The impact of early life gut colonization on metabolic and obesogenic outcomes: what have animal models shown us?

The rise in the occurrence of obesity to epidemic proportions has made it a global concern. Great difficulty has been experienced in efforts to control this growing problem with lifestyle interventions. Thus, attention has been directed to understanding the events of one of the most critical periods of development, perinatal life. Early life adversity driven by maternal obesity has been associated with an increased risk of metabolic disease and obesity in the offspring later in life. Although a mechanistic link explaining the relationship between maternal and offspring obesity is still under investigation, the gut microbiota has come forth as a new factor that may play a role modulating metabolic function of both the mother and the offspring. Emerging evidence suggests that the gut microbiota plays a much larger role in mediating the risk of developing non-communicable disease, including obesity and metabolic dysfunction in adulthood. With the observation that the early life colonization of the neonatal and postnatal gut is mediated by the perinatal environment, the number of studies investigating early life gut microbial establishment continues to grow. This paper will review early life gut colonization in experimental animal models, concentrating on the role of the early life environment in offspring gut colonization and the ability of the gut microbiota to dictate risk of disease later in life.

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Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

Experimental Diabetes Research ◽

10.1155/2011/592408 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 96

Author(s):

M. Li ◽

D. M. Sloboda ◽

M. H. Vickers

Keyword(s):

Animal Models ◽

Early Life ◽

Metabolic Disorders ◽

Maternal Obesity ◽

Maternal Weight ◽

Critical Window ◽

Obesity Epidemic ◽

Obesity And Overweight ◽

Increased Risk ◽

Maternal Overnutrition

The incidence of obesity and overweight has reached epidemic proportions in the developed world as well as in those countries transitioning to first world economies, and this represents a major global health problem. Concern is rising over the rapid increases in childhood obesity and metabolic disease that will translate into later adult obesity. Although an obesogenic nutritional environment and increasingly sedentary lifestyle contribute to our risk of developing obesity, a growing body of evidence links early life nutritional adversity to the development of long-term metabolic disorders. In particular, the increasing prevalence of maternal obesity and excess maternal weight gain has been associated with a heightened risk of obesity development in offspring in addition to an increased risk of pregnancy-related complications. The mechanisms that link maternal obesity to obesity in offspring and the level of gene-environment interactions are not well understood, but the early life environment may represent a critical window for which intervention strategies could be developed to curb the current obesity epidemic. This paper will discuss the various animal models of maternal overnutrition and their importance in our understanding of the mechanisms underlying altered obesity risk in offspring.

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Inflammatory and Epigenetic Pathways for Perinatal Depression

Biological Research For Nursing ◽

10.1177/1099800415614892 ◽

2015 ◽

Vol 18 (3) ◽

pp. 331-343 ◽

Cited By ~ 14

Author(s):

Lindsey Garfield ◽

Herbert L. Mathews ◽

Linda Witek Janusek

Keyword(s):

Early Life ◽

Infant Health ◽

Perinatal Depression ◽

Life Experiences ◽

Perinatal Period ◽

Early Life Adversity ◽

Targeted Interventions ◽

Increased Risk ◽

History Of ◽

The Impact

Depression during the perinatal period is common and can have adverse consequences for women and their children. Yet, the biobehavioral mechanisms underlying perinatal depression are not known. Adverse early life experiences increase the risk for adult depression. One potential mechanism by which this increased risk occurs is epigenetic embedding of inflammatory pathways. The purpose of this article is to propose a conceptual model that explicates the linkage between early life adversity and the risk for maternal depression. The model posits that early life adversity embeds a proinflammatory epigenetic signature (altered DNA methylation) that predisposes vulnerable women to depression during pregnancy and the postpartum period. As proposed, women with a history of early life adversity are more likely to exhibit higher levels of proinflammatory cytokines and lower levels of oxytocin in response to the demands of pregnancy and new motherhood, both of which are associated with the risk for perinatal depression. The model is designed to guide investigations into the biobehavioral basis for perinatal depression, with emphasis upon the impact of early life adversity. Testing this model will provide a better understanding of maternal depressive risk and improve identification of vulnerable women who would benefit from targeted interventions that can reduce the impact of perinatal depression on maternal–infant health.

