上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2023 , Vol. 43 >Issue 5: 641 - 647

DOI: https://doi.org/10.3969/j.issn.1674-8115.2023.05.016

综述

肠道菌群及其代谢产物与妊娠期糖尿病相关性的研究进展

  • 刘芊若 ,
  • 方子晨 ,
  • 吴宇涵 ,
  • 钟羡欣 ,
  • 国沐禾 ,
  • 贾洁
展开
  • 1.上海交通大学医学院附属新华医院临床营养科，上海 200092
    2.上海交通大学医学院医学技术学院临床营养系，上海 200025
    3.上海交通大学医学院儿科学院，上海 200025
    4.上海交通大学医学院附属第九人民医院临床医学院，上海 200011
    5.上海交通大学医学院附属新华医院，上海市小儿消化与营养重点实验室，上海 200092
刘芊若（2001—），女，本科生；电子信箱：kinnal@163.com。
贾　洁，电子信箱：jie. jia@shsmu.edu.cn。

收稿日期: 2022-12-12

  录用日期: 2023-02-21

  网络出版日期: 2023-07-11

基金资助

国家自然科学基金(81501338);上海交通大学医学院大学生创新训练计划(S202210248311)

收起

Research progress in the relationship between gut microbia and its metabolites and gestational diabetes mellitus

  • Qianruo LIU ,
  • Zichen FANG ,
  • Yuhan WU ,
  • Xianxin ZHONG ,
  • Muhe GUO ,
  • Jie JIA
Expand
  • 1.Department of Clinical Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
    2.Department of Clinical Nutrition, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    3.School of Pediatrics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    4.College of Clinical Medicine, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
    5.Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
JIA Jie, E-mail: jie. jia@shsmu.edu.cn.

Received date: 2022-12-12

  Accepted date: 2023-02-21

  Online published: 2023-07-11

Supported by

National Natural Science Foundation of China(81501338);Undergraduate Innovation Program of Shanghai Jiao Tong University School of Medicine(S202210248311)

Fold

摘要

近年来，妊娠期糖尿病（gestational diabetes mellitus，GDM）在全球的发病率持续攀升。研究显示，GDM可增加孕妇不良妊娠结局的发生风险，并导致恶性代际循环。该疾病成因复杂且发病机制尚未被完全阐明，孕期膳食评估和指导是目前临床上管理GDM的一线方法。孕期合理饮食对肠道菌群及其代谢产物有重要作用，而肠道菌群功能的紊乱则与代谢性疾病的发生密切相关。已有研究显示，短链脂肪酸、氧化三甲胺、胆汁酸等肠道菌群代谢产物可受到饮食的强烈影响，并在与胰岛素抵抗相关的代谢紊乱（如GDM）中发挥重要作用。目前，医学营养疗法改善肠道菌群以防治代谢性疾病取得了一定进展，这为控制GDM提供了新的方向。该文针对GDM的现状、GDM孕妇肠道菌群的变化特征、GDM相关肠道菌群代谢产物、调控肠道菌群及其代谢产物防治GDM的方式进行综述。

关键词： 妊娠期糖尿病; 肠道菌群; 肠道菌群代谢产物; 膳食评估

本文引用格式

刘芊若 , 方子晨 , 吴宇涵 , 钟羡欣 , 国沐禾 , 贾洁 . 肠道菌群及其代谢产物与妊娠期糖尿病相关性的研究进展[J]. 上海交通大学学报（医学版）, 2023 , 43(5) : 641 -647 . DOI: 10.3969/j.issn.1674-8115.2023.05.016

Abstract

The global incidence of gestational diabetes mellitus (GDM) continues to rise in recent years. Research has shown that GDM can increase the risk of adverse pregnancy outcomes in pregnant women and lead to malignant intergenerational circulation. The etiology of GDM is complex and the pathogenesis has not been fully elucidated. Maternal dietary assessment and guidance is the first-line method for managing GDM in clinical practice. Reasonable diet plays an important role in gut microbia and its metabolites during pregnancy, and the dysfunction of gut microbia is closely related to the occurrence of metabolic diseases. It has been shown that gut microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine oxide (TMAO) and bile acids are strongly influenced by diet and play an important role in metabolic disorders related to insulin resistance (such as GDM). Progress has been made in the prevention and treatment of metabolic diseases by improving gut microbia through medical nutrition therapy, which provides a new direction for the control of GDM. The status quo of GDM, the characteristics and alteration of gut microbia in pregnant women with GDM, the GDM-related gut microbial metabolites, and the feasible prevention and treatment of GDM by targeting gut microbia and its metabolites are reviewed.

Key words： gestational diabetes mellitus (GDM); gut microbia; gut microbia metabolite; dietary estimation

参考文献

1 DENG K, SHUAI M, ZHANG Z, et al. Temporal relationship among adiposity, gut microbiota, and insulin resistance in a longitudinal human cohort[J]. BMC Med, 2022, 20(1): 171.
2 ASSOCIATION A D. Diagnosis and classification of diabetes mellitus[J]. Diabetes Care, 2013, 36(Suppl 1): S67-S74.
3 JOHNS E C, DENISON F C, NORMAN J E, et al. Gestational diabetes mellitus: mechanisms, treatment, and complications[J]. Trends Endocrinol Metab, 2018, 29(11): 743-754.
4 DE GENNARO G, PALLA G, BATTINI L, et al. The role of adipokines in the pathogenesis of gestational diabetes mellitus[J]. Gynecol Endocrinol, 2019, 35(9): 737-751.
5 GAO C H, SUN X, LU L, et al. Prevalence of gestational diabetes mellitus in mainland China: a systematic review and meta-analysis[J]. J Diabetes Investig, 2019, 10(1): 154-162.
6 KAPUR K, KAPUR A, HOD M. Nutrition management of gestational diabetes mellitus[J]. Ann Nutr Metab, 2021: 1-13.
7 韩睿盈, 姜志深, 高灿宇, 等. 常见肠道菌群代谢产物作为疾病诊断的指针的研究进展 [J]. 微生物学通报, 2021, 48(11): 4261-4274.
7 HAN R Y, JIANG Z S, GAO C Y, et al. Research progress of intestinal flora metabolites as indicators for disease diagnosis [J]. Microbiology China, 2021, 48(11): 4261-4274.
8 REN W K, YIN J, XIAO H, et al. Intestinal microbiota-derived GABA mediates interleukin-17 expression during enterotoxigenic Escherichia coli infection[J]. Front Immunol, 2017, 7: 685.
9 AGUS A, CLéMENT K, SOKOL H. Gut microbiota-derived metabolites as central regulators in metabolic disorders[J]. Gut, 2021, 70(6): 1174-1182.
10 KOREN O, GOODRICH J K, CULLENDER T C, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy[J]. Cell, 2012, 150(3): 470-480.
11 KUANG Y S, LU J H, LI S H, et al. Connections between the human gut microbiome and gestational diabetes mellitus[J]. Gigascience, 2017, 6(8): 1-12.
12 MA S J, YOU Y P, HUANG L T, et al. Alterations in gut microbiota of gestational diabetes patients during the first trimester of pregnancy[J]. Front Cell Infect Microbiol, 2020, 10: 58.
13 CRUSELL M K W, HANSEN T H, NIELSEN T, et al. Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum[J]. Microbiome, 2018, 6(1): 89.
14 SU M L, NIE Y Y, SHAO R C, et al. Diversified gut microbiota in newborns of mothers with gestational diabetes mellitus[J]. PLoS One, 2018, 13(10): e0205695.
15 GHOLIZADEH P, MAHALLEI M, PORMOHAMMAD A, et al. Microbial balance in the intestinal microbiota and its association with diabetes, obesity and allergic disease[J]. Microb Pathog, 2019, 127: 48-55.
16 KUMBHARE S V, PATANGIA D V V, PATIL R H, et al. Factors influencing the gut microbiome in children: from infancy to childhood[J]. J Biosci, 2019, 44(2): 49.
17 TAN J, MCKENZIE C, POTAMITIS M, et al. The role of short-chain fatty acids in health and disease[J]. Adv Immunol, 2014, 121: 91-119.
18 TOLHURST G, HEFFRON H, LAM Y S, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2[J]. Diabetes, 2012, 61(2): 364-371.
19 KIMURA I, MIYAMOTO J, OHUE-KITANO R, et al. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice[J]. Science, 2020, 367(6481): eaaw8429.
20 LIU X N, LI X, XIA B, et al. High-fiber diet mitigates maternal obesity-induced cognitive and social dysfunction in the offspring via gut-brain axis[J]. Cell Metab, 2021, 33(5): 923-938.e6.
21 CHITTIM C L, MARTíNEZ DEL CAMPO A, BALSKUS E P. Gut bacterial phospholipase Ds support disease-associated metabolism by generating choline[J]. Nat Microbiol, 2019, 4(1): 155-163.
22 CHO C E, TAESUWAN S, MALYSHEVA O V, et al. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: a randomized controlled trial[J]. Mol Nutr Food Res, 2017, 61(1). doi: 10.1002/mnfr.201600324.
23 WANG Z N, BERGERON N, LEVISON B S, et al. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women[J]. Eur Heart J, 2019, 40(7): 583-594.
24 HUO X X, LI J, CAO Y F, et al. Trimethylamine N-oxide metabolites in early pregnancy and risk of gestational diabetes: a nested case-control study[J]. J Clin Endocrinol Metab, 2019, 104(11): 5529-5539.
25 LI P Y, ZHONG C R, LI S Z, et al. Plasma concentration of trimethylamine-N-oxide and risk of gestational diabetes mellitus[J]. Am J Clin Nutr, 2018, 108(3): 603-610.
26 LIN X J, ZHANG Y Q, HE X L, et al. The choline metabolite TMAO inhibits NETosis and promotes placental development in GDM of humans and mice[J]. Diabetes, 2021, 70(10): 2250-2263.
27 LIU J N, LI J, YANG K, et al. Ceramides and their interactive effects with trimethylamine-N-oxide metabolites on risk of gestational diabetes: a nested case-control study[J]. Diabetes Res Clin Pract, 2021, 171: 108606.
28 JIA W, XIE G X, JIA W P. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(2): 111-128.
29 CHIANG J Y L, FERRELL J M. Bile acid metabolism in liver pathobiology[J]. Gene Expr, 2018, 18(2): 71-87.
30 李婧. 肠道菌群相关代谢产物与妊娠糖尿病及巨大儿的关联研究 [D]. 天津: 天津医科大学, 2019.
30 LI J. Gut microbiota-related metabolites and risks of gestational diabetes and macrosomia[D]. Tianjin: Tianjin Medical University, 2019.
31 MCINTYRE H D, SACKS D A, BARBOUR L A, et al. Issues with the diagnosis and classification of hyperglycemia in early pregnancy[J]. Diabetes Care, 2016, 39(1): 53-54.
32 LIU Y, SUN R, LI Y, et al. Changes in serum total bile acid concentrations are associated with the risk of developing adverse maternal and perinatal outcomes in pregnant Chinese women[J]. Clin Chim Acta, 2021, 520: 160-167.
33 KONG M, LU Z, ZHONG C, et al. A higher level of total bile acid in early mid-pregnancy is associated with an increased risk of gestational diabetes mellitus: a prospective cohort study in Wuhan, China[J]. J Endocrinol Invest, 2020, 43(8): 1097-1103.
34 HE J, JIANG D M, CUI X W, et al. Vitamin B12 status and folic acid/vitamin B12 related to the risk of gestational diabetes mellitus in pregnancy: a systematic review and meta-analysis of observational studies[J]. BMC Pregnancy Childbirth, 2022, 22(1): 587.
35 KANWAL A, BASHIR A. Vitamin B12 in pregnancy and its relationship with maternal BMI and gestational diabetes mellitus: a study from Pakistan[J]. Pak J Med Sci, 2022, 38(4Part-II): 807-810.
36 CHEN X T, ZHANG Y, CHEN H Y, et al. Association of maternal folate and vitamin B12 in early pregnancy with gestational diabetes mellitus: a prospective cohort study[J]. Diabetes Care, 2021, 44(1): 217-223.
37 SARAVANAN P, SUKUMAR N, ADAIKALAKOTESWARI A, et al. Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: a prospective UK cohort study (PRiDE study)[J]. Diabetologia, 2021, 64(10): 2170-2182.
38 JACOBSON A N, CHOUDHURY B P, FISCHBACH M A. The biosynthesis of lipooligosaccharide from Bacteroides thetaiotaomicron[J]. mBio, 2018, 9(2): e02289-e02217.
39 FERROCINO I, PONZO V, GAMBINO R, et al. Changes in the gut microbiota composition during pregnancy in patients with gestational diabetes mellitus (GDM)[J]. Sci Rep, 2018, 8(1): 12216.
