Decrease in abundance of bacteria of the genus Bifidobacterium in gut microbiota may be related to pre-eclampsia progression in women from East China
Background: Pre-eclampsia (PE) can result in severe damage to maternal and fetal health. It has been reported that gut microbiota (GM) had important roles in regulating the metabolic and inflammatory responses of the mother. However, investigations on GM in PE are rare.
Objective: The objective of the present study was to investigate the changes of GM in PE and how to alter the GM composition in PE by dietary or dietary supplements.
Design: We analyzed the composition changes in GM as well as the relationship between bacteria of different genera and clinical indices by amplifying the V4 region of the 16S ribosomal RNA gene in 12 PE patients and eight healthy pregnant women in East China.
Results: In the PE group, the Observed Species Index was lower than that in the control group, indicating that the α-diversity of the microbiome in the PE group decreased. At phylum, family, and genus levels, the relative abundance of different bacteria in PE patients displayed substantial differences to those from healthy women. We noted a decreased abundance of bacteria of the phylum Actinobacteria (P = 0.042), decreased abundance of bacteria of the family Bifidobacteriaceae (P = 0.039), increased abundance of bacteria of the genus Blautia (P = 0.026) and Ruminococcus (P = 0.048), and decreased abundance of bacteria of the genus Bifidobacterium (P = 0.038). Among three enriched genera, bacteria of the genus Bifidobacterium showed a negative correlation with the systolic blood pressure (SBP), diastolic blood pressure (DBP), and dyslipidemia, which involved glucose metabolism, lipid metabolism, and the oxidative-phosphorylation pathway. The increased abundance of bacteria of the genera Blautia and Ruminococcus was positively correlated with obesity and dyslipidemia, which involved lipid metabolism, glycosyltransferases, biotin metabolism, and the oxidative-phosphorylation pathways. Moreover, women in the PE group ate more than women in the control group, so fetuses were more prone to overnutrition in the PE group.
Conclusion: There is a potential for GM dysbiosis in PE patients, and they could be prone to suffer from metabolic syndrome. We speculate that alterations in the abundance of bacteria of certain genera (e.g. increased abundance of Blautia and Ruminococcus, and decreased abundance of Bifidobacterium) were associated with PE development to some degree. Our data could help to monitor the health of pregnant women and may be helpful for preventing and assisting treatment of PE by increasing dietary fiber or probiotics supplement.
- Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, Groot CJMD, Hofmeyr GJ. Pre-eclampsia. Lancet 2016; 387(10022): 999–1011. doi: 10.1016/S0140-6736(15)00070-7
- Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol 2019; 15(5): 275–89. doi: 10.1038/s41581-019-0119-6
- Lu HQ, Hu R. The role of immunity in the pathogenesis and development of pre- eclampsia. Scand J Immunol 2019; 90(5): e12756. doi: 10.1111/sji.12756
- Karumanchi SA. Angiogenic factors in preeclampsia: from diagnosis to therapy. Hypertension 2016; 67(6): 1072–9. doi: 10.1161/HYPERTENSIONAHA.116.06421
- Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science 2005; 308(5728): 1635–8. doi: 10.1126/science.1110591
- Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009; 9(5): 313–23. doi: 10.1038/nri2515
- Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486(7402): 207–14. doi: 10.1038/nature 11234
- Liu J, Yang H, Yin Z, Jiang X, Zhong H, Qiu D, et al. Remodeling of the gut microbiota and structural shifts in Preeclampsia patients in South China. Eur J Clin Microbiol Infect Dis 2017; 36(4): 713–19. doi: 10.1007/s10096-016-2853-z
- American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins-Obstetrics. Gestational hypertension and preeclampsia: ACOG practice bulletin, number 222. Obstet Gynecol 2020; 135(6): e237–60. doi: 10.1097/AOG.0000000000003891
- Chang Y, Chen Y, Zhou Q, Wang C, Chen L, Di W, et al. Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia. Clin Sci (Lond) 2020; 134(2): 289–302. doi: 10.1042/CS20191253
- Magoč T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 2011; 27(21): 2957–63. doi: 10.1093/bioinformatics/btr507
- Edgar RC. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods 2013; 10(10): 996–8. doi: 10.1038/nmeth.2604.
- Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics 2011; 27(16): 2194–200. doi: 10.1093/bioinformatics/btr381
- Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 2010; 7(5): 335–6. doi: 10.1038/nmeth.f.303
- Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 2010; 26(19): 2460–1. doi: 10.1093/bioinformatics/btq461
- James JL, Whitley GS, Cartwright JE. Pre-eclampsia: fitting together the placental, immune and cardiovascular pieces. J Pathol 2010; 221(4): 363–78. doi: 10.1002/path.2719
- Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 2013; 31(9): 814–21. doi: 10.1038/nbt.2676
- Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 2017; 45(D1): D353–61. doi: 10.1093/nar/gkw1092
- Su M, Nie Y, Shao R, Duan S, Jiang Y, Wang M, et al. Diversified gut microbiota in newborns of mothers with gestational diabetes mellitus. PLoS One 2018; 13(10): e0205695. doi: 10.1371/journal.pone.0205695
- Luo M, Liu Y, Wu P, Luo DX, Sun Q, Zheng H, et al. Alternation of gut microbiota in patients with pulmonary tuberculosis. Front Physiol 2017; 8: 822. doi: 10.3389/fphys.2017.00822
- Amarasekara R, Jayasekara RW, Senanayake H, Dissanayake VH. Microbiome of the placenta in pre-eclampsia supports the role of bacteria in the multifactorial cause of pre-eclampsia. J Obstet Gynaecol Res 2015; 41(5): 662–9. doi: 10.1111/jog.12619
- Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490(7418): 55–60. doi: 10.1038/nature11450
- Verdam FJ, Fuentes S, de Jonge C, Zoetendal EG, Erbil R, Greve JW, et al. Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring) 2013; 21(12): E607–15. doi: 10.1002/oby.20466
- Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, et al. Gut dysbiosis is linked to hypertension. Hypertension 2015; 65(6): 1331–40. doi: 10.1161/HYPERTENSIONAHA.115.05315
- Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 2017; 5(1): 24. doi: 10.1186/s40168-017-0242-1
- Li W, Wu X, Hu X, Wang T, Liang S, Duan Y, et al. Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features. Sci China Life Sci 2017; 60(11): 1223–33. doi: 10.1007/s11427-016-9001-4
- Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Bäckhed HK, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 2012; 150(3): 470–80. doi: 10.1016/j.cell.2012.07.008
- Mariat D, Firmesse O, Levenez F, Guimarăes V, Sokol H, Doré J, et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 2009; 9: 123. doi: 10.1186/1471-2180-9-123
- Gomez-Arango LF, Barrett HL, McIntyre HD, Callaway LK, Morrison M, Dekker Nitert M, et al. Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy. Hypertension 2016; 68(4): 974–81. doi: 10.1161/HYPERTENSIONAHA.116.07910
- Mell B, Jala VR, Mathew AV, Byun J, Waghulde H, Zhang Y, et al. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics 2015; 47(6): 187–97. doi: 10.1152/physiolgenomics.00136.2014
- Gómez-Guzmán M, Toral M, Romero M, Jiménez R, Galindo P, Sánchez M, et al. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Mol Nutr Food Res 2015; 59(11): 2326–36. doi: 10.1002/mnfr.201500290
- Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, et al. Prebiotic effects: metabolic and health benefits. Br J Nutr 2010; 104 Suppl 2: S1–63. doi: 10.1017/S0007114510003363
- Park HE, Kim YJ, Do KH, Kim JK, Ham JS, Lee WK. Effects of Queso blanco cheese containing Bifidobacterium longum KACC 91563 on the intestinal microbiota and short chain fatty acid in healthy companion dogs. Korean J Food Sci Anim Resour 2018; 38(6): 1261–72. doi: 10.5851/kosfa.2018.e62
