных в исследуемых группах выявил значительные различия, имеющие клиническое значение. В частности, увеличение пропорции Clostridiales Ruminococcaceae Oscillospira на 1,0 % коррелировало с приростом массы тела новорожденных на 331,7 г; повышение уровня Coriobacteriales Coriobacteriaceae Collinsella на 1,0 % ассоциировалось со снижением массы тела новорожденных на 476,2 г. Отношение Firmicutes к Bacteroides составило 2,0 в основной группе и 3,6 в контрольной группе (р = 0,02), что может свидетельствовать о микробиологическом дисбиозе с возможными патофизиологическими последствиями. Установлена значимая связь между повышенным уровнем лейкоцитов (при отсутствии других проявлений воспалительных процессов) и вероятностью развития синдрома ЗРП. При лейкоцитозе ≥ 11,05×109/л риск ЗРП прогнозируется с чувствительностью 60,6 % и специфичностью 79,2 %.Также скорость оседания эритроцитов ≥ 41,5 мм/час ассоциировалась с повышенным риском ЗРП, демонстрируя чувствительность 85,7 % и специфичность 70,6 %.

Заключение

Заключение. Дисбиоз кишечника, вероятно, играет роль в формировании поздней идиопатической ЗРП. Уменьшение соотношения Firmicutes/Bacteroides, а также преобладание Actinobacteria отрицательно коррелируют с массой плода при рождении.

синдром поздней задержки роста плодаЗРПкишечный микробиомосложнения беременностиlate fetal growth retardationFGRintestinal microbiomepregnancy complicationsReferencesКлинические рекомендации – Недостаточный рост плода, требующий предоставления медицинской помощи матери (задержка роста плода) – 2022-2023-2024 (14.02.2022). М.: Министерство здравоохранения Россиийской Федерации, 2022. 47 с. Режим доступа: https://cr.minzdrav.gov.ru/recomend/722_1. [Дата обращения: 14.07.2024].. Clinical guidelines – Insufficient fetal growth requiring maternalmedical care (fetal growth retardation) – 2022-2023-2024 (14.02.2022). [Klinicheskie rekomendacii – Nedostatochnyj rost ploda, trebuyushchij predostavleniya medicinskoj pomoshchi materi (zaderzhka rosta ploda) – 2022-2023-2024 (14.02.2022). Moscow: Ministerstvo zdravoohraneniya Rossiijskoj Federacii, 2022. 47 p. (In Russ.). Available at: https://cr.minzdrav.gov.ru/recomend/722_1. [Accessed: 14.07.2024].Centers for Disease Control and Prevention (CDC). World Health Organization, 2021. Режим доступа: https://www.who.int/teams/regulation-prequalification/regulation-and-safety/pharmacovigilance/networks/vaccine-safety-net/vsn-members/centers-for-disease-controland-prevention. [Дата обращения: 14.07.2024].Centers for Disease Control and Prevention (CDC). World Health Organization, 2021. Available at: https://www.who.int/teams/regulationprequalification/regulation-and-safety/pharmacovigilance/networks/vaccine-safety-net/vsn-members/centers-for-disease-control-andprevention. [Accessed: 14.07.2024].MacLeod R., Paulson J.N., Okalany N. et al. Intraventricular haemorrhage in a Ugandan cohort of low-birth weight neonates: the IVHU study. BMC Pediatr. 2021;21(1):12. https://doi.org/10.1186/s12887-020-02464-4.MacLeod R., Paulson J.N., Okalany N. et al. Intraventricular haemorrhage in a Ugandan cohort of low-birth weight neonates: the IVHU study. BMC Pediatr. 2021;21(1):12. https://doi.org/10.1186/s12887-020-02464-4.Dinu M., Stancioi-Cismaru A.F., Gheonea M. et al. Intrauterine growth restriction – prediction and peripartum data on hospital care. Medicina. 2023;59(4):773. https://doi.org/10.3390/medicina59040773.Dinu M., Stancioi-Cismaru A.F., Gheonea M. et al. Intrauterine growth restriction – prediction and peripartum data on hospital care. Medicina. 2023;59(4):773. https://doi.org/10.3390/medicina59040773.Kaplina A., Kononova S., Zaikova E. et al. Necrotizing enterocolitis: the role of hypoxia, gut microbiome, and microbial metabolites. Int J Mol Sci. 2023;24(3):2471. https://doi.org/10.3390/ijms24032471.Kaplina A., Kononova S., Zaikova E. et al. Necrotizing enterocolitis: the role of hypoxia, gut microbiome, and microbial metabolites. Int J Mol Sci. 2023;24(3):2471. https://doi.org/10.3390/ijms24032471.Fernandez-Rodriguez B., de Alba C., Galindo A. et al. Obstetric and pediatric growth charts for the detection of late-onset fetal growth restriction and neonatal adverse outcomes. J Perinat Med. 2020;49(2):216–24. https://doi.org/10.1515/jpm-2020-0210.Fernandez-Rodriguez B., de Alba C., Galindo A. et al. Obstetric and pediatric growth charts for the detection of late-onset fetal growth restriction and neonatal adverse outcomes. J Perinat Med. 2020;49(2):216–24. https://doi.org/10.1515/jpm-2020-0210.Ross M.G., Beall M.H. Adult sequelae of intrauterine growth restriction. Semin Perinatol. 