The Role of Gut Microbiota in Bone Homeostasis

Overview

Journal Bone Joint Res

Date 2021 Jan 15

PMID 33448869

Citations 32

Authors

Jie Li

Wing Tung Percy Ho

Chaoran Liu

Simon Kwoon-Ho Chow

Margaret Ip

Jun Yu

Hei Sunny Wong

Wing-hoi Cheung

Joseph Jao Yiu Sung

Ronald Man Yeung Wong

Affiliations

Soon will be listed here.

Abstract

Aims: The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

Methods: Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted.

Results: A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss.

Conclusion: Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article: 2021;10(1):51-59.

Citing Articles

Gut microbiota and short-chain fatty acids signatures in postmenopausal osteoporosis patients: A retrospective study.

Li S, Wang J, Zhang Y, Wang J, Zhou T, Xie Y Medicine (Baltimore). 2025; 103(47):e40554.

PMID: 39809201 PMC: 11596502. DOI: 10.1097/MD.0000000000040554.

Gut microbiome and bone health: update on mechanisms, clinical correlations, and possible treatment strategies.

Ticinesi A, Siniscalchi C, Meschi T, Nouvenne A Osteoporos Int. 2024; 36(2):167-191.

PMID: 39643654 DOI: 10.1007/s00198-024-07320-0.

Gut microbiota alterations in adolescent idiopathic scoliosis: a comparison study with healthy control and congenital scoliosis.

Fang Y, Tian Z, Li W, Li D, Li J, Hu Z Spine Deform. 2024; 13(2):497-507.

PMID: 39438431 DOI: 10.1007/s43390-024-00988-8.

Integrated metagenomic and metabonomic mechanisms for the therapeutic effects of Duhuo Jisheng decoction on intervertebral disc degeneration.

Song C, Liu F, Mei Y, Cai W, Cheng K, Guo D PLoS One. 2024; 19(10):e0310014.

PMID: 39418241 PMC: 11486403. DOI: 10.1371/journal.pone.0310014.

Dihydromyricetin ameliorate postmenopausal osteoporosis in ovariectomized mice: Integrative microbiomic and metabolomic analysis.

Xu L, Sun X, Han X, Li H, Li X, Zhu L Front Pharmacol. 2024; 15:1452921.

PMID: 39415843 PMC: 11479887. DOI: 10.3389/fphar.2024.1452921.

References

Quach D, Britton R . Gut Microbiota and Bone Health. Adv Exp Med Biol. 2017; 1033:47-58. DOI: 10.1007/978-3-319-66653-2_4. View

Zaiss M, Jones R, Schett G, Pacifici R . The gut-bone axis: how bacterial metabolites bridge the distance. J Clin Invest. 2019; 129(8):3018-3028. PMC: 6668676. DOI: 10.1172/JCI128521. View

Latorre J, Hernandez-Velasco X, Bielke L, Vicente J, Wolfenden R, Menconi A . Evaluation of a Bacillus direct-fed microbial candidate on digesta viscosity, bacterial translocation, microbiota composition and bone mineralisation in broiler chickens fed on a rye-based diet. Br Poult Sci. 2015; 56(6):723-32. DOI: 10.1080/00071668.2015.1101053. View

Quach D, Collins F, Parameswaran N, McCabe L, Britton R . Microbiota Reconstitution Does Not Cause Bone Loss in Germ-Free Mice. mSphere. 2018; 3(1). PMC: 5750390. DOI: 10.1128/mSphereDirect.00545-17. View

Nilsson A, Sundh D, Backhed F, Lorentzon M . Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018; 284(3):307-317. DOI: 10.1111/joim.12805. View

Sjogren K, Engdahl C, Henning P, Lerner U, Tremaroli V, Lagerquist M . The gut microbiota regulates bone mass in mice. J Bone Miner Res. 2012; 27(6):1357-67. PMC: 3415623. DOI: 10.1002/jbmr.1588. View

Xie X, Liu M, Meng Q . Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res. 2019; 8(7):323-332. PMC: 6691372. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2. View

Latorre J, Hernandez-Velasco X, Vicente J, Wolfenden R, Hargis B, Tellez G . Effects of the inclusion of a Bacillus direct-fed microbial on performance parameters, bone quality, recovered gut microflora, and intestinal morphology in broilers consuming a grower diet containing corn distillers dried grains with solubles. Poult Sci. 2017; 96(8):2728-2735. PMC: 5850462. DOI: 10.3382/ps/pex082. View

Schepper J, Collins F, Rios-Arce N, Raehtz S, Schaefer L, Gardinier J . Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption. J Bone Miner Res. 2019; 34(4):681-698. PMC: 6557403. DOI: 10.1002/jbmr.3635. View

10.

Ohlsson C, Nigro G, Gomperts Boneca I, Backhed F, Sansonetti P, Sjogren K . Regulation of bone mass by the gut microbiota is dependent on NOD1 and NOD2 signaling. Cell Immunol. 2017; 317:55-58. DOI: 10.1016/j.cellimm.2017.05.003. View

11.

Lucas S, Omata Y, Hofmann J, Bottcher M, Iljazovic A, Sarter K . Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun. 2018; 9(1):55. PMC: 5754356. DOI: 10.1038/s41467-017-02490-4. View

12.

Xiao L, Feng Q, Liang S, Sonne S, Xia Z, Qiu X . A catalog of the mouse gut metagenome. Nat Biotechnol. 2015; 33(10):1103-8. DOI: 10.1038/nbt.3353. View

13.

Wang J, Wang Y, Gao W, Wang B, Zhao H, Zeng Y . Diversity analysis of gut microbiota in osteoporosis and osteopenia patients. PeerJ. 2017; 5:e3450. PMC: 5474093. DOI: 10.7717/peerj.3450. View

14.

Tanabe K, Nakamura S, Moriyama-Hashiguchi M, Kitajima M, Ejima H, Imori C . Dietary Fructooligosaccharide and Glucomannan Alter Gut Microbiota and Improve Bone Metabolism in Senescence-Accelerated Mouse. J Agric Food Chem. 2019; 67(3):867-874. DOI: 10.1021/acs.jafc.8b05164. View

15.

Ohlsson C, Sjogren K . Effects of the gut microbiota on bone mass. Trends Endocrinol Metab. 2014; 26(2):69-74. DOI: 10.1016/j.tem.2014.11.004. View

16.

Mariat D, Firmesse O, Levenez F, Guimaraes V, Sokol H, Dore J . The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 2009; 9:123. PMC: 2702274. DOI: 10.1186/1471-2180-9-123. View

17.

Khosla S, Hofbauer L . Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 2017; 5(11):898-907. PMC: 5798872. DOI: 10.1016/S2213-8587(17)30188-2. View

18.

Tellez G, Latorre J, Kuttappan V, Kogut M, Wolfenden A, Hernandez-Velasco X . Utilization of rye as energy source affects bacterial translocation, intestinal viscosity, microbiota composition, and bone mineralization in broiler chickens. Front Genet. 2014; 5:339. PMC: 4174888. DOI: 10.3389/fgene.2014.00339. View

19.

Britton R, Irwin R, Quach D, Schaefer L, Zhang J, Lee T . Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized mouse model. J Cell Physiol. 2014; 229(11):1822-30. PMC: 4129456. DOI: 10.1002/jcp.24636. View

20.

Conley M, Roberts C, Sharpton T, Iwaniec U, Hord N . Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats. Mol Nutr Food Res. 2017; 61(5). PMC: 5434898. DOI: 10.1002/mnfr.201600372. View