The Role of the Gut Microbiota on Bone Mass in Health and Disease

Editorial

05 January 2024

Editorial: The role of the gut microbiota on bone mass in health and disease

Sadiq Umar

Owen Cronin

and

Abdul Malik Tyagi

1,753 views

0 citations

Editors

Abdul Malik Tyagi

Central Drug Research Institute (CSIR)

Sadiq Umar

University of Illinois Chicago

Owen Cronin

Bon Secours Hospital Cork

Impact

Average composition of the (A) Class (B) Family (C) Genus (D) Species. Differences in gut microbiota at the (E) Family (F) Genus (G) Species levels. In the column diagram, the red bar represents Sham, the light blue bar represents OVX, the green bar represents EE-L, and the dark blue bar represents EE-H. *p<0.05, **p<0.01.

Original Research

07 November 2023

Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota

Tianyu Zhou

, 6 more and

Ping Sun

2,177 views

4 citations

Review

17 October 2023

Exploring the mechanism of traditional Chinese medicine in regulating gut-derived 5-HT for osteoporosis treatment

Kai Sun

, 6 more and

Xilin Xu

2,753 views

3 citations

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.

Review

09 October 2023

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

Stacyann Bailey

and

Keith Fraser

3,402 views

0 citations

Original Research

14 August 2023

Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study

Shuai Chen

, 3 more and

Zhiwei Li

Background: Recent studies have reported that the gut microbiota is essential for preventing and delaying the progression of osteoporosis. Nonetheless, the causal relationship between the gut microbiota and the risk of osteoporosis has not been fully revealed.

Methods: A two-sample Mendelian randomization (MR) analysis based on a large-scale genome-wide association study (GWAS) was conducted to investigate the causal relationship between the gut microbiota and bone mineral density (BMD). Instrumental variables for 211 gut microbiota taxa were obtained from the available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. The summary-level data for BMD were from the Genetic Factors for Osteoporosis (GEFOS) Consortium, which involved a total of 32,735 individuals of European ancestry. The inverse variance-weighted (IVW) method was performed as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses by using multiple methods. Finally, a reverse MR analysis was applied to evaluate reverse causality.

Results: According to the IVW method, we found that nine, six, and eight genetically predicted gut microbiota were associated with lumbar spine (LS) BMD, forearm (FA) BMD, and femoral neck (FN) BMD, respectively. Among them, the higher genetically predicted Genus Prevotella9 level was correlated with increased LS-BMD [β = 0.125, 95% confidence interval (CI): 0.050–0.200, P = 0.001] and FA-BMD (β = 0.129, 95% CI: 0.007–0.251, P = 0.039). The higher level of genetically predicted Family Prevotellaceae was associated with increased FA-BMD (β = 0.154, 95% CI: 0.020–0.288, P = 0.025) and FN-BMD (β = 0.080, 95% CI: 0.015–0.145, P = 0.016). Consistent directional effects for all analyses were observed in both the MR-Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on BMD (P > 0.05). In reverse MR analysis, there was no evidence of reverse causality between LS-BMD, FA-BMD, and FN-BMD and gut microbiota (P > 0.05).

Conclusion: Genetic evidence suggested a causal relationship between the gut microbiota and BMD and identified specific bacterial taxa that regulate bone mass variation. Further exploration of the potential microbiota-related mechanisms of bone metabolism might provide new approaches for the prevention and treatment of osteoporosis.

5,489 views

15 citations

Identical criteria were applied to exclusions of samples from the Framingham Heart Study and the Osteoporotic Fractures in Men Study cohorts including participants who reported use of antibiotics within 30 days of collection, a history of colon surgery in the year prior to collection, and samples from individuals lacking covariate data.

Original Research

21 September 2023

A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength

Paul C. Okoro

, 12 more and

Douglas P. Kiel

12,013 views

4 citations

Review

09 March 2023

Effect of Bifidobacterium on osteoclasts: TNF-α/NF-κB inflammatory signal pathway-mediated mechanism

Yue Wu

, 6 more and

Qiu Chen

The interaction between RANK and RANKL (which can exacerbate this effect in the presence of M-CSF) promotes the recruitment of the TRAF family bridging proteins, one of which TRAF6 contributes to OC formation and activation of the NF-κB signaling pathway, leading to the transcription of genes involved in OC formation and OC production. OPG is a decoy receptor that binds RANKL and can block the binding and activation of RANK and RANKL, reducing OC production. TNF-α/NF-κB is an inflammatory signaling pathway. In the presence of TNF-α, NF-κB pathway is activated, OC production is increased, and the interaction between RANKL and RANK is enhanced, which results in activation of the downstream signaling pathways. In addition to the above-mentioned effects, TNF-α also synergizes with RANKL and directly promotes OC production. In the presence of RANKL and M-CSF, the expression of genes involved in OC formation leading to the development of mature OC.

Osteoporosis is a systemic multifactorial bone disease characterized by low bone quality and density and bone microstructure damage, increasing bone fragility and fracture vulnerability. Increased osteoclast differentiation and activity are important factors contributing to bone loss, which is a common pathological manifestation of bone diseases such as osteoporosis. TNF-a/NF-κB is an inflammatory signaling pathway with a key regulatory role in regulating osteoclast formation, and the classical pathway RANKL/RANK/OPG assists osteoclast formation. Activation of this inflammatory pathway promotes the formation of osteoclasts and accelerates the process of osteoporosis. Recent studies and emerging evidence have consistently demonstrated the potential of probiotics to modulate bone health. Secretions of Bifidobacterium, a genus of probiotic bacteria in the phylum Actinobacteria, such as short-chain fatty acids, equol, and exopolysaccharides, have indicated beneficial effects on bone health. This review discusses the molecular mechanisms of the TNF-a/NF-κB inflammatory pathway in regulating osteoclast formation and describes the secretions produced by Bifidobacterium and their potential effects on bone health through this pathway, opening up new directions for future research.

6,712 views

29 citations