Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota

Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alter gut microbial composition, diversity, and short-chain fatty acid (SCFA) levels in neonates. We investigated 46 full-term neonates born to normal-weight or overweight/obese mothers with and without GDM, accounting for confounders including cesarean delivery, lack of breastfeeding, and exposure to antibiotics. Gut microbiota in 2-week-old neonates born to mothers with GDM exhibited differences in abundance of 26 microbial taxa; 14 of which showed persistent differential abundance after adjusting for pre-pregnancy BMI. Key pioneering gut taxa, including potentially important taxa for establishing neonatal immunity, were reduced. Lactobacillus, Flavonifractor, Erysipelotrichaceae, and unspecified families in Gammaproteobacteria were significantly reduced in neonates from mothers with GDM. GDM was associated with an increase in microbes involved in suppressing early immune cell function (Phascolarctobacterium). No differences in infant stool SCFA levels by maternal phenotype were noted; however, significant correlations were found between microbial abundances and SCFA levels in neonates. Our results suggest that GDM alone and together with maternal overweight/obesity uniquely influences seeding of specific infant microbiota in patterns that set the stage for future risk of inflammatory and metabolic disease.

Download Full-text

Maternal modifiers of the infant gut microbiota: metabolic consequences

Journal of Endocrinology ◽

10.1530/joe-17-0303 ◽

2017 ◽

Vol 235 (1) ◽

pp. R1-R12 ◽

Cited By ~ 41

Author(s):

Christopher M Mulligan ◽

Jacob E Friedman

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Maternal Obesity ◽

Metabolic Diseases ◽

Immune Cell ◽

Neonatal Period ◽

Microbial Colonization ◽

Portal System ◽

Cell Axis ◽

Mother To Child

Transmission of metabolic diseases from mother to child is multifactorial and includes genetic, epigenetic and environmental influences. Evidence in rodents, humans and non-human primates support the scientific premise that exposure to maternal obesity or high-fat diet during pregnancy creates a long-lasting metabolic signature on the infant innate immune system and the juvenile microbiota, which predisposes the offspring to obesity and metabolic diseases. In neonates, gastrointestinal microbes introduced through the mother are noted for their ability to serve as direct inducers/regulators of the infant immune system. Neonates have a limited capacity to initiate an immune response. Thus, disruption of microbial colonization during the early neonatal period results in disrupted postnatal immune responses that highlight the neonatal period as a critical developmental window. Although the mechanisms are poorly understood, increasing evidence suggests that maternal obesity or poor diet influences the development and modulation of the infant liver and other end organs through direct communication via the portal system, metabolite production, alterations in gut barrier integrity and the hematopoietic immune cell axis. This review will focus on how maternal obesity and dietary intake influence the composition of the infant gut microbiota and how an imbalance or maladaptation in the microbiota, including changes in early pioneering microbes, might contribute to the programming of offspring metabolism with special emphasis on mechanisms that promote chronic inflammation in the liver. Comprehension of these pathways and mechanisms will elucidate our understanding of developmental programming and may expand the avenue of opportunities for novel therapeutics.

Download Full-text

Effect of maternal high body mass index on outcome of pregnancy in women with recurrent miscarriages

Indian Journal of Forensic and Community Medicine ◽

10.18231/j.ijfcm.2021.048 ◽

2021 ◽

Vol 8 (4) ◽

pp. 237-241

Author(s):

Malangori Parande ◽

Tanvi V Wagh ◽

Anjali V Wagh ◽

Nandkumar Salunke

Keyword(s):

Gestational Diabetes ◽

Preterm Delivery ◽

Maternal Obesity ◽

Tertiary Care ◽

Overweight And Obesity ◽

Care Hospital ◽

Pregnancy Induced Hypertension ◽

Recurrent Miscarriages ◽

Induced Hypertension ◽

Maternal Overweight

The epidemic of obesity is spreading worldwide and subsequently, rate of obesity during pregnancy has also increased. Maternal overweight and obesity are widely associated with adverse pregnancy outcomes. Recurrent miscarriage is an important reproductive health issue, because it affects many couples. So the present study is planned to study the relationship between maternal obesity and pregnancy outcome in women with recurrent miscarriages. Observational Cross sectional study was conducted in a tertiary care hospital. 111 Postnatal women between 18 to 44 years of age with history of two or more miscarriages less than 20 weeks of gestation in previous pregnancy were included in the study. First trimester weight at the first visit (registration) was recorded, BMI was calculated & women were divided into obese and non obese groups. The outcome of present pregnancy was noted as Mode of delivery, Gestational diabetes mellitus, Pregnancy induced hypertension, Preterm delivery etc. Statistical tests were used to quantify the risk. Gestational diabetes (OR= 13.6) and pregnancy induced hypertension (OR=4.2) were significantly associated with obesity in women with recurrent miscarriages. [At 95% CI] The incidence of LSCS and preterm delivery was more in overweight and obese mothers, though not statistically significant. Maternal obesity significantly contributes to poor prognosis for the mother and the baby during delivery. Hence the women of this group should be regarded as ‘high risk’ and counselling and the risk assessment should be done during ANC visits.

