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Abstract
The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
Here, the authors apply DESI-MS, a sample preparation-free, direct on-swab mass spectrometry analytical tool, to profile the cervicovaginal metabolome of two independent cohorts of pregnant women and, combined with matched metataxonomic and immuno-profiling data, show that DESI-MS predicts vaginal microbiota composition and local inflammatory status associated with preterm birth and clinical interventions used during pregnancy.
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1 Faculty of Medicine Imperial College London, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
2 Faculty of Medicine Imperial College London, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, National Phenome Centre, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
3 March of Dimes Prematurity Research Centre at Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Digestion and Reproduction, Imperial College London, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, Queen Charlotte’s & Chelsea Hospital, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
4 March of Dimes Prematurity Research Centre at Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Digestion and Reproduction, Imperial College London, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
5 Digestion and Reproduction, Imperial College London, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, Queen Charlotte’s & Chelsea Hospital, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
6 Digestion and Reproduction, Imperial College London, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); University College London, Elizabeth Garrett Anderson Institute for Women’s Health, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201)
7 University West of England, Faculty of Health and Applied Sciences, Bristol, UK (GRID:grid.6518.a) (ISNI:0000 0001 2034 5266)
8 Faculty of Medicine Imperial College London, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); March of Dimes Prematurity Research Centre at Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
9 Imperial College London, MRC Centre for Molecular Bacteriology and Infection, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
10 Faculty of Medicine Imperial College London, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Queen’s University Belfast, School of Biological Sciences, Institute for Global Food Security, Belfast, UK (GRID:grid.4777.3) (ISNI:0000 0004 0374 7521)
11 University College London, Elizabeth Garrett Anderson Institute for Women’s Health, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201)
12 University of Edinburgh, MRC Centre for Reproductive Health, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988)
13 University of Edinburgh, MRC Centre for Reproductive Health, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Bristol, Faculty of Health Sciences, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603)
14 March of Dimes Prematurity Research Centre at Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Digestion and Reproduction, Imperial College London, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Chelsea & Westminster Hospital, NHS Trust, London, UK (GRID:grid.439369.2) (ISNI:0000 0004 0392 0021)
15 Imperial College Healthcare NHS Trust, St Mary’s Hospital, London, UK (GRID:grid.417895.6) (ISNI:0000 0001 0693 2181)
16 March of Dimes Prematurity Research Centre at Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Digestion and Reproduction, Imperial College London, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, Queen Charlotte’s & Chelsea Hospital, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, Tommy’s National Centre for Miscarriage Research, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
17 Faculty of Medicine Imperial College London, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, National Phenome Centre, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); March of Dimes Prematurity Research Centre at Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
18 March of Dimes Prematurity Research Centre at Imperial College London, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Digestion and Reproduction, Imperial College London, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, Tommy’s National Centre for Miscarriage Research, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)