The Human Gut Microbiota: A Key Mediator of Osteoporosis and Osteogenesis

Abstract

An expanding body of research asserts that the gut microbiota has a role in bone metabolism and the pathogenesis of osteoporosis. This review considers the human gut microbiota composition and its role in osteoclastogenesis and the bone healing process, specifically in the case of osteoporosis. Although the natural physiologic processes of bone healing and the pathogenesis of osteoporosis and bone disease are now relatively well known, recent literature suggests that a healthy microbiome is tied to bone homeostasis. Nevertheless, the mechanism underlying this connection is still somewhat enigmatic. Based on the literature, a relationship between the microbiome, osteoblasts, osteoclasts, and receptor activator of nuclear factor-kappa-Β ligand (RANKL) is contemplated and explored in this review. Studies have proposed various mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including micro-RNA, insulin-like growth factor 1, and immune system mediation. However, alterations to the gut microbiome secondary to pharmaceutical and surgical interventions cannot be discounted and are discussed in the context of clinical therapeutic consideration. The literature on probiotics and their mechanisms of action is examined in the context of bone healing. The known and hypothesized interactions of common osteoporosis drugs and the human gut microbiome are examined. Since dysbiosis in the gut microbiota can function as a biomarker of bone metabolic activity, it may also be a pharmacological and nutraceutical (i.e., pre- and probiotics) therapeutic target to promote bone homeostasis.

Dietary Resistant Starch From Potato Regulates Bone Mass by Modulating Gut Microbiota and Concomitant Short-Chain Fatty Acids Production in Meat Ducks

“…How do alterations in gut microbiota and concomitant SCFAs production induced by dietary RS promote bone mass? It was established that dysbiosis has been associated with bone loss in patients and experimentally ovariectomized rodent models ( 3 ) and manipulating intestinal microbiota via oral antibiotics and production germ-free mice could apparently affect bone quality in rodent models ( 6 , 23 ). In this study, along with the improvement of tibia strength, ash, and BV/TV of proximal bone, the dietary 12% RPS treatment significantly affected the microbial composition demonstrated by the higher proportion of Firmicutes and the lower the abundance of Bacteroidetes, which multiplied proven by our team previous studies ( 14 ).…”

“…In response to this, a complex interplay between pathological and nutritional factors contributes to the etiopathogenesis of leg abnormalities ( 2 ). Of note, gut microbiome dysbiosis has been observed in both osteoporosis patients and experimentally ovariectomized rodent models ( 3 ). Manipulating microbiota (e.g., establishing germ-free, oral antibiotics, probiotics, etc.)…”

Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis

“…GIT and bone tissue interact with one another through a complex network modulated by the gut microbiota, in which osteoblasts, osteoclasts, and receptor activator of nuclear factor kappa-Β ligand (RANKL) participate [ 123 ]. Recently, several studies have focused on establishing the role of the gut microbiota in the onset of osteoporosis, considering its modulation as a potential therapeutic strategy to reduce bone loss [ 124 , 125 , 126 ].…”

“…Recently, several studies have focused on establishing the role of the gut microbiota in the onset of osteoporosis, considering its modulation as a potential therapeutic strategy to reduce bone loss [ 124 , 125 , 126 ]. For instance, restoring gut microbiota eubiosis has positive effects on the treatment of dysbiosis-related extraintestinal disorders—for instance, in bones and muscles—such as osteoporosis, osteoarthritis, and sarcopenia [ 123 , 124 , 127 , 128 , 129 , 130 , 131 , 132 ]. In particular, gut microbiota modulation can be achieved primarily through diet, but also with probiotics, prebiotics, synbiotics (mixtures of probiotics and prebiotics that beneficially affect the host), postbiotics (bioactive compounds produced by food-grade microorganisms during fermentation), and obviously also by antibiotics and fecal microbiota transplantation (FMT) [ 132 , 133 , 134 , 135 ].…”

Bacterial Involvement in Progression and Metastasis of Colorectal Neoplasia

“…However, a relationship between gut microbiome dysbiosis and lung cancer has been established [ 232 ], suggesting that similar mechanisms may be at play. An increasing amount of literature shows important relationships between the gut microbiome and physiological processes in the body that involve anatomic sites of CRC metastasis such as brain [ 233 ], bone [ 234 ], and lung [ 232 ].…”