Osteoarthritis treatment via the GLP-1–mediated gut-joint axis targets intestinal FXR signaling
Open accessAbstract
Whether a gut-joint axis exists to regulate osteoarthritis is unknown. In two independent cohorts, we identified altered microbial bile acid metabolism with reduced glycoursodeoxycholic acid (GUDCA) in osteoarthritis. Suppressing farnesoid X receptor (FXR)—the receptor of GUDCA—alleviated osteoarthritis through intestine-secreted glucagon-like peptide 1 (GLP-1) in mice. GLP-1 receptor blockade attenuated these effects, whereas GLP-1 receptor activation mitigated osteoarthritis. Osteoarthritis patients exhibited a lower relative abundance of Clostridium bolteae , which promoted the formation of ursodeoxycholic acid (UDCA), a precursor of GUDCA. Treatment with C. bolteae and Food and Drug Administration–approved UDCA alleviated osteoarthritis through the gut FXR–joint GLP-1 axis in mice. UDCA use was associated with lower risk of osteoarthritis-related joint replacement in humans. These findings suggest that orchestrating the gut microbiota–GUDCA–intestinal FXR–GLP-1–joint pathway offers a potential strategy for osteoarthritis treatment.
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Gut dysbiosis has been implicated in RA-associated immune activation.
“Gut dysbiosis has been implicated in RA-associated immune activation, whereas modulation of microbial BA metabolism and glucagon-like peptide-1 secretion has emerged as a potential therapeutic route in OA [130].”
From Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies (2026) · cites this paper as [130]
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Cohort Profile: The Xiangya Osteoarthritis (XO) Study
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Self-citation"Osteoarthritis" on imaging may be normal wear and tear
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Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits
Wong, C. K., & Drucker, D. J. (2025) · Journal of Clinical Investigation · doi:10.1172/jci194751 · Cited by 112 · see citing works
Osteoarthritis as a systemic disease
Collins, K. H., Haugen, I. K., Neogi, T., & Guilak, F. (2025) · Nature Reviews Rheumatology · doi:10.1038/s41584-025-01332-8 · Cited by 48 · see citing works
“Although initial studies aimed to understand the role of the gut microbiome as a link between diet and OA 135–138 , data now indicate that the gut microbiota–GLP1 axis could be a highly attractive drug target for OA 47 .”
Emerging Frontiers in GLP-1 Therapeutics: A Comprehensive Evidence Base (2025)
Patel, S., & Niazi, S. K. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17081036 · Cited by 46 · see citing works
“It demonstrated that GLP-1 RAs can modulate intestinal farnesoid X receptor (FXR) signaling to improve joint health [168].”
Glucagon-like peptide-1 receptor agonists in arthritis: current insights and future directions
Karacabeyli, D., & Lacaille, D. V. (2025) · Nature Reviews Rheumatology · doi:10.1038/s41584-025-01302-0 · Cited by 31 · see citing works
“People with OA have lower serum GLP-1 levels 63 , and intra-articular liraglutide injection alleviates pain 55 and attenuates cartilage degradation in OA mouse models 63 .”
Influential3D bioprinting bone/cartilage organoids: construction, applications, and challenges
Gao, D., Li, R., Pan, J., Li, C., Zhang, W., Qin, L., & Lai, Y. (2025) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2025.08.008 · Cited by 22 · see citing works
“Epidemiological data from the World Health Organization reveal that osteoarthritis alone affects over 500 million individuals globally, with prevalence rates surpassing 20 % in populations aged 65 years and older [4].”
Self-citationNuclear receptors in metabolism and diseases: Mechanistic and therapeutic insights
Zhu, C.-Y., Yu, P., Sun, Q., Hong, D., Yang, C., & Naranmandura, H. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107862 · Cited by 18 · see citing works
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“A gut bacteria – bile acid – intestinal FXR – GLP-1 cascade has been shown to modulate articular cartilage integrity, highlighting the potential of this pathway as a therapeutic target for OA treatment [92].”
