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For: Li GH, Huang SJ, Li X, Liu XS, Du QL. Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients. World J Gastroenterol 2020; 26(46): 7338-7351 [PMID: 33362388 DOI: 10.3748/wjg.v26.i46.7338] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] Open

For:	Li GH, Huang SJ, Li X, Liu XS, Du QL. Response of gut microbiota to serum metabolome changes in intrahepatic cholestasis of pregnant patients. World J Gastroenterol 2020; 26(46): 7338-7351 [PMID: 33362388 DOI: 10.3748/wjg.v26.i46.7338] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] Open

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Cited by Other Article(s)

Lotankar M, Houttu N, Benchraka C, Lahti L, Laitinen K. Links between gut microbiota with specific serum metabolite groups in pregnant women with overweight or obesity. Nutr Metab Cardiovasc Dis 2025:104095. [PMID: 40348632 DOI: 10.1016/j.numecd.2025.104095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 04/10/2025] [Accepted: 04/14/2025] [Indexed: 05/14/2025]

Abstract

BACKGROUND AND AIM

Gut microbiota may regulate metabolism but is incompletely characterized in pregnancy. Our objective was to investigate the relations using omics techniques.

METHODS AND RESULTS

In a cross-sectional setting, fecal and serum samples of 361 healthy pregnant women with overweight or obesity were analyzed with a combinatorial approach of metagenomics and targeted NMR-based metabolomics, with statistical and machine learning techniques to identify and analyze the extent to which the gut microbiota composition and predicted functions would be reflected in the serum metabolome. We identified five biclusters, each of which consisted of a set of gut microbial species and serum metabolites with correlated abundance profiles. Two of the biclusters included metabolites that have been linked to the cardiovascular health; one was linked with factors known to increase the risk i.e., various sizes of lipoprotein subclasses (VLDL and LDL), subclasses of relative lipoprotein lipid concentrations (VLDL, IDL, and LDL), apolipoprotein B, and an inflammation marker, glycoprotein acetylation. These metabolites were associated with abundances of species such as, Enterocloster bolteae and Ruminococcus gnavus. The second bicluster included metabolites linked with a reduced cardiovascular risk, such as different sizes of HDL (high-density lipoprotein), subclasses for relative lipoprotein lipid concentrations and mean diameter for HDL particles, and fatty acid ratios. These metabolites were associated with abundances of species, such as Bacteroides cellulosilyticus and Alistipes finegoldii. We did not observe any biclusters between predicted pathways and serum metabolites.

CONCLUSION

Overall, we identified five biclusters of co-abundant gut bacteria and serum metabolites , of which two were linked to pro-atherogenic and anti-atherogenic properties.

TRIAL REGISTRATION

www.

CLINICALTRIALS

Gov: NCT01922791.

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Zhang F, Liu F, Xu X, Su W, Rong Y, Tian FY, Xiao W, Wu Y, Law KP, Wen P. Metabolomic profiling of serum and tongue coating of pregnant women with intrahepatic cholestasis in pregnancy. Clin Chim Acta 2024;557:117854. [PMID: 38513931 DOI: 10.1016/j.cca.2024.117854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 02/08/2024] [Accepted: 03/03/2024] [Indexed: 03/23/2024]

Tian Z, Zhang X, Yao G, Jin J, Zhang T, Sun C, Wang Z, Zhang Q. Intestinal flora and pregnancy complications: Current insights and future prospects. IMETA 2024;3:e167. [PMID: 38882493 PMCID: PMC11170975 DOI: 10.1002/imt2.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/27/2023] [Accepted: 12/22/2023] [Indexed: 06/18/2024]

Affiliation(s)

