Skip to main content

Advertisement

SpringerLink
Log in

Gut Microbiota Dysbiosis as One Cause of Osteoporosis by Impairing Intestinal Barrier Function

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Gut microbiota (GM) dysbiosis is closely related to several metabolic diseases such as hypertension, obesity, and Alzheimer’s disease. However, little is known about the causal relationship between GM dysbiosis and osteoporosis. In our work, 32 3-month-old female SD rats were randomly divided into two groups: the fecal microbiota transplantation (FMT) group and the control group. The supernatant of feces from senile osteoporotic rats was transplanted to the FMT group and the same amount of sterile saline was given to the control rats. After 12 and 24 weeks, all rats were sacrificed, and the serum, bone, fecal feces, and intestine tissue were collected for the subsequent analysis. The osteocalcin (OC), CTX, and P1NP of the FMT group increased significantly at 12 and 24 weeks compared with the control group (P < 0.05). Furthermore, the BV, BV/TV, Tb.N, and Tb.Th decreased significantly in the FMT group (P < 0.05). The alpha diversity (ACE, Chao) of the FMT group was higher than the control at 24 weeks (P < 0.05). The beta diversity was close between the FMT rats and the donor rats. In addition, GM from donor rats changed the GM composition and function of the FMT rats, which was similar to that of the donor rats at 24 weeks. The impaired intestinal structure and the decreased expression of occludin, claudin, and ZO-1 were found in FMT rats. In conclusion, GM dysbiosis by transferring the feces from senile osteoporotic rats to young rats could induce osteoporosis. The changed GM and the impaired intestinal barrier contributed to the pathogenesis of osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ensrud KE, Crandall CJ (2017) Osteoporosis. Ann Intern Med 167:ITC17–ITC32. https://doi.org/10.7326/AITC201708010

    Article  PubMed  Google Scholar 

  2. Brown C (2017) Osteoporosis: staying strong. Nature 550:S15–S17. https://doi.org/10.1038/550S15a

    Article  CAS  PubMed  Google Scholar 

  3. Riggs BL, Melton LJ (1983) Evidence for two distinct syndromes of involutional osteoporosis. Am J Med 75:899–901. https://doi.org/10.1016/0002-9343(83)90860-4

    Article  CAS  PubMed  Google Scholar 

  4. Voreades N, Kozil A, Weir TL (2014) Diet and the development of the human intestinal microbiome. Front Microbiol 5:494. https://doi.org/10.3389/fmicb.2014.00494

    Article  PubMed  PubMed Central  Google Scholar 

  5. Abenavoli L, Scarpellini E, Colica C et al (2019) Gut microbiota and obesity: a role for probiotics. Nutrients. https://doi.org/10.3390/nu11112690

    Article  PubMed  PubMed Central  Google Scholar 

  6. Benakis C, Brea D, Caballero S et al (2016) Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med 22:516–523. https://doi.org/10.1038/nm.4068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gurung M, Li Z, You H et al (2020) Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine 51:102590. https://doi.org/10.1016/j.ebiom.2019.11.051

    Article  PubMed  PubMed Central  Google Scholar 

  8. Liu F, Fan C, Zhang L et al (2020) Alterations of gut microbiome in Tibetan patients with coronary heart disease. Front Cell Infect Microbiol 10:373. https://doi.org/10.3389/fcimb.2020.00373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sjögren K, Engdahl C, Henning P et al (2012) The gut microbiota regulates bone mass in mice. J Bone Miner Res 27:1357–1367. https://doi.org/10.1002/jbmr.1588

    Article  CAS  PubMed  Google Scholar 

  10. Yan J, Herzog JW, Tsang K et al (2016) Gut microbiota induce IGF-1 and promote bone formation and growth. Proc Natl Acad Sci USA 113:E7554–E7563. https://doi.org/10.1073/pnas.1607235113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schwarzer M, Makki K, Storelli G et al (2016) Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science 351:854–857. https://doi.org/10.1126/science.aad8588

    Article  CAS  PubMed  Google Scholar 

  12. Ma S, Qin J, Hao Y et al (2020) Structural and functional changes of gut microbiota in ovariectomized rats and their correlations with altered bone mass. Aging (Albany NY). https://doi.org/10.18632/aging.103290