2008;32(3):213–8. https://doi.org/10.1053/j.semperi.2007.11.005.Ross M.G., Beall M.H. Adult sequelae of intrauterine growth restriction. Semin Perinatol. 2008;32(3):213–8. https://doi.org/10.1053/j.semperi.2007.11.005.Børte S., Winsvold B.S., Stensland S.Ø. et al. The effect of fetal growth restriction on the development of migraine and tension-type headache in adulthood. The HUNT Study. PLoS One. 2017;12(4):e0175908. https://doi.org/10.1371/journal.pone.0175908.Børte S., Winsvold B.S., Stensland S.Ø. et al. The effect of fetal growth restriction on the development of migraine and tension-type headache in adulthood. The HUNT Study. PLoS One. 2017;12(4):e0175908. https://doi.org/10.1371/journal.pone.0175908.Hu J., Benny P., Wang M. et al. Intrauterine growth restriction is associated with unique features of the reproductive microbiome. Reprod Sci. 2021;28(3):828–37. https://doi.org/10.1007/s43032-020-00374-5.Hu J., Benny P., Wang M. et al. Intrauterine growth restriction is associated with unique features of the reproductive microbiome. Reprod Sci. 2021;28(3):828–37. https://doi.org/10.1007/s43032-020-00374-5.Tu X., Duan C., Lin B. et al. Characteristics of the gut microbiota in pregnant women with fetal growth restriction. BMC Pregnancy Childbirth. 2022;22(1):297. https://doi.org/10.1186/s12884-022-04635-w.Tu X., Duan C., Lin B. et al. Characteristics of the gut microbiota in pregnant women with fetal growth restriction. BMC Pregnancy Childbirth. 2022;22(1):297. https://doi.org/10.1186/s12884-022-04635-w.Miao T., Yu Y., Sun J. 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://doi.org/10.29219/fnr.V65.5781.Miao T., Yu Y., Sun J. 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://doi.org/10.29219/fnr.V65.5781.Li G., Yin P., Chu S. et al. Correlation analysis between FGR and gut microbial composition in late pregnancy. J Diabetes Res. 2021;2021:8892849. https://doi.org/10.1155/2021/8892849.Li G., Yin P., Chu S. et al. Correlation analysis between FGR and gut microbial composition in late pregnancy. J Diabetes Res. 2021;2021:8892849. https://doi.org/10.1155/2021/8892849.Kyono K., Hashimoto T., Nagai Y., Sakuraba Y. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod Med Biol. 2018;17(3):297–306. https://doi.org/10.1002/rmb2.12105.Kyono K., Hashimoto T., Nagai Y., Sakuraba Y. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod Med Biol. 2018;17(3):297–306. https://doi.org/10.1002/rmb2.12105.Yao Y., Cai X., Chen C. et al. The role of microbiomes in pregnant women and offspring: research progress of recent years. Front Pharmacol. 2020;11:643. https://doi.org/10.3389/fphar.2020.00643.Yao Y., Cai X., Chen C. et al. The role of microbiomes in pregnant women and offspring: research progress of recent years. Front Pharmacol. 2020;11:643. https://doi.org/10.3389/fphar.2020.00643.Cadaret C.N., Posont R.J., Beede K.A. et al. Maternal inflammation at midgestation impairs subsequent fetal myoblast function and skeletal muscle growth in rats, resulting in intrauterine growth restriction at term. Transl Anim Sci. 2019;3(2):txz037. https://doi.org/10.1093/tas/txz037.Cadaret C.N., Posont R.J., Beede K.A. et al. Maternal inflammation at midgestation impairs subsequent fetal myoblast function and skeletal muscle growth in rats, resulting in intrauterine growth restriction at term. Transl Anim Sci. 2019;3(2):txz037. https://doi.org/10.1093/tas/txz037.Железова М.Е., Бектур Б.K., Мальцева Л.И. и др. Значение материнского микробиома в развитии поздней задержки роста плода. Практическая медицина. 2022;20(5):34–9. https://doi.org/10.32000/2072-1757-2022-5-34-39.Zhelezova M.E., Bektur B.K., Maltseva L.I., et al. Influence of the maternal microbiome on the development of late fetal growth retardation. [Znachenie materinskogo mikrobioma v razvitii pozdnej zaderzhki rosta ploda]. Prakticheskaya medicina. 2022;20(5):34–9. (In Russ.). https://doi.org/10.32000/2072-1757-2022-5-34-39.Sokol H., Seksik P., Furet J.P. et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15(8):1183–9. https://doi.org/10.1002/ibd.20903.Sokol H., Seksik P., Furet J.P. et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15(8):1183–9. https://doi.org/10.1002/ibd.20903.Дудун А.А., Бонарцев А.П., Жаркова И.Г., Воинова В.В. Роль кишечной микробиоты в лечении различных заболеваний и антибактериальные препараты нового поколения. Учебно-методическое пособие. М.: Мир науки, 2020. 129 с. Режим доступа: https://izd-mn.com/PDF/17MNNPU20.pdf. [Дата обращения: 14.07.2024].Dudun A.A., Bonartsev A.P., Zharkova I.G., Voinova V.V. The role of intestinal microbiota in the treatment of various diseases and new generation antibacterial drugs. Study guide. [Rol' kishechnoj mikrobioty v lechenii razlichnyh zabolevanij i antibakterial'nye preparaty novogo pokoleniya. Uchebno-metodicheskoe posobie]. Moscow: Mir nauki, 2020. 129 p. (In Russ.). Available at: https://izd-mn.com/PDF/17MNNPU20.pdf. [Accessed: 14.07.2024].Mizgier М., Jarzabek-Bielecka G., Mruczyk K., Kedzia W. The role of diet and probiotics in prevention and treatment of bacterial vaginosis and vulvovaginal candidiasis in adolescent girls and non-pregnant women. Ginekol Pol. 2020;91(7):412–6. https://doi.org/10.5603/GP.2020.0070.Mizgier М., Jarzabek-Bielecka G., Mruczyk K., Kedzia W. The role of diet and probiotics in prevention and treatment of bacterial vaginosis and vulvovaginal candidiasis in adolescent girls and non-pregnant women. Ginekol Pol. 2020;91(7):412–6. https://doi.org/10.5603/GP.2020.0070.Gorczyca K., Obuchowska A., Kimber-Trojnar Ż. et al. Changes in the gut microbiome and pathologies in pregnancy. Int J Environ Res Public Health. 2022;19(16):9961. https://doi.org/10.3390/ijerph19169961.Gorczyca K., Obuchowska A., Kimber-Trojnar Ż. et al. Changes in the gut microbiome and pathologies in pregnancy. Int J Environ Res Public Health. 2022;19(16):9961. https://doi.org/10.3390/ijerph19169961.Koren O., Goodrich J.K., Cullender T.C. et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470–80. https://doi.org/10.1016/j.cell.2012.07.008.Koren O., Goodrich J.K., Cullender T.C. et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470–80. https://doi.org/10.1016/j.cell.2012.07.008.Zixin T., Yun Ch., Fang H. et al. Alterations in the gut microbiome and metabolisms in pregnancies with fetal growth restriction. Microbiol Spectr. 2023;11(3):e00076-23. https://doi.org/10.1128/spectrum.00076-23.Zixin T., Yun Ch., Fang H. et al. Alterations in the gut microbiome and metabolisms in pregnancies with fetal growth restriction. Microbiol Spectr. 2023;11(3):e00076-23. https://doi.org/10.1128/spectrum.00076-23.Jin J., Gao L., Zou X. et al. Gut dysbiosis promotes preeclampsia by regulating macrophages and trophoblasts. Circ Res. 2022;131(6):492–506. https://doi.org/10.1161/CIRCRESAHA.122.320771.Jin J., Gao L., Zou X. et al. Gut dysbiosis promotes preeclampsia by regulating macrophages and trophoblasts. Circ Res. 2022;131(6):492–506. https://doi.org/10.1161/CIRCRESAHA.122.320771.Salafia C.M., Ernst L.M., Pezzullo J.C. et al. The very low birthweight infant: maternal complications leading to preterm birth, placental lesions, and intrauterine growth. Am J Perinatol. 1995;12(2):106–10. https://doi.org/10.1055/s-2007-994417.Salafia C.M., Ernst L.M., Pezzullo J.C. et al. The very low birthweight infant: maternal complications leading to preterm birth, placental lesions, and intrauterine growth. Am J Perinatol. 1995;12(2):106–10. https://doi.org/10.1055/s-2007-994417.Marcorelles P. Placental features in intrauterine growth retardation. J Gynecol Obstet Biol Reprod. 2013;42(8):996–1007. (In French). https://doi.org/10.1016/j.jgyn.2013.09.021.Marcorelles P. Placental features in intrauterine growth retardation. J Gynecol Obstet Biol Reprod. 2013;42(8):996–1007. (In French). https://doi.org/10.1016/j.jgyn.2013.09.021.

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