Publications by authors named "Marloes Dekker Nitert"

79 Publications

Capillary Triglycerides in Late Pregnancy-Challenging to Measure, Hard to Interpret: A Cohort Study of Practicality.

Nutrients 2021 Apr 13;13(4). Epub 2021 Apr 13.

The Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia.

Background: Maternal triglycerides are increasingly recognised as important predictors of infant growth and fat mass. The variability of triglyceride patterns during the day and their relationship to dietary intake in women in late pregnancy have not been explored. This prospective cohort study aimed to examine the utility of monitoring capillary triglycerides in women in late pregnancy.

Methods: Twenty-nine women (22 with gestational diabetes (GDM) and 7 without) measured capillary glucose and triglycerides using standard meters at home for four days. On two of those days, they consumed one of two standard isocaloric breakfast meals: a high-fat/low-carbohydrate meal (66% fat) or low fat/high carbohydrate meal (10% fat). Following the standard meals, glucose and triglyceride levels were monitored.

Results: Median capillary triglycerides were highly variable between women but did not differ between GDM and normoglycaemic women. There was variability in capillary triglycerides over four days of home monitoring and a difference in incremental area under the curve for capillary triglycerides and glucose between the two standard meals. The high-fat standard meal lowered the incremental area under the curve for capillary glucose ( < 0.0001). Fasting (rho 0.66, = 0.0002) and postpradial capillary triglycerides measured at home correlated with venous triglyceride levels.

Conclusions: The lack of differences in response to dietary fat intake and the correlation between capillary and venous triglycerides suggest that monitoring of capillary triglycerides before and after meals in pregnancy is unlikely to be useful in the routine clinical practice management of women with gestational diabetes mellitus.
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http://dx.doi.org/10.3390/nu13041266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070156PMC
April 2021

Probiotics for preventing gestational diabetes.

Cochrane Database Syst Rev 2021 04 19;4:CD009951. Epub 2021 Apr 19.

School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Australia.

Background: Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. This is an update of a review last published in 2014.

Objectives: To systematically assess the effects of probiotic supplements used either alone or in combination with pharmacological and non-pharmacological interventions on the prevention of GDM.

Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (20 March 2020), and reference lists of retrieved studies.

Selection Criteria: Randomised and cluster-randomised trials comparing the use of probiotic supplementation with either placebo or diet for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies were not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results were only included if study authors confirmed that data in the abstract came from the final analysis. Otherwise, the abstract was left awaiting classification.

Data Collection And Analysis: Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy.

Main Results: In this update, we included seven trials with 1647 participants. Two studies were in overweight and obese women, two in obese women and three did not exclude women based on their weight. All included studies compared probiotics with placebo. The included studies were at low risk of bias overall except for one study that had an unclear risk of bias. We excluded two studies, eight studies were ongoing and three studies are awaiting classification. Six included studies with 1440 participants evaluated the risk of GDM. It is uncertain if probiotics have any effect on the risk of GDM compared to placebo (mean risk ratio (RR) 0.80, 95% confidence interval (CI) 0.54 to 1.20; 6 studies, 1440 women; low-certainty evidence). The evidence was low certainty due to substantial heterogeneity and wide CIs that included both appreciable benefit and appreciable harm. Probiotics increase the risk of pre-eclampsia compared to placebo (RR 1.85, 95% CI 1.04 to 3.29; 4 studies, 955 women; high-certainty evidence) and may increase the risk of hypertensive disorders of pregnancy (RR 1.39, 95% CI 0.96 to 2.01, 4 studies, 955 women), although the CIs for hypertensive disorders of pregnancy also indicated probiotics may have no effect. There were few differences between groups for other primary outcomes. Probiotics make little to no difference in the risk of caesarean section (RR 1.00, 95% CI 0.86 to 1.17; 6 studies, 1520 women; high-certainty evidence), and probably make little to no difference in maternal weight gain during pregnancy (MD 0.30 kg, 95% CI -0.67 to 1.26; 4 studies, 853 women; moderate-certainty evidence). Probiotics probably make little to no difference in the incidence of large-for-gestational age infants (RR 0.99, 95% CI 0.72 to 1.36; 4 studies, 919 infants; moderate-certainty evidence) and may make little to no difference in neonatal adiposity (2 studies, 320 infants; data not pooled; low-certainty evidence). One study reported adiposity as fat mass (MD -0.04 kg, 95% CI -0.12 to 0.04), and one study reported adiposity as percentage fat (MD -0.10%, 95% CI -1.19 to 0.99). We do not know the effect of probiotics on perinatal mortality (RR 0.33, 95% CI 0.01 to 8.02; 3 studies, 709 infants; low-certainty evidence), a composite measure of neonatal morbidity (RR 0.69, 95% CI 0.36 to 1.35; 2 studies, 623 infants; low-certainty evidence), or neonatal hypoglycaemia (mean RR 1.15, 95% CI 0.69 to 1.92; 2 studies, 586 infants; low-certainty evidence). No included studies reported on perineal trauma, postnatal depression, maternal and infant development of diabetes or neurosensory disability.

