Association between gut microbiota, bone metabolism, and fracture risk in postmenopausal Japanese women

Abstract

Introduction We investigated the relationship between gut microbiota composition and osteoporosis/fracture risk in Japanese postmenopausal women using 16S rRNA gene sequencing, FRAX, bone mineral density, biochemical bone parameters, and a self-administered questionnaire. Variation in abundance of specific microbiota was found to be significantly associated with fracture risk and vitamin K levels. Gut microbiota data with respect to bone metabolism and fracture risk is limited. Vitamin K is produced by certain intestinal bacteria and has been reported to play a role in maintaining bone quality. Purpose We investigated relationships among gut microbiota composition, bone metabolism, and fracture risk in postmenopausal Japanese women. Methods Bone mineral density (BMD) was evaluated in 38 postmenopausal women (mean age 62.9 years) using forearm dualenergy X-ray absorptiometry. We collected and analyzed serum bone turnover markers (vitamin K fraction and tartrate-resistant acid phosphatase 5b; TRACP-5b), gut microbiota profiling (16S rRNA gene sequencing), and self-administered questionnaire data, including fracture history and vitamin K intake. Vitamin K2, BMD, and TRACP-5b data were divided into high-and lowlevel groups using cutoff values of 0.06 ng/mL, 87.05%, and 420 mU/dL, respectively; the proportions of bacteria were analyzed. Fracture incidence and relative risk were investigated for each bacterium. Results The genus Bacteroides was predominant in the high vitamin K2 group (29.73% vs 21.58%, P = 0.022). Fracture incidence was significantly higher in the low Bacteroides group, with a 5.6-times higher risk ratio of fracture history. The family Rikenellaceae was more abundant in the low BMD group and more abundant in the high TRACP-5b group (2.15% vs 0.82%, P = 0.004; 2.38% vs 1.12%, P = 0.013, respectively). Conclusion Bacteroides and Rikenellaceae may be involved in bone metabolism and fracture risk. Further investigations of the underlying microbiota-related pathways in bone metabolism may reveal treatment strategies, and facilitate the prevention of osteoporosis.

Ultra-Processed Food Impairs Bone Quality, Increases Marrow Adiposity and Alters Gut Microbiome in Mice

“…Bacteroidetes phylum frequency was lower in all the experimental groups as reported upon consumption of HFD [ 45 ] and in the state of obesity [ 46 ]. In addition, bone fracture incidence is significantly higher in low Bacteroides subjects as reported previously [ 47 ]. Firmicutes phylum frequency was lower in the UPF group, similarly to patients with osteoporosis [ 48 ].…”

The Association Between Cholecystectomy and the Risk for Fracture: A Nationwide Population-Based Cohort Study in Korea

“…The association of gut microbiota with bone metabolism is further supported by studies demonstrating that antibiotic, probiotic, and prebiotic treatments impact gut microbiota composition and regulate bone metabolism (45). Similar results were demonstrated in human studies (46)(47)(48)(49). Considering this, alteration in gut microbiota caused by cholecystectomy could be associated with the increased fracture risk through bone mass regulation by immune system mediation, which in turn regulated osteoclastogenesis, thereby disturbing osteoblast' and osteoclast' activities.…”

Intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats

“…RANKL, a member of the TNF family, play a key role in osteoclast formation and induction of resorptive function [35]. In this study, it was found that the levels of serum CTX, P1NP and RANKL and TRAP5b in OVX group were signi cantly higher than those in Sham group after operation, which con rmed that estrogen de ciency accelerated bone turnover [36,37]. Moreover, we observed that the bone turnover indexes of IVPA group and EVPA group were signi cantly higher than that of OVX group.…”