- Lv LJ, Li SH, Li SC, Zhong ZC, Duan HL, Tian C, et al. Early-onset preeclampsia is associated with gut microbial alterations in antepartum and postpartum women. Front Cell Infect Microbiol 2019; 9: 224. doi: 10.3389/fcimb.2019.00224
- Ottosson F, Brunkwall L, Ericson U, Nilsson PM, Almgren P, Fernandez C, et al. Connection between BMI-related plasma metabolite profile and gut microbiota. J Clin Endocrinol Metab 2018; 103(4): 1491–501. doi: 10.1210/jc.2017-02114.224
- Kashtanova DA, Tkacheva ON, Doudinskaya EN, Strazhesko ID, Kotovskaya YV, Popenko AS, et al. Gut microbiota in patients with different metabolic statuses: Moscow study. Microorganisms 2018; 6(4): 98. doi: 10.3390/microorganisms6040098
- Egshatyan L, Kashtanova D, Popenko A, Tkacheva O, Tyakht A, Alexeev D, et al. Gut microbiota and diet in patients with different glucose tolerance. Endocr Connect 2016; 5(1): 1–9. doi: 10.1530/EC-15-0094
- Stanislawski MA, Dabelea D, Wagner BD, Sontag MK, Lozupone CA, Eggesbø M. Pre-pregnancy weight, gestational weight gain, and the gut microbiota of mothers and their infants. Microbiome 2017; 5(1): 113. doi: 10.1186/s40168-017-0332-0
- Crusell MKW, Hansen TH, Nielsen T, Allin KH, Rühlemann MC, Damm P, et al. Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum. Microbiome 2018; 6(1): 89. doi: 10.1186/s40168-018-0472-x
- Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, et al. Human gut microbiota changes reveal the progression of glucose intolerance. PLoS One 2013; 8(8): e71108. doi: 10.1371/journal.pone.0071108
- Gomez-Arango LF, Barrett HL, McIntyre HD, Callaway LK, Morrison M, Dekker Nitert M, et al. Connections between the gut microbiome and metabolic hormones in early pregnancy in overweight and obese women. Diabetes 2016; 65(8): 2214–23. doi: 10.2337/db16-0278
- Taylor BD, Ness RB, Olsen J, Hougaard DM, Skogstrand K, Roberts JM, et al. Serum leptin measured in early pregnancy is higher in women with preeclampsia compared with normotensive pregnant women. Hypertension 2015; 65(3): 594–9. doi: 10.1161/HYPERTENSIONAHA.114.03979
- Miehle K, Stepan H, Fasshauer M. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf) 2012; 76(1): 2–11. doi: 10.1111/j.1365-2265.2011.04234.x
- Sohn K, Underwood MA. Prenatal and postnatal administration of prebiotics and probiotics. Semin Fetal Neonatal Med 2017; 22(5): 284–9. doi: 10.1016/j.siny.2017.07.002
- VandeVusse L, Hanson L, Safdar N. Perinatal outcomes of prenatal probiotic and prebiotic administration: an integrative review. J Perinat Neonatal Nurs 2013; 27(4): 288–301; quiz E1–2. doi: 10.1097/JPN.0b013e3182a1e15d
- Brantsaeter AL, Myhre R, Haugen M, Myking S, Sengpiel V, Magnus P, et al. Intake of probiotic food and risk of preeclampsia in primiparous women: the Norwegian mother and child cohort study. Am J Epidemiol 2011; 174(7): 807–15. doi: 10.1093/aje/kwr168
- Lindsay KL, Walsh CA, Brennan L, McAuliffe FM. Probiotics in pregnancy and maternal outcomes: a systematic review. J Matern Fetal Neonatal Med 2013; 26(8): 772–8. doi: 10.3109/14767058
- Nordqvist M, Jacobsson B, Brantsæter AL, Myhre R, Nilsson S, Sengpiel V. Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway. BMJ Open 2018; 8(1): e018021. doi: 10.1136/bmjopen-2017-018021
- de Brito AJL, de Oliveira Y, Carvalho NNC, Cavalcante RGS, Souza ELD. Gut microbiota and probiotic intervention as a promising therapeutic for pregnant women with cardiometabolic disorders: present and future directions. Pharmacol Res 2019; 145: 104252. doi: 10.1016/j.phrs.2019.104252
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation. Read the full Copyright- and Licensing Statement.