Authors' Conclusions: Low-certainty evidence from six trials has not clearly identified the effect of probiotics on the risk of GDM. However, high-certainty evidence suggests there is an increased risk of pre-eclampsia with probiotic administration. There were no other clear differences between probiotics and placebo among the other primary outcomes. The certainty of evidence for this review's primary outcomes ranged from low to high, with downgrading due to concerns about substantial heterogeneity between studies, wide CIs and low event rates. Given the risk of harm and little observed benefit, we urge caution in using probiotics during pregnancy. The apparent effect of probiotics on pre-eclampsia warrants particular consideration. Eight studies are currently ongoing, and we suggest that these studies take particular care in follow-up and examination of the effect on pre-eclampsia and hypertensive disorders of pregnancy. In addition, the underlying potential physiology of the relationship between probiotics and pre-eclampsia risk should be considered.
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http://dx.doi.org/10.1002/14651858.CD009951.pub3DOI Listing
April 2021

Pregnant women who develop preeclampsia have lower abundance of the butyrate-producer Coprococcus in their gut microbiota.

Pregnancy Hypertens 2021 Mar 26;23:211-219. Epub 2021 Jan 26.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address:

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and dysfunction of several organs, that is associated with maternal and fetal complications. The human gut microbiota is related to health and disease including hypertension. Alterations in gut microbiota composition can change the short-chain fatty acid profile released by the bacteria and contribute to hypertension and metabolic syndrome. It is unclear if the composition of the gut microbiota is altered in women who develop late-onset preeclampsia. In this study, we investigated the composition of the gut microbiota at 28 weeks gestation in women who developed late-onset (>34 weeks gestation) preeclampsia (DPE) by 16S rRNA gene amplicon sequencing of fecal samples obtained from 213 pregnant women in the SPRING cohort (Study of Probiotics IN Gestational diabetes). Quantitative real-time PCR was used to assess the density of butyrate-producing genes. Gut microbiota composition was compared between women with and without DPE. The abundance of the butyrate-producing Coprococcus genus significantly decreased in DPE. Abundance of Coprococcus is significantly and positively correlated with the abundance of genes encoding the terminal step in bacterial butyrate formation (but and buk). Women with DPE also had significantly reduced levels of serum butyrate prior to the development of symptoms than controls. This study suggests that a reduction in the abundance of butyrate-producing bacteria, and Coprococcus spp. in particular, may contribute to an increased risk of developing preeclampsia in pregnant women.
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http://dx.doi.org/10.1016/j.preghy.2021.01.002DOI Listing
March 2021

Ketones in Pregnancy: Why Is It Considered Necessary to Avoid Them and What Is the Evidence Behind Their Perceived Risk?

Diabetes Care 2021 Jan;44(1):280-289

Mater Research Institute, The University of Queensland, and Mater Hospital Brisbane, South Brisbane, Queensland, Australia.

Current dietary advice for women with gestational diabetes mellitus is to avoid diets that result in elevated ketone levels. This guidance stems from a concern that maternal ketones are associated with poor fetal and childhood outcomes, including reduced childhood intelligence quota. The evidence behind these guidelines is conflicting and inconsistent. Given that dietary counseling is the initial treatment strategy for women with diabetes in pregnancy, it is important that clinicians understand the concern regarding maternal ketones. This review examines the physiology of ketogenesis in pregnancy, the prevalence of elevated maternal ketone levels, and the relationship between maternal ketones and fetal and childhood outcomes.
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http://dx.doi.org/10.2337/dc20-2008DOI Listing
January 2021

Dietary Fiber Intake Alters Gut Microbiota Composition but Does Not Improve Gut Wall Barrier Function in Women with Future Hypertensive Disorders of Pregnancy.

Nutrients 2020 Dec 17;12(12). Epub 2020 Dec 17.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.

Pregnancy alters the inflammatory state, metabolic hormones, and gut microbiota composition. It is unclear if the lower abundance of dietary fiber-fermenting, short-chain fatty acid-producing bacteria observed in hypertension also occurs in hypertensive disorders of pregnancy (HDP). This study investigated the relationship between dietary fiber intake and the gut microbiota profile at 28 weeks gestation in women who developed HDP in late pregnancy ( = 22) or remained normotensive ( = 152) from the Study of PRobiotics IN Gestational diabetes (SPRING). Dietary fiber intake was classified as above or below the median of 18.2 g/day. Gut microbiota composition was examined using 16S rRNA gene amplicon sequencing. The gut permeability marker zonulin was measured in a subset of 46 samples. In women with future HPD, higher dietary fiber intake was specifically associated with increased abundance of lower abundance of and and higher zonulin levels than normotensive women. Fiber intake and zonulin levels were negatively correlated in women with normotensive pregnancies but not in pregnancies with future HDP. In women with normotensive pregnancies, dietary fiber intake may improve gut barrier function. In contrast, in women who develop HDP, gut wall barrier function is impaired and not related to dietary fiber intake.
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http://dx.doi.org/10.3390/nu12123862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766248PMC
December 2020

The Gut Microbiota and Inflammation: An Overview.

Int J Environ Res Public Health 2020 10 19;17(20). Epub 2020 Oct 19.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne 3168, Australia.

