The intestinal microbiome and skeletal fitness: Connecting bugs and bones

Charles, Julia F.; Ermann, Joerg; Aliprantis, Antonios O.

doi:10.1016/j.clim.2015.03.019

Cited by 55 publications

(50 citation statements)

References 66 publications

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“…Disturbances in the microbiome have been suggested to play a role in the pathogenesis of metabolic disorders and the composition of gut microbes is strongly influenced by diet 23 . Further, gut microbes influence gut motility and absorption of nutrients, thus an unbalanced microbiome may result in reduced absorption of vitamin D. There is also the role of the microbiome in development and maintenance of the immune system 24 . A disruption of the microbiome that alters immune function may also alter immune cell requirements or use of vitamin D.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting

Kimball

Mirhosseini

Holick

2017

Dermato-Endocrinology

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Supplementation by the general public with vitamin D at doses above the Tolerable Upper Level of Intake (UL) is becoming quite common. The objective of the current analysis was to characterize the effect of vitamin D supplementation at doses up to 15,000 IU/d in a community-based program on vitamin D status, calcium homeostasis as well as on kidney, liver and immune function. We evaluated data collected for 3,882 participants in a community program for whom there were blood measurements at program entry and at follow-up within 6–18 months between 2013 and 2015. Participants were supplemented with a wide range of vitamin D doses (1,000 – 15,000 IU/d) aimed at achieving serum 25-hydroxyvitamin D [25(OH)D] levels of at least 100 nmol/L. Serum 25(OH)D concentrations up to 300 nmol/L were achieved without perturbation of calcium homeostasis or incidence of toxicity. Hypercalcemia and hypercalciuria were not related to an increase in 25(OH)D concentrations nor vitamin D dose. To achieve serum 25(OH)D levels >100 nmol/L on average, required vitamin D intakes of 6,000 IU/d for normal Body Mass Index (BMI), 7,000 IU/d for overweight and 8,000 IU/d for obese. Doses of vitamin D in excess of 6,000 IU/d were required to achieve serum 25(OH)D concentrations above 100 nmol/L, especially in individuals who were overweight or obese without any evidence of toxicity. Serum 25(OH)D concentrations up to 300 nmol/L were found to be safe.

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Section: Discussionmentioning

confidence: 99%

Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting

Kimball

Mirhosseini

Holick

2017

Dermato-Endocrinology

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“…In the last decade, there have been significant advances in our understanding of how this diverse set of gene products shapes physiology, including well-documented effects on host systemic immune function and metabolic parameters, including body weight and systemic insulin resistance 123 . Increasingly, evidence suggests that bone health is also impacted by gut microbiota 4 . Investigation of the impact of gut microbiota on bone physiology primarily involves studies performed in mice, utilizing either germ-free (GF) mice or manipulation of the gut microbiota in conventionally raised mice.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiome and Bone: to Build, Destroy, or Both?

Yan

Charles

2017

Curr Osteoporos Rep

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Purpose of the Review The gut microbiota can be considered a hidden organ that plays essential roles in host homeostasis. Exploration of the effects of microbiota on bone have just begun. Complimentary studies using germ-free mice, antibiotic and probiotic treatments reveal a complicated relationship between microbiota and bone. Here we review recent reports addressing the effect of gut microbiota on bone health, discuss potential reasons for discrepant findings, and explore potential mechanisms for these effects. Recent findings Manipulation of microbiota by colonization of germ free mice, antibiotics or probiotic supplementation significantly alters bone remodeling, bone development and growth, as well as bone mechanical strength. Different experimental models reveal context dependent effects of gut microbiota on bone. Summary By examining phenotypic effects, experimental context and proposed mechanisms, revealed by recent reports, we hope to provide comprehensive and fresh insights into the many facets of microbiota and bone interactions.

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“…If resorption outpaces formation, the net effect is catabolic. Hormonal, immune, and metabolic pathways all affect this balance, and the gut microbiota could affect any of these pathways (19). Bone mass is the major determinant of fracture risk with aging (19), and a better understanding of how gut microbiota affect bone remodeling in adults may lead to new therapeutic approaches.…”

mentioning

confidence: 99%

Gut microbiota induce IGF-1 and promote bone formation and growth

Yan

Herzog

Tsang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.

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The intestinal microbiome and skeletal fitness: Connecting bugs and bones

Cited by 55 publications

References 66 publications

Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting

Evaluation of vitamin D3 intakes up to 15,000 international units/day and serum 25-hydroxyvitamin D concentrations up to 300 nmol/L on calcium metabolism in a community setting

Gut Microbiome and Bone: to Build, Destroy, or Both?

Gut microbiota induce IGF-1 and promote bone formation and growth

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