Zhenyu Tian National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
Xinjie Zhang Department of Biology University College London London UK
Guixiang Yao National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
Jiajia Jin National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
Tongxue Zhang National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China
Chunhua Sun Department of Health Management Center, Qilu Hospital, Cheeloo College of Medicine Shandong University Jinan China
Zhe Wang Department of Geriatrics Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China
Qunye Zhang National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology Qilu Hospital of Shandong University Jinan China Cardiovascular Disease Research Center of Shandong First Medical University Central Hospital Affiliated to Shandong First Medical University Jinan China

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Liu T, Zhao M, Zhang Y, Xu R, Fu Z, Jin T, Song J, Huang Y, Wang M, Zhao C. Polysaccharides from Phellinus linteus attenuate type 2 diabetes mellitus in rats via modulation of gut microbiota and bile acid metabolism. Int J Biol Macromol 2024;262:130062. [PMID: 38340923 DOI: 10.1016/j.ijbiomac.2024.130062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 02/02/2024] [Accepted: 02/06/2024] [Indexed: 02/12/2024]

Tang M, Xiong L, Cai J, Fu J, Liu H, Ye Y, Yang L, Xing S, Yang X. Intrahepatic cholestasis of pregnancy: insights into pathogenesis and advances in omics studies. Hepatol Int 2024;18:50-62. [PMID: 37957532 DOI: 10.1007/s12072-023-10604-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 09/28/2023] [Indexed: 11/15/2023]

Davies J, Mayer MJ, Juge N, Narbad A, Sayavedra L. Bacteroides thetaiotaomicron enhances H₂S production in Bilophila wadsworthia. Gut Microbes 2024;16:2431644. [PMID: 39609271 PMCID: PMC11610557 DOI: 10.1080/19490976.2024.2431644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 11/06/2024] [Accepted: 11/14/2024] [Indexed: 11/30/2024] Open

Sun H, Su X, Liu Y, Li G, Du Q. Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats. iScience 2023;26:108392. [PMID: 38025767 PMCID: PMC10679810 DOI: 10.1016/j.isci.2023.108392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 09/25/2023] [Accepted: 11/01/2023] [Indexed: 12/01/2023] Open

Xiang D, Yang J, Liu L, Yu H, Gong X, Liu D. The regulation of tissue-specific farnesoid X receptor on genes and diseases involved in bile acid homeostasis. Biomed Pharmacother 2023;168:115606. [PMID: 37812893 DOI: 10.1016/j.biopha.2023.115606] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 09/23/2023] [Accepted: 09/26/2023] [Indexed: 10/11/2023] Open

Mo Z, Wang J, Meng X, Li A, Li Z, Que W, Wang T, Tarnue KF, Ma X, Liu Y, Yan S, Wu L, Zhang R, Pei J, Wang X. The Dose-Response Effect of Fluoride Exposure on the Gut Microbiome and Its Functional Pathways in Rats. Metabolites 2023;13:1159. [PMID: 37999254 PMCID: PMC10672837 DOI: 10.3390/metabo13111159] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/13/2023] [Accepted: 11/14/2023] [Indexed: 11/25/2023] Open

Abstract

Metabolic activities within the gut microbiome are intimately linked to human health and disease, especially within the context of environmental exposure and its potential ramifications. Perturbations within this microbiome, termed "gut microbiome perturbations", have emerged as plausible intermediaries in the onset or exacerbation of diseases following environmental chemical exposures, with fluoride being a compound of particular concern. Despite the well-documented adverse impacts of excessive fluoride on various human physiological systems-ranging from skeletal to neurological-the nuanced dynamics between fluoride exposure, the gut microbiome, and the resulting dose-response relationship remains a scientific enigma. Leveraging the precision of 16S rRNA high-throughput sequencing, this study meticulously examines the ramifications of diverse fluoride concentrations on the gut microbiome's composition and functional capabilities within Wistar rats. Our findings indicate a profound shift in the intestinal microbial composition following fluoride exposure, marked by a dose-dependent modulation in the abundance of key genera, including Pelagibacterium, Bilophila, Turicibacter, and Roseburia. Moreover, discernible alterations were observed in critical functional and metabolic pathways of the microbiome, such as D-lyxose ketol-isomerase and DNA polymerase III subunit gamma/tau, underscoring the broad-reaching implications of fluoride exposure. Intriguingly, correlation analyses elucidated strong associations between specific bacterial co-abundance groups (CAGs) and these shifted metabolic pathways. In essence, fluoride exposure not only perturbs the compositional equilibrium of the gut microbiota but also instigates profound shifts in its metabolic landscape. These intricate alterations may provide a mechanistic foundation for understanding fluoride's potential toxicological effects mediated via gut microbiome modulation.

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Affiliation(s)

Zhe Mo Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.) Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China
Jian Wang Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Xinyue Meng Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Ailin Li Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Zhe Li Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Wenjun Que Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Tuo Wang Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Korto Fatti Tarnue Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Xu Ma Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Ying Liu Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Shirui Yan Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Lei Wu Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Rui Zhang Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Junrui Pei Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China; (Z.M.); (J.W.); (X.M.); (A.L.); (Z.L.); (W.Q.); (T.W.); (K.F.T.); (X.M.); (Y.L.); (S.Y.); (L.W.); (R.Z.)
Xiaofeng Wang Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China

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Li X, Xie H, Chao JJ, Jia YH, Zuo J, An YP, Bao YR, Jiang X, Ying H. Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy. BMC Microbiol 2023;23:282. [PMID: 37784030 PMCID: PMC10546765 DOI: 10.1186/s12866-023-02983-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 08/17/2023] [Indexed: 10/04/2023] Open

Abstract

BACKGROUND

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.

METHODS

We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites.

RESULTS

An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP.

CONCLUSIONS

Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.

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Affiliation(s)

Xiang Li Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai, 200040, People's Republic of China
Han Xie Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai, 200040, People's Republic of China
Jia-Jing Chao Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai, 200040, People's Republic of China
Yuan-Hui Jia Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China
Jia Zuo Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai, 200040, People's Republic of China
Yan-Peng An State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China
Yi-Rong Bao Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai, 200040, People's Republic of China
Xiang Jiang Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China. Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai, 200040, People's Republic of China. Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China.
Hao Ying Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai, 200040, China. Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, No. 2699, West Gaoke Road, Shanghai, 200040, People's Republic of China.

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Li C, Li N, Liu C, Yin S. Causal association between gut microbiota and intrahepatic cholestasis of pregnancy: mendelian randomization study. BMC Pregnancy Childbirth 2023;23:568. [PMID: 37543573 PMCID: PMC10403878 DOI: 10.1186/s12884-023-05889-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 08/01/2023] [Indexed: 08/07/2023] Open

Abstract

BACKGROUND

Previous observational cohort studies have shown that the composition of the gut microbiota is related to the risk of intrahepatic cholestasis of pregnancy (ICP), although it is unclear if the association is causative. This study used Mendelian randomization (MR) to systematically examine whether the gut microbiota was causally linked to ICP.

METHODS

We obtained the genome-wide association study (GWAS) summary statistics of gut microbiota and ICP from published GWASs. Maximum likelihood (ML), MR-Egger regression, weighted median, inverse variance weighted (IVW), and weighted model were used to investigate the causal association between gut microbiota and ICP. We further conducted a series of sensitivity analyses to confirm the robustness of the primary results of the MR analyses. Reverse MR analysis was performed on the bacterial taxa that were reported to be causally linked to ICP risk in forwarding MR analysis to evaluate the possibility of reverse causation.

