Eje intestino–sistema osteomioarticular: mecanismos fisiopatológicos y aplicaciones clínicas.

Vicente Martinez Cardenas; Vivian R. Mena Miranda

doi:10.12873/454vmmartinez

Autores/as

Vicente Martinez Cardenas Children’s Medical Center. Lake city. Florida. USA.
Vivian R. Mena Miranda Hospital pediátrico Centro. La Habana, Cuba.

DOI:

https://doi.org/10.12873/454vmmartinez

Palabras clave:

Microbiota intestinal; Ácidos grasos de cadena corta; Permeabilidad intestinal; GLP-2; GLP-1; Osteoporosis; Osteoartritis; Sarcopenia.

Resumen

Introducción: La microbiota intestinal influye en procesos inmunológicos, endocrinos y metabólicos que impactan la homeostasis ósea, muscular y articular. Este eje intestino–sistema osteomioarticular integra metabolitos bacterianos, citoquinas y hormonas intestinales; su desregulación se relaciona con osteoporosis, sarcopenia y enfermedades articulares inflamatorias. Objetivo: Revisar los mecanismos fisiopatológicos que vinculan la microbiota intestinal con el sistema osteomioarticular y explorar aplicaciones clínicas potenciales. Método: Revisión narrativa con elementos sistematizados (PRISMA 2020). Fuentes: PubMed/MEDLINE, Scopus/Embase y Web of Science (2015–2025). Criterios predefinidos para inclusión/exclusión, selección por pares, evaluación del sesgo (RoB2, ROBINS-I, JBI, SYRCLE) y calificación de certeza (GRADE). Se identificaron 612 registros; 58 estudios cumplieron criterios y se incorporaron a la síntesis cualitativa. Resultados: La disbiosis intestinal incrementa la permeabilidad intestinal y la translocación de lipopolisacáridos, activando receptores TLR4 en hueso y cartílago, lo que favorece inflamación crónica y degradación de matriz. El desequilibrio Th17/Treg estimula la osteoclastogénesis, mientras que los ácidos grasos de cadena corta favorecen la función osteoblástica y muscular. Probióticos y prebióticos han mostrado efectos antiinflamatorios y osteoprotectores en modelos animales y estudios piloto en humanos. Conclusiones: El eje intestino–sistema osteomioarticular es un campo emergente con aplicaciones clínicas prometedoras. Su modulación mediante estrategias nutricionales y terapias dirigidas podría contribuir a la prevención y tratamiento de patologías metabólicas óseas y articulares.

Referencias

1. Zaiss MM, Jones RM, Schett G, Pacifici R. The gut-bone axis: how bacterial metabolites bridge the distance. J Clin Invest. 2019 Jul 15;129(8):3018-28. doi: 10.1172/JCI128521. PMID: 31305265; PMCID: PMC6668676. DOI: https://doi.org/10.1172/JCI128521

2. Behera J, Ison J, Tyagi SC, Tyagi N. The role of gut microbiota in bone homeostasis. Bone. 2020 Jun;135:115317. doi: 10.1016/j.bone.2020.115317. PMID: 32169602; PMCID: PMC8457311. DOI: https://doi.org/10.1016/j.bone.2020.115317

3. Chen Y, Ye J, Cao L, et al. Gut Microbiota and Bone Diseases: A Growing Partnership. Front Microbiol. 2022;13:877776. doi: 10.3389/fmicb.2022.877776. DOI: https://doi.org/10.3389/fmicb.2022.877776

4. Xie B, Tian J, Wei Y, et al. The Impact of GLP-1 Receptor Agonists on Osteoporosis. Front Pharmacol. 2021;12:697442. doi: 10.3389/fphar.2021.697442. PMID: 34220521; PMCID: PMC8243369. Frontiers DOI: https://doi.org/10.3389/fphar.2021.697442

5. Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, Holst JJ, Christiansen C. Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women. Bone. 2007 Mar;40(3):723-9. doi: 10.1016/j.bone.2006.09.025. PMID: 17081815. PubMed DOI: https://doi.org/10.1016/j.bone.2006.09.025

6. Brubaker PL. Glucagon-Like Peptide-2 and the Regulation of Intestinal Functions. Compr Physiol. 2018;8(3):1049-82. doi: 10.1002/cphy.c170055. PMID: 29978894. Wiley Online Library DOI: https://doi.org/10.1002/cphy.c170055

7. Liu H, Xiao H, Lin S, Zhou H, Cheng Y, Xie B, Xu D. Effect of gut hormones on bone metabolism and their possible mechanisms in the treatment of osteoporosis. Front Pharmacol. 2024 Apr 25;15:1372399. doi: 10.3389/fphar.2024.1372399. PMID: 38725663; PMCID: PMC11079205. PMC DOI: https://doi.org/10.3389/fphar.2024.1372399

8. Schiellerup SP, Skov-Jeppesen K, Windeløv JA, et al. Gut Hormones and Their Effect on Bone Metabolism. Front Endocrinol (Lausanne). 2019;10:75. doi: 10.3389/fendo.2019.00075. PMID: 30863364; PMCID: PMC6399108. Frontiers DOI: https://doi.org/10.3389/fendo.2019.00075

9. Zhu X, Ge H, Zhang X, et al. The critical role of Toll-like receptor 4 in bone remodeling and osteoporosis. Front Immunol. 2024;15:1333086. doi: 10.3389/fimmu.2024.1333086. PMID: 38504994. PMC DOI: https://doi.org/10.3389/fimmu.2024.1333086

10. Alonso-Pérez A, Franco-Trepat E, Guillán-Fresco M, Jorge-Mora A, López V, Pino J, Gualillo O, Gómez R. Role of Toll-Like Receptor 4 on Osteoblast Metabolism and Function. Front Physiol. 2018;9:504. doi: 10.3389/fphys.2018.00504. PMID: 29867550; PMCID: PMC5952219. PMC DOI: https://doi.org/10.3389/fphys.2018.00504

11. Bartels YL, van Lent PLEM, van der Kraan PM, Blom AB, Bonger KM, van den Bosch MHJ. Inhibition of TLR4 signalling to dampen joint inflammation in osteoarthritis. Rheumatology (Oxford). 2024 Mar 1;63(3):608-618. doi:10.1093/rheumatology/kead493. PMID: 37788083; PMCID: PMC10907820. PMC DOI: https://doi.org/10.1093/rheumatology/kead493

12. Sengprasert P, Kamenkit O, Tanavalee A, Reantragoon R. The Immunological Facets of Chondrocytes in Osteoarthritis: A Narrative Review. J Rheumatol. 2024 Jan;51(1):13-24. doi:10.3899/jrheum.2023-0816. PMID: 37914220. JRheum+1 DOI: https://doi.org/10.3899/jrheum.2023-0816

13. Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copricorrelates with enhanced susceptibility to arthritis. eLife. 2013 Nov 5;2:e01202. doi:10.7554/eLife.01202. PMID: 24192039; PMCID: PMC3816614. eLife DOI: https://doi.org/10.7554/eLife.01202

14. Gill T, Asquith M, Rosenbaum JT, Colbert RA. The intestinal microbiome in spondyloarthritis. Curr Opin Rheumatol. 2015 Jul;27(4):319-25. doi:10.1097/BOR.0000000000000187. PMID: 26002022; PMCID: PMC4489849. PMC DOI: https://doi.org/10.1097/BOR.0000000000000187

15. Pirozzi C, Francisco V, Guida FD, Gómez R, Lago F, Pino J, Meli R, Gualillo O. Butyrate modulates inflammation in chondrocytes via GPR43 receptor. Cell Physiol Biochem. 2018;51(1):228-43. doi:10.1159/000495203. Epub 2018 Nov 16. PMID: 30448827. PubMed

