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Positive effects of diet-induced microbiome modification on GDM in mice following human faecal transfer
  1. Sigal Frishman1,2,
  2. Meital Nuriel-Ohayon3,
  3. Sondra Turjeman3,
  4. Yishay Pinto3,
  5. Or Yariv4,
  6. Kinneret Tenenbaum-Gavish5,
  7. Yoav Peled1,
  8. Eran Poran4,
  9. Joseph Pardo1,
  10. Rony Chen1,
  11. Efrat Muller6,
  12. Elhanan Borenstein1,7,
  13. Moshe Hod1,
  14. Yoram Louzoun8,
  15. Betty Schwartz2,
  16. Eran Hadar9,
  17. Maria Carmen Collado10,
  18. Omry Koren3,11
  1. 1 Tel Aviv University, Tel Aviv, Israel
  2. 2 Faculty of Agriculture, Hebrew University, Rehovot, Israel
  3. 3 Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
  4. 4 Clalit Health Services, Tel Aviv, Israel
  5. 5 Rabin Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  6. 6 The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
  7. 7 Santa Fe Institute, Santa Fe, New Mexico, USA
  8. 8 Department of Mathematics, Bar-Ilan University, Ramat Gan, Israel
  9. 9 Helen Schneider Hospital for Women, Rabin Medical Center, Petach-Tikva, Israel
  10. 10 Biotechnology, Unit of Probiotic, IATA-CSIC, Valencia, Spain
  11. 11 Kyung Hee University, Seoul, Korea (the Republic of)
  1. Correspondence to Dr Omry Koren, Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel; omry.koren{at}biu.ac.il

https://doi.org/10.1136/gutjnl-2023-331456

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    We recently reported in Gut that the microbiome is unequivocally implicated in early gestational diabetes mellitus (GDM) aetiology, starting in the first trimester (T1),1 and other groups have shown continued microbiota dysbiosis in women with GDM in second trimester (T2) and third trimester (T3).2 In continuation of our T1 research, we now have data showing that dietary interventions, the preferred and primary treatment of GDM, are effective in part by altering the gut microbiota. To elucidate the causal role of the microbiome on GDM, we performed faecal microbiota transplant (FMT) of samples from age/body mass index-matched women with and without GDM (n=5 each, table 1 and online supplemental table 1) in T2 and in T3, following dietary intervention, to germ-free mice to elucidate microbiome-mediated effects of diet on GDM (figure 1A). Retrospective analysis of donor samples suggests different microbiota compositions between the groups, irrespective of trimester (figure 1B,C); no differentially abundant taxa were identified.

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    [gutjnl-2023-331456supp001.pdf]

    Figure 1

    GDM phenotype transfer experiments based on faecal microbiota transplants (FMTs) from women in T2 and T3 of pregnancy. (A) Experimental design. (B,C) Faecal microbiota characterisation of the FMT donor samples. (B) Pregnant donors had trends of different α diversity between GDM status with a trending interaction effect of trimester (Faith’s PD, p<0.075). (C) There was also a trend toward different β diversity (unweighted UniFrac, p=0.068). (D–G) Mouse results from FMT experiment. (D) There was no difference in fasting glucose levels (time 0), but glucose levels were significantly higher in mice receiving the GDM FMT from T2 at 30 min after injection. (E) Similarly, in T3 FMT, …

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