Gut microbiota at 16 weeks and future hypertensive disorders of pregnancy

Transcription

1 Gut microbiota at 16 weeks and future hypertensive disorders of pregnancy Marloes Dekker Nitert

2 Blood pressure (mmhg) Butyrate producing capacity (centroid value) Blood pressure and microbiome control hypertension Yang et al. Hypertension 2015; 65(6): In early pregnancy: *** *** 1.0 P= OV OB OV OB SBP DBP 0.0 OV OB Gomez-Arango et al Hypertension 2016

3 Hypothesis: Women who develop hypertensive disorders of pregnancy have altered gut microbiota composition in early gestation Subjects Samples Baseline: 16 weeks gestation 218 placebo Blood Stool 1 st fecal microbiome assessment Dietary questionnaires Medical history BMI stratified (> 25-30; > 30-40; > 40 kg/m 2 ) 218 probiotics 28 weeks gestation Blood Stool 2 nd fecal microbiome assessment Dietary questionnaires Medical history 75 g OGTT Inclusion criteria Exclusion criteria Delivery < 15 weeks pregnant Preexisting diabetes or glucose intolerance Singleton pregnancy On medications influencing glucose metabolism Infant gender Birth weight Infant fat mass Infant oral swab Cord blood Umbilical cord Placenta BMI 25.0 Medical conditions affecting glucose metabolism Fetal abnormality on 12 weeks ultrasound Ingesting probiotics by capsule

4 Participant characteristics Control HDP P-value N BMI (kg/m 2 ) 31.4 ( ) 33.0 ( ) 0.10 Age (years) 33 (29-35) 33 (29-36) 0.56 SBP (mmhg) 110 ( ) 110 ( ) 0.02 DBP (mmhg) 70 (60-70) 70 (67-75) 0.03 GA (days) 105 (99-110) 109 ( ) 0.09 Parity 1 (0-1) 1 (0-1) 0.58 Fasting glucose (mm) 4.8 ( ) 5.0 ( ) 0.26 Fibre (mg fibre/kj energy) 2.8 ( ) 3.1 ( ) 0.08

5 BP over gestation

6 Alpha diversity of the microbiota C HDP

7 Beta diversity of the microbiota All C HDP

8 Network analysis Megasphaera Collinsella Acidaminococcus Coriobacteriaceae HDP control Christensenellaceae Ruminococcus Haemophilus Suterella Bifidobacterium Rikenellaceae

9 Abundance differences control HDP

10 Conclusions Women who develop HDP have different overall gut microbiota composition Carbohydrate fermenters are more prevalent Unclear if this composition is reflective of BMI only or contributes to hypertension (via insulin resistance?) No major differences in butyrate producers at 16 weeks What is next? Is change over gestation different in women with HDP? Relationship with diet needs to be investigated?

11 Acknowledgments UQ/RBWH Leonie Callaway Helen Barrett Katie Foxcroft Luisa Gomez Arango Barbara Lingwood Mark Morrisson QIMR Peter O Rourke University of Melbourne Jacinta Tobin UQ/Mater Mothers Hospital David McIntyre Anne Tremellen Shelley Wilkinson Redcliffe Hospital Alka Kothari Sharney Grant CSIRO Chris McSweeney Provider No

12 LefSE analysis

13 Influence of diet on gut microbiota and blood pressure Marques, F. Z. et al. (2017) Beyond gut feelings: how the gut microbiota regulates blood pressure Nat. Rev. Cardiol. doi: /nrcardio

14 Gut microbiome, butyrate and blood pressure Miyamoto et al. Curr Opin Nephrol Hypertens 2016; 25(5):379-83

15 Bacterial butyrate production from intestinal carbohydrates Pryde et al. FEMSML 217: Methanogenesis 2. Reductive acetogenesis 3. ButyrylCoA:acetateCoA transferase But 4. Butyrate kinase Buk 5. Acetate kinase 6. Lactate dehydrogenase 7. Acrylate pathway 8. Succinate decarboxylation

16 Butyrate and PAI-1 PAI-1? PAI-1? Canfora, E. E. et al. (2015) Short-chain fatty acids in control of body weight and insulin sensitivity Nat. Rev. Endocrinol. doi: /nrendo

17 A Odoribacter abundance Butyrate Circulating PAI-1 Normal blood pressure Gut lumen Epithelium Circulation B Lower Odoribacter abundance Less Butyrate Higher circulating PAI- 1 Increased blood pressure Gut lumen Epithelium Circulation

18 dietary fiber microbiome butyrate intestinal wall circulation kidney adipocyte inflammatory markers blood pressure