132 Early Establishment of the Human Gut Microbiome—a Tale of Moms, Their Diets, and Babes Guts

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 68-68
Author(s):  
Kjersti M Aagaard
Keyword(s):  
Gut Microbiome ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Dietary Exposure ◽  
Metabolic Phenotype ◽  
Strong Impact ◽  
High Fat ◽  
Lower Genital Tract ◽  
And Function ◽  
The Impact

Abstract Human microbial communities are characterized by their metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. We are only beginning to characterize the complex set of interactions which alters both community membership and function in early development. With respect to the potential source of microbiota at birth, it has been generally assumed that the majority of seeding microbes originate from the maternal lower genital tract, with microbiota ascending into the otherwise sterile intrauterine. However, we and subsequently others have recently demonstrated that (1) the vaginal and gut microbiome communities are distinctly structured in pregnancy, and (2) the intrauterine environment and the fetus is in fact not sterile, but rather harbors a low-abundance microbiome which varies by several measured exposures, and (3) the maternal diet during both gestation and lactation, and notably a high fat diet, has a particularly strong impact on the developing and early in life microbial community structure. We have taken two dynamic approaches to answering these questions in our studies. First, we use large and robust longitudinal cohorts of maternal-infant dyads collected across gestation and into infancy to gain deeper insight into both source and sink of the early developmental microbiome and its role on determining length of gestation. Second, we utilize our well established primate models of maternal high fat dietary exposure, both in the absence and presence of maternal obesity, to determine the impact of maternal diet on both the microbiome and the resultant offspring metabolic phenotype.

scholarly journals The impact of chemerin or chemokine-like receptor 1 loss on the mouse gut microbiome

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5494 ◽  
Author(s):  
Helen J. Dranse ◽  
Ashlee Zheng ◽  
André M. Comeau ◽  
Morgan G.I. Langille ◽  
Brian A. Zabel ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Gut Microbiome ◽  
Inflammatory Diseases ◽  
Alpha Diversity ◽  
Metabolic Phenotype ◽  
Microbiome Composition ◽  
Signalling Molecule ◽  
Dramatic Difference ◽  
And Function ◽  
The Impact

Chemerin is an adipocyte derived signalling molecule (adipokine) that serves as a ligand activator of Chemokine-like receptor 1(CMKLR1). Chemerin/CMKLR1 signalling is well established to regulate fundamental processes in metabolism and inflammation. The composition and function of gut microbiota has also been shown to impact the development of metabolic and inflammatory diseases such as obesity, diabetes and inflammatory bowel disease. In this study, we assessed the microbiome composition of fecal samples isolated from wildtype, chemerin, or CMKLR1 knockout mice using Illumina-based sequencing. Moreover, the knockout mice and respective wildtype mice used in this study were housed at different universities allowing us to compare facility-dependent effects on microbiome composition. While there was no difference in alpha diversity within samples when compared by either facility or genotype, we observed a dramatic difference in the presence and abundance of numerous taxa between facilities. There were minor differences in bacterial abundance between wildtype and chemerin knockout mice, but significantly more differences in taxa abundance between wildtype and CMKLR1 knockout mice. Specifically, CMKLR1 knockout mice exhibited decreased abundance of Akkermansia and Prevotella, which correlated with body weight in CMKLR1 knockout, but not wildtype mice. This is the first study to investigate a linkage between chemerin/CMKLR1 signaling and microbiome composition. The results of our study suggest that chemerin/CMKLR1 signaling influences metabolic processes through effects on the gut microbiome. Furthermore, the dramatic difference in microbiome composition between facilities might contribute to discrepancies in the metabolic phenotype of CMKLR1 knockout mice reported by independent groups. Considered altogether, these findings establish a foundation for future studies to investigate the relationship between chemerin signaling and the gut microbiome on the development and progression of metabolic and inflammatory disease.

scholarly journals Inheritable testicular metabolic memory of high-fat diet causes transgenerational sperm defects in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luís Crisóstomo ◽  
Ivana Jarak ◽  
Luís P. Rato ◽  
João F. Raposo ◽  
Rachel L. Batterham ◽  
...  
Keyword(s):  
Sperm Quality ◽  
Feeding Habits ◽  
Reproductive Function ◽  
Principal Component ◽  
Testicular Tissue ◽  
Sperm Parameters ◽  
Metabolic Memory ◽  
High Fat ◽  
And Function ◽  
The Impact

