Skip to main content Accessibility help
×
Home
Hostname: page-component-564cf476b6-wkm24 Total loading time: 0.194 Render date: 2021-06-23T00:34:03.793Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true }

Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice

Published online by Cambridge University Press:  14 September 2020

Yu Liu
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Shengtang Qin
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Ye Feng
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Yilin Song
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Na Lv
Affiliation:
Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Fei Liu
Affiliation:
Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Xiaoming Zhang
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Shuxian Wang
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Yumei Wei
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Shuang Li
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Shiping Su
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Wanyi Zhang
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Yong Xue
Affiliation:
Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Yanan Hao
Affiliation:
Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Baoli Zhu
Affiliation:
Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Jingmei Ma
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China
Huixia Yang
Affiliation:
Department of Obstetrics and Gynaecology, Peking University First Hospital, Beijing, China Beijing Key Laboratory of Maternal Foetal Medicine of Gestational Diabetes Mellitus, Beijing, China Peking University, Beijing, China

Abstract

Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.

Type
Original Article
Copyright
© The Author(s), 2020. Published by Cambridge University Press in association with the International Society for Developmental Origins of Health and Disease

Access options

Get access to the full version of this content by using one of the access options below.

References

Zhu, WW, Yang, HX, Wei, YM, et al. Evaluation of the value of fasting plasma glucose in the first prenatal visit to diagnose gestational diabetes mellitus in china. Diabetes Care. 2013; 36(3), 586590.CrossRefGoogle ScholarPubMed
Lowe, WL, , Jr, Scholtens, DM, Sandler, V, Hayes, MG. Genetics of gestational diabetes mellitus and maternal metabolism. Curr Diab Rep. 2016; 16(2), 15.CrossRefGoogle ScholarPubMed
Damm, P, Houshmand-Oeregaard, A, Kelstrup, L, Lauenborg, J, Mathiesen, ER, Clausen, TD. Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia. 2016; 59(7), 13961399.CrossRefGoogle Scholar
Lauenborg, J, Hansen, T, Jensen, DM, et al. Increasing incidence of diabetes after gestational diabetes: a long-term follow-up in a Danish population. Diabetes Care. 2004; 27(5), 11941199.CrossRefGoogle Scholar
Cho, I, Blaser, MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012; 13(4), 260270.CrossRefGoogle ScholarPubMed
Karlsson, FH, Tremaroli, V, Nookaew, I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013; 498(7452), 99103.CrossRefGoogle ScholarPubMed
Le Chatelier, E, Nielsen, T, Qin, J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013; 500(7464), 541546.CrossRefGoogle ScholarPubMed
Ley, RE, Turnbaugh, PJ, Klein, S, Gordon, JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006; 444(7122), 10221023.CrossRefGoogle ScholarPubMed
Backhed, F, Manchester, JK, Semenkovich, CF, Gordon, JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007; 104(3), 979984.CrossRefGoogle ScholarPubMed
Ferretti, P, Pasolli, E, Tett, A, et al. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe. 2018; 24(1), 133145 e135.Google ScholarPubMed
Jenmalm, MC. The mother-offspring dyad: microbial transmission, immune interactions and allergy development. J Intern Med. 2017; 282(6), 484495.CrossRefGoogle ScholarPubMed
Smith, PM, Howitt, MR, Panikov, N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013; 341(6145), 569573.CrossRefGoogle ScholarPubMed
Nicholson, JK, Holmes, E, Kinross, J, et al. Host-gut microbiota metabolic interactions. Science. 2012; 336(6086), 12621267.CrossRefGoogle ScholarPubMed
Robertson, RC, Manges, AR, Finlay, BB, Prendergast, AJ. The human microbiome and child growth – first 1000 days and beyond. Trends Microbiol. 2019; 27(2), 131147.CrossRefGoogle ScholarPubMed
Newbern, D, Freemark, M. Placental hormones and the control of maternal metabolism and fetal growth. Curr Opin Endocrinol Diabetes Obes. 2011; 18(6), 409416.CrossRefGoogle ScholarPubMed
Edwards, SM, Cunningham, SA, Dunlop, AL, Corwin, EJ. The maternal gut microbiome during pregnancy. MCN Am J Matern Child Nurs. 2017; 42(6), 310317.Google ScholarPubMed
