Epigenetic Mechanisms Link Maternal Diets and Gut Microbiome to Obesity in the Offspring

Li, Yuanyuan

doi:10.3389/fgene.2018.00342

Cited by 107 publications

(84 citation statements)

References 97 publications

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“…D11120103) or the HFD (Research Diets product no. D11120105) for [11][12][13][14][15] weeks. The contents of these diets (details provided in Supplementary Table 1, available on the Arthritis & Rheumatology web site at http://onlin elibr ary.wiley.com/doi/10.1002/art.41147/ abstract) have been reported previously (5).…”

Section: Methodsmentioning

confidence: 99%

Intergenerational Transmission of Diet‐Induced Obesity, Metabolic Imbalance, and Osteoarthritis in Mice

Harasymowicz

Choi

et al. 2020

Arthritis & Rheumatology

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Objective Obesity and osteoarthritis (OA) are 2 major public health issues affecting millions of people worldwide. Whereas parental obesity affects the predisposition to diseases such as cancer or diabetes in children, transgenerational influences on musculoskeletal conditions such as OA are poorly understood. This study was undertaken to assess the intergenerational effects of a parental/grandparental high‐fat diet on the metabolic and skeletal phenotype, systemic inflammation, and predisposition to OA in 2 generations of offspring in mice. Methods Metabolic phenotype and predisposition to OA were investigated in the first and second (F1 and F2) generations of offspring (n = 10–16 mice per sex per diet) bred from mice fed a high‐fat diet (HFD) or a low‐fat control diet. OA was induced by destabilizing the medial meniscus. OA, synovitis, and adipose tissue inflammation were determined histologically, while bone changes were measured using micro–computed tomography. Serum and synovial cytokines were measured by multiplex assay. Results Parental high‐fat feeding showed an intergenerational effect, with inheritance of increased weight gain (up to 19% in the F1 generation and 9% in F2), metabolic imbalance, and injury‐induced OA in at least 2 generations of mice, despite the fact that the offspring were fed the low‐fat diet. Strikingly, both F1 and F2 female mice showed an increased predisposition to injury‐induced OA (48% higher predisposition in F1 and 19% in F2 female mice fed the HFD) and developed bone microarchitectural changes that were attributable to parental and grandparental high‐fat feeding. Conclusion The results of this study reveal a detrimental effect of parental HFD and obesity on the musculoskeletal integrity of 2 generations of offspring, indicating the importance of further investigation of these effects. An improved understanding of the mechanisms involved in the transmissibility of diet‐induced changes through multiple generations may help in the development of future therapies that would target the effects of obesity on OA and related conditions.

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Section: Methodsmentioning

confidence: 99%

Intergenerational Transmission of Diet‐Induced Obesity, Metabolic Imbalance, and Osteoarthritis in Mice

Harasymowicz

Choi

et al. 2020

Arthritis & Rheumatology

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“…Epigenetic alterations include changes in DNA methylation, histone modification, and newly defined regulatory noncoding RNAs (ncRNAs). These changes may be retained by the cell throughout its lifespan and passed to future generations for germline cells [2]. Recently, more and more studies on epigenetics have demonstrated the importance of epigenetic regulation of gene expression in normal development, aging, and age-related diseases including OA [3].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Mechanisms Underlying the Aging of Articular Cartilage and Osteoarthritis

et al. 2019

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Aging is a progressive and complicated bioprocess with overall decline in physiological function. Osteoarthritis (OA) is the most common joint disease in middle-aged and older populations. Since the prevalence of OA increases with age and breakdown of articular cartilage is its major hallmark, OA has long been thought of as “wear and tear” of joint cartilage. Nevertheless, recent studies have revealed that changes in the chondrocyte function and matrix components may reduce the material properties of articular cartilage and predispose the joint to OA. The aberrant gene expression in aging articular cartilage that is regulated by various epigenetic mechanisms plays an important role in age-related OA pathogenesis. This review begins with an introduction to the current understanding of epigenetic mechanisms, followed by mechanistic studies on the aging of joint tissues, epigenetic regulation of age-dependent gene expression in articular cartilage, and the significance of epigenetic mechanisms in OA pathogenesis. Our recent findings on age-dependent expression of 2 transcription factors, nuclear factor of activated T cell 1 (NFAT1) and SOX9, and their roles in the formation and aging of articular cartilage are summarized in the review. Chondrocyte dysfunction in aged mice, which is mediated by epigenetically regulated spontaneous reduction of NFAT1 expression in articular cartilage, is highlighted as an important advance in epigenetics and cartilage aging. Potential therapeutic strategies for age-related cartilage degeneration and OA using epigenetic molecular tools are discussed at the end.

