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Lactobacillus rhamnosus GG Promotes Intestinal Vitamin D Absorption by Upregulating Vitamin D Transporters in Senile Osteoporosis

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Abstract

Intestinal absorption of vitamin D is an important way to improve the vitamin D level in senile osteoporosis (SOP). There is a link between oral probiotics and vitamin D, but the mechanism is still unclear. We aimed to evaluate whether Lactobacillus rhamnosus GG culture supernatant (LCS) can affect cholecalciferol absorption, transport, and hydroxylation in SOP, and explore underlying mechanisms. In the study, specific-pathogen-free SAMP6 mice were randomly divided into an experimental group administered undiluted LCS and a control group administered normal drinking water. Furthermore, levels of cholecalciferol absorption were compared between Caco-2 cells cultured with varying concentrations of cholecalciferol and stimulated with LCS or de Man, Rogosa, and Sharpe (MRS) broth (control). Similarly, LCS-stimulated HepG2 cells were compared with MRS-stimulated HepG2 cells. Finally, protein levels of VD transporters in small intestine tissues and Caco-2 cells, as well as vitamin D-binding protein and 25-hydroxylase in liver tissues and HepG2 cells, were detected by western blot. The results showed that plasma concentrations of cholecalciferol and 25OHD3 were higher in mice of the LCS group compared with the control group, and these values were positively correlated. With the addition of LCS, cholecalciferol uptake was increased with 0.5 μM or 10 μM cholecalciferol in the medium. Protein levels of CD36 and NPC1L1 were higher in the LCS group compared with the control group, while SR-BI protein was decreased, both in vitro and in vivo. In conclusion, LCS can promotes intestinal absorption cholecalciferol by affecting protein levels of VD transporters and improves 25OHD3 levels in SOP.

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Data Availability

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Qadir A, Liang S, Wu Z, Chen Z, Hu L, Qian A (2020) Senile osteoporosis: the involvement of differentiation and senescence of bone marrow stromal cells. Int J Mol Sci 21(1):349. https://doi.org/10.3390/ijms21010349

    Article  CAS  PubMed Central  Google Scholar 

  2. Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, El-Hajj Fuleihan G et al (2009) Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int 20(11):1807–1820. https://doi.org/10.1007/s00198-009-0954-6

    Article  CAS  PubMed  Google Scholar 

  3. Marcelli C, Chavoix C, Dargent-Molina P (2015) Beneficial effects of vitamin D on falls and fractures: is cognition rather than bone or muscle behind these benefits? Osteoporos Int 26(1):1–10. https://doi.org/10.1007/s00198-014-2829-8

    Article  CAS  PubMed  Google Scholar 

  4. Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, Köstenberger M, Tmava Berisha A, Martucci G et al (2020) Vitamin D deficiency 20: an update on the current status worldwide. Eur J Clin Nutr 74(11):1498–1513. https://doi.org/10.1038/s41430-020-0558-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lee JS, Kim JW (2018) Prevalence of vitamin D deficiency in postmenopausal high- and low-energy fracture patient. Arch Osteoporos 13(1):109. https://doi.org/10.1007/s11657-018-0524-7

    Article  PubMed  Google Scholar 

  6. Meckel K, Li YC, Lim J, Kocherginsky M, Weber C, Almoghrabi A, Chen X et al (2016) Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis. Am J Clin Nutr 104(1):113–120. https://doi.org/10.3945/ajcn.115.123786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen TC, Chimeh F, Lu Z, Mathieu J, Person KS, Zhang A, Kohn N et al (2007) Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch Biochem Biophys 460(2):213–217. https://doi.org/10.1016/j.abb.2006.12.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. MacLaughlin J, Holick MF (1985) Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 76(4):1536–15388. https://doi.org/10.1172/JCI112134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Council on Environmental Health, Section on Dermatology (2011) Ultraviolet radiation: a hazard to children and adolescents. Pediatrics 127(3):588–597. https://doi.org/10.1542/peds.2010-3501

    Article  PubMed  Google Scholar 

  10. Margier M, Collet X, le May C, Desmarchelier C, André F, Lebrun C, Defoort C et al (2019) ABCB1 (P-glycoprotein) regulates vitamin D absorption and contributes to its transintestinal efflux. FASEB J 33(2):2084–2094. https://doi.org/10.1096/fj.201800956R