Koren, O, Goodrich, JK, Cullender, TC, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012; 150(3), 470480.CrossRefGoogle ScholarPubMed
Wang, J, Zheng, J, Shi, W, et al. Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus. Gut. 2018; 67(9), 16141625.CrossRefGoogle ScholarPubMed
Kuang, YS, Lu, JH, Li, SH, et al. Connections between the human gut microbiome and gestational diabetes mellitus. Gigascience. 2017; 6(8), 112.CrossRefGoogle ScholarPubMed
International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger, BE, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010; 33(3), 676682.CrossRefGoogle ScholarPubMed
Ridaura, VK, Faith, JJ, Rey, FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013; 341(6150), 1241214.CrossRefGoogle ScholarPubMed
Magoc, T, Salzberg, SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics. 2011; 27(21), 29572963.CrossRefGoogle ScholarPubMed
Chao, A. Nonparametric estimation of the number of classes in a population. Scand J Statistics. 1984; 11(4), 265270.Google Scholar
Shannon, CE. A mathematical theory of communication. Bell System Technical J. 1948; 27(4), 623656.CrossRefGoogle Scholar
Krebs, CJ. Ecological Methodology, 654 pp., 1989. New York: Harper Collins Inc. Google Scholar
Segata, N, Izard, J, Waldron, L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011; 12(6), R60.CrossRefGoogle ScholarPubMed
Ihaka, R, Gentleman, R. R: a language for data analysis and graphics. J Comput Graph Stat. 1996; 5(3), 299314.Google Scholar
Enquobahrie, DA, Williams, MA, Qiu, C, Luthy, DA. Early pregnancy lipid concentrations and the risk of gestational diabetes mellitus. Diab Res Clin Pract. 2005; 70(2), 134142.CrossRefGoogle ScholarPubMed
Zheng, W, Xu, Q, Huang, W, et al. Gestational diabetes mellitus is associated with reduced dynamics of gut microbiota during the first half of pregnancy. mSystems. 2020; 5(2). doi: 10.1128/mSystems.00109-20 Google ScholarPubMed
Fugmann, M, Breier, M, Rottenkolber, M, et al. The stool microbiota of insulin resistant women with recent gestational diabetes, a high risk group for type 2 diabetes. Sci Rep. 2015; 5(1), 13212.CrossRefGoogle Scholar
Crusell, MKW, Hansen, TH, Nielsen, T, 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.Google ScholarPubMed
Ponzo, V, Fedele, D, Goitre, I, et al. Diet-gut microbiota interactions and gestational diabetes mellitus (GDM). Nutrients. 2019; 11(2), 330.CrossRefGoogle Scholar
Sokol, H, Pigneur, B, Watterlot, L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008; 105(43), 1673116736.CrossRefGoogle ScholarPubMed
Goodrich, JK, Waters, JL, Poole, AC, et al. Human genetics shape the gut microbiome. Cell. 2014; 159(4), 789799.CrossRefGoogle ScholarPubMed
Canfora, EE, Jocken, JW, Blaak, EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015; 11(10), 577591.CrossRefGoogle ScholarPubMed
Lee, H, Lee, Y, Kim, J, et al. Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes. 2018; 9(2), 155165.CrossRefGoogle ScholarPubMed
Dao, MC, Everard, A, Aron-Wisnewsky, J, et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016; 65(3), 426436.CrossRefGoogle ScholarPubMed
Cani, PD, de Vos, WM. Next-generation beneficial microbes: the case of Akkermansia muciniphila. Front Microbiol. 2017; 8, 1765.CrossRefGoogle ScholarPubMed
Cortez, RV, Taddei, CR, Sparvoli, LG, et al. Microbiome and its relation to gestational diabetes. Endocrine. 2019; 64(2), 254264.CrossRefGoogle ScholarPubMed
Depommier, C, Everard, A, Druart, C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019; 25(7), 10961103.CrossRefGoogle ScholarPubMed
Plovier, H, Everard, A, Druart, C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017; 23(1), 107113.CrossRefGoogle ScholarPubMed
de la Cuesta-Zuluaga, J, Mueller, NT, Corrales-Agudelo, V, et al. Metformin is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care. 2017; 40(1), 5462.CrossRefGoogle Scholar
Lee, H, Ko, G. Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol. 2014; 80(19), 59355943.CrossRefGoogle ScholarPubMed
Wu, H, Esteve, E, Tremaroli, V, et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med. 2017; 23(7), 850858.CrossRefGoogle ScholarPubMed
Everard, A, Belzer, C, Geurts, L, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013; 110(22), 90669071.CrossRefGoogle ScholarPubMed
Wahlstrom, A, Kovatcheva-Datchary, P, Stahlman, M, Khan, MT, Backhed, F, Marschall, HU. Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota. J Lipid Res. 2017; 58(2), 412419.CrossRefGoogle ScholarPubMed
Supplementary material: File

Liu et al. supplementary material

Tables S1-S3

Download Liu et al. supplementary material(File)
File 32 KB
1
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *