Early Factors Leading to Later Obesity: Interactions of the Microbiome, Epigenome, and Nutrition

Chang, Lilly L; Neu, Josef

doi:10.1016/j.cppeds.2015.03.003

Cited by 32 publications

(28 citation statements)

References 47 publications

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“…Among such factors, nutrition, maternal obesity, delivery mode, intestinal permeability, pathogenic infections, and antibiotic use have been highlighted (270,(329)(330)(331). In addition, recent literature also implicates microbiota-related epigenetic changes during early development (332). Furthermore, the impact of gut microbiota on brain developmental programming of obesity has also been suggested (333).…”

Section: Metabolic Disordersmentioning

confidence: 99%

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota

Milani

Duranti

Bottacini

et al. 2017

Microbiol Mol Biol Rev

1,307

1,189

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The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease.

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Section: Metabolic Disordersmentioning

confidence: 99%

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota

Milani

Duranti

Bottacini

et al. 2017

Microbiol Mol Biol Rev

1,307

1,189

View full text Add to dashboard Cite

show abstract

“…The ontogenic periods, when developmentally programmed DNA methylation is being established, are vulnerable to environmental influences [ 14 ]. DNA methylation requires enzymes, DNA methyltransferases (DNMTs), and nutrition-dependent metabolic pathways that supply methyl groups [ 15 – 17 ]. It has become clear that postnatal establishment of gut microbiota plays a key role in several aspects of intestinal physiology, including morphological features [ 18 , 19 ], altered glycosylation patterns [ 20 – 22 ], and stem cell activity [ 23 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome

et al. 2015

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BackgroundDNA methylation is an epigenetic mechanism central to development and maintenance of complex mammalian tissues, but our understanding of its role in intestinal development is limited.ResultsWe use whole genome bisulfite sequencing, and find that differentiation of mouse colonic intestinal stem cells to intestinal epithelium is not associated with major changes in DNA methylation. However, we detect extensive dynamic epigenetic changes in intestinal stem cells and their progeny during the suckling period, suggesting postnatal epigenetic development in this stem cell population. We find that postnatal DNA methylation increases at 3′ CpG islands (CGIs) correlate with transcriptional activation of glycosylation genes responsible for intestinal maturation. To directly test whether 3′ CGI methylation regulates transcription, we conditionally disrupted two major DNA methyltransferases, Dnmt1 or Dnmt3a, in fetal and adult intestine. Deficiency of Dnmt1 causes severe intestinal abnormalities in neonates and disrupts crypt homeostasis in adults, whereas Dnmt3a loss was compatible with intestinal development. These studies reveal that 3′ CGI methylation is functionally involved in the regulation of transcriptional activation in vivo, and that Dnmt1 is a critical regulator of postnatal epigenetic changes in intestinal stem cells. Finally, we show that postnatal 3′ CGI methylation and associated gene activation in intestinal epithelial cells are significantly altered by germ-free conditions.ConclusionsOur results demonstrate that the suckling period is critical for epigenetic development of intestinal stem cells, with potential important implications for lifelong gut health, and that the gut microbiome guides and/or facilitates these postnatal epigenetic processes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0763-5) contains supplementary material, which is available to authorized users.

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“…It remains to be discovered which additional mechanisms and organ systems can additionally influence this process, e.g. the (maternal) intestine as the largest human immune organ or rather the microbiome, which is highly (epi-)genetically, transcriptionally, and metabolically active [46]. The role of the father is increasingly gaining attention among the scientific community since their epigenetic information can also be transferred, e.g.…”

Section: Selected Factors Of Molecular Biology and Geneticsmentioning

confidence: 99%

Metabolic Syndrome in Children and Adolescents

Gräf

Ferrari²

2016

Visc Med

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Background: Juvenile obesity is associated with multiple cardiometabolic comorbidities, which may culminate in the metabolic syndrome (MetS). Methods: Based on a narrative review, the current knowledge of prevalence and the underlying metabolic principles regarding juvenile obesity and MetS are summarized to compile up-to-date information. In addition, the role of lifestyle as well as positive and negative influencing factors are focused on. Results: The prevalence of MetS occurs between 1 and up to 23% in the total pediatric population and in up to 60% amongst the obese and overweight. It can be considered as the consequence of multiple processes in terms of lifestyle, perinatal programming, and (epi-)genetic pathways; however, the complex underlying mechanisms and their interplay are not completely understood. Conclusion: Besides preventive approaches, the growing number of obese children and youth as well as its consequences call for effective and lasting therapeutic measures.

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Early Factors Leading to Later Obesity: Interactions of the Microbiome, Epigenome, and Nutrition

Cited by 32 publications

References 47 publications

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota

Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome

Metabolic Syndrome in Children and Adolescents

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