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Early life adversity, dispositional mindfulness, and longitudinal stress experience during the COVID-19 pandemic

10.31234/osf.io/5kt6z ◽

2020 ◽

Author(s):

Annika Benz ◽

Maria Meier ◽

Ulrike U. Bentele ◽

Stephanie J. Dimitroff ◽

Bernadette Denk ◽

...

Keyword(s):

Perceived Stress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Dispositional Mindfulness ◽

Early Life Adversity ◽

Stress Buffering ◽

Psychopathological Symptoms ◽

Increased Risk ◽

The Impact

Experiencing severe or prolonged stressors in early life is associated with increased risk for mental and physical disorders in adulthood. Further, individuals who experienced early life stress (ELS) may use dysfunctional coping strategies like stress-related eating, in contrast to more beneficial stress buffering mechanisms e.g. based on mindfulness. Whether these mechanisms contribute to increased levels of perceived stress and symptoms of mental disorders in individuals with ELS in times of crisis is yet unclear. As part of a larger project, we assessed changes in perceived stress and psychopathological symptoms in a sample of N=102 participants (81% female; meanage=23.49, SDage= 7.11, range 18–62) from October/December 2019 (prior to the Covid-19 pandemic) to April/June 2020 (after the German government introduced Covid-19 related restrictions). Additionally, we assessed ELS and dispositional mindfulness.Perceived stress and depression significantly increased while anxiety levels decreased. No significant change was observed for somatization. ELS and dispositional mindfulness were not associated with change scores, but with perceived stress and psychopathological symptoms at both assessments. The increase in perceived stress during the pandemic in a majority of participants demonstrates the impact of the pandemic in the general population.

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Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

10.31234/osf.io/7gcuw ◽

2020 ◽

Author(s):

Jamie Lars Hanson ◽

Brendon Nacewicz

Keyword(s):

Animal Models ◽

Early Life ◽

Allostatic Load ◽

Child Poverty ◽

Past Research ◽

Early Life Adversity ◽

Stress Buffering ◽

Behavioral Studies ◽

New Findings ◽

The Impact

Early life adversity (ELA), such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe integrative models of stress neurodevelopment, grounded in “allostatic load”, will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA.

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The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism

Bioscience Reports ◽

10.1042/bsr20171234 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 21

Author(s):

Liyuan Zhou ◽

Xinhua Xiao

Keyword(s):

Gut Microbiota ◽

Animal Studies ◽

Maternal Obesity ◽

Metabolic Diseases ◽

Microbial Colonization ◽

Global Epidemic ◽

Increased Risk ◽

Colonization Hypothesis ◽

The Impact

Obesity is considered a global epidemic. Specifically, obesity during pregnancy programs an increased risk of the offspring developing metabolic disorders in addition to the adverse effects on the mother per se. Large numbers of human and animal studies have demonstrated that the gut microbiota plays a pivotal role in obesity and metabolic diseases. Similarly, maternal obesity during pregnancy is associated with alterations in the composition and diversity of the intestine microbial community. Recently, the microbiota in the placenta, amniotic fluid, and meconium in healthy gestations has been investigated, and the results supported the “in utero colonization hypothesis” and challenged the traditional “sterile womb” that has been acknowledged worldwide for more than a century. Thus, the offspring microbiota, which is crucial for the immune and metabolic function and further health in the offspring, might be established prior to birth. As a detrimental intrauterine environment, maternal obesity influences the microbial colonization and increases the risk of metabolic diseases in offspring. This review discusses the role of the microbiota in the impact of maternal obesity during pregnancy on offspring metabolism and further analyzes related probiotic or prebiotic interventions to prevent and treat obesity and metabolic diseases.

