Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome

Ussar, Siegfried; Griffin, Nicholas W.; Bézy, Olivier; Fujisaka, Shiho; Vienberg, Sara G.; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I.; Kahn, C. Ronald

doi:10.1016/j.cmet.2015.07.007

Cited by 461 publications

(301 citation statements)

References 48 publications

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“…The upper airway has a rich microbial community dominated by bacteria from the Firmicute, Actinobacteria and Proteobacteria phyla,8 with the skin being home to mainly Actinobacteria, Proteobacteria and Firmicutes 2. Throughout life, diet9, 10 and host genetics11, 12 are thought to play a role in shaping microbiota composition, with infection13, 14, 15 and antibiotic treatment16, 17, 18, 19 being examples of major causes of microbiota disruption (dysbiosis).…”

Section: Introductionmentioning

confidence: 99%

The regulation of host defences to infection by the microbiota

Brown

Clarke

2016

Immunology

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SummaryThe skin and mucosal epithelia of humans and other mammals are permanently colonized by large microbial communities (the microbiota). Due to this life‐long association with the microbiota, these microbes have an extensive influence over the physiology of their host organism. It is now becoming apparent that nearly all tissues and organ systems, whether in direct contact with the microbiota or in deeper host sites, are under microbial influence. The immune system is perhaps the most profoundly affected, with the microbiota programming both its innate and adaptive arms. The regulation of immunity by the microbiota helps to protect the host against intestinal and extra‐intestinal infection by many classes of pathogen. In this review, we will discuss the experimental evidence supporting a role for the microbiota in regulating host defences to extra‐intestinal infection, draw together common mechanistic themes, including the central role of pattern recognition receptors, and outline outstanding questions that need to be answered.

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Section: Introductionmentioning

confidence: 99%

The regulation of host defences to infection by the microbiota

Brown

Clarke

2016

Immunology

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“…The changes in the metabolic phenotype could be associated with changes in specific bacterial taxa. Although facility-specific bacterial abundance increased in all models over time, the phenotype of the B6J strain remained fairly unaffected [3].…”

Section: Bbbmentioning

confidence: 96%

“…This commentary discusses two recent rodent studies on the potential importance of the intestinal microbiota in metabolic disease. Ussar and co-workers [3] studied the complex interaction between environmental and genetic factors in microbiota-related metabolic disease development in mice, while Perry and co-workers [4] investigated a potential mechanism underlying microbiota-driven disease development using a rat model.…”

Section: Bbbmentioning

confidence: 99%

“…The complexity and importance of factors that interact to determine intestinal microbiota composition and metabolic disease development was particularly illustrated in work from Ussar and co-workers [3]. The researchers assessed the longterm effects of environmental changes on the interaction between host genetics, microbiota composition and metabolic phenotype in three commonly used mouse models with differing susceptibility to high-fat diet (HFD)-induced obesity and diabetes.…”

Section: Bbbmentioning

confidence: 99%

“…Although there were no differences in weight gain between any of the recipient groups, these data indicate that vendor-based intestinal microbiota can transfer part of the glucose metabolic phenotype. Additionally, observations that genetically identical mice (the 129 models) have different responses to HFD feeding when raised in different facilities negatively impacts controllability and reproducibility of metabolic studies in rodents [3]. Although data from the studies performed by Ussar and coworkers clearly suggest that crosstalk between microbiota, host genetic background and dietary challenge plays a significant role in development of metabolic disease, mechanisms underlying these observations still need to be determined.…”

Section: Bbbmentioning

confidence: 99%

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Emerging role of intestinal microbiota and microbial metabolites in metabolic control

Herrema

IJzerman²,

Nieuwdorp

2016

Diabetologia

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The role of the intestinal microbiota and microbial metabolites in the maintenance of host health and development of metabolic disease has gained significant attention over the past decade. Mechanistic insight revealing causality, however, is scarce. Work by Ussar and co-workers demonstrates that a complex interaction between microbiota, host genetics and environmental factors is involved in metabolic disease development in mice. In addition, Perry and coworkers show that the microbial metabolite acetate augments insulin resistance in rats. These studies underscore an important role of the microbiota in the development of obesity and symptoms of type 2 diabetes in rodents. If causality can be demonstrated in humans, development of novel diagnostic and therapeutic tools that target the gut microbiota will have high potential.Keywords Gut microbiota . Insulin resistance . Obesity . Short-chain fatty acids . Type 2 diabetes Abbreviations BBB Blood-brain barrier FMT Faecal microbiota transfer GSIS Glucose-stimulated insulin secretion HFD High-fat diet ICV Intracerebroventricular SCFA Short-chain fatty acidThe symbiotic relationship with our intestinal microbiota is exemplified by a broad range of beneficial effects for the host metabolism, including digestion of complex carbohydrates and maturation of the immune response. In addition, the intestinal microbiota serves an endocrine role by producing a vast amount of metabolites with the potential to modulate host metabolism [1]. The intestinal microbiota has, as such, also been implicated in the development of obesity and type 2 diabetes in human and rodent models [2]. This adds another layer of complexity to studying the origin of these multifactorial metabolic pathologies that arise from a complicated interplay between genetic risk factors and external factors, including dietary intake and physical activity. This commentary discusses two recent rodent studies on the potential importance of the intestinal microbiota in metabolic disease. Ussar and co-workers [3] studied the complex interaction between environmental and genetic factors in microbiota-related metabolic disease development in mice, while Perry and co-workers [4] investigated a potential mechanism underlying microbiota-driven disease development using a rat model.Colonisation of the gastrointestinal tract starts as early as in utero [5], and a core microbiome composed mainly of Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria and Verrucomicrobia is established around the third year of life. Extrinsic factors, including host genetic makeup [6], cohousing/family members [7], oral antibiotic use early in life [8] and diet [9] are dominating factors in shaping the intestinal microbiota. Whether these early life events are determinants of microbiota-related disease in later life remains to be

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Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

Ross

Reveles

2020

American J Primatol

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Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition. K E Y W O R D S aging, fecal microbiota transplantation, gut microbiota, healthspan 1 | BACKGROUND In 2030, when the last baby boomer turns 65, one out of every five Americans (about 72 million people) will be 65 years or older (Centers for Disease & Prevention, 2003, 2015). This shift to an aged population is likely to increase overall economic burden, including costs of medical care and an increase in the percentage of the population not working (Dall et al., 2013; Weil, 1997). Due to the dynamic alteration of human population needs in the near future, aging researchers are no longer simply focused on extending human lifespan; they are interested in increasing quality of life, extending the length of time people are living independently, and overall healthspan for the aging population. Therefore, the focus of aging research has now shifted to treating aging as a systemic problem and determining whether an increase in lifespan alters the ability for that individual to remain disease free. The hope is that the treatment for multiple age-related diseases including diabetes, cardiovascular disease, Alzheimer's disease, dementia, and sarcopenia could be

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Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome

Cited by 461 publications

References 48 publications

The regulation of host defences to infection by the microbiota

The regulation of host defences to infection by the microbiota

Emerging role of intestinal microbiota and microbial metabolites in metabolic control

Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

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