Download Full-text

The effects of gut microbiota on metabolic outcomes in pregnant women and their offspring

Food & Function ◽

10.1039/c8fo00601f ◽

2018 ◽

Vol 9 (9) ◽

pp. 4537-4547 ◽

Cited By ~ 4

Author(s):

You Lv ◽

Zi Yan ◽

Xue Zhao ◽

Xiaokun Gang ◽

Guangyu He ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gut Microbiota ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Metabolic Diseases ◽

Health Issues ◽

Metabolic Outcomes

Metabolic diseases such as gestational diabetes mellitus and obesity during pregnancy have become severe health issues due to adverse pregnant outcomes in recent years.

Download Full-text

The Potential Effects of Probiotics and ω-3 Fatty Acids on Chronic Low-Grade Inflammation

Nutrients ◽

10.3390/nu12082402 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2402 ◽

Cited By ~ 1

Author(s):

Ashley N. Hutchinson ◽

Lina Tingö ◽

Robert Jan Brummer

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Cell Function ◽

Immune Cell ◽

Low Grade ◽

Beneficial Effects ◽

Positive Effects ◽

Immune Mediators ◽

Low Grade Inflammation ◽

Microbiota Diversity

Chronic low-grade inflammation negatively impacts health and is associated with aging and obesity, among other health outcomes. A large number of immune mediators are present in the digestive tract and interact with gut bacteria to impact immune function. The gut microbiota itself is also an important initiator of inflammation, for example by releasing compounds such as lipopolysaccharides (LPS) that may influence cytokine production and immune cell function. Certain nutrients (e.g., probiotics, ω-3 fatty acids [FA]) may increase gut microbiota diversity and reduce inflammation. Lactobacilli and Bifidobacteria, among others, prevent gut hyperpermeability and lower LPS-dependent chronic low-grade inflammation. Furthermore, ω-3 FA generate positive effects on inflammation-related conditions (e.g., hypertriglyceridemia, diabetes) by interacting with immune, metabolic, and inflammatory pathways. Ω-3 FA also increase LPS-suppressing bacteria (i.e., Bifidobacteria) and decrease LPS-producing bacteria (i.e., Enterobacteria). Additionally, ω-3 FA appear to promote short-chain FA production. Therefore, combining probiotics with ω-3 FA presents a promising strategy to promote beneficial immune regulation via the gut microbiota, with potential beneficial effects on conditions of inflammatory origin, as commonly experienced by aged and obese individuals, as well as improvements in gut-brain-axis communication.

Download Full-text

Minireview: Gut Microbiota: The Neglected Endocrine Organ

Molecular Endocrinology ◽

10.1210/me.2014-1108 ◽

2014 ◽

Vol 28 (8) ◽

pp. 1221-1238 ◽

Cited By ~ 408

Author(s):

Gerard Clarke ◽

Roman M. Stilling ◽

Paul J. Kennedy ◽

Catherine Stanton ◽

John F. Cryan ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Peptide Yy ◽

Body Weight Gain ◽

Bacterial Species ◽

Plasma Concentrations ◽

Regulatory Control ◽

Microbial Composition ◽

Direct Role ◽

Endocrine Organ

The concept that the gut microbiota serves as a virtual endocrine organ arises from a number of important observations. Evidence for a direct role arises from its metabolic capacity to produce and regulate multiple compounds that reach the circulation and act to influence the function of distal organs and systems. For example, metabolism of carbohydrates results in the production of short-chain fatty acids, such as butyrate and propionate, which provide an important source of nutrients as well as regulatory control of the host digestive system. This influence over host metabolism is also seen in the ability of the prebiotic inulin to influence production of relevant hormones such as glucagon-like peptide-1, peptide YY, ghrelin, and leptin. Moreover, the probiotic Lactobacillus rhamnosus PL60, which produces conjugated linoleic acid, has been shown to reduce body-weight gain and white adipose tissue without effects on food intake. Manipulating the microbial composition of the gastrointestinal tract modulates plasma concentrations of tryptophan, an essential amino acid and precursor to serotonin, a key neurotransmitter within both the enteric and central nervous systems. Indirectly and through as yet unknown mechanisms, the gut microbiota exerts control over the hypothalamic-pituitary-adrenal axis. This is clear from studies on animals raised in a germ-free environment, who show exaggerated responses to psychological stress, which normalizes after monocolonization by certain bacterial species including Bifidobacterium infantis. It is tempting to speculate that therapeutic targeting of the gut microbiota may be useful in treating stress-related disorders and metabolic diseases.

Download Full-text

Association of maternal gut microbiota and plasma metabolism with congenital heart disease in offspring: a multi-omic analysis

Scientific Reports ◽

10.1038/s41598-021-84901-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tingting Wang ◽

Lizhang Chen ◽

Peng Huang ◽

Tubao Yang ◽

Senmao Zhang ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Gut Microbiota ◽

Congenital Heart ◽

Maternal Obesity ◽

Disease Risk ◽

Plasma Metabolites ◽

Rrna Gene ◽

Microbial Composition ◽

Obesity And Diabetes

AbstractCongenital heart disease (CHD) is the most common congenital disorder diagnosed in newborns. Although lots of related studies have been published, yet the pathogenesis has not been fully elucidated. A growing body of evidence indicates perturbations of the gut microbiota may contribute in a significant way to the development of obesity and diabetes. Given that maternal obesity and diabetes are well-known risk factors for CHD, maternal gut microbiota may be considered as one of the environmental factors involved in the pathogenesis of CHD. The object of this study is to explore the association between maternal gut microbiota and risk of congenital heart disease (CHD) in offspring, as well as the possible mechanisms linking gut microbiota and disease risk. A case–control study was conducted in mothers of infants with CHD (n = 101) and mothers of infants without CHD (n = 95). By applying 16S rRNA gene sequencing and metabolic approaches to 196 stool and plasma samples, we determined microbiome and metabolome profiles in mothers of infants with CHD and controls, and their association with risk of CHD in offspring. The gut microbiome of mothers of infants with CHD was characterized with lower alpha-diversity and distinct overall microbial composition compared with mothers of infants without CHD. A distinct different metabolic profile was found between mothers of infants with CHD and controls. After controlling for the possible confounders, thirty-four bacterial genera and fifty-three plasma metabolites showed distinct abundances between the two groups. The results of the Spearman correlation analyses revealed a great number of significant correlations between the abundant bacterial genera and differentially expressed metabolites. In particular, the genus Bifidobacterium and Streptococcus showed comparable moderate positive correlations with a range of metabolites that involved in lipid metabolism pathway. Our findings suggest that perturbations of maternal gut microbiota and plasma metabolites may be associated with risk of CHD in offspring, and co-variation between microbiota and metabolites may play a part in the linkage between gut microbiota and risk of CHD in offspring.

Download Full-text

Metagenomic Diversity of Gut Microbiota of Gestational Diabetes Mellitus of Pregnant Women

Biomedika ◽

10.31001/biomedika.v13i1.747 ◽

2020 ◽

Vol 13 (1) ◽

pp. 1-8

Author(s):

Minarti Minarti ◽

Nurhidayat Triananinsi ◽

Nurqalbi Nurqalbi ◽

Sumarni Sumarni ◽

Mudyawati Kamaruddin

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gut Microbiota ◽

Gestational Diabetes Mellitus ◽

Pregnant Women ◽

Public Health Problem ◽

Genus Level ◽

Significant Public Health Problem ◽

Significant Public Health ◽

Varied Composition

Gestational Diabetes Mellitus (GDM) is defined as a condition in which a woman without diabetes develops abnormal glucose tolerance that is first recognized during pregnancy. GDM is a significant public health problem with an incidence of 1.9 – 3.6% of all pregnancies in Indonesia. Additionally, women with GDM during pregnancy have a high risk of developing diabetes when they are not pregnant, such as type 2 diabetes (T2D). One alternative variable in the management of T2D globally is gut microbiota. Here, to find out the role of gut microbiota in pregnancy, we characterized the stools of 30 pregnant women, each consisting of fifteen GDM-detected pregnant women, and healthy pregnant women using metagenomic approach with genome analysis by directly isolating genomic DNA from the microbiota ecosystem that occupies the digestive tract. DNA sequencing results were analyzed by MEGA 6 software with the BLASTn algorithm in NCBI. Thus fifteen GDM-detected showed high nucleotide sequence homology with the Proteobacteria at phylum level, and Escherichia, Orchobacterium, Cronobacter, Shigella, Salmonella, Enterobacter, Klebsiella, Kosakonia, Vibrio dan Gamma-Proteobacterium at genus level compared to the healthy pregnant women which found by Firmicutes at phylum level and Ruminococcus, Clostridium, Clostridiales, Lachnospiraceae, Roseburia, Weisella, Eubacterium at genus level had a higher abundance in healthy pregnant women. In this result, we found also one of the fifteen healthy pregnant women showed differential abundance with enrichment of Prevotella species. Gut microbiota of GDM-diagnosed pregnant women has more varied composition, and dominated by the phylum Proteobacteria than in normal pregnant women.

Download Full-text

Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review

PLoS ONE ◽

10.1371/journal.pone.0252343 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0252343

Author(s):

Gitte Hedermann ◽

Paula L. Hedley ◽

Ida N. Thagaard ◽

Lone Krebs ◽

Charlotte Kvist Ekelund ◽

...

Keyword(s):

Metabolic Syndrome ◽

Gestational Diabetes ◽

Cohort Studies ◽

Congenital Heart Defects ◽

Congenital Heart ◽

Metabolic Disorders ◽

Maternal Obesity ◽

Heart Defects ◽

Increased Risk ◽

Maternal Overweight

Background Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors. Methods A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score. Results Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes. Conclusions Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and–particularly–in combination, with CHDs are needed.

Download Full-text

Gut microbiota in cardiovascular disease and heart failure

Clinical Science ◽

10.1042/cs20171090 ◽

2018 ◽

Vol 132 (1) ◽

pp. 85-91 ◽

Cited By ~ 25

Author(s):

Takeshi Kitai ◽

W.H. Wilson Tang

Keyword(s):

Heart Failure ◽

Gut Microbiota ◽

Energy Homeostasis ◽

Metabolic Diseases ◽

Microbial Composition ◽

Metabolic Potential ◽

Technological Developments ◽

Biochemical Analyses ◽

Host Metabolism

Accumulating evidence supports a relationship between the complexity and diversity of the gut microbiota and host diseases. In addition to alterations in the gut microbial composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent technological developments of molecular and biochemical analyses enable us to detect and characterize the gut microbiota via assessment and classification of its genomes and corresponding metabolites. These advances have provided emerging data supporting the role of gut microbiota in various physiological activities including host metabolism, neurological development, energy homeostasis, and immune regulation. Although few human studies have looked into the causative associations and underlying pathophysiology of the gut microbiota and host disease, a growing body of preclinical and clinical evidence supports the theory that the gut microbiota and its metabolites have the potential to be a novel therapeutic and preventative target for cardiovascular and metabolic diseases. In this review, we highlight the interplay between the gut microbiota and its metabolites, and the development and progression of hypertension, heart failure, and chronic kidney disease.

Download Full-text

Role of S-Equol, Indoxyl Sulfate, and Trimethylamine N-Oxide on Vascular Function

American Journal of Hypertension ◽

10.1093/ajh/hpaa053 ◽

2020 ◽

Vol 33 (9) ◽

pp. 793-803 ◽

Cited By ~ 3

Author(s):

Takayuki Matsumoto ◽

Mihoka Kojima ◽

Keisuke Takayanagi ◽

Kumiko Taguchi ◽

Tsuneo Kobayashi

Keyword(s):

Smooth Muscle ◽

Gut Microbiota ◽

Vascular Function ◽

Metabolic Diseases ◽

Cell Function ◽

Vascular System ◽

Antioxidant Activities ◽

Microvascular Complications ◽

Indoxyl Sulfate ◽

Uremic Toxin

Abstract Gut microbiota have been emerging as important contributors to the regulation of host homeostasis. Accordingly, several substances converted by gut microbiota can have beneficial or adverse effects on human health. Among them, S-equol, which is produced from the isoflavone daidzein in the human and animal gut by certain microbiota, exerts estrogenic and antioxidant activities. Indoxyl sulfate, which is metabolized in the liver from indole converted from dietary tryptophan by bacterial tryptophanases in the colon, is known as a protein-bound uremic toxin. Trimethylamine N-oxide, which is generated via the oxidization of gut microbiota-derived trimethylamine by hepatic flavin monooxygenases, is known as an accelerator of atherosclerosis. The aforementioned gut-derived substances could be potential regulators of systematic tissue/organ function, including the vascular system. Macro- and microvascular complications of cardiovascular and metabolic diseases, including atherosclerosis, hypertension, and diabetes, occur systemically and represent the principal cause of morbidity and mortality. Vascular endothelial and smooth muscle dysfunction play pivotal roles in the development and progression of vasculopathies. We herein review the link between the aforementioned gut-derived substances and endothelial and vascular smooth muscle cell function. This information will provide a conceptual framework that would allow the development of novel preventive and/or therapeutic approaches against vasculopathies.

Download Full-text