Prebiotic and Probiotic Regulation of Bone Health: Role of the Intestine and its Microbiome

McCabe, Laura R.; Britton, Robert A.; Parameswaran, Narayanan

doi:10.1007/s11914-015-0292-x

Cited by 189 publications

(141 citation statements)

References 76 publications

(105 reference statements)

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“…Consistent with this, Sjogren et al found that bacterial colonization of young adult GF animals resulted in loss of trabecular bone mass and an increase in bone-resorbing osteoclasts (13). However, other studies have suggested that treatment with beneficial microbes modestly increases bone mineral density (21)(22)(23)(24)(25)(26) and protects against bone loss after sex steroid deficiency (27). Discrepant results in studies examining the effect of microbiota on bone may reflect differences in the composition of the resident microbiota, age of the animal at colonization and necropsy, mouse strain, and sex.…”

mentioning

confidence: 87%

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

Yan

Herzog

Tsang

et al. 2016

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

558

531

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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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mentioning

confidence: 87%

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

Yan

Herzog

Tsang

et al. 2016

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

558

531

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“…Nevertheless, carrageenan-induced paw edema was not affected by the isolated harpagoside constituent. This signifies that harpagoside may not have an anti-inflammatory effect, at least in the dosage used in this study [70,71]. This suggests that other HP constituents may be responsible for the anti-inflammatory effect.…”

Section: Harpagophytum Procumbens Fam Pedaliaceaementioning

confidence: 79%

“…Importantly, dried plum is rich in soluble and insoluble fibers, including pectin, fructans, hemicelluloses, and cellulose [23,40], which are known to increase mineral absorption (e.g., calcium) [71]. For instance, fibers are fermented by colonic bacteria, resulting in the production of short-chain fatty acids (SCFA).…”

Section: Mdpimentioning

confidence: 99%

Dietary Bioactives and Bone Health

2018

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“…Exposure of weaning mice to antibiotics increases bone mass (15), suggesting that alteration of the normal microbiota may, in fact, recapitulate the beneficial skeletal actions of a germ-free environment. An alternative strategy in lieu of antibiotics would be to use probioticslive microorganisms that provide health benefits to the host (16). Probiotics have been long known to increase bone strength in chickens (17) and to improve eggshell hardness (16).…”

Section: Discussionmentioning

confidence: 99%

“…An alternative strategy in lieu of antibiotics would be to use probioticslive microorganisms that provide health benefits to the host (16). Probiotics have been long known to increase bone strength in chickens (17) and to improve eggshell hardness (16). Several other notable observations underscore the premise that altering the microbiota using probiotics can alter bone remodeling and/or bone mass in hypogonadal states.…”

Section: Discussionmentioning

confidence: 99%

From the gut to the strut: where inflammation reigns, bone abstains

Iqbal¹,

Yuen²,

Sun³

et al. 2016

Journal of Clinical Investigation

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C o m m e n t a r y2 0 4A new player in sex steroid deficiency-related bone lossOsteoporosis is a leading cause of morbidity in the increasing population of aging adults. In postmenopausal women, fracture incidence far exceeds the combined incidence of breast cancer, stroke, and myocardial infarction. Bone loss arises from accelerated resorption by osteoclasts, which outpaces the accompanying increase in bone formation by osteoblasts (1). Postmenopausal osteoporosis has traditionally been solely attributed to declining estrogen levels. However, the rapid loss of bone during the late perimenopausal transition, particularly when estrogen levels are relatively normal, is proposed to be mediated, at least in part, by rising follicle-stimulating hormone levels (FSH levels) (2, 3). Nonetheless, these hormonal changes do not fully explain the increased bone formation, high BM T cell counts, or macrophage activation that have been noted across the menopausal transition (4). Alterations in immune cell function have largely been attributed to increased production of TNFα, which further enhances osteoclast formation and function (5, 6). Consistent with this, ablation of the Tnfa gene in mice prevents gonadectomy-induced bone loss, osteoclast and osteoblast activation, and accompanying immune cell abberations (5). However, the mechanisms that drive TNFα production during hypogonadal states remain relatively unclear. In this issue, Li et al. (7) show that gut microbiota play a fundamental role in the enhanced TNFα production that occurs upon the induction of estrogen deficiency in mice. It has previously been shown that lowering the inflammatory burden does suppress the effects of estrogen deficiency. For example, TNFα or IL-1 blockade in early postmenopausal women decreases bone resorption markers (8). Likewise, mice in which Tnfa or Il6 is deleted are relatively resistant to ovariectomy-induced bone loss (9). Li et al. evaluated how gut microbiota contribute to the inflammation seen with estrogen deficiency by using a strategy in which mice raised in an environment devoid of gut bacterial colonization (germ-free mice) were chemically castrated with leuprolide (7). Impressively, these hypogonadal, germ-free mice did not experience the marked bone loss that occurred in hypogonadal mice with unperturbed gut flora. Likewise, osteoclast numbers were not increased in germ-free mice. Even more impressive was the observation that the reintroduction of flora into germ-free mice reversed the osteoprotection exerted by an absence of microbiota; this, in essence, proved a fundamental role for gut microbiota in regulating skeletal integrity. Mice raised in a germ-free environment are indeed known to have increased bone mass and fewer osteoclasts (10). The findings of Li et al. now suggest that the same pathways are responsible for the bone loss accompanying sex steroid deficiency. Germ-free mice maintain barrier functionWhat is the mechanism through which gut microbiota mediate bone loss during sex steroid deficiency? It is widely acce...

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Prebiotic and Probiotic Regulation of Bone Health: Role of the Intestine and its Microbiome

Cited by 189 publications

References 76 publications

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

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

Dietary Bioactives and Bone Health

From the gut to the strut: where inflammation reigns, bone abstains

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