    Article  PubMed Central  Google Scholar 

  13. Ma S, Qin J, Hao Y, Fu L (2020) Association of gut microbiota composition and function with an aged rat model of senile osteoporosis using 16S rRNA and metagenomic sequencing analysis. Aging (Albany NY). https://doi.org/10.18632/aging.103293

    Article  PubMed Central  Google Scholar 

  14. Wang J, Wang Y, Gao W et al (2017) Diversity analysis of gut microbiota in osteoporosis and osteopenia patients. PeerJ 5:e3450. https://doi.org/10.7717/peerj.3450

    Article  PubMed  PubMed Central  Google Scholar 

  15. Li C, Huang Q, Yang R et al (2019) Gut microbiota composition and bone mineral loss-epidemiologic evidence from individuals in Wuhan, China. Osteoporos Int 30:1003–1013. https://doi.org/10.1007/s00198-019-04855-5

    Article  CAS  PubMed  Google Scholar 

  16. Das M, Cronin O, Keohane DM et al (2019) Gut microbiota alterations associated with reduced bone mineral density in older adults. Rheumatology (Oxford) 58:2295–2304. https://doi.org/10.1093/rheumatology/kez302

    Article  Google Scholar 

  17. Xu Z, Xie Z, Sun J et al (2020) Gut microbiome reveals specific dysbiosis in primary osteoporosis. Front Cell Infect Microbiol 10:160. https://doi.org/10.3389/fcimb.2020.00160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. He J, Xu S, Zhang B et al (2020) Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis. Aging (Albany NY). https://doi.org/10.18632/aging.103168

    Article  PubMed Central  Google Scholar 

  19. Chen C, Ahn EH, Kang SS et al (2020) Gut dysbiosis contributes to amyloid pathology, associated with C/EBPβ/AEP signaling activation in Alzheimer’s disease mouse model. Sci Adv 6:eaba0466. https://doi.org/10.1126/sciadv.aba0466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ma C, Sun Z, Zeng B et al (2018) Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis. Microbiome 6:200. https://doi.org/10.1186/s40168-018-0578-1

    Article  PubMed  PubMed Central  Google Scholar 

  21. Li J, Zhao F, Wang Y et al (2017) Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 5:14. https://doi.org/10.1186/s40168-016-0222-x

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gomes AC, Hoffmann C, Mota JF (2018) The human gut microbiota: metabolism and perspective in obesity. Gut Microbes 9:308–325. https://doi.org/10.1080/19490976.2018.1465157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chang C-J, Lin C-S, Lu C-C et al (2015) Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun 6:7489. https://doi.org/10.1038/ncomms8489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fu L, Wu W, Sun X, Zhang P (2020) Glucocorticoids enhanced osteoclast autophagy through the PI3K/Akt/mTOR signaling pathway. Calcif Tissue Int 107:60–71. https://doi.org/10.1007/s00223-020-00687-2

    Article  CAS  PubMed  Google Scholar 

  25. Quast C, Pruesse E, Yilmaz P et al (2013) The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 41:D590-596. https://doi.org/10.1093/nar/gks1219

    Article  CAS  Google Scholar 

  26. Li L, Li X, Zhong W et al (2019) Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice. EBioMedicine 48:301–315. https://doi.org/10.1016/j.ebiom.2019.09.021

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zhu Y, He C, Li X et al (2019) Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice. J Gastroenterol 54:347–358. https://doi.org/10.1007/s00535-018-1529-0

    Article  CAS  PubMed  Google Scholar 

  28. Kelly JR, Borre Y, O’Brien C et al (2016) Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 82:109–118. https://doi.org/10.1016/j.jpsychires.2016.07.019

    Article  PubMed  Google Scholar 

  29. Matsuoka K, Kanai T (2015) The gut microbiota and inflammatory bowel disease. Semin Immunopathol 37:47–55. https://doi.org/10.1007/s00281-014-0454-4

    Article  CAS  PubMed  Google Scholar 

  30. Bostanciklioğlu M (2019) The role of gut microbiota in pathogenesis of Alzheimer’s disease. J Appl Microbiol 127:954–967. https://doi.org/10.1111/jam.14264

    Article  PubMed  Google Scholar 

  31. Wen L, Duffy A (2017) Factors influencing the gut microbiota, inflammation, and type 2 diabetes. J Nutr 147:1468S-1475S. https://doi.org/10.3945/jn.116.240754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shen F, Zheng R-D, Sun X-Q et al (2017) Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease. Hepatobiliary Pancreat Dis Int 16:375–381. https://doi.org/10.1016/S1499-3872(17)60019-5

    Article  PubMed  Google Scholar 

  33. Zou R, Xu F, Wang Y et al (2020) Changes in the gut microbiota of children with autism spectrum disorder. Autism Res 13:1614–1625. https://doi.org/10.1002/aur.2358

    Article  PubMed  Google Scholar 

  34. Huang H, Ren Z, Gao X et al (2020) Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma. Genom Med 12:102. https://doi.org/10.1186/s13073-020-00796-5

    Article  CAS  Google Scholar 

  35. Liu S, An Y, Cao B et al (2020) The composition of gut microbiota in patients bearing Hashimoto’s thyroiditis with euthyroidism and hypothyroidism. Int J Endocrinol 2020:5036959. https://doi.org/10.1155/2020/5036959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Atarashi K, Tanoue T, Shima T et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341. https://doi.org/10.1126/science.1198469

    Article  CAS  PubMed  Google Scholar 

  37. Van den Abbeele P, Belzer C, Goossens M et al (2013) Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model. ISME J 7:949–961. https://doi.org/10.1038/ismej.2012.158

    Article  CAS  PubMed  Google Scholar 

  38. Loo Y-M, Gale M (2011) Immune signaling by RIG-I-like receptors. Immunity 34:680–692. https://doi.org/10.1016/j.immuni.2011.05.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Grigorian A, Lee S-U, Tian W et al (2007) Control of T cell-mediated autoimmunity by metabolite flux to N-glycan biosynthesis. J Biol Chem 282:20027–20035. https://doi.org/10.1074/jbc.M701890200

    Article  CAS  PubMed  Google Scholar 

  40. Sugita K, Kabashima K (2020) Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases. J Leukoc Biol 107:749–762. https://doi.org/10.1002/JLB.5MR0120-230R

    Article  CAS  PubMed  Google Scholar 

  41. Li J-Y, Chassaing B, Tyagi AM et al (2016) Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics. J Clin Invest 126:2049–2063. https://doi.org/10.1172/JCI86062

    Article  PubMed  PubMed Central  Google Scholar 

  42. Schepper JD, Collins F, Rios-Arce ND et al (2020) Involvement of the gut microbiota and barrier function in glucocorticoid-induced osteoporosis. J Bone Miner Res. https://doi.org/10.1002/jbmr.3947

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by National Natural Science Foundation of China (Grant No. 82172456), the Cross-disciplinary Fund Projects of the Ninth People’s Hospital (Grant No. JYJC201809), Seeds Fund of Engineering Research Center of Digital Medicine of the Ministry of Education (Grant No. 20210407), Shanghai Clinical Medical Center (Grant No. 2017ZZ01023) and Shanghai Municipal Key Clinical Specialty.

Author information

Author notes

  1. Ning Wang and Sicong Ma have contributed equally to this work.

Authors and Affiliations

  1. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China

    Ning Wang, Sicong Ma & Lingjie Fu

Authors
  1. Ning Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sicong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lingjie Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LF designed the experiments and supervised the project. SM performed the experiments and acquired the data. SM and NW analyzed the data. NW wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lingjie Fu.

Ethics declarations

Conflict of interest

Ning Wang, Sicong Ma, and Lingjie Fu declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

The use of animals in this study was approved by the Animal Care and Use Committee of Shanghai Ninth People’s Hospital. All applicable institutional and/or national guidelines for the care and use of animals were followed.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 228 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, N., Ma, S. & Fu, L. Gut Microbiota Dysbiosis as One Cause of Osteoporosis by Impairing Intestinal Barrier Function. Calcif Tissue Int 110, 225–235 (2022). https://doi.org/10.1007/s00223-021-00911-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-021-00911-7

Keywords

Search

Navigation