    Article  CAS  PubMed  Google Scholar 

  11. Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A, Povoroznyuk V et al (2018) Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol 175:125–135. https://doi.org/10.1016/j.jsbmb.2017.01.021

    Article  CAS  PubMed  Google Scholar 

  12. Dereje S, Muradov I, Nazzal S, Nguyen T (2017) Cholecalciferol (D3) versus ergocalciferol (D2) in older adults. Consult Pharm 32(6):337–339. https://doi.org/10.4140/TCP.n.2017.337

    Article  PubMed  Google Scholar 

  13. Barko PC, McMichael MA, Swanson KS, Williams DA (2018) The gastrointestinal microbiome: a review. J Vet Intern Med 32(1):9–25. https://doi.org/10.1111/jvim.14875

    Article  CAS  PubMed  Google Scholar 

  14. Jones ML, Martoni CJ, Prakash S (2013) Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post hoc analysis of a randomized controlled trial. J Clin Endocrinol Metab 98(7):2944–2951. https://doi.org/10.1210/jc.2012-4262

    Article  CAS  PubMed  Google Scholar 

  15. Jamilian M, Amirani E, Asemi Z (2019) The effects of vitamin D and probiotic co-supplementation on glucose homeostasis, inflammation, oxidative stress and pregnancy outcomes in gestational diabetes: a randomized, double-blind, placebo-controlled trial. Clin Nutr 38(5):2098–2105. https://doi.org/10.1016/j.clnu.2018.10.028

    Article  CAS  PubMed  Google Scholar 

  16. Karbaschian Z, Mokhtari Z, Pazouki A, Kabir A, Hedayati M, Moghadam SS, Mirmiran P et al (2018) Probiotic supplementation in morbid obese patients undergoing one anastomosis gastric bypass-mini gastric bypass (OAGB-MGB) surgery: a randomized, double-blind, placebo-controlled. Clin Trial Obes Surg 28(9):2874–2885. https://doi.org/10.1007/s11695-018-3280-2

    Article  Google Scholar 

  17. Mokhtari Z, Karbaschian Z, Pazouki A, Kabir A, Edayati M, Mirmiran P, Hekmatdoost A (2019) The effects of probiotic supplements on blood markers of endotoxin and lipid peroxidation in patients undergoing gastric bypass surgery; a randomized, double-blind, placebo-controlled, clinical trial with 13 months follow-up. Obes Surg 29(4):1248–1258. https://doi.org/10.1007/s11695-018-03667-6

    Article  PubMed  Google Scholar 

  18. Savino F, Ceratto S, Poggi E, Cartosio ME, Cordero di Montezemolo L, Giannattasio A (2015) Preventive effects of oral probiotic on infantile colic: a prospective, randomised, blinded, controlled trial using Lactobacillus reuteri DSM 17938. Benef Microbes 6(3):245–251. https://doi.org/10.3920/BM2014.0090

    Article  CAS  PubMed  Google Scholar 

  19. Castagliuolo I, Scarpa M, Brun P, Bernabe G, Sagheddu V, Elli M, Fiore W et al (2021) Co-administration of vitamin D3 and Lacticaseibacillus paracasei DG increase 25-hydroxyvitamin D serum levels in mice. Ann Microbiol 71(1):42. https://doi.org/10.1186/s13213-021-01655-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Capurso L (2019) Thirty years of Lactobacillus rhamnosus GG: a review. J Clin Gastroenterol 53(Suppl 1):S1–S41. https://doi.org/10.1097/MCG.0000000000001170

    Article  CAS  PubMed  Google Scholar 

  21. Reboul E, Goncalves A, Comera C, Bott R, Nowicki M, Landrier JF, Jourdheuil-Rahmani D et al (2011) Vitamin D intestinal absorption is not a simple passive diffusion: evidences for involvement of cholesterol transporters. Mol Nutr Food Res 55(5):691–702. https://doi.org/10.1002/mnfr.201000553

    Article  CAS  PubMed  Google Scholar 

  22. Zhong-jian X, Qun C, Yu D (2018) Metabolism and functions of vitamin D. Chin J Osteoporosis Bone Mine Res 011(001):26–33

    Google Scholar 

  23. Liu S-Y, Sheng Z-F, Wang X-B (2018) Clinical study on vitamin D binding protein. Chin J Osteop Bone Mine Res 011(003):296–304

    Google Scholar 

  24. Zhu JG, Ochalek JT, Kaufmann M, Jones G, Deluca HF (2013) CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo. Proc Natl Acad Sci USA 110(39):15650–15655. https://doi.org/10.1073/pnas.1315006110

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cao YN, Feng LJ, Liu YY, Jiang K, Zhang MJ, Gu YX, Wang BM et al (2018) Effect of Lactobacillus rhamnosus GG supernatant on serotonin transporter expression in rats with post-infectious irritable bowel syndrome. World J Gastroenterol 24(3):338–350. https://doi.org/10.3748/wjg.v24.i3.338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Goncalves A, Roi S, Nowicki M, Dhaussy A, Huertas A, Amiot MJ, Reboul E (2015) Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption. Food Chem 172:155–160. https://doi.org/10.1016/j.foodchem.2014.09.021

    Article  CAS  PubMed  Google Scholar 

  27. Porter JL, Varacallo M (2020) Osteoporosis. StatPearls Publishing, Treasure Island (FL)

    Google Scholar 

  28. Holick MF (2017) The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 18(2):153–165. https://doi.org/10.1007/s11154-017-9424-1

    Article  CAS  PubMed  Google Scholar 

  29. Azuma K, Zhou Q, Kubo KY (2018) Morphological and molecular characterization of the senile osteoporosis in senescence-accelerated mouse prone 6 (SAMP6). Med Mol Morphol 51(3):139–146. https://doi.org/10.1007/s00795-018-0188-9

    Article  CAS  PubMed  Google Scholar 

  30. Tanabe K, Nakamura S, Moriyama-Hashiguchi M, Kitajima M, Ejima H, Imori C, Oku T (2019) Dietary fructooligosaccharide and glucomannan alter gut microbiota and improve bone metabolism in senescence-accelerated mouse. J Agric Food Chem 67(3):867–874. https://doi.org/10.1021/acs.jafc.8b05164

    Article  CAS  PubMed  Google Scholar 

  31. Chai Y, Pu X, Wu Y, Tian X, Li Q, Zeng F, Wang J et al (2021) Inhibitory effect of Astragalus membranaceus on osteoporosis in SAMP6 mice by regulating vitaminD/FGF23/Klotho signaling pathway. Bioengineered 12(1):4464–4474. https://doi.org/10.1080/21655979.2021.1946633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hollander D, Muralidhara KS, Zimmerman A (1978) Vitamin D-3 intestinal absorption in vivo: influence of fatty acids, bile salts, and perfusate pH on absorption. Gut 19(4):267–272. https://doi.org/10.1136/gut.19.4.267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shen WJ, Hu J, Hu Z, Kraemer FB, Azhar S (2014) Scavenger receptor class B type I (SR-BI): a versatile receptor with multiple functions and actions. Metabolism 63(7):875–886. https://doi.org/10.1016/j.metabol.2014.03.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Goncalves A, Gleize B, Roi S, Nowicki M, Dhaussy A, Huertas A, Amiot MJ et al (2013) Fatty acids affect micellar properties and modulate vitamin D uptake and basolateral efflux in Caco-2 cells. J Nutr Biochem 24(10):1751–1757. https://doi.org/10.1016/j.jnutbio.2013.03.004

    Article  CAS  PubMed  Google Scholar 

  35. Werder M, Han CH, Wehrli E, Bimmler D, Schulthess G, Hauser H (2001) Role of scavenger receptors SR-BI and CD36 in selective sterol uptake in the small intestine. Biochemistry 40(38):11643–11650. https://doi.org/10.1021/bi0109820

    Article  CAS  PubMed  Google Scholar 

  36. Lobo MV, Huerta L, Ruiz-Velasco N, Teixeiro E, de la Cueva P, Celdrán A, Martín-Hidalgo A et al (2001) Localization of the lipid receptors CD36 and CLA-1/SR-BI in the human gastrointestinal tract: towards the identification of receptors mediating the intestinal absorption of dietary lipids. J Histochem Cytochem 49(10):1253–1260. https://doi.org/10.1177/002215540104901007

    Article  CAS  PubMed  Google Scholar 

  37. Cifarelli V, Abumrad NA (2018) Intestinal CD36 and other key proteins of lipid utilization: role in absorption and gut homeostasis. Compr Physiol 8(2):493–507. https://doi.org/10.1002/cphy.c170026

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shen WJ, Azhar S, Kraemer FB (2018) SR-B1: a unique multifunctional receptor for cholesterol influx and efflux. Annu Rev Physiol 80:95–116. https://doi.org/10.1146/annurev-physiol-021317-121550

    Article  CAS  PubMed  Google Scholar 

  39. Zhong CY, Sun WW, Ma Y, Zhu H, Yang P, Wei H, Zeng BH et al (2015) Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice. Sci Rep 5:10512. https://doi.org/10.1038/srep10512

    Article  PubMed  PubMed Central  Google Scholar 

  40. Stancu CS, Sanda GM, Deleanu M, Sima AV (2014) Probiotics determine hypolipidemic and antioxidant effects in hyperlipidemic hamsters. Mol Nutr Food Res 58(3):559–568. https://doi.org/10.1002/mnfr.201300224

    Article  CAS  PubMed  Google Scholar 

  41. Le B, Yang SH (2019) Identification of a novel potential probiotic Lactobacillus plantarum FB003 isolated from salted-fermented shrimp and its effect on cholesterol absorption by regulation of NPC1L1 and PPARα. Probiotics Antimicrob Proteins 11(3):785–793. https://doi.org/10.1007/s12602-018-9469-9

    Article  CAS  PubMed  Google Scholar 

  42. Szentirmai É, Millican NS, Massie AR, Kapás L (2019) Butyrate, a metabolite of intestinal bacteria, enhances sleep. Sci Rep 9(1):7035. https://doi.org/10.1038/s41598-019-43502-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hernández MAG, Canfora EE, Jocken JWE, Blaak EE (2019) The short-chain fatty acid acetate in body weight control and insulin sensitivity. Nutrients 11(8):1943. https://doi.org/10.3390/nu11081943

    Article  CAS  Google Scholar 

  44. Kübeck R, Bonet-Ripoll C, Hoffmann C, Walker A, Müller VM, Schüppel VL, Lagkouvardos I et al (2016) Dietary fat and gut microbiota interactions determine diet-induced obesity in mice. Mol Metab 5(12):1162–1174. https://doi.org/10.1016/j.molmet.2016.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Feng Q, Chen WD, Wang YD (2018) Gut microbiota: an integral moderator in health and disease. Front Microbiol 9:151. https://doi.org/10.3389/fmicb.2018.00151

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

National Natural Science Foundation of China (Grant No: 81970477).

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Author notes

  1. Jing Cheng and Jianhua Zhai were co-first authors.

Authors and Affiliations

  1. Gastroenterology Department, Tianjin Medical University General Hospital, Tianjin, China

    Jing Cheng, Jianhua Zhai, Weilong Zhong, Jingwen Zhao, Lu Zhou & Bangmao Wang

  2. Department of Orthointernal, Tianjin Hospital, Tianjin, China

    Jing Cheng

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  1. Jing Cheng
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Contributions

BW, LZ, WZ and JC contributed to the conception of the study; JC performed the experiment; JZ and JZ helped perform for part of the experiment; JC contributed significantly to analysis and manuscript preparation; JC performed the data analyses and wrote the manuscript.

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Correspondence to Lu Zhou or Bangmao Wang.

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The present study did not involve a clinical study. The animal experiment has been approved by the Ethics Committee of Tianjin Hospital.

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Cheng, J., Zhai, J., Zhong, W. et al. Lactobacillus rhamnosus GG Promotes Intestinal Vitamin D Absorption by Upregulating Vitamin D Transporters in Senile Osteoporosis. Calcif Tissue Int 111, 162–170 (2022). https://doi.org/10.1007/s00223-022-00975-z

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