RESULTS

MR analysis revealed that phylum Tenericutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), class Bacteroidia (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), class Mollicutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), and order Bacteroidales (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), and were positively associated with the risk of ICP. And we identified that the relative abundance of genus Dialister (OR: 0.562, 95%CI: 0.323-0.977, P = 0.041), genus Erysipelatoclostridium (OR: 0.695, 95%CI: 0.490-0.987, P = 0.042), genus Eubacterium (brachy group) (OR: 0.661, 95%CI: 0.497-0.880, P = 0.005), genus Eubacterium (hallii group) (OR: 0.664, 95%CI: 0.451-0.977, P = 0.037), genus Holdemania (OR: 0.590, 95%CI: 0.414-0.840, P = 0.003), genus Ruminococcus (torques group) (OR: 0.448, 95%CI: 0.235-0.854, P = 0.015), and genus Veillonella (OR: 0.513, 95%CI: 0.294-0.893, P = 0.018) were related to a lower risk of ICP. Additional sensitivity analyses confirmed the robustness of the association between specific gut microbiota composition and ICP. No evidence of reverse causality from ICP to identified bacterial taxa was found in the findings of the reverse MR analyses.

CONCLUSIONS

Under MR assumptions, our findings propose new evidence of the relationship between gut microbiota and ICP risk. Our results show that the gut microbiota may be useful target of intervention for ICP.

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Hualin X, Yupin X, Guoqiang Z, Xukun F, Hongmei L. Intrahepatic cholestasis of pregnancy worsening perinatal depressive tendency: A follow-up study from the second trimester to the sixth week postpartum. Heliyon 2023;9:e15845. [PMID: 37215870 PMCID: PMC10199176 DOI: 10.1016/j.heliyon.2023.e15845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 04/11/2023] [Accepted: 04/25/2023] [Indexed: 05/24/2023] Open

Distribution of endotoxin in maternal and fetal body with intrahepatic cholestasis of pregnancy and its association with adverse fetal outcome. BMC Pregnancy Childbirth 2022;22:920. [PMID: 36482374 PMCID: PMC9733156 DOI: 10.1186/s12884-022-05235-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 11/20/2022] [Indexed: 12/13/2022] Open

Abstract

BACKGROUND

Intrahepatic cholestasis of pregnancy is a pregnancy-specific liver disease. In this study, we sought to explore the distribution of lipopolysaccharide in the maternal body, and its effect on the fetal body in the intrahepatic cholestasis of pregnancy mice. It provides a new sight for the clinical treatment of women with intrahepatic cholestasis of pregnancy.

METHODS

The serum levels of lipopolysaccharide and lipopolysaccharide binding protein in women with intrahepatic cholestasis of pregnancy were analyzed. To assess the association between lipopolysaccharide levels and adverse fetal outcomes, ursodeoxycholic acid, resveratrol, and phosphatidylinositol-3-kinase inhibitor were employed in intrahepatic cholestasis of pregnancy mice, and we studied the fluorescence intensity and distribution of lipopolysaccharide in mice with intrahepatic cholestasis of pregnancy.

RESULTS

Our data indicated significantly elevated levels of lipopolysaccharide and lipopolysaccharide binding protein in women with intrahepatic cholestasis of pregnancy. In vivo fluorescence imaging revealed that the intensity of lipopolysaccharide in mice with intrahepatic cholestasis of pregnancy was higher than that in the control group, and decreased after ursodeoxycholic and resveratrol treatment. The fluorescence intensity analysis indicated that lipopolysaccharide levels in maternal liver, placenta, fetal brain and fetal liver were significantly higher in the intrahepatic cholestasis pregnancy mice group than in the control group.

CONCLUSIONS

This study provided evidence of endotoxin distribution in maternal liver, placenta, fetal liver and fetal brain in mice with intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid and resveratrol treatment effectively reduced lipopolysaccharide levels in pregnant mice with intrahepatic cholestasis of pregnancy.

