Abstract
The general public spends one-third of its time under artificial lighting, which lacks bands beneficial to human health, and long-term exposure will have a negative impact on bone health. Here, we report the effects of long-term, low-dose ultraviolet (UV) supplementation to white light-emitting diode (LED) light exposure on intestinal microorganisms and bone metabolism, as well as the correlations between the two. Normal and ovariectomized rats were irradiated with LED white light with or without supplementation with UV. The effects of UV supplementation on the intestinal flora and the relationship between the intestinal flora and bone were investigated by measuring the intestinal flora, bone metabolism markers, and bone histomorphology. UV supplementation affected the bone density and bone mass by changing the relative content of Firmicutes, Saccharibacteria, and Proteobacteria; however, the intestinal flora were not the only factors affecting bone. Ultraviolet supplementation changed the composition and function of the gut flora in the bone loss model. By increasing the synthesis of short-chain fatty acids and affecting immunomodulatory, intestinal flora directly or indirectly regulate the activity of osteoclasts and thus mediate UV-mediated improvements in bone metabolism. Our work shows that UV supplementation affects bone density by influencing the intestinal flora, introducing a novel strategy to develop healthier artificial light sources and prevent bone loss.
Key points
• We measured the bone metabolism markers and bone histomorphometry of rats.
• The diversity, composition, and function of intestinal flora were analyzed.
• The relationship between gut microbiota and host bone physiology was analyzed.
Similar content being viewed by others
References
Abulmeaty MMA (2017) Sunlight exposure vs. vitamin D supplementation on bone homeostasis of vitamin D deficient rats. Metab Clin Exp 11:1–9. https://doi.org/10.1016/j.yclnex.2016.10.003
Ai C, Ma N, Zhang Q, Wang G, Liu X, Tian F, Chen P, Chen W (2016) Immunomodulatory effects of different lactic acid bacteria on allergic response and its relationship with in vitro properties. PLoS One 11(10):e0164697. https://doi.org/10.1371/journal.pone.0164697
Aßhauer KP, Wemheuer B, Daniel R, Meinicke P (2015) Tax4Fun: predicting functional profiles from metagenomic 16S rRNA data. Bioinformatics 31(17):2882–2884. https://doi.org/10.1093/bioinformatics/btv287
Babidge W, Millard S, Roediger W (1998) Sulfides impair short chain fatty acid β-oxidation at acyl-CoA dehydrogenase level in colonocytes: implications for ulcerative colitis. Mol Cell Biochem 181(1-2):117–124. https://doi.org/10.1023/a:1006838231432
Bastian M, Heymann S, Jacomy M (2009) Gephi: an open source software for exploring and manipulating networks. Icwsm 8(2009):361–362. https://doi.org/10.13140/2.1.1341.1520
Bukowska-Damska A, Skowronska-Jozwiak E, Peplonska B (2019) Night shift work and osteoporosis: evidence and hypothesis. Chronobiol Int 36(2):171–180. https://doi.org/10.1080/07420528.2018.1528553
Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336. https://doi.org/10.1038/nmeth.f.303
Carvalho FA, Koren O, Goodrich JK, Johansson ME, Nalbantoglu I, Aitken JD, Su Y, Chassaing B, Walters WA, González A (2012) Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 12(2):139–152. https://doi.org/10.1016/j.chom.2012.07.004
Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D (2007) Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (158):1
David Yatsonsky I, Pan K, Shendge VB, Liu J, Ebraheim NA (2019) Linkage of microbiota and osteoporosis: a mini literature review. World J Gastroenterol 10(3):123–127. https://doi.org/10.5312/wjo.v10.i3.123
Davidson D, Letts M, Khoshhal K (2003) Pelvic osteomyelitis in children: a comparison of decades from 1980–1989 with 1990–2001. J Pediatr Orthop 23(4):514–521. https://doi.org/10.1097/01241398-200307000-00019
