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Original research
Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial
  1. Kati Mokkala1,
  2. Niklas Paulin2,
  3. Noora Houttu1,
  4. Ella Koivuniemi1,
  5. Outi Pellonperä3,
  6. Sofia Khan2,
  7. Sami Pietilä2,
  8. Kristiina Tertti3,
  9. Laura L Elo2,4,
  10. Kirsi Laitinen1
  1. 1 Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
  2. 2 Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
  3. 3 Department of Obstetrics and Gynecology, Turku University Hospital, University of Turku, Turku, Finland
  4. 4 Institute of Biomedicine, University of Turku, Turku, Finland
  1. Correspondence to Dr Kati Mokkala, Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku 20014, Finland; Kati.Mokkala{at}utu.fi

Abstract

Objective Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics.

Design The gut microbiota of 270 overweight/obese women participating in a mother–infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test.

Results Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions.

Conclusions The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.

  • intestinal bacteria
  • nutritional supplementation
  • diabetes mellitus

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Footnotes

  • Correction notice This article has been corrected since it published Online First. In the methods and table 4, mean 13.9 (14.1) was corrected to 13.9 (2.0).

  • Contributors KL designed the original clinical study, directed the project, curated the data and acquired the financial support for the study. KL and KM designed the research and its conceptualisation; EK and NH participated in sample and data collection; OP and KT interpreted the GDM diagnoses; NP, SK and SP performed bioinformatics; LE supervised bioinformatics analyses; KM performed the SPSS analyses; KM and KL interpreted the results; NP, SK, SP and LE contributed to the interpretation of the results; KM wrote the manuscript with support from KL. All authors read, critically revised, approved and take responsibility of the final version of the paper.

  • Funding This clinical trial was supported by the State Research Funding for university-level health research in the Turku University Hospital Expert Responsibility Area, Academy of Finland (#258606), the Diabetes Research Foundation and the Juho Vainio Foundation. Funding to the University of Turku for the metagenomics analyses and reporting was provided by Janssen Research & Development, LLC. These funding sources had no role in the design, execution, analyses, interpretation of the data or decision to submit these results. LE reports grants for bioinformatics from the European Research Council ERC (677943), European Union's Horizon 2020 research and innovation programme (675395), Academy of Finland (296801, 304995, 310561, 314443, and 329278), Juvenile Diabetes Research Foundation JDRF (2-2013-32), and Sigrid Juselius Foundation, during the conduct of the study. Our research is also supported by University of Turku, Åbo Akademi University, Turku Graduate School (UTUGS), Biocenter Finland and ELIXIR Finland.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting or dissemination plans of this research. Refer to the Methods section for further details.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are stored on the Turku university server; anonymised data are available upon reasonable request. There are restrictions to the availability of the results due to patient confidentiality reasons.