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Liu X, Li M, Jian C, Wei F, Liu H, Li K, Qin X. Astragalus Polysaccharide Alleviates Constipation in the Elderly Via Modification of Gut Microbiota and Fecal Metabolism. Rejuvenation Res 2022;25:275-290. [PMID: 36205566 DOI: 10.1089/rej.2022.0039] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open

Affiliation(s)

Xiaojie Liu Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.,Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, China
Mengyu Li Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.,Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, China
Chen Jian Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.,Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, China
Fuxiao Wei Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.,Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, China
Huanle Liu Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.,Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, China
Ke Li Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.,Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, China
Xuemei Qin Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.,The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, China.,Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, Shanxi University, Taiyuan, China

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Application of metabolomics in intrahepatic cholestasis of pregnancy: a systematic review. Eur J Med Res 2022;27:178. [PMID: 36104763 PMCID: PMC9472355 DOI: 10.1186/s40001-022-00802-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 08/07/2022] [Indexed: 11/10/2022] Open

Huang S, Liu Y, Guo N, Liu X, Li G, Du Q. Serum profiles of inflammatory cytokines associated with intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med 2022;35:10072-10081. [PMID: 35762044 DOI: 10.1080/14767058.2022.2089551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]

Abstract

BACKGROUND

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is not clear, and some researchers have compared the differences in serum levels of inflammatory cytokines between ICP patients and normal pregnant women, but there are few studies and different conclusions.

AIM

To investigate the levels of inflammatory cytokines such as interleukins (IL) -4, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) in patients with ICP and their potential role in pathophysiology.

METHODS

This case-control study was conducted in Shanghai First Maternity and Infant Health Hospital, and we recruited ICP patients and age-matched healthy pregnant women as a control group. Plasma samples from 40 subjects with ICP and 40 subjects without ICP were tested for concentration of the following inflammatory cytokines: interferon-gamma, IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α. Analyzed inflammatory cytokines were then assessed, either individually or in combination with regard to ICP.

RESULTS

The cytokine composition of the ICP and CTL group was significantly different. We compared levels of inflammatory cytokines with regard to the presence of ICP symptoms. Levels of IL-4, IL-6, and TNF-α were significantly lower in ICP subjects, and IL-8 were significantly higher in ICP subjects, compared with CTL subjects. The TNF-α showed the best performance for ICP identification (area under the curve [AUC]: 0.829). Performance was increased when TNF-α was combined with IL-4 and IL-8 analysis (AUC, 0.901). Spearman correlation and linear regression analysis revealed that the TNF-α concentrations correlated with IL-4 and IL-6 levels, and inversely correlated to TBA, ALT, AST, and IL-8 levels.

CONCLUSION

IL-4, IL-6, and TNF-α were significantly decreased, while IL-8 was significantly increased in the ICP group compared with the healthy control group. TNF showed the best single marker discriminatory potential; however, combining TNF-α, IL-4, and IL-8 analyses increased performance for ICP identification.

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Lin QX, Huang WW, Shen W, Deng XS, Tang ZY, Chen ZH, Zhao W, Fan HY. Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota. Front Immunol 2022;13:889646. [PMID: 35769469 PMCID: PMC9234109 DOI: 10.3389/fimmu.2022.889646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/05/2022] [Indexed: 11/13/2022] Open

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that is characterized by increased bile acid levels in maternal serum. Studies have shown that cholestatic pregnancy can result in long-term metabolic disturbances in the offspring. However, how ICP shapes the offspring’s immunity and predisposition to inflammatory disorders at an early stage is unknown. In this study, we investigated the effect of maternal cholestasis on neonatal offspring metabolism and immune function. We compared 71 neonates with ICP mothers and 63 neonates with healthy mothers and found that the incidence of jaundice and infection was significantly higher in ICP offspring. Maternal serum total bile acid level was associated with blood cell counts in full-term ICP offspring. In animal experiments, a compensatory activation of hepatic and ileal farnesoid X receptor (FXR) and altered gut microbiota in the first week were found in ICP offspring. We also investigated lipopolysaccharide (LPS)-induced inflammatory responses in neonatal rats and found that ICP offspring were more susceptible to inflammation. To understand the correlation between congenital abnormal FXR activation and tissue immunity dysregulation, we assessed the effects of the FXR agonist GW4064 and FXR antagonist E/Z-GS in ICP offspring after LPS exposure. The expression of several pro-inflammatory cytokines significantly decreased after treatment with E/Z-GS but increased after treatment with GW4064. Treatment with the probiotic Lactobacillus rhamnosus LRX01 that inhibits FXR expression in the ileum reduced susceptibility to LPS exposure in ICP offspring. The current study indicated that cholestatic pregnancy may increase the susceptibility of the offspring to inflammation by altering bile acid metabolism and gut microbiota at an early stage. We suggest that supplementation with Lactobacillus rhamnosus LRX01, which inhibits FXR expression in the ileum, may improve intestinal immunity in ICP offspring.

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Liu ZZ, Sun JH, Wang WJ. Gut microbiota in gastrointestinal diseases during pregnancy. World J Clin Cases 2022;10:2976-2989. [PMID: 35647135 PMCID: PMC9082698 DOI: 10.12998/wjcc.v10.i10.2976] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/18/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open

Ren S, Zhou Y, Xuan R. Research progress in the role of gut microbiota and its metabolites in intrahepatic cholestasis of pregnancy. Expert Rev Gastroenterol Hepatol 2021;15:1361-1366. [PMID: 34845962 DOI: 10.1080/17474124.2021.2011211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]

Ruebel ML, Gilley SP, Sims CR, Zhong Y, Turner D, Chintapalli SV, Piccolo BD, Andres A, Shankar K. Associations between Maternal Diet, Body Composition and Gut Microbial Ecology in Pregnancy. Nutrients 2021;13:3295. [PMID: 34579172 PMCID: PMC8468685 DOI: 10.3390/nu13093295] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 09/13/2021] [Accepted: 09/17/2021] [Indexed: 12/22/2022] Open

Affiliation(s)

Meghan L. Ruebel Department of Pediatrics, Section of Nutrition, Anschutz Medical Campus, School of Medicine, University of Colorado, Aurora, CO 80045, USA; (M.L.R.); (S.P.G.)
Stephanie P. Gilley Department of Pediatrics, Section of Nutrition, Anschutz Medical Campus, School of Medicine, University of Colorado, Aurora, CO 80045, USA; (M.L.R.); (S.P.G.)
Clark R. Sims Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA; (C.R.S.); (Y.Z.); (D.T.); (S.V.C.); (B.D.P.); (A.A.) Department of Pediatrics, Section of Developmental Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Ying Zhong Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA; (C.R.S.); (Y.Z.); (D.T.); (S.V.C.); (B.D.P.); (A.A.)
Donald Turner Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA; (C.R.S.); (Y.Z.); (D.T.); (S.V.C.); (B.D.P.); (A.A.)
Sree V. Chintapalli Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA; (C.R.S.); (Y.Z.); (D.T.); (S.V.C.); (B.D.P.); (A.A.) Department of Pediatrics, Section of Developmental Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Brian D. Piccolo Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA; (C.R.S.); (Y.Z.); (D.T.); (S.V.C.); (B.D.P.); (A.A.) Department of Pediatrics, Section of Developmental Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Aline Andres Arkansas Children’s Nutrition Center, Little Rock, AR 72202, USA; (C.R.S.); (Y.Z.); (D.T.); (S.V.C.); (B.D.P.); (A.A.) Department of Pediatrics, Section of Developmental Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Kartik Shankar Department of Pediatrics, Section of Nutrition, Anschutz Medical Campus, School of Medicine, University of Colorado, Aurora, CO 80045, USA; (M.L.R.); (S.P.G.)

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The Differential Metabolomes in Cumulus and Mural Granulosa Cells from Human Preovulatory Follicles. Reprod Sci 2021;29:1343-1356. [PMID: 34374964 PMCID: PMC8907092 DOI: 10.1007/s43032-021-00691-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 07/04/2021] [Indexed: 01/11/2023]