AbstractThe consumption of energy-dense diets has contributed to an increase in the prevalence of obesity and its comorbidities worldwide. The adoption of unhealthy feeding habits often occurs at early age, prompting the early onset of metabolic disease with unknown consequences for reproductive function later in life. Recently, evidence has emerged regarding the intergenerational and transgenerational effects of high-fat diets (HFD) on sperm parameters and testicular metabolism. Hereby, we study the impact of high-fat feeding male mice (F0) on the testicular metabolome and function of their sons (F1) and grandsons (F2). Testicular content of metabolites related to insulin resistance, cell membrane remodeling, nutritional support and antioxidative stress (leucine, acetate, glycine, glutamine, inosine) were altered in sons and grandsons of mice fed with HFD, comparing to descendants of chow-fed mice. Sperm counts were lower in the grandsons of mice fed with HFD, even if transient. Sperm quality was correlated to testicular metabolite content in all generations. Principal Component Analysis of sperm parameters and testicular metabolites revealed an HFD-related phenotype, especially in the diet-challenged generation and their grandsons. Ancestral HFD, even if transient, causes transgenerational “inherited metabolic memory” in the testicular tissue, characterized by changes in testicular metabolome and function.

scholarly journals Mechanisms Underlying the Cognitive and Behavioural Effects of Maternal Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 240
Author(s):  
Kyoko Hasebe ◽  
Michael D. Kendig ◽  
Margaret J. Morris
Keyword(s):  
Animal Models ◽  
Adverse Effects ◽  
Gut Microbiome ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Affective State ◽  
Brain Regions ◽  
Brain Network ◽  
Physical And Mental Health ◽  
Obesogenic Diet

The widespread consumption of ‘western’-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome.

scholarly journals The association between the maternal diet and the maternal and infant gut microbiome: a systematic review

2020 ◽  
pp. 1-29 ◽  
Author(s):  
Siofra E. Maher ◽  
Eileen C. O’Brien ◽  
Rebecca L. Moore ◽  
David F. Byrne ◽  
Aisling A. Geraghty ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Gut Microbiome ◽  
Dietary Intervention ◽  
Maternal Diet ◽  
Rrna Gene ◽  
High Fat ◽  
High Fat Diets ◽  
Culture Independent ◽  
Infant Gut Microbiome ◽  
Fat Diets

Abstract During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.

scholarly journals Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring

2007 ◽  
Vol 293 (3) ◽  
pp. R1056-R1062 ◽  
Author(s):  
Jacqueline Férézou-Viala ◽  
Anne-France Roy ◽  
Colette Sérougne ◽  
Daniel Gripois ◽  
Michel Parquet ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Maternal Diet ◽  
The Body ◽  
Female Rats ◽  
Leptin Resistance ◽  
High Fat ◽  
Leptin Sensitivity ◽  
The Impact

Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adulthood. In this paper, we investigated the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received a HF or a control normal-fat (C) diet for 6 wk before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 wk. Body weight gain and metabolic and endocrine parameters were measured in the eight groups of rats formed according to a postweaning diet, maternal diet, and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin or saline intraperitoneal bolus. Pups exhibited similar body weights at birth, but at weaning, those born to HF dams weighed significantly less (−12%) than those born to C dams. When given the HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+17%) with hyperleptinemia and hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood.

scholarly journals Maternal High-Fat Diet Exposure During Gestation and Lactation Affects Intestinal Development in Suckling Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Monika Słupecka-Ziemilska ◽  
Paulina Grzesiak ◽  
Paweł Kowalczyk ◽  
Piotr Wychowański ◽  
Jarosław Woliński
Keyword(s):  
High Fat Diet ◽  
Metabolic Diseases ◽  
Maternal Diet ◽  
Dependent Manner ◽  
Intestinal Development ◽  
High Fat ◽  
Rat Pups ◽  
Diet Induced Obesity ◽  
Cholinergic Signaling ◽  
And Function

Maternal health and diet influence metabolic status and play a crucial role in the development of metabolic function in offspring and their susceptibility to metabolic diseases in adulthood. The pathogenesis of various metabolic disorders is often associated with impairment in intestinal structure and function. Thus, the aim of the current study was to determine the effects of maternal exposure to a high fat diet (HFD), during gestation and lactation, on small intestinal growth and maturation in rat pups at 21 days old. Female, Wistar Han rats were fed either a breeding diet (BD) or high fat diet (HFD), from mating until the 21st day of lactation. Maternal HFD exposure increased body weight, BMI and adiposity. Compared to the maternal BD, HFD exposure influenced small intestine histomorphometry in a segment-dependent manner, changed the activity of brush border enzymes and had an impact on intestinal contractility via changes in cholinergic signaling. Moreover, offspring from the maternal HFD group had upregulated mRNA expression of cyclooxygenase (COX)-2, which plays a role in the inflammatory process. These results suggest that maternal HFD exposure, during gestation and lactation, programs the intestinal development of the offspring in a direction toward obesity as observed changes are also commonly reported in models of diet-induced obesity. The results also highlight the importance of maternal diet preferences in the process of developmental programming of metabolic diseases.

scholarly journals It’s the fiber, not the fat: Significant effects of dietary challenge on the gut microbiome

2019 ◽  
Author(s):  
Kathleen E. Morrison ◽  
Eldin Jašarević ◽  
Christopher D. Howard ◽  
Tracy L. Bale
Keyword(s):  
Body Weight ◽  
Gut Microbiota ◽  
Dietary Fat ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Chow Diet ◽  
Soluble Fiber ◽  
High Fat ◽  
The Impact

AbstractBackgroundDietary effects on the gut microbiome has been shown to play a key role in the pathophysiology of behavioral dysregulation, inflammatory disorders, metabolic syndrome, and obesity. Often overlooked is that experimental diets vary significantly in the proportion and source of dietary fiber. Commonly, treatment comparisons are made between animals that are fed refined diets that lack soluble fiber and animals fed vivarium-provided chow diet that contain a rich source of soluble fiber. Despite the well-established role of soluble fiber on metabolism, immunity, and behavior via the gut microbiome, the extent to which measured outcomes may be driven by differences in dietary fiber is unclear. Further, the significant impact of sex and age in response to dietary challenge is likely important and should also be considered.ResultsWe compared the impact of transitioning young and aged male and female mice from a chow diet to a refined low soluble fiber diet on body weight and gut microbiota. Then, to determine the contribution of dietary fat, we examined the impact of transitioning a subset of animals from refined low fat to refined high fat diet. Serial tracking of body weights revealed that consumption of low fat or high fat refined diet increased body weight in young and aged adult male mice. Young adult females showed resistance to body weight gain, while high fat diet-fed aged females had significant body weight gain. Transition from a chow diet to low soluble fiber refined diet accounted for most of the variance in community structure and composition across all groups. This dietary transition was characterized by a loss of taxa within the phylum Bacteroidetes and a concurrent bloom of Clostridia and Proteobacteria in a sex- and age-specific manner. Most notably, no changes to gut microbiota community structure and composition were observed between mice consuming either low- or high-fat diet, suggesting that transition to the refined diet that lacks soluble fiber is the primary driver of gut microbiota alterations, with limited additional impact of dietary fat on gut microbiota.ConclusionCollectively, our results show that the choice of control diet has a significant impact on outcomes and interpretation related to body weight and gut microbiota. These data also have broad implications for rodent studies that draw comparisons between refined high fat diets and chow diets to examine dietary fat effects on metabolic, immune, behavioral, and neurobiological outcomes.

scholarly journals Maternal High-Fat–High-Carbohydrate Diet-Induced Obesity Is Associated with Increased Appetite in Peripubertal Male but Not Female C57Bl/6J Mice

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2919 ◽  
Author(s):  
Debra Kulhanek ◽  
Rachel Weigel ◽  
Megan E. Paulsen
Keyword(s):  
Energy Homeostasis ◽  
Maternal Obesity ◽  
Maternal Nutrition ◽  
Maternal Diet ◽  
Critical Role ◽  
Caloric Intake ◽  
Maternal Weight ◽  
High Fat ◽  
High Carbohydrate ◽  
Nutritional Influences

Diet-induced maternal obesity might play a critical role in altering hypothalamic development, predisposing the offspring to obesity and metabolic disease later in life. The objective of this study was to describe both phenotypic and molecular sex differences in peripubertal offspring energy homeostasis, using a mouse model of maternal obesity induced by a high-fat–high-carbohydrate (HFHC) diet. We report that males, not females, exposed to a maternal HFHC diet had increased energy intake. Males exposed to a maternal HFHC diet had a 15% increased meal size and a 46% increased frequency, compared to the control (CON) males, without a change in energy expenditure. CON and HFHC offspring did not differ in body weight, composition, or plasma metabolic profile. HFHC diet caused decreased hypothalamic glucocorticoid expression, which was further decreased in males compared to females. Maternal weight, maternal caloric intake, and male offspring meal frequency were inversely correlated with offspring hypothalamic insulin receptor (IR) expression. There was a significant interaction between maternal-diet exposure and sex in hypothalamic IR. Based on our preclinical data, we suggest that interventions focusing on normalizing maternal nutrition might be considered to attenuate nutritional influences on obesity programming and curb the continuing rise in obesity rates.

scholarly journals Nutrient–nutrient interactions: competition, bioavailability, mechanism and function in health and diseases

2019 ◽  
Vol 78 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Emilie Combet ◽  
Stuart R. Gray
Keyword(s):  
Food Processing ◽  
Maternal Diet ◽  
Nutrient Status ◽  
Round Table ◽  
Nutrient Interactions ◽  
Short And Long Term ◽  
Dietary Components ◽  
And Function ◽  
The Impact

The Nutrition Society Spring Conference 2018, held in Glasgow, brought together experts focusing on the interaction between different nutrients and how this impacts absorption, metabolism and health from biochemical and physiological perspectives. This cross-cutting theme was examined from a range of perspectives, bringing together experts on topics ranging from food processing to the impact of inflammation on nutrient status. Two plenary lectures provided a food landscape and lifecourse background to the proceedings, with on the first day a focus on processed/ultra-processed foods and their nutrient composition and, on the second day, a plenary lecture exploring the role that nutrient–nutrient interactions within the maternal diet have for the lifelong health of the offspring. The meeting was framed around three symposia, examining the competition and bioavailability of dietary components, nutrient–nutrient interactions and their role in protection from chronic diseases and the mechanisms of nutrient–nutrient interactions. The meeting ended with a round table, and an overall conclusion highlighting the opportunities to derive further understanding of the short- and long-term implications of diets through the study of nutrient–nutrient interactions.

scholarly journals A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload

2008 ◽  
Vol 295 (6) ◽  
pp. H2495-H2502 ◽  
Author(s):  
Michael J. Raher ◽  
Helene B. Thibault ◽  
Emmanuel S. Buys ◽  
Darshini Kuruppu ◽  
Nobuyuki Shimizu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Myocardial Perfusion ◽  
Short Duration ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
High Fat ◽  
Lv Remodeling ◽  
And Function ◽  
The Impact

Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or a standard diet (SD) for 9 days and then underwent transverse aortic constriction (TAC). LV size and function were assessed in SD- and HFD-fed mice using serial echocardiography before and 7, 21, and 28 days after TAC. Serial echocardiography was also performed on nonoperated SD- and HFD-fed mice over a period of 6 wk. LV perfusion was assessed before and 7 and 28 days after TAC. Nine days of HFD induced systemic and myocardial insulin resistance (assessed by myocardial 18F-fluorodeoxyglucose uptake), and myocardial perfusion response to acetylcholine was impaired. High-fat feeding for 28 days did not change LV size and function in nonbanded mice; however, TAC induced greater hypertrophy, more marked LV systolic and diastolic dysfunction, and decreased survival in HFD-fed compared with SD-fed mice. Compared with SD-fed mice, myocardial perfusion reserve was decreased 7 days after TAC, and capillary density was decreased 28 days after TAC in HFD-fed mice. A short duration of HFD induces insulin resistance in mice. These metabolic changes are accompanied by increased LV remodeling and dysfunction after TAC, highlighting the impact of insulin resistance in the development of pressure-overload-induced heart failure.

Sign in / Sign up

Export Citation Format

Share Document