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Review
. 2023 Oct 9:14:1229796.
doi: 10.3389/fendo.2023.1229796. eCollection 2023.

Advancing our understanding of the influence of drug induced changes in the gut microbiome on bone health

Stacyann Bailey  1   2 , Keith Fraser  3   4
Affiliations
Review

Advancing our understanding of the influence of drug induced changes in the gut microbiome on bone health

Stacyann Bailey et al. Front Endocrinol (Lausanne). .

Abstract

The gut microbiome has been implicated in a multitude of human diseases, with emerging evidence linking its microbial diversity to osteoporosis. This review article will explore the molecular mechanisms underlying perturbations in the gut microbiome and their influence on osteoporosis incidence in individuals with chronic diseases. The relationship between gut microbiome diversity and bone density is primarily mediated by microbiome-derived metabolites and signaling molecules. Perturbations in the gut microbiome, induced by chronic diseases can alter bacterial diversity and metabolic profiles, leading to changes in gut permeability and systemic release of metabolites. This cascade of events impacts bone mineralization and consequently bone mineral density through immune cell activation. In addition, we will discuss how orally administered medications, including antimicrobial and non-antimicrobial drugs, can exacerbate or, in some cases, treat osteoporosis. Specifically, we will review the mechanisms by which non-antimicrobial drugs disrupt the gut microbiome's diversity, physiology, and signaling, and how these events influence bone density and osteoporosis incidence. This review aims to provide a comprehensive understanding of the complex interplay between orally administered drugs, the gut microbiome, and osteoporosis, offering new insights into potential therapeutic strategies for preserving bone health.

Keywords: Osteoporosis management; bone mineralization; microbiome and health; microbiome-derived metabolites; pharmacomicrobiomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic of the physiological impact of dysbiosis in the gut microbiome in humans. Shown here is the ability of molecules produced in the gut to influence neurodevelopmental, neurodegenerative, metabolic, cardiovascular, and inflammatory disease states.
Figure 2
Figure 2
Several factors including diet, pharmaceutical use, pre- and probiotic consumption and fecal microbial transplant (FMT) influence the composition, diversity, and metabolic profile of microorganisms present in the gut microbiome. As the organismal mix and metabolic landscape in the gut microbiome shifts the permeability of the intestinal lining becomes compromised, gut metabolites and signaling molecules enter into systemic circulation and perturb immune signaling. Collectively these changes accelerate bone resorption that is the hallmark of osteoporosis.
Figure 3
Figure 3
Dysbiosis in the gut microbiome induces the production of multiple pro-inflammatory cytokines such as TNF-α, IL-6, IL-17 amongst others. The availability of these inflammatory molecules and activated T cells inhibit Tregs and their production of cytokines such as TGF-β and IL-10 that reduce bone loss. Lastly, antigens that are produced in the gut microbiome can perturb the normal regulatory function of the immune system and stimulate autoimmune activity.
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