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Pregnancy, obesity and insulin resistance: maternal overnutrition and the target windows of fetal development

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0029 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Beverly S. Muhlhausler ◽

Jessica R. Gugusheff ◽

Zhi Yi Ong ◽

Mini A. Vithayathil

Keyword(s):

Insulin Resistance ◽

Early Life ◽

Maternal Obesity ◽

Nutrient Supply ◽

Personal Perspective ◽

Human Populations ◽

Maternal Undernutrition ◽

Increased Risk ◽

Maternal Overnutrition ◽

The Impact

AbstractA substantial body of literature has demonstrated that the nutritional environment an individual experiences before birth or in early infancy is a key determinant of their health outcomes across the life course. This concept, the developmental origins of health and disease (DOHaD) hypothesis, was initially focused on the adverse consequences of exposure to a suboptimal nutrient supply and provided evidence that maternal undernutrition, fetal growth restriction, and low birth weight were associated with heightened risk of central adiposity, insulin resistance, and cardiovascular disease. More recently, the epidemic rise in the incidence of maternal obesity has seen the attention of the DOHaD field turn toward identifying the impact on the offspring of exposure to an excess nutrient supply in early life. The association between maternal obesity and increased risk of obesity in the offspring has been documented in human populations worldwide, and animal models have provided critical insights into the biological mechanisms that drive this relationship. This review will discuss the important roles that programming of the adipocyte and programming of the central neural networks which control appetite and reward play in the early life programming of metabolic disease by maternal overnutrition. It will also highlight the important research gaps and challenges that remain to be addressed and provide a personal perspective on where the field should be heading in the coming 5–10 years.

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Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.624705 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jamie L. Hanson ◽

Brendon M. Nacewicz

Keyword(s):

Animal Models ◽

Early Life ◽

Allostatic Load ◽

Child Poverty ◽

Past Research ◽

Early Life Adversity ◽

Stress Buffering ◽

Behavioral Studies ◽

New Findings ◽

The Impact

Early life adversity (ELA), such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe integrative models of stress neurodevelopment, grounded in “allostatic load,” will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA.

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Early-Life Development of the Bifidobacterial Community in the Infant Gut

International Journal of Molecular Sciences ◽

10.3390/ijms22073382 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3382

Author(s):

Silvia Saturio ◽

Alicja M. Nogacka ◽

Marta Suárez ◽

Nuria Fernández ◽

Laura Mantecón ◽

...

Keyword(s):

Gut Microbiota ◽

Gestational Age ◽

Early Life ◽

Feeding Habits ◽

Its Region ◽

23S Rrna ◽

Delivery Mode ◽

Short And Long Term ◽

Quantitative Changes ◽

The Impact

The establishment of the gut microbiota poses implications for short and long-term health. Bifidobacterium is an important taxon in early life, being one of the most abundant genera in the infant intestinal microbiota and carrying out key functions for maintaining host-homeostasis. Recent metagenomic studies have shown that different factors, such as gestational age, delivery mode, or feeding habits, affect the gut microbiota establishment at high phylogenetic levels. However, their impact on the specific bifidobacterial populations is not yet well understood. Here we studied the impact of these factors on the different Bifidobacterium species and subspecies at both the quantitative and qualitative levels. Fecal samples were taken from 85 neonates at 2, 10, 30, 90 days of life, and the relative proportions of the different bifidobacterial populations were assessed by 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing. Absolute levels of the main species were determined by q-PCR. Our results showed that the bifidobacterial population establishment is affected by gestational age, delivery mode, and infant feeding, as it is evidenced by qualitative and quantitative changes. These data underline the need for understanding the impact of perinatal factors on the gut microbiota also at low taxonomic levels, especially in the case of relevant microbial populations such as Bifidobacterium. The data obtained provide indications for the selection of the species best suited for the development of bifidobacteria-based products for different groups of neonates and will help to develop rational strategies for favoring a healthy early microbiota development when this process is challenged.

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