Luisa F. Gomez-Arango, 1,2 Helen L. Barrett, 1,2,3 H. David McIntyre, 1,4 Leonie K. Callaway, 1,2,3 Mark Morrison, 5 and Marloes Dekker Nitert, 1,2 for the SPRING Trial Group Connections Between the Gut Microbiome and Metabolic Hormones in Early Pregnancy in Overweight and Obese Women Diabetes 2016;65:2214–2223 | DOI: 10.2337/db16-0278 Overweight and obese women are at a higher risk for gestational diabetes mellitus. The gut microbiome could modulate metabolic health and may affect insulin resis- tance and lipid metabolism. The aim of this study was to reveal relationships between gut microbiome composition and circulating metabolic hormones in overweight and obese pregnant women at 16 weeks’ gestation. Fecal microbiota profiles from overweight (n = 29) and obese (n = 41) pregnant women were assessed by 16S rRNA sequencing. Fasting metabolic hormone (insulin, C-peptide, glucagon, incretin, and adipokine) concentrations were measured using multiplex ELISA. Metabolic hormone lev- els as well as microbiome profiles differed between over- weight and obese women. Furthermore, changes in some metabolic hormone levels were correlated with alterations in the relative abundance of specific microbes. Adipokine levels were strongly correlated with Ruminococcaceae and Lachnospiraceae, which are dominant families in en- ergy metabolism. Insulin was positively correlated with the genus Collinsella. Gastrointestinal polypeptide was posi- tively correlated with the genus Coprococcus but nega- tively with family Ruminococcaceae. This study shows novel relationships between gut microbiome composition and the metabolic hormonal environment in overweight and obese pregnant women at 16 weeks’ gestation. These results suggest that manipulation of the gut microbiome composition may influence pregnancy metabolism. The increasing prevalence of maternal obesity and its subsequent health outcomes are a significant public health concern and a major challenge for obstetrics practice. In early pregnancy, overweight and obese women are at an increased risk of metabolic complications that affect placen- tal and embryonic development (1). Metabolic adjustments, such as a decline in insulin sensitivity and an increase in nutrient absorption, are necessary to support a healthy pregnancy (2,3); however, these metabolic changes occur on top of preexisting higher levels of insulin resistance in overweight and obese pregnant women, increasing the risk of overt hyperglycemia because of a lack of sufficient insulin secretion to compensate for the increased insulin resistance (3). The potential role of the gut microbiome (the com- posite of the bacteria present in the gastrointestinal tract) in pregnancy has become the subject of considerable interest. In normal pregnancy, the maternal gut microbiota changes from first to third trimester with a decline in butyrate-producing bacteria and an increase in Bifidobacteria, Proteobacteria, and lactic acid–producing bacteria. In- flammation and weight gain that occurs during preg- nancy might be the result of microbe-driven processes to increase energy supply for the fetus (4). These alter- ations might also be linked with the maternal metabolic profile and thereby contribute to the development of pregnancy complications (5,6) as well as affect the meta- bolic and immunological health of the offspring (7). In summation, modi fications in the metabolic hormone milieu during gestation are proposed to be linked with changes in the maternal microbiota; however, no studies 1 School of Medicine, The University of Queensland, Brisbane, Queensland, Australia 2 The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia 3 Obstetric Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia 4 Mater Research, The University of Queensland, Brisbane, Queensland, Australia 5 Faculty of Medicine and Biomedical Sciences, The University of Queensland Diamantina Institute, Brisbane, Queensland, Australia Corresponding author: Marloes Dekker Nitert, m.dekker@uq.edu.au. Received 28 February 2016 and accepted 11 May 2016. Clinical trial reg. no. ANZCTR12611001208998, www.anzctr.org.au. This article contains Supplementary Data online at http://diabetes .diabetesjournals.org/lookup/suppl/doi:10.2337/db16-0278/-/DC1. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. 2214 Diabetes Volume 65, August 2016 METABOLISM Downloaded from http://diabetesjournals.org/diabetes/article-pdf/65/8/2214/583551/db160278.pdf by guest on 11 January 2023