The gut microbiota encompasses a diverse community of bacteria that carry out various functions influencing the overall health of the host. These comprise nutrient metabolism, immune system regulation and natural defence against infection. The presence of certain bacteria is associated with inflammatory molecules that may bring about inflammation in various body tissues. Inflammation underlies many chronic multisystem conditions including obesity, atherosclerosis, type 2 diabetes mellitus and inflammatory bowel disease. Inflammation may be triggered by structural components of the bacteria which can result in a cascade of inflammatory pathways involving interleukins and other cytokines. Similarly, by-products of metabolic processes in bacteria, including some short-chain fatty acids, can play a role in inhibiting inflammatory processes. In this review, we aimed to provide an overview of the relationship between the gut microbiota and inflammatory molecules and to highlight relevant knowledge gaps in this field. Based on the current literature, it appears that as the gut microbiota composition differs between individuals and is contingent on a variety of factors like diet and genetics, some individuals may possess bacteria associated with pro-inflammatory effects whilst others may harbour those with anti-inflammatory effects. Recent technological advancements have allowed for better methods of characterising the gut microbiota. Further research to continually improve our understanding of the inflammatory pathways that interact with bacteria may elucidate reasons behind varying presentations of the same disease and varied responses to the same treatment in different individuals. Furthermore, it can inform clinical practice as anti-inflammatory microbes can be employed in probiotic therapies or used to identify suitable prebiotic therapies.
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http://dx.doi.org/10.3390/ijerph17207618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589951PMC
October 2020

Altered Gut Microbiota Composition Is Associated With Back Pain in Overweight and Obese Individuals.

Front Endocrinol (Lausanne) 2020 2;11:605. Epub 2020 Sep 2.

Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.

Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses. We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity. Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with ( = 14) or without ( = 22) back pain. Individuals with back pain had a higher abundance of the genera ( = 0.0008; FDR = 0.027) ( = 0.0098; FDR = 0.17), and ( = 0.02; FDR = 0.27) than those without back pain. abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year. was positively correlated with BMI (rho = 0.35, = 0.03), serum adipsin (rho = 0.33, = 0.047), and serum leptin (rho = 0.38, = 0.02). Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering abundance to treat back pain.
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http://dx.doi.org/10.3389/fendo.2020.00605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492308PMC
September 2020

The influence of wasabi on the gut microbiota of high-carbohydrate, high-fat diet-induced hypertensive Wistar rats.

J Hum Hypertens 2021 Feb 26;35(2):170-180. Epub 2020 May 26.

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia.

The human gut microbiota plays a critical role in the regulation of adiposity, obesity and metabolic and cardiovascular disease. Wasabi is a pungent spice and its active component, allyl isothiocyanate, improves plasma triacylglycerol, cholesterol and high blood pressure in rodents, but it is unclear if this occurs through alterations to the composition of the microbiota. The aim of this study was to determine the effectiveness of Wasabi japonica stem and rhizome blend on ameliorating cardiovascular disease parameters including plasma sodium concentration, systolic blood pressure (SBP), plasma endothelin-1 and angiotensin II concentrations by altering the gut microbiota in a Wistar rat model of obesity and metabolic syndrome. Rats were randomized to receive a corn starch or high-carbohydrate/high-fat diet for 8 weeks before being allocated to supplementation with wasabi powder (5% (w/w) in food) or not for an additional 8 weeks. At the end of the trial, rats were grouped according to blood pressure status. Wasabi supplementation prevented the development of hypertension and was also associated with significantly increased abundance of Allobaculum, Sutterella, Uncl. S247, Uncl. Coriobacteriaceae and Bifidobacterium. Hypertension was positively correlated with higher abundance of Oscillospira, Uncl. Lachnospiraceae and Uncl. Clostridiales, Uncl. Bacteroidales and Butyricimonas. Oscillospira and Butyricimonas abundances were specifically positively correlated with systolic blood pressure. Overall, the improved host cardiovascular health in diet-induced obese rats supplemented with wasabi powder may involve changes to the gut microbiota composition.
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http://dx.doi.org/10.1038/s41371-020-0359-8DOI Listing
February 2021

Self-reported periconception weight loss attempts do not alter infant body composition.

Nutrition 2020 09 29;77:110781. Epub 2020 Feb 29.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia. Electronic address:

Objectives: Maternal obesity increases the risk for adverse infant outcomes; therefore, achieving an optimal body mass index before conception is recommended. Periconceptional maternal weight loss, however, has been associated with adverse outcomes for the fetus, including altered body composition in animal studies. It is not clear whether periconception weight loss alters infant body composition in humans. The aim of this study was to compare body composition in offspring of women who attempted to lose or maintain weight in the periconception period.

Methods: Women who delivered a healthy term infant were grouped according to attempt to lose weight. Infant body composition was determined by air displacement plethysmography and anthropometric measurements.

Results: In a cohort of 73 women, 27 attempted to lose weight and 46 maintained weight in the periconception period. Infant birth weight, percent body fat, and head and arm circumference were not altered by maternal attempts to lose weight. Infant abdominal circumference was increased in the offspring of women who attempted to lose weight in the periconception period. Infant percent body fat was increased in overweight and obese mothers and in female infants.

Conclusion: The results of this study showed that attempts to lose weight in the periconception period do not significantly alter infant body composition. The increase in abdominal circumference may indicate a difference in fat distribution in offspring of women who attempted to lose weight, which may increase their risk for future metabolic and cardiovascular disease.
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http://dx.doi.org/10.1016/j.nut.2020.110781DOI Listing
September 2020

Pregnancy and diet-related changes in the maternal gut microbiota following exposure to an elevated linoleic acid diet.

Am J Physiol Endocrinol Metab 2020 02 17;318(2):E276-E285. Epub 2019 Dec 17.

Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia.