Self-citationGut microbiota and bone aging: Focusing on the gut-X axis modes
Zhang, Y.-W., Li, R.-Y., Wu, Y., Wang, P., Zhou, Q., & Su, J. (2026) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2026.101064 · Cited by 16 · see citing works
“Yang et al. [87] found a novel osteoarthritis treatment via the GLP-1 – mediated gut-joint axis targets intestinal FXR signaling.”
Self-citationCao, Z., Zhang, C., Lei, H., Lin, W., Yu, W.-K., Gao, X., He, Y., Li, X., Xiang, Q., Zhang, Z., et al. (2025) · Advanced Science · doi:10.1002/advs.202515794 · Cited by 15 · see citing works
Differential roles of individual bile acid in physiology and disease
Fan, M., Yang, Z., Jin, L., & Huang, W. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107845 · Cited by 13 · see citing works
Self-citationThe Role of Extracellular Vesicles in Musculoskeletal Diseases
Fu, P., Luo, Y., Zheng, S., Ma, Z., Xiao, W., Li, H., & Li, Y. (2025) · Journal of Extracellular Vesicles · doi:10.1002/jev2.70205 · Cited by 10 · see citing works
Self-citationAssociation of organs-crosstalk with the pathogenesis of osteoarthritis: cartilage as a key player
Qin, Y., Di, J., Guo, Z., Chen, S., & Xiang, C. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1593658 · Cited by 9 · see citing works
Pain mechanisms in osteoarthritis: recent discoveries and opportunities ahead
Hoffman, D. B., Miller, R. E., & Malfait, A. (2025) · Connective Tissue Research · doi:10.1080/03008207.2025.2531414 · Cited by 9 · see citing works
“Recent work published in Science suggests the connection between GLP-1 and OA is not just related to weight and metabolism, but is strongly mediated through gut microbiota 35 , which represents a promising therapeutic strategy.”
Direct Targeting of Gene Regulators by Iridium(III) and Rhodium(III) Complexes
Wu, L., Kong, L., Wang, W., & Leung, C. (2025) · Accounts of Chemical Research · doi:10.1021/acs.accounts.5c00570 · Cited by 9 · see citing works
Wang, T., Xu, Y., Zha, H., & Wu, L. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1685962 · Cited by 9 · see citing works
“…local levels of these pro-inflammatory metabolites—including LPS, peptidoglycan and fatty acids—are elevated and cause damage in joint tissues by bringing about metabolic endotoxaemia, macrophage invasion and chronic low-grade inflammation (Han et al., 2025; Hao et al., 2025; He M. et al., 2025).”
Self-citationLi, Y.-L., Liu, K., Li, Y.-G., Tang, Z.-X., Li, Y., Li, A.-Y., & Zhang, H. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112245 · Cited by 11 · see citing works
Self-citationXie, D., Wang, Y., Li, J., Yang, T., Zhang, Y., Zhang, W., Doherty, M., Zhu, Y., Yang, Z., Wang, Y., et al. (2025) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2025.07.004 · Cited by 8 · see citing works
Self-citationWang, Z., Wang, W. J., Wang, Y., Hu, H., Wang, B., Zhu, W., Li, X., Hou, X., Sun, W., Liu, Z., et al. (2025) · European journal of medical research · doi:10.1186/s40001-025-02795-x · Cited by 8 · see citing works
Self-citationZhang, J., Jiang, F., Xia, W., Guo, Y., Zhu, Y., Zhao, M., Xiao, L., Wei, Z., Xia, Y., & Dai, Y. (2025) · Advanced Science · doi:10.1002/advs.202507953 · Cited by 8 · see citing works
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Microbial transformation of secondary bile acids: roles in gut ecology and autoimmune diseases
Ren, L., Li, M., Wu, L., Lin, Z. M., & Chen, A. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1769792 · Cited by 8 · see citing works
“Circulating GLP-1 subsequently targets joint tissues, promoting cartilage synthesis in chondrocytes and synovial cells via a speci fi c receptor (243).”
Zheng, M., Zhao, J., Wang, Y., Cui, Z., Qiao, Z., Wu, H., Shi, C., & