{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:29Z","timestamp":1787028509950,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"publisher","award":["DS 128"],"award-info":[{"award-number":["DS 128"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A comparative analysis of the placental microbiome in pregnancies with late fetal growth restriction (FGR) was performed with normal pregnancies to assess the impact of bacteria on placental development and function. The presence of microorganisms in the placenta, amniotic fluid, fetal membranes and umbilical cord blood throughout pregnancy disproves the theory of the \u201csterile uterus\u201d. FGR occurs when the fetus is unable to follow a biophysically determined growth path. Bacterial infections have been linked to maternal overproduction of pro-inflammatory cytokines, as well as various short- and long-term problems. Proteomics and bioinformatics studies of placental biomass allowed the development of new diagnostic options. In this study, the microbiome of normal and FGR placentas was analyzed by LC-ESI-MS\/MS mass spectrometry, and the bacteria present in both placentas were identified by analysis of a set of bacterial proteins. Thirty-six pregnant Caucasian women participated in the study, including 18 women with normal pregnancy and eutrophic fetuses (EFW &gt; 10th percentile) and 18 women with late FGR diagnosed after 32 weeks of gestation. Based on the analysis of the proteinogram, 166 bacterial proteins were detected in the material taken from the placentas in the study group. Of these, 21 proteins had an exponentially modified protein abundance index (emPAI) value of 0 and were not included in further analysis. Of the remaining 145 proteins, 52 were also present in the material from the control group. The remaining 93 proteins were present only in the material collected from the study group. Based on the proteinogram analysis, 732 bacterial proteins were detected in the material taken from the control group. Of these, 104 proteins had an emPAI value of 0 and were not included in further analysis. Of the remaining 628 proteins, 52 were also present in the material from the study group. The remaining 576 proteins were present only in the material taken from the control group. In both groups, we considered the result of ns prot \u2265 60 as the cut-off value for the agreement of the detected protein with its theoretical counterpart. Our study found significantly higher emPAI values of proteins representative of the following bacteria: Actinopolyspora erythraea, Listeria costaricensis, E. coli, Methylobacterium, Acidobacteria bacterium, Bacteroidetes bacterium, Paenisporsarcina sp., Thiodiazotropha endol oripes and Clostridiales bacterium. On the other hand, in the control group statistically more frequently, based on proteomic data, the following were found: Flavobacterial bacterium, Aureimonas sp. and Bacillus cereus. Our study showed that placental dysbiosis may be an important factor in the etiology of FGR. The presence of numerous bacterial proteins present in the control material may indicate their protective role, while the presence of bacterial proteins detected only in the material taken from the placentas of the study group may indicate their potentially pathogenic nature. This phenomenon is probably important in the development of the immune system in early life, and the placental microbiota and its metabolites may have great potential in the screening, prevention, diagnosis and treatment of FGR.<\/jats:p>","DOI":"10.3390\/ijms24086922","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"6922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Comparative Analysis of the Placental Microbiome in Pregnancies with Late Fetal Growth Restriction versus Physiological Pregnancies"],"prefix":"10.3390","volume":"24","author":[{"given":"Aleksandra","family":"Stupak","sequence":"first","affiliation":[{"name":"Chair and Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1940-4342","authenticated-orcid":false,"given":"Tomasz","family":"G\u0119ca","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kwa\u015bniewska","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rados\u0142aw","family":"Mlak","sequence":"additional","affiliation":[{"name":"Body Composition Research Laboratory, Department of Preclinical Science, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Piwowarczyk","sequence":"additional","affiliation":[{"name":"2nd Department of Anesthesiology and Intensive Care Unit, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8936-0018","authenticated-orcid":false,"given":"Robert","family":"Nawrot","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Institute of Experimental Biology, Adam Mickiewicz University in Poznan, 61-712 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Go\u017adzicka-J\u00f3zefiak","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology, Institute of Experimental Biology, Adam Mickiewicz University in Poznan, 61-712 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7522-1401","authenticated-orcid":false,"given":"Wojciech","family":"Kwa\u015bniewski","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Gynecology, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","first-page":"332","article-title":"Intrauterine growth retardation (IUGR): Epidemiology and etiology","volume":"6","author":"Romo","year":"2009","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1007\/s00404-017-4341-9","article-title":"Fetal growth restriction: Current knowledge","volume":"295","author":"Nardozza","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/uog.15884","article-title":"Consensus definition of fetal growth restriction: A Delphi procedure","volume":"48","author":"Gordijn","year":"2016","journal-title":"Ultrasound Obs. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/FM9.0000000000000161","article-title":"Fetal Growth Restriction: Mechanisms, Epidemiology, and Management","volume":"4","author":"Kamphof","year":"2022","journal-title":"Matern.-Fetal Med."},{"key":"ref_5","unstructured":"Chew, L.C., and Verma, R.P. (2023, March 05). Fetal Growth Restriction, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK562268\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/ijgo.13522","article-title":"FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction","volume":"152","author":"Melamed","year":"2021","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/00003081-200606000-00006","article-title":"Fetal Growth Restriction: The Etiology","volume":"49","author":"Maulik","year":"2006","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1016\/S0378-3782(14)70014-3","article-title":"IUGR and infections","volume":"90","author":"Longo","year":"2014","journal-title":"Early Hum. Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1128\/jcm.32.9.2162-2168.1994","article-title":"Genital flora in pregnancy and its association with intrauterine growth retardation","volume":"32","author":"Germain","year":"1994","journal-title":"J. Clin. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e22722","DOI":"10.1097\/MD.0000000000022722","article-title":"Study of the Fetal and Maternal Microbiota in Pregnant Women with Intrauterine Growth Restriction and Its Relationship with Inflammatory Biomarkers: A Case-Control Study Protocol (SPIRIT Compliant)","volume":"99","author":"Torrecillas","year":"2020","journal-title":"Medicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/nm.4176","article-title":"Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation","volume":"22","author":"Fujimura","year":"2016","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.3389\/fimmu.2019.02494","article-title":"Maturation of Gut Microbiota and Circulating Regulatory T Cells and Development of IgE Sensitization in Early Life","volume":"10","author":"Ruohtula","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1038\/s41467-018-06929-0","article-title":"The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD","volume":"9","author":"Soderborg","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_14","unstructured":"(2023, March 30). Available online: https:\/\/www.nature.com\/subjects\/microbiome."},{"key":"ref_15","unstructured":"Whipps, J.M., Lewis, K., and Cooke, R.C. (1988). Fungi in Biological Control Systems, ed 2001, Manchester University Press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13073-021-01005-7","article-title":"Maternal and early life exposures and their potential to influence development of the microbiome","volume":"14","author":"Bolte","year":"2022","journal-title":"Genome Med."},{"key":"ref_17","first-page":"17","article-title":"Part 1: The Human Gut Microbiome in Health and Disease","volume":"13","author":"Bull","year":"2014","journal-title":"Integr. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/MOG.0000000000000139","article-title":"The gut microbiome in health and in disease","volume":"31","author":"Shreiner","year":"2015","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1136\/gutjnl-2018-316723","article-title":"Human gut microbiome: Hopes, threats and promises","volume":"67","author":"Cani","year":"2018","journal-title":"Gut"},{"key":"ref_20","unstructured":"(2023, March 30). Available online: http:\/\/www.commonfund.nih.gov\/hmp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1055\/s-0033-1361821","article-title":"Potential influence of the microbiome on infertility and assisted reproductive technology","volume":"32","author":"Sirota","year":"2014","journal-title":"Semin. Reprod. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1471-0528.2010.02840.x","article-title":"The vaginal microbiome: New information about genital tract flora using molecular based techniques","volume":"118","author":"Lamont","year":"2011","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/LGT.0000000000000643","article-title":"The Vaginal Microbiome: I. Research Development, Lexicon, Defining \"Normal\" and the Dynamics Throughout Women\u2019s Lives","volume":"26","author":"Verstraelen","year":"2022","journal-title":"J. Low. Genit. Tract Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1080\/1040841X.2021.1999903","article-title":"The search for aliens within us: A review of evidence and theory regarding the fetal microbiome","volume":"48","author":"Takayasu","year":"2022","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/biolre\/ioac067","article-title":"Comparing the maternal-fetal microbiome of humans and cattle: A translational assessment of the reproductive, placental, and fetal gut microbiomes","volume":"107","author":"Hummel","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_26","unstructured":"Polin, R.A., Abman, S.H., Rowitch, D.H., Benitz, W.E., and Fox, W.W. (2017). Fetal and Neonatal Physiology, Elsevier. [5th ed.]."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3892\/mmr.2022.12872","article-title":"Placental proteome in late-onset of fetal growth restriction","volume":"26","author":"Stupak","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1126\/science.aad2571","article-title":"The maternal microbiota drives early postnatal innate immune development","volume":"351","author":"Fuhrer","year":"2016","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103455","DOI":"10.1016\/j.jri.2021.103455","article-title":"The evidence for placental microbiome and its composition in healthy pregnancies: A systematic review","volume":"149","author":"Zakis","year":"2022","journal-title":"J. Reprod. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.preghy.2021.01.002","article-title":"Pregnant Women Who Develop Preeclampsia Have Lower Abundance of the Butyrate-Producer Coprococcus in Their Gut Microbiota","volume":"23","author":"Altemani","year":"2021","journal-title":"Pregnancy Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1161\/CIRCRESAHA.122.320771","article-title":"Gut Dysbiosis Promotes Preeclampsia by Regulating Macrophages and Trophoblasts","volume":"131","author":"Jin","year":"2022","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1038\/s41598-017-03066-4","article-title":"Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women","volume":"7","author":"Barrett","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nitert, M.D., Barrett, H.L., Foxcroft, K., Tremellen, A., Wilkinson, S., Lingwood, B., Tobin, J.M., McSweeney, C., O\u2019Rourke, P., and McIntyre, H. (2013). SPRING: An RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women. BMC Pregnancy Childbirth, 13.","DOI":"10.1186\/1471-2393-13-50"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e12364","DOI":"10.1111\/hel.12364","article-title":"Helicobacter Pylori Colonization and Pregnancies Complicated by Preeclampsia, Spontaneous Prematurity, and Small for Gestational Age Birth","volume":"22","author":"Holster","year":"2017","journal-title":"Helicobacter"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Groer, M.W., Luciano, A.A., Dishaw, L.J., Ashmeade, T.L., Miller, E., and Gilbert, J.A. (2014). Development of the Preterm Infant Gut Microbiome: A Research Priority. Microbiome, 2.","DOI":"10.1186\/2049-2618-2-38"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1136\/gutjnl-2021-326482","article-title":"Unfavourable Intrauterine Environment Contributes to Abnormal Gut Microbiome and Metabolome in Twins","volume":"71","author":"Yang","year":"2022","journal-title":"Gut"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tu, X., Duan, C., Lin, B., Li, K., Gao, J., Yan, H., Wang, K., and Zhao, Z. (2022). Characteristics of the Gut Microbiota in Pregnant Women with Fetal Growth Restriction. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-022-04635-w"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1007\/s43032-020-00374-5","article-title":"Intrauterine Growth Restriction Is Associated with Unique Features of the Reproductive Microbiome","volume":"28","author":"Hu","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_39","unstructured":"(2023, March 30). Available online: https:\/\/www.uniprot.org\/uniprotkb\/A0A099D2A0\/entry."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1021\/np200603g","article-title":"Actinopolysporins AC and tubercidin as a Pdcd4 stabilizer from the halophilic actinomycetes Actinopolyspora erythraea YIM 90600","volume":"74","author":"Zhao","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"744","DOI":"10.3389\/fmicb.2016.00744","article-title":"The Ecology of Acidobacteria: Moving beyond Genes and Genomes","volume":"7","author":"Kielak","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Szwetkowski, K.J., and Falkinham, J.O. (2020). Methylobacterium spp. as Emerging Opportunistic Premise Plumbing Pathogens. Pathogens, 9.","DOI":"10.3390\/pathogens9020149"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gschwind, R., Fournier, T., Kennedy, S., Tsatsaris, V., Cordier, A.G., Barbut, F., Butel, M.J., and Wydawu-Dematteis, S. (2020). Evidence for contamination as the origin for bacteria found in human placenta rather than a microbiota. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0237232"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0002-9378(85)90298-4","article-title":"Estimation of fetal weight with the use of head, body, and femur measurements\u2014A prospective study","volume":"151","author":"Hadlock","year":"1985","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/uog.4088","article-title":"Middle cerebral artery blood flow velocities and pulsatility index and the cerebroplacental pulsatility ratio: Longitudinal reference ranges and terms for serial measurements","volume":"30","author":"Ebbing","year":"2007","journal-title":"Ultrasound Obs. Gynecol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/uog.4094","article-title":"New Doppler index for prediction of perinatal brain damage in growth-restricted and hypoxic fetuses","volume":"30","author":"Tumbri","year":"2007","journal-title":"Ultrasound Obs. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1214\/10-AOAS341","article-title":"Liquid Chromatography Mass Spectrometry-Based Proteomics: Biological and Technological Aspects","volume":"4","author":"Karpievitch","year":"2010","journal-title":"Ann. Appl. Stat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1126\/science.2511628","article-title":"Similarity between the transcriptional silencer binding proteins ABF1 and RAP1","volume":"246","author":"Diffley","year":"1998","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.phytochem.2007.03.039","article-title":"Proteomic analysis of Chelidonium majus milky sap using two-dimensial gel electrophoresis and tandem mass spectrometry","volume":"68","author":"Nawrot","year":"2007","journal-title":"Phyochemistry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1074\/mcp.M500061-MCP200","article-title":"Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein","volume":"4","author":"Ishihama","year":"2005","journal-title":"Mol. Cell. Proteom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6922\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:12:21Z","timestamp":1760123541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/6922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":50,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24086922"],"URL":"https:\/\/doi.org\/10.3390\/ijms24086922","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,7]]}}}