Dietary intakes of linoleic acid (LA) have increased, including in women of reproductive age. Changes in maternal gut microbiome have been implicated in the metabolic adaptions that occur during pregnancy. We aimed to investigate whether consumption of a diet with elevated LA altered fecal microbiome diversity before and during pregnancy. Female Wistar-Kyoto rats consumed a high-LA diet (HLA: 6.21% of energy) or a low-LA diet (LLA: 1.44% of energy) for 10 wk before mating and during pregnancy. DNA was isolated from fecal samples before pregnancy [embryonic day 0 (E0)], or during pregnancy at E10 and E20. The microbiome composition was assessed with 16S rRNA sequencing. At E0, the beta-diversity of LLA and HLA groups differed with HLA rats having significantly lower abundance of the genera , and but higher abundance of and . Over gestation, in LLA but not HLA rats, there was a reduction in alpha-diversity and an increase in beta-diversity. In the LLA group, the abundance of , and decreased over gestation, whereas increased. In the HLA group; only the abundance of decreased. At E20, there were no differences in alpha- and beta-diversity, and the abundance of was significantly increased in the HLA group. In conclusion, consumption of a HLA diet alters gut microbiota composition, as does pregnancy in rats consuming a LLA diet. In pregnancy, consumption of a HLA diet does not alter gut microbiota composition.
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http://dx.doi.org/10.1152/ajpendo.00265.2019DOI Listing
February 2020

Effect of Vitamin D Supplementation on Faecal Microbiota: A Randomised Clinical Trial.

Nutrients 2019 Nov 27;11(12). Epub 2019 Nov 27.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, VIC 3168 Australia.

In animal studies, vitamin D supplementation has been shown to improve gut microbiota and intestinal inflammation. However, limited evidence exists on the effect of vitamin D supplementation on the human gut microbiota. We examined the effect of vitamin D supplementation on faecal microbiota in 26 vitamin D-deficient (25-hydroxyvitamin D (25(OH)D) ≤50 nmol/L), overweight or obese (BMI ≥25 kg/m) otherwise healthy adults. Our study was ancillary to a community based double-blind randomised clinical trial, conducted between 2014 and 2016. The participants provided stool samples at baseline and after 100,000 international units (IU) loading dose of cholecalciferol followed by 4000 IU daily or matching placebo for 16 weeks. Faecal microbiota was analysed using 16S rRNA sequencing; V6-8 region. There was no significant difference in microbiome α-diversity between vitamin D and placebo groups at baseline and follow-up (all > 0.05). In addition, no clustering was found based on vitamin D supplementation at follow-up ( = 0.3). However, there was a significant association between community composition and vitamin D supplementation at the genus level ( = 0.04). The vitamin D group had a higher abundance of genus , and lower abundance of genus (linear discriminate analysis >3.0). Moreover, individuals with 25(OH)D >75 nmol/L had a higher abundance of genus and lower abundance of genus compared to those with 25(OH)D <50 nmol/L. Our findings suggest that vitamin D supplementation has some distinct effects on faecal microbiota. Future studies need to explore whether these effects would translate into improved clinical outcomes.
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http://dx.doi.org/10.3390/nu11122888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950585PMC
November 2019

Glucolipotoxicity Alters Insulin Secretion via Epigenetic Changes in Human Islets.

Diabetes 2019 10 16;68(10):1965-1974. Epub 2019 Aug 16.

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden

Type 2 diabetes (T2D) is characterized by insufficient insulin secretion and elevated glucose levels, often in combination with high levels of circulating fatty acids. Long-term exposure to high levels of glucose or fatty acids impair insulin secretion in pancreatic islets, which could partly be due to epigenetic alterations. We studied the effects of high concentrations of glucose and palmitate combined for 48 h (glucolipotoxicity) on the transcriptome, the epigenome, and cell function in human islets. Glucolipotoxicity impaired insulin secretion, increased apoptosis, and significantly (false discovery rate <5%) altered the expression of 1,855 genes, including 35 genes previously implicated in T2D by genome-wide association studies (e.g., and ). Additionally, metabolic pathways were enriched for downregulated genes. Of the differentially expressed genes, 1,469 also exhibited altered DNA methylation (e.g., , , , and ). A luciferase assay showed that increased methylation of directly reduces its transcription in pancreatic β-cells, supporting the idea that DNA methylation underlies altered expression after glucolipotoxicity. Follow-up experiments in clonal β-cells showed that knockdown of and alters insulin secretion. Together, our novel data demonstrate that glucolipotoxicity changes the epigenome in human islets, thereby altering gene expression and possibly exacerbating the secretory defect in T2D.
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http://dx.doi.org/10.2337/db18-0900DOI Listing
October 2019

Ketonuria Is Associated with Changes to the Abundance of in the Gut Microbiota of Overweight and Obese Women at 16 Weeks Gestation: A Cross-Sectional Observational Study.

Nutrients 2019 Aug 8;11(8). Epub 2019 Aug 8.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.

The gut microbiome in pregnancy has been associated with various maternal metabolic and hormonal markers involved in glucose metabolism. Maternal ketones are of particular interest due to the rise in popularity of low-carbohydrate diets. We assessed for differences in the composition of the gut microbiota in pregnant women with and without ketonuria at 16 weeks gestation. Fecal samples were obtained from 11 women with fasting ketonuria and 11 matched controls. The samples were analyzed to assess for differences in gut microbiota composition by 16S rRNA sequencing. Supervised hierarchical clustering analysis showed significantly different beta-diversity between women with and without ketonuria, but no difference in the alpha-diversity. Group comparisons and network analysis showed that ketonuria was associated with an increased abundance of the butyrate-producing genus The bacteria that contributed the most to the differences in the composition of the gut microbiota included , , and in women with ketonuria and , , and in women without ketonuria. This study found that the genus is more abundant in the gut microbiota of pregnant women with ketonuria. is a butyrate producing bacterium and may increase serum ketone levels.
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http://dx.doi.org/10.3390/nu11081836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723895PMC
August 2019

Faecal Microbiota Are Related to Insulin Sensitivity and Secretion in Overweight or Obese Adults.

J Clin Med 2019 Apr 4;8(4). Epub 2019 Apr 4.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Diabetes and Vascular Medicine Unit, Monash Health, Clayton 3168, Australia.

Emerging evidence suggests a role for the gut microbiota in glucose metabolism and diabetes. Few studies have examined the associations between the faecal microbiome and insulin sensitivity and secretion using gold-standard methods in high-risk populations prior to diabetes onset. We investigated the relationships between faecal microbiota composition (16S rRNA sequencing) and gold-standard measures of insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and insulin secretion (intravenous glucose tolerance test) in 38 overweight or obese otherwise healthy individuals. Genus was positively associated with insulin sensitivity, and genera and were related to both insulin sensitivity and secretion. Insulin sensitivity was associated with a higher abundance of and lower abundance of . Those with higher insulin secretion had a higher abundance of and lower abundance of , compared to those with lower insulin secretion. Body mass index (BMI) was positively correlated with abundance whereas abundance was negatively correlated to BMI and percent body fat. These results suggest that faecal microbiota is related to insulin sensitivity and secretion in overweight or obese adults. These correlations are distinct although partially overlapping, suggesting different pathophysiological pathways. Our findings can inform future trials aiming to manipulate gut microbiome to improve insulin sensitivity and secretion and prevent type 2 diabetes.
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http://dx.doi.org/10.3390/jcm8040452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518043PMC
April 2019

Probiotics for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Women: Findings From the SPRING Double-Blind Randomized Controlled Trial.

Diabetes Care 2019 03 18;42(3):364-371. Epub 2019 Jan 18.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia.

Objective: Given the role of gut microbiota in regulating metabolism, probiotics administered during pregnancy might prevent gestational diabetes mellitus (GDM). This question has not previously been studied in high-risk overweight and obese pregnant women. We aimed to determine whether probiotics ( and subspecies ) administered from the second trimester in overweight and obese women prevent GDM as assessed by an oral glucose tolerance test (OGTT) at 28 weeks' gestation. Secondary outcomes included maternal and neonatal complications, maternal blood pressure and BMI, and infant body composition.

Research Design And Methods: This was a double-blind randomized controlled trial of probiotic versus placebo in overweight and obese pregnant women in Brisbane, Australia.

Results: The study was completed in 411 women. GDM occurred in 12.3% (25 of 204) in the placebo arm and 18.4% (38 of 207) in the probiotics arm ( = 0.10). At OGTT, mean fasting glucose was higher in women randomized to probiotics (79.3 mg/dL) compared with placebo (77.5 mg/dL) ( = 0.049). One- and two-hour glucose measures were similar. Preeclampsia occurred in 9.2% of women randomized to probiotics compared with 4.9% in the placebo arm ( = 0.09). Excessive weight gain occurred in 32.5% of women in the probiotics arm (55 of 169) compared with 46% in the placebo arm (81 of 176) ( = 0.01). Rates of small for gestational age (<10th percentile) were 2.4% in the probiotics arm (5 of 205) and 6.5% in the placebo arm (13 of 199) ( = 0.042). There were no differences in other secondary outcomes.

Conclusions: The probiotics used in this study did not prevent GDM in overweight and obese pregnant women.
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http://dx.doi.org/10.2337/dc18-2248DOI Listing
March 2019

Knights in Shining Armor.

Circ Res 2019 01;124(1):12-14

From the School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia.

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http://dx.doi.org/10.1161/CIRCRESAHA.118.314246DOI Listing
January 2019

Placental mitochondrial adaptations in preeclampsia associated with progression to term delivery.

Cell Death Dis 2018 11 19;9(12):1150. Epub 2018 Nov 19.

School of Medical Science, Griffith University, Gold Coast Campus, Southport, QLD, Australia.

Preeclampsia is a devastating pregnancy disorder. Severity varies widely, and while severe preeclampsia often requires pre-term delivery, women with mild preeclampsia may reach term with minor interventions. The mechanisms that mediate disease severity are poorly understood, but may include adaptive processes by the placenta. We aimed to establish whether in pregnancies that reached term and those that delivered pre-term, the placental response to preeclampsia was intrinsically different, and explore potential adaptive mechanisms. Hydrogen peroxide production and antioxidant activity were increased in term preeclamptic placentae, whereas pre-term preeclamptic placentae had reduced hydrogen peroxide production and reduced function of the antioxidant system superoxide dismutase compared to control placentae. Markers of mitochondrial fission/fusion, apoptosis and the expression level of mitochondrial complexes were differentially disrupted in term compared to pre-term preeclamptic placentae. Mitochondrial respiration and content were increased in term preeclamptic placentae, but mitochondria had a lower respiratory reserve capacity. Mitochondrial respiration and hydrogen peroxide production were increased in healthy term placentae after in vitro hypoxia/reoxygenation. Placentae from preeclamptic pregnancies that reached term showed multiple adaptions that were not present in pre-term preeclamptic placentae. Increased antioxidant activity, and expression of markers of mitochondrial fusion and apoptotic suppression, may relate to salvaging damaged mitochondria. Increased mitochondrial respiration may allow ongoing tissue function even with reduced respiratory efficiency in term preeclamptic pregnancies. Response after in vitro hypoxia/reoxygenation suggests that disruption of oxygen supply is key to placental mitochondrial adaptations. Reactive oxygen species signalling in term preeclamptic placentae may be at a level to trigger compensatory antioxidant and mitochondrial responses, allowing tissue level maintenance of function when there is organelle level dysfunction.
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http://dx.doi.org/10.1038/s41419-018-1190-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242930PMC
November 2018

A Vegetarian Diet Is a Major Determinant of Gut Microbiota Composition in Early Pregnancy.

Nutrients 2018 Jul 12;10(7). Epub 2018 Jul 12.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.

The composition of the gut microbiota can be influenced by dietary composition. In pregnancy, the maternal gut microbiome has associations with maternal and infant metabolic status. There is little known regarding the impact of a vegetarian diet in pregnancy on maternal gut microbiota. This study explored the gut microbiota profile in women who were vegetarian or omnivorous in early gestation. Women were selected from participants in the Study of PRobiotics IN Gestational diabetes (SPRING) randomised controlled trial. Nine women identified as vegetarians were matched to omnivorous women in a 1:2 ratio. Microbiota analyses were performed using 16S rRNA gene amplicon sequencing and analysed using the Quantitative Insights Into Microbial Ecology (QIIME) and Calypso software tools. There was no difference in alpha diversity, but beta diversity was slightly reduced in vegetarians. There were differences seen in the relative abundance of several genera in those on a vegetarian diet, specifically a reduction in , , and increases in the relative abundances of and . In this sub-analysis of gut microbiota from women in early pregnancy, a vegetarian as compared to omnivorous diet, was associated with a different gut microbiome, with features suggesting alterations in fermentation end products from a mixed acid fermentation towards more acetate/butyrate.
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http://dx.doi.org/10.3390/nu10070890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073691PMC
July 2018

Prevalence of maternal urinary ketones in pregnancy in overweight and obese women.

Obstet Med 2018 Jun 5;11(2):79-82. Epub 2017 Dec 5.

UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia.

Background: Ketonuria may be associated with adverse fetal outcomes. This study aimed to determine the prevalence of ketonuria at three time points in pregnancy and to assess whether ketonuria correlates with a clinical indication for performing a urine test.

Methods: Women had fasting urinary ketone levels measured at 16 and 28 weeks gestation and random ketone levels measured close to 36 weeks gestation. All ketone levels in the third trimester were recorded along with the clinical indication for the test.

Results: One hundred and eighty-seven women were included in the study. Twenty-two per cent of women had ketonuria at either 16 or 28 weeks gestation and 8% at 36 weeks gestation. Ketonuria was significantly more likely if a test was performed for a clinical indication ( = 0.0002).

Conclusion: Ketonuria in pregnancy is common affecting at least one in five women. Ketonuria is more common in women who have a clinical indication for performing a urine test.
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http://dx.doi.org/10.1177/1753495X17743163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038017PMC
June 2018

Iron supplementation has minor effects on gut microbiota composition in overweight and obese women in early pregnancy.

Br J Nutr 2018 08 23;120(3):283-289. Epub 2018 May 23.

2UQ Centre for Clinical Research,The University of Queensland,Herston,QLD 4029,Australia.

Fe is an essential nutrient for many bacteria, and Fe supplementation has been reported to affect the composition of the gut microbiota in both Fe-deficient and Fe-replete individuals outside pregnancy. This study examined whether the dose of Fe in pregnancy multivitamin supplements affects the overall composition of the gut microbiota in overweight and obese pregnant women in early pregnancy. Women participating in the SPRING study with a faecal sample obtained at 16 weeks' gestation were included in this substudy. For each subject, the brand of multivitamin used was recorded. Faecal microbiome composition was assessed by 16S rRNA sequencing and analysed with the QIIME software suite. Dietary intake of Fe was assessed using a FFQ at 16 weeks' gestation. Women were grouped as receiving low (<60 mg/d, n 94) or high (≥60 mg/d; n 65) Fe supplementation. The median supplementary Fe intake in the low group was 10 (interquartile range (IQR) 5-10) v. 60 (IQR 60-60) mg/d in the high group (P<0·001). Dietary Fe intake did not differ between the groups (10·0 (IQR 7·4-13·3) v. 9·8 (IQR 8·2-13·2) mg/d). Fe supplementation did not significantly affect the composition of the faecal microbiome at any taxonomic level. Network analysis showed that the gut microbiota in the low Fe supplementation group had a higher predominance of SCFA producers. Pregnancy multivitamin Fe content has a minor effect on the overall composition of the gut microbiota of overweight and obese pregnant women at 16 weeks' gestation.
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http://dx.doi.org/10.1017/S0007114518001149DOI Listing
August 2018

The effects of high glucose exposure on global gene expression and DNA methylation in human pancreatic islets.

Mol Cell Endocrinol 2018 09 26;472:57-67. Epub 2017 Nov 26.

Epigenetics and Diabetes, Lund University Diabetes Centre (LUDC), Box 50332, 20213 Malmö, Sweden. Electronic address:

Background: Type 2 diabetes (T2D) is a complex disease characterised by chronic hyperglycaemia. The effects of elevated glucose on global gene expression in combination with DNA methylation patterns have not yet been studied in human pancreatic islets. Our aim was to study the impact of 48 h exposure to high (19 mM) versus control (5.6 mM) glucose levels on glucose-stimulated insulin secretion, gene expression and DNA methylation in human pancreatic islets.

Results: While islets kept at 5.6 mM glucose secreted significantly more insulin in response to short term glucose-stimulation (p = 0.0067), islets exposed to high glucose for 48 h were desensitised and unresponsive to short term glucose-stimulation with respect to insulin secretion (p = 0.32). Moreover, the exposure of human islets to 19 mM glucose resulted in significantly altered expression of eight genes (FDR<5%), with five of these (GLRA1, RASD1, VAC14, SLCO5A1, CHRNA5) also exhibiting changes in DNA methylation (p < 0.05). A gene set enrichment analysis of the expression data showed significant enrichment of e.g. TGF-beta signalling pathway, Notch signalling pathway and SNARE interactions in vesicular transport; these pathways are of relevance for islet function and possibly also diabetes. We also found increased DNA methylation of CpG sites annotated to PDX1 in human islets exposed to 19 mM glucose for 48 h. Finally, we could functionally validate a role for Glra1 in insulin secretion.

Conclusion: Our data demonstrate that high glucose levels affect human pancreatic islet gene expression and several of these genes also exhibit epigenetic changes. This might contribute to the impaired insulin secretion seen in T2D.
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http://dx.doi.org/10.1016/j.mce.2017.11.019DOI Listing
September 2018

Mid-to-Late Gestational Changes in Inflammatory Gene Expression in the Rat Placenta.

Reprod Sci 2018 Feb 19;25(2):222-229. Epub 2017 Nov 19.

1 UQ Centre for Clinical Research, The University of Queensland, Herston, Queensland, Australia.

Background: The placenta plays an important role during pregnancy providing maternal blood supply from the uterus to the developing fetus. The structure and function of the placenta changes with gestation, as the fetus develops and its demands change. This study aims to elucidate changes in cytokine and chemokine gene expression throughout mid-to-late gestation in rat placenta.

Methods: Sprague Dawley rats were time-mated, and placentae were obtained from 6 pregnant dams at 4 different gestational periods: E14.25, E15.25, E17.25, and E20. Changes in placental gene expression were measured by microarray analysis. Differentially expressed inflammatory genes were functionally categorized by pathway analysis. To validate the microarray results, a subset of genes was analyzed by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort of 22 rats.

Results: Changes in messenger RNA (mRNA) expression of various cytokines, chemokines, and genes of the tumor growth factor β and tumor necrosis factor family were analyzed in rat placentae at E14.25, E15.25, E17.25, and E20. Forty-six genes were differentially expressed, and of these 21 genes had increased expression in late gestation (E20). The gestational age pattern of gene expression was confirmed by qPCR in the validation cohort.

Conclusion: The observed acute, prelabor changes in the expression of these genes during gestation warrant further investigation to elucidate their role in pregnancy and parturition.
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http://dx.doi.org/10.1177/1933719117741375DOI Listing
February 2018

Low dietary fiber intake increases Collinsella abundance in the gut microbiota of overweight and obese pregnant women.

Gut Microbes 2018 13;9(3):189-201. Epub 2018 Mar 13.

a UQ Centre for Clinical Research, The University of Queensland , Brisbane , Australia.

The gut microbiota contributes to the regulation of glucose metabolism in pregnancy. Abundance of the genus Collinsella is positively correlated with circulating insulin; however, it is unclear what determines Collinsella abundance. This study aims to validate the correlation between Collinsella and insulin and to elucidate if macronutrient intake alters Collinsella abundance and gut microbiota composition. Gut microbiota profiles were assessed by 16S rRNA sequencing in 57 overweight and 73 obese pregnant women from the SPRING (Study of PRobiotics IN Gestational diabetes) trial at 16 weeks gestation and correlated with metabolic hormone levels and macronutrient intake. Gut microbiota composition in the top and bottom 10% of dietary fiber intake was evaluated through network analysis. Collinsella abundance correlated positively with circulating insulin (rho = 0.30, p = 0.0006), independent of maternal BMI, but negatively with dietary fiber intake (rho = -0.20, p = 0.025) in this cohort. Low dietary fiber intake was associated with a gut microbiota favoring lactate fermentation while high fiber intake promotes short-chain fatty acid-producing bacteria. Low dietary fiber may enable overgrowth of Collinsella and alter the overall fermentation pattern in gut microbiota. This suggests that dietary choices during pregnancy can modify the nutritional ecology of the gut microbiota, with potential deleterious effects on the metabolic and inflammatory health of the host.

Trial Registration: ANZCTR 12611001208998, registered 23/11/2011.
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http://dx.doi.org/10.1080/19490976.2017.1406584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219589PMC
September 2018

Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women.

Sci Rep 2017 06 6;7(1):2860. Epub 2017 Jun 6.

UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia.

A distinct bacterial signature of the placenta was reported, providing evidence that the fetus does not develop in a sterile environment. The oral microbiome was suggested as a possible source of the bacterial DNA present in the placenta based on similarities to the oral non-pregnant microbiome. Here, the possible origin of the placental microbiome was assessed, examining the gut, oral and placental microbiomes from the same pregnant women. Microbiome profiles from 37 overweight and obese pregnant women were examined by 16SrRNA sequencing. Fecal and oral contributions to the establishment of the placental microbiome were evaluated. Core phylotypes between body sites and metagenome predictive functionality were determined. The placental microbiome showed a higher resemblance and phylogenetic proximity with the pregnant oral microbiome. However, similarity decreased at lower taxonomic levels and microbiomes clustered based on tissue origin. Core genera: Prevotella, Streptococcus and Veillonella were shared between all body compartments. Pathways encoding tryptophan, fatty-acid metabolism and benzoate degradation were highly enriched specifically in the placenta. Findings demonstrate that the placental microbiome exhibits a higher resemblance with the pregnant oral microbiome. Both oral and gut microbiomes contribute to the microbial seeding of the placenta, suggesting that placental colonization may have multiple niche sources.
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http://dx.doi.org/10.1038/s41598-017-03066-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460277PMC
June 2017

Antibiotic treatment at delivery shapes the initial oral microbiome in neonates.

Sci Rep 2017 02 27;7:43481. Epub 2017 Feb 27.

UQ Centre for Clinical Research, The University of Queensland, Brisbane Australia.

Oral microorganisms are important determinants of health and disease. The source of the initial neonatal microbiome and the factors dictating initial human oral microbiota development are unknown. This study aimed to investigate this in placental, oral and gut microbiome profiles from 36 overweight or obese mother-baby dyads as determined by 16S rRNA sequencing. Expression of five antibiotic resistance genes of the β-lactamase class was analysed in the infant oral microbiota samples by QPCR. The neonatal oral microbiota was 65.35% of maternal oral, 3.09% of placental, 31.56% of unknown and 0% of maternal gut origin. Two distinct neonatal oral microbiota profiles were observed: one strongly resembling the maternal oral microbiota and one with less similarity. Maternal exposure to intrapartum antibiotics explained the segregation of the profiles. Families belonging to Proteobacteria were abundant after antibiotics exposure while the families Streptococcaceae, Gemellaceae and Lactobacillales dominated in unexposed neonates. 26% of exposed neonates expressed the Vim-1 antibiotic resistance gene. These findings indicate that maternal intrapartum antibiotic treatment is a key regulator of the initial neonatal oral microbiome.
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http://dx.doi.org/10.1038/srep43481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378909PMC
February 2017

Review: Alterations in placental glycogen deposition in complicated pregnancies: Current preclinical and clinical evidence.

Placenta 2017 06 11;54:52-58. Epub 2017 Jan 11.

School of Biomedical Sciences, The University of Queensland, St Lucia, QLD, 4072, Australia; Mater Medical Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, 4101, Australia.

Normal placental function is essential for optimal fetal growth. Transport of glucose from mother to fetus is critical for fetal nutrient demands and can be stored in the placenta as glycogen. However, the function of this glycogen deposition remains a matter of debate: It could be a source of fuel for the placenta itself or a storage reservoir for later use by the fetus in times of need. While the significance of placental glycogen remains elusive, mounting evidence indicates that altered glycogen metabolism and/or deposition accompanies many pregnancy complications that adversely affect fetal development. This review will summarize histological, biochemical and molecular evidence that glycogen accumulates in a) placentas from a variety of experimental rodent models of perturbed pregnancy, including maternal alcohol exposure, glucocorticoid exposure, dietary deficiencies and hypoxia and b) placentas from human pregnancies with complications including preeclampsia, gestational diabetes mellitus and intrauterine growth restriction (IUGR). These pregnancies typically result in altered fetal growth, developmental abnormalities and/or disease outcomes in offspring. Collectively, this evidence suggests that changes in placental glycogen deposition is a common feature of pregnancy complications, particularly those associated with altered fetal growth.
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http://dx.doi.org/10.1016/j.placenta.2017.01.114DOI Listing
June 2017

Review: Is rapid fat accumulation in early life associated with adverse later health outcomes?

Placenta 2017 06 11;54:125-130. Epub 2017 Jan 11.

UQ Centre for Clinical Research, The University of Queensland, Herston, Queensland 4029, Australia; Grantley Stable Neonatal Unit, Royal Brisbane and Women's Hospital, Herston, Queensland 4029, Australia. Electronic address:

This review discusses ways in which the maternal environment and placental function affect the birth weight and adult health outcomes of offspring. These maternal and placental factors have varying and sometimes opposing effects on birth weight, resulting in infants that are born small for gestational age (SGA), large for gestational age (LGA) or preterm. However, all these alterations in weight have similar effects on adult health, increasing the risk of obesity and its associated cardiovascular and metabolic disorders. While birth weight has been used as a marker for risk of adverse adult health, we propose that a common feature of all these scenarios - early accumulation of excess body fat - may be a better marker than birth weight alone. Furthermore, altered neonatal fat accumulation may be more closely related to the mechanism by which maternal environment and placental adaptation mediate effects on adult health. We suggest that more research should be focussed on early fat accretion, factors that promote fat accretion and if it can be avoided, and whether it would be beneficial to try to reduce fat accumulation in early life.
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http://dx.doi.org/10.1016/j.placenta.2017.01.101DOI Listing
June 2017

Review: Maternal health and the placental microbiome.

Placenta 2017 06 2;54:30-37. Epub 2016 Dec 2.

UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.

Over the past decade, the role of the microbiome in regulating metabolism, immune function and behavior in humans has become apparent. It has become clear that the placenta is not a sterile organ, but rather has its own endogenous microbiome. The composition of the placental microbiome is distinct from that of the vagina and has been reported to resemble the oral microbiome. Compared to the gut microbiome, the placental microbiome exhibits limited microbial diversity. This review will focus on the current understanding of the placental microbiota in normal healthy pregnancy and also in disease states including preterm birth, chorioamnionitis and maternal conditions such as obesity, gestational diabetes mellitus and preeclampsia. Factors known to alter the composition of the placental microbiota will be discussed in the final part of this review.
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http://dx.doi.org/10.1016/j.placenta.2016.12.003DOI Listing
June 2017