40 MAHIZIR D, BRIFFA J F, WOOD J L, et al. Exercise improves metabolic function and alters the microbiome in rats with gestational diabetes[J]. FASEB J, 2020, 34(1): 1728-1744.
41 WU N, ZHOU J W, MO H, et al. The gut microbial signature of gestational diabetes mellitus and the association with diet intervention[J]. Front Cell Infect Microbiol, 2021, 11: 800865.
42 MAGNE F, GOTTELAND M, GAUTHIER L, et al. The firmicutes/bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients?[J]. Nutrients, 2020, 12(5): 1474.
43 LI G L, XIE C, LU S Y, et al. Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota[J]. Cell Metab, 2017, 26(5): 801.
44 MOTIANI K K, COLLADO M C, ESKELINEN J J, et al. Exercise training modulates gut microbiota profile and improves endotoxemia[J]. Med Sci Sports Exerc, 2020, 52(1): 94-104.
45 TURNBAUGH P J, LEY R E, MAHOWALD M A, et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature, 2006, 444(7122): 1027-1031.
46 RAJILI?-STOJANOVI? M, DE VOS W M. The first 1000 cultured species of the human gastrointestinal microbiota[J]. FEMS Microbiol Rev, 2014, 38(5): 996-1047.
47 TONUCCI L B, OLBRICH DOS SANTOS K M, LICURSI DE OLIVEIRA L, et al. Clinical application of probiotics in type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study[J]. Clin Nutr, 2017, 36(1): 85-92.
48 ZHENG Q X, JIANG X M, WANG H W, et al. Probiotic supplements alleviate gestational diabetes mellitus by restoring the diversity of gut microbiota: a study based on 16S rRNA sequencing[J]. J Microbiol, 2021, 59(9): 827-839.
49 CHEN Y T, LU J, WICKENS K, et al. Effect of Lactobacillus rhamnosus probiotic in early pregnancy on plasma conjugated bile acids in a randomised controlled trial[J]. Nutrients, 2021, 13(1): 209.
50 HASAIN Z, CHE ROOS N A, RAHMAT F, et al. Diet and pre-intervention washout modifies the effects of probiotics on gestational diabetes mellitus: a comprehensive systematic review and meta-analysis of randomized controlled trials[J]. Nutrients, 2021, 13(9): 3045.
51 SHAHRIARI A, KARIMI E, SHAHRIARI M, et al. The effect of probiotic supplementation on the risk of gestational diabetes mellitus among high-risk pregnant women: a parallel double-blind, randomized, placebo-controlled clinical trial[J]. Biomedecine Pharmacother, 2021, 141: 111915.
52 GIBSON G R, HUTKINS R, SANDERS M E, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(8): 491-502.
53 AHMADI S, JAMILIAN M, TAJABADI-EBRAHIMI M, et al. The effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes: a randomised, double-blind, placebo-controlled trial-Expression of concern[J]. Br J Nutr, 2022, 127(1): 153.
54 苗苗. 菊粉对妊娠期糖尿病小鼠糖脂代谢及妊娠结局的影响研究 [D]. 南京: 东南大学, 2020.
54 MIAO M. Effect of inulin on glycolipid metabolism and pregnancy outcomes in gestational diabetes mellitus[D]. Nanjing: Dongnan University, 2020.
55 VITALI B, NDAGIJIMANA M, CRUCIANI F, et al. Impact of a synbiotic food on the gut microbial ecology and metabolic profiles[J]. BMC Microbiol, 2010, 10: 4.
56 NABHANI Z, HEZAVEH S J G, RAZMPOOSH E, et al. The effects of synbiotic supplementation on insulin resistance/sensitivity, lipid profile and total antioxidant capacity in women with gestational diabetes mellitus: a randomized double blind placebo controlled clinical trial[J]. Diabetes Res Clin Pract, 2018, 138: 149-157.
Options
文章导航

/

〈 〉