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. 2024 Jul 10;32(7):1192-1206.e5.
doi: 10.1016/j.chom.2024.06.005. Epub 2024 Jul 1.

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring

Shilan Wang  1 , Yingzhi Liu  2 , Wing Hung Tam  3 , Jessica Y L Ching  1 , Wenye Xu  1 , Shuai Yan  2 , Biyan Qin  2 , Ling Lin  2 , Ye Peng  4 , Jie Zhu  2 , Chun Pan Cheung  1 , Ka Long Ip  1 , Yuen Man Wong  1 , Pui Kuan Cheong  1 , Yuk Ling Yeung  3 , Wing Him Betty Kan  3 , Ting Fan Leung  5 , Tak Yeung Leung  3 , Eugene B Chang  6 , David T Rubin  6 , Erika C Claud  7 , William K K Wu  8 , Hein M Tun  4 , Francis K L Chan  9 , Siew C Ng  10 , Lin Zhang  11
Affiliations
Free article

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring

Shilan Wang et al. Cell Host Microbe. .
Free article

Abstract

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth.

Keywords: early life; gestational diabetes mellitus; gut microbiome; gut-brain axis; head circumference index; maternal health; metagenomic sequencing; mother-infant transmission; pregnancy; sex-dependent manner.

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Conflict of interest statement

Declaration of interests F.K.L.C. is a board member of CUHK Medical Centre. He is a co-founder, non-executive board chairman, and shareholder of GenieBiome Ltd. He receives patent royalties through his affiliated institutions. He has received fees as an advisor and honoraria as a speaker for EISAI Co. Ltd, AstraZeneca, Pfizer Inc., Takeda Pharmaceutical Co., and Takeda (China) Holdings Co. Ltd. S.C.N. has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda. S.C.N. has received research grants through her affiliated institutions from Olympus, Ferring, and AbbVie. S.C.N. is a scientific co-founder and shareholder of GenieBiome Ltd. S.C.N. receives patent royalties through her affiliated institutions. F.K.L.C., S.C.N., L.Z., and H.M.T. are named inventors of patent applications held by the CUHK and MagIC that cover the therapeutic and diagnostic use of the microbiome.

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