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“…However, this was not the case among this Afro-Caribbean cohort. Therefore, in addition to genetic factors [53], it is likely that cervicovaginal microbial communities are also influenced by geophysical environments and sub-culture factors acting upon host gene expression (analogous to the impact of diet on foetal/neonatal gut microbiome development) [54,55]. Based on our results, the highly diverse cervicovaginal microbiome of the Afro-Caribbean women is a reservoir of antibiotic resistance genes.…”

Section: Cervicovaginal Microbiome Of Afro-caribbean Womenmentioning

confidence: 63%

Structure and regulation of the cervicovaginal microbiome in a cohort of Afro-Caribbean women

Roachford¹,

Alleyne²,

Kuelbs³

et al. 2020

Preprint

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Background The cervicovaginal microbiome, with its well documented dynamic community state types (CSTs I-V) is known to interact with the host immune system in a complex regulatory ecosystem that guards against dysbiosis and invading pathogens. However, the regulatory mechanism of the cervicovaginal microbiome in vaginal eubiosis is not well understood. Therefore, we characterized the cervicovaginal microbiome in a cohort of Afro-Caribbean women to the species-strain taxonomic level using high-throughput targeted sequencing and shotgun metagenomics and conceptualized a hypothetical model that aids in understanding vaginal ecosystem regulation. Results Compared to targeted 16S rRNA V4 sequencing, whole genome shotgun (WGS) metagenomics offered greater species resolution of the cervicovaginal microbiome in the Afro-Caribbean women cohort. Community state type IV predominated in the microbiome of these women, with Prevotella (13.91%), Gardnerella (12.14%) and Lactobacillus (9.37%) being the three most abundant genera. For Prevotella and Lactobacillus the most abundant species-strains were P. timonensis DSM 22865 (5.0%) and L. iners DSM 13335 (7.0%), respectively. The less virulent strain of Gardnerella, G. vaginalis 409-05 (8.0%) was more abundant than G. vaginalis ATCC 14019 (4.0%). In the resistome, 2,753 antimicrobial resistance (AMR) genes consisting of 28 types (mostly tet and Emr; abundances 51% and 15%, respectively) which confer resistance to tetracyclines and the macrolide-lincosamide streptogramin B (MLSb phenotype) group were observed. Functional profiling showed a high abundance of biological processes (bacterial-type flagellum-dependent cell motility, cell adhesion, response to biotic stimulus and quorum sensing) associated with biofilm activity. Conclusions Characterized for the first time, the cervicovaginal microbiome in Afro-Caribbean women is predominantly CST IV with the three most abundant taxa consisting of bacterial strains P. timonensis DSM 22865, G. vaginalis 409-05 and L. iners DSM 13335. Its resistome had multiple AMR genes that confer resistance to antibiotics commonly used in the treatment of sexually transmitted infections (STIs) and bacterial vaginosis (BV). In this study, the occurrence of biofilm activity within the cervicovaginal microbiome suggested a possible regulatory role. We present a conceptual immuno-munibiome model that advances a mechanistic approach for the structure and regulation of the vaginal ecosystem in the Afro-Caribbean women cohort.

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Epigenetic Mechanisms Link Maternal Diets and Gut Microbiome to Obesity in the Offspring

Cited by 107 publications

References 97 publications

Intergenerational Transmission of Diet‐Induced Obesity, Metabolic Imbalance, and Osteoarthritis in Mice

Intergenerational Transmission of Diet‐Induced Obesity, Metabolic Imbalance, and Osteoarthritis in Mice

Epigenetic Mechanisms Underlying the Aging of Articular Cartilage and Osteoarthritis

Structure and regulation of the cervicovaginal microbiome in a cohort of Afro-Caribbean women

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