. 2021 Aug 6;9(1):167.

doi: 10.1186/s40168-021-01104-y.

Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome

Alexandra J Roth-Schulze^{1

2}, Megan A S Penno³, Katrina M Ngui^{1

2}, Helena Oakey³, Esther Bandala-Sanchez^{1

2}, Alannah D Smith^{1

2}, Theo R Allnutt^{1

2}, Rebecca L Thomson³, Peter J Vuillermin⁴, Maria E Craig^{5

6}, William D Rawlinson^{7

8}, Elizabeth A Davis⁹, Mark Harris^{10

11}, Georgia Soldatos¹², Peter G Colman¹³, John M Wentworth^{1

2

13}, Aveni Haynes⁹, Simon C Barry³, Richard O Sinnott¹⁴, Grant Morahan¹⁵, Naiara G Bediaga^{1

2}, Gordon K Smyth^{1

16}, Anthony T Papenfuss^{1

16

17

18}, Jennifer J Couper^{3

19}, Leonard C Harrison^{20

21}; ENDIA Study Group

Affiliations

¹ Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, 3052, Australia.
² Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3010, Australia.
³ The University of Adelaide, Robinson Research Institute, Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia.
⁴ Faculty of School of Medicine, Deakin University and Child Health Research Unit, Barwon Health, Geelong, VIC, 3220, Australia.
⁵ School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
⁶ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, NSW, 2145, Australia.
⁷ Virology Research Laboratory, Serology and Virology Division, South Eastern Area Laboratory Services Microbiology, Prince of Wales Hospital, Sydney, NSW, 2031, Australia.
⁸ School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
⁹ Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, WA, 6009, Australia.
¹⁰ The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Translational Research Institute, Woolloongabba, QLD, 4102, Australia.
¹¹ Queensland Children's Hospital, South Brisbane, QLD, 4101, Australia.
¹² Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne and Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, VIC, 3168, Australia.
¹³ Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia.
¹⁴ Melbourne eResearch Group, School of Computing and Information Services, University of Melbourne, Melbourne, VIC, 3010, Australia.
¹⁵ Centre for Diabetes Research, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, 6009, Australia.
¹⁶ Department of Medical Biology and School of Mathematics and Statistics, University of Melbourne, Melbourne, VIC, 3010, Australia.
¹⁷ Bioinformatics and Cancer Genomics Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.
¹⁸ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3010, Australia.
¹⁹ Women's and Children's Hospital, Adelaide, SA, 5006, Australia.
²⁰ Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, 3052, Australia. harrison@wehi.edu.au.
²¹ Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3010, Australia. harrison@wehi.edu.au.

PMID: 34362459
PMCID: PMC8349100
DOI: 10.1186/s40168-021-01104-y

Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome

Alexandra J Roth-Schulze et al. Microbiome. 2021.

. 2021 Aug 6;9(1):167.

doi: 10.1186/s40168-021-01104-y.

Authors

Affiliations

¹ Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, 3052, Australia.
² Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3010, Australia.
³ The University of Adelaide, Robinson Research Institute, Adelaide Medical School, University of Adelaide, Adelaide, SA, 5005, Australia.
⁴ Faculty of School of Medicine, Deakin University and Child Health Research Unit, Barwon Health, Geelong, VIC, 3220, Australia.
⁵ School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
⁶ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, NSW, 2145, Australia.
⁷ Virology Research Laboratory, Serology and Virology Division, South Eastern Area Laboratory Services Microbiology, Prince of Wales Hospital, Sydney, NSW, 2031, Australia.
⁸ School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.
⁹ Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, WA, 6009, Australia.
¹⁰ The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Translational Research Institute, Woolloongabba, QLD, 4102, Australia.
¹¹ Queensland Children's Hospital, South Brisbane, QLD, 4101, Australia.
¹² Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne and Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, VIC, 3168, Australia.
¹³ Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, VIC, 3050, Australia.
¹⁴ Melbourne eResearch Group, School of Computing and Information Services, University of Melbourne, Melbourne, VIC, 3010, Australia.
¹⁵ Centre for Diabetes Research, Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, 6009, Australia.
¹⁶ Department of Medical Biology and School of Mathematics and Statistics, University of Melbourne, Melbourne, VIC, 3010, Australia.
¹⁷ Bioinformatics and Cancer Genomics Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.
¹⁸ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3010, Australia.
¹⁹ Women's and Children's Hospital, Adelaide, SA, 5006, Australia.
²⁰ Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, 3052, Australia. harrison@wehi.edu.au.
²¹ Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3010, Australia. harrison@wehi.edu.au.

PMID: 34362459
PMCID: PMC8349100
DOI: 10.1186/s40168-021-01104-y

Abstract

Background: The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D.

Results: Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage.

Conclusions: Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means. Video abstract.

Keywords: Gut; Inflammation markers; Metagenomics; Microbiome; Pregnancy; Quantitative PCR; Type 1 diabetes.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Fecal samples obtained in pregnancy. n: number of samples; T1: trimester 1; T2: trimester 2; T3: trimester 3; T1D: women with type 1 diabetes; Non-T1D: women without T1D

**Fig. 2**
Beta diversity analysis by T1D status. PCoA ordination plots based on Bray-Curtis distances between samples at the strain and species taxonomic levels separated by trimesters in pregnancy. T1D: women with type 1 diabetes (red); Non-T1D: women without T1D (blue)

**Fig. 3**
Means and standard errors of the log2-transformed fitted values shown as a point in each trimester for differentially abundant taxa in women with (red) and without (blue) T1D. * in the top right corner denotes a significant difference (FDR < 0.1) between groups throughout pregnancy; * between points denotes a significant difference (FDR < 0.1) between groups in that trimester

**Fig. 4**
Beta diversity analysis by type 1 diabetes (T1D) status. PCoA ordination plots based on Bray-Curtis distances between samples for a pathways, b KOs and c MetaCyc reactions in trimester 3. T1D: women with type 1 diabetes (red); women without T1D (blue)

**Fig. 5**
Means and standard errors of the log2-transformed fitted values shown as a point in each trimester for differentially abundant functional features in women with (red) and without (blue) T1D. One example for each of six broad categories is shown: lipopolysaccharide (LPS) production (CMP–3–deoxy–d–manno–octulosonate synthesis [PWY–1269]), vitamin K2 synthesis (superpathway of menaquinol–8 synthesis [PWY–5838]), vitamin B6 synthesis (pyridoxal 5′–phosphate synthase [K06215]), vitamin B12 synthesis (adenosylcobalamin salvage from cobinamide [COBALSYN–PWY]), short-chain fatty acid (SCFA) production (3–hydroxybutyryl–CoA dehydrogenase [K00074]) and mucin degradation (beta–N–acetylhexosaminidase [K01207]). * in the top right corner denotes a significant difference (FDR < 0.1) between groups throughout pregnancy; * between points denotes a significant difference (FDR < 0.1) between groups in that trimester

See this image and copyright information in PMC

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Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome

Affiliations

Type 1 diabetes in pregnancy is associated with distinct changes in the composition and function of the gut microbiome

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Medical

Research Materials