Dhama K, Latheef KS, Munjal KA, Khandia R, Samad AH, Iqbal HMN, Joshi SK (2016) Probiotics in curing allergic and inflammatory conditions-research progress and futuristic vision. Recent Patents Inflamm Allergy Drug Discov 10(2):105–118. https://doi.org/10.2174/1872213X10666161226162229
Edgar RC (2013) UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods 10(10):996–998. https://doi.org/10.1038/NMETH.2604
Edgar R (2016) SINTAX: a simple non-Bayesian taxonomy classifier for 16S and ITS sequences. BioRxiv 074161. https://doi.org/10.1101/074161
Falkenbach A, Unkelbach U, Boehm B, Regeniter A, Stein J, Seiffert U, Wendt T (1993) Bone metabolism before and after irradiation with ultraviolet light. Eur J Appl Physiol 66(1):55–59. https://doi.org/10.1007/BF00863400
Grčević D, Lee S-K, Marušić A, Lorenzo JA (2000) Depletion of CD4 and CD8 T lymphocytes in mice in vivo enhances 1, 25-dihydroxyvitamin D3-stimulated osteoclast-like cell formation in vitro by a mechanism that is dependent on prostaglandin synthesis. J Immunol 165(8):4231–4238. https://doi.org/10.4049/jimmunol.165.8.4231
Guo R, Du Y, Zhang S, Liu H, Fu Y (2018) The effects of ultraviolet supplementation to the artificial lighting on rats’ bone metabolism, bone mineral density, and skin. J Photochem Photobiol B-Biol 188:12–18. https://doi.org/10.1016/j.jphotobiol.2018.08.020
Hernandez CJ, Guss JD, Luna M, Goldring SR (2016) Links between the microbiome and bone. J Bone Miner Res 31(9):1638–1646. https://doi.org/10.1002/jbmr.2887
Ho-Pham LT, Nguyen ND, Nguyen TV (2013) Quantification of the relative contribution of estrogen to bone mineral density in men and women. BMC Musculoskelet Disord 14(1):366. https://doi.org/10.1186/1471-2474-14-366
Hsu E, Pacifici R (2018) From osteoimmunology to osteomicrobiology: how the microbiota and the immune system regulate bone. Calcif Tissue Int 102(5):512–521. https://doi.org/10.1007/s00223-017-0321-0
Jou J-H, Tai T-C, Liu S-H, He Z-K, Chen C-L, Chavhan SD, Chen Y-H, Chen C-C, Lee M-T, Lee J-R (2019) Pseudo-sunlight organic light-emitting diodes. Opt Laser Technol 112:494–499. https://doi.org/10.1016/j.optlastec.2018.11.046
Kasselman LJ, Vernice NA, DeLeon J, Reiss AB (2018) The gut microbiome and elevated cardiovascular risk in obesity and autoimmunity. Atherosclerosis 271:203–213. https://doi.org/10.1016/j.atherosclerosis.2018.02.036
Kuehbacher T, Rehman A, Lepage P, Hellmig S, Fölsch UR, Schreiber S, Ott SJ (2008) Intestinal TM7 bacterial phylogenies in active inflammatory bowel disease. J Med Microbiol 57(12):1569–1576. https://doi.org/10.1099/jmm.0.47719-0
Li C, Huang Q, Yang R, Dai Y, Zeng Y, Tao L, Li X, Zeng J, Wang Q (2019) Gut microbiota composition and bone mineral loss—epidemiologic evidence from individuals in Wuhan, China. Osteoporos Int 30(5):1003–1013. https://doi.org/10.1007/s00198-019-04855-5
Lucas S, Omata Y, Hofmann J, Böttcher M, Iljazovic A, Sarter K, Albrecht O, Schulz O, Krishnacoumar B, Krönke G (2018) Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun 9(1):1–10. https://doi.org/10.1038/s41467-017-02490-4
Luria T, Matsliah Y, Adir Y, Josephy N, Moran DS, Evans RK, Abramovich A, Eliakim A, Dan N (2010) Effects of a prolonged submersion on bone strength and metabolism in young healthy submariners. Calcif Tissue Int 86(1):8–13. https://doi.org/10.1007/s00223-009-9308-9
McCarty M, Russell A, Seed M (2000) Sulfated glycosaminoglycans and glucosamine may synergize in promoting synovial hyaluronic acid synthesis. Med Hypotheses 54(5):798–802. https://doi.org/10.1054/mehy.1999.0954
Mead MN (2008) Benefits of sunlight: a bright spot for human health. Environ Health Perspect 116(4):A160–A167. https://doi.org/10.1289/ehp.116-a160
Micić I, Jeon I-H, Park S-H, Hwa S-S, Chun J-M, Stojiljković P (2013) The effect of short-term low-energy ultraviolet B irradiation on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis: a randomized single-blinded controlled clinical trial. Srp Ark Celok Lek 141(9-10):615–622. https://doi.org/10.2298/SARH1310615M
Morita D, Nishida Y, Higuchi Y, Seki T, Ikuta K, Asano H, Ishiguro N (2016) Short-range ultraviolet irradiation with LED device effectively increases serum levels of 25 (OH) D. J Photochem Photobiol B 164:256–263. https://doi.org/10.1016/j.jphotobiol.2016.09.036
Nikolikj-Dimitrova E (2013) The role of physical agents in treatment of osteoporosis. Maced J Med Sci 6(2):189–193. https://doi.org/10.3889/mjms.1857-5773.2013.0286
Oksanen J, Kindt R, Legendre P, O’Hara B, Stevens MHH, Oksanen MJ, Suggests M (2007) The vegan package. Community ecology package 10:631–637 http://r-forge.r-project.org/projects/vegan/
Rognes T, Flouri T, Nichols B, Quince C, Mahé F (2016) VSEARCH: a versatile open source tool for metagenomics. PeerJ 4:e2584. https://doi.org/10.7717/peerj.2584
Ronca F, Palmieri L, Panicucci P, Ronca G (1998) Anti-inflammatory activity of chondroitin sulfate. Osteoarthr Cartil 6:14–21. https://doi.org/10.1016/S1063-4584(98)80006-X
Sjögren K, Engdahl C, Henning P, Lerner UH, Tremaroli V, Lagerquist MK, Bäckhed F, Ohlsson C (2012) The gut microbiota regulates bone mass in mice. J Bone Miner Res 27(6):1357–1367. https://doi.org/10.1016/j.bone.2012.02.272
Team RC (2013) R: A language and environment for statistical computing. http://www.R-project.org
Wagner MA, Roger AJ, Flax JL, Brusseau GA, Stahl DA (1998) Phylogeny of dissimilatory sulfite reductases supports an early origin of sulfate respiration. J Bacteriol 180(11):2975–2982. https://doi.org/10.1128/JB.180.11.2975-2982.1998
Wu Z, Pan D, Guo Y, Sun Y, Zeng X (2015) Peptidoglycan diversity and anti-inflammatory capacity in Lactobacillus strains. Carbohydr Polym 128:130–137. https://doi.org/10.1016/j.carbpol.2015.04.026
Yan J, Herzog JW, Tsang K, Brennan CA, Bower MA, Garrett WS, Sartor BR, Aliprantis AO, Charles JF (2016) Gut microbiota induce IGF-1 and promote bone formation and growth. P Natl Acad Sci USA 113(47):E7554–E7563. https://doi.org/10.1073/pnas.1607235113
Yan J, Takakura A, Zandi-Nejad K, Charles JF (2018) Mechanisms of gut microbiota-mediated bone remodeling. Gut Microbes 9(1):84–92. https://doi.org/10.1080/19490976.2017.1371893
Acknowledgements
This work was financially supported by grants from the National Natural Science Foundation of China (81871520, 31870852) and the Foundation for the Excellent Youth Scholars of Shandong Educational Committee (72).
Availability of data and material
The data that support the findings of this study are openly available in the NCBI SRA repository, reference number PRJNA671564.
Funding
This work was financially supported by grants from the National Natural Science Foundation of China (81871520, 31870852) and the Foundation for the Excellent Youth Scholars of Shandong Educational Committee (72).
Author information
Authors and Affiliations
Contributions
JC and YF conceived and designed research. JC conducted experiments. JC, ZY, and CD analyzed data. YF and HL guided most experiments. JC and YF wrote the manuscript. All authors read and approved the manuscript.
Corresponding author
Ethics declarations
Ethics approval
All animal experiments were performed with approval by the Science and Ethics Committee of the School of Beihang University (Approval ID: BM20180003).
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
ESM 1
(PDF 2330 kb)
Rights and permissions
About this article
Cite this article
Cui, J., Fu, Y., Yi, Z. et al. The beneficial effects of ultraviolet light supplementation on bone density are associated with the intestinal flora in rats. Appl Microbiol Biotechnol 105, 3705–3715 (2021). https://doi.org/10.1007/s00253-021-11282-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-021-11282-2