16. Ding SL, Pang ZY, Chen XM, Li Z, Liu XX, Zhai QL, et al. Urolithin A attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes. J Inflamm (Lond). 2020;17:13. doi:10.1186/s12950-020-00242-8. PMID: 32210738; PMCID: PMC7092521. BioMed Central DOI: https://doi.org/10.1186/s12950-020-00242-8

17. Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013 Dec 19;504(7480):446-50. doi:10.1038/nature12721. Epub 2013 Nov 13. Erratum in: Nature. 2014 Feb 13;506(7487):254. PMID: 24226770. PubMed DOI: https://doi.org/10.1038/nature12721

18. Wen C, Wang Q, Gu S, Jin J, Yang N. Emerging perspectives in the gut-muscle axis: The gut microbiota and its metabolites as important modulators of meat quality. Microb Biotechnol. 2024 Jan;17(1):e14361. doi:10.1111/1751-7915.14361. Epub 2023 Oct 30. PMID: 37902307; PMCID: PMC10832551. PMC DOI: https://doi.org/10.1111/1751-7915.14361

19. Barry DJ, Wu SSX, Cooke MB. The Relationship Between Gut Microbiota, Muscle Mass and Physical Function in Older Individuals: A Systematic Review. Nutrients. 2025;17(1):81. doi:10.3390/nu17010081. PMID: 39796514. MDPI DOI: https://doi.org/10.3390/nu17010081

20. Mai X, Yang S, Chen Q, Chen K. Gut microbial composition is altered in sarcopenia: a systematic review and meta-analysis of clinical studies. PLoS One. 2024;19(8):e0308360. doi:10.1371/journal.pone.0308360. PMID: 39106230; PMCID: PMC11302912. PLOS DOI: https://doi.org/10.1371/journal.pone.0308360

21. Thomas RL, Jiang L, Adams JS, Xu ZZ, Shen J, Janssen S, et al. Vitamin D metabolites and the gut microbiome in older men. Nat Commun. 2020;11:5997. doi:10.1038/s41467-020-19793-8. PMID: 33244003; PMCID: PMC7693238. Nature DOI: https://doi.org/10.1038/s41467-020-19793-8

22. Jin D, Wu S, Zhang Y-G, Lu R, Xia Y, Dong H, Sun J. Lack of vitamin D receptor causes dysbiosis and changes the functions of the murine intestinal microbiome. Clin Ther. 2015 May;37(5):996-1009.e1007. doi:10.1016/j.clinthera.2015.04.004. PMID: 26046242. Clinical Therapeutics DOI: https://doi.org/10.1016/j.clinthera.2015.04.004

23. Bora SA, Kennett MJ, Smith PB, Patterson AD, Cantorna MT. The gut microbiota regulates endocrine vitamin D metabolism through fibroblast growth factor 23. Front Immunol. 2018 Mar 2;9:408. doi:10.3389/fimmu.2018.00408. PMID: 29599772; PMCID: PMC5863497. Frontiers DOI: https://doi.org/10.3389/fimmu.2018.00408

24. Yan Q, Zhang Z, Liu J, et al. The biological responses of vitamin K2: a comprehensive review. Front Nutr. 2023;10:1110163. doi:10.3389/fnut.2023.1110163. PMID: 37051359; PMCID: PMC10084986. PMC

25. Lai Y, Masatoshi H, Ma Y, Guo Y, Zhang B. Role of Vitamin K in Intestinal Health. Front Immunol. 2022 Jan 5;12:791565. doi:10.3389/fimmu.2021.791565. PMID: 35069573; PMCID: PMC8769504. Frontiers DOI: https://doi.org/10.3389/fimmu.2021.791565

26. Skov-Jeppesen K, Svane MS, Martinussen C, Gasbjerg LS, Rosenkilde MM, Rejnmark L, et al. The antiresorptive effect of GIP, but not GLP-2, is preserved in hypoparathyroidism—randomized crossover. J Bone Miner Res. 2021 Aug;36(8):1448-1458. doi:10.1002/jbmr.4308. PMID: 33852173; PMCID: PMC8338760. Wiley Online Library DOI: https://doi.org/10.1002/jbmr.4308

27. Jensen SBK, Sørensen V, Sandsdal RM, Lehmann EW, Lundgren JR, Juhl CR, et al. Bone Health After Exercise Alone, GLP-1 Receptor Agonist Treatment, or Combination Treatment: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 25;7(6):e2416775. doi:10.1001/jamanetworkopen.2024.16775. PMID: 38916894. JAMA Network DOI: https://doi.org/10.1001/jamanetworkopen.2024.16775

28. Paul AK, Paul A, Jahan R, Jannat K, Bondhon TA, Hasan A, Nissapatorn V, Pereira ML, Wilairatana P, Rahmatullah M. Probiotics and amelioration of rheumatoid arthritis: significant roles of Lactobacillus casei and Lactobacillus acidophilus. Microorganisms. 2021 May;9(5):1070. doi:10.3390/microorganisms9051070. PMID: 34065638; PMCID: PMC8157104. DOI: https://doi.org/10.3390/microorganisms9051070

29. Yu M, Tyagi AM, Li J-Y, Adams J, Denning TL, Weitzmann MN, Jones RM, Pacifici R. PTH induces bone loss via microbial-dependent expansion of intestinal TNF⁺ T cells and Th17 cells. Nat Commun. 2020;11:468. doi:10.1038/s41467-019-14148-4. PMID: 31980603; PMCID: PMC6981196. DOI: https://doi.org/10.1038/s41467-019-14148-4

30. Moyseos M, Michael J, Ferreira N, Sophocleous A. The effect of probiotics on the management of pain and inflammation in osteoarthritis: a systematic review and meta-analysis of clinical studies. Nutrients. 2024 Jul;16(14):2243. doi:10.3390/nu16142243. PMID: 39064686; PMCID: PMC11279588. DOI: https://doi.org/10.3390/nu16142243

31. Pirozzi C, Francisco V, Guida FD, Gómez R, Lago F, Pino J, Meli R, Gualillo O. Butyrate modulates inflammation in chondrocytes via GPR43 receptor. Cell Physiol Biochem. 2018;51(1):228-243. doi:10.1159/000495203. PMID: 30448827. DOI: https://doi.org/10.1159/000495203

32. Elam RE, Bůžková P, Barzilay JI, Wang Z, Nemet I, Budoff MJ, Cauley JA, Fink HA, Lee Y, Robbins JA, Wang M, Hazen SL, Mozaffarian D, Carbone LD. Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The Cardiovascular Health Study. Bone. 2022;161:116431. doi:10.1016/j.bone.2022.116431. PMID: 35577327; PMCID: PMC10712255. ScienceDirect DOI: https://doi.org/10.1016/j.bone.2022.116431

33. Lin Y-H, Lian W-S, Wu R-W, Chen Y-S, Wu S-L, Ko J-Y, Wang S-Y, Jahr H, Wang F-S. Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding. Cell Mol Life Sci. 2024 Dec 24;82(1):13. doi:10.1007/s00018-024-05501-y. PMID: 39719538; PMCID: PMC11668722. PMC DOI: https://doi.org/10.1007/s00018-024-05501-y

34. Li L, An J, Bai J, Zhang Y, Li X, Lv H. Association between systemic immune-inflammation index and trimethylamine N-oxide levels in peripheral blood and osteoporosis in overweight and obese patients. Front Endocrinol (Lausanne). 2025 Feb 13;16:1539594. doi:10.3389/fendo.2025.1539594. PMID: 40017693; PMCID: PMC11864960. DOI: https://doi.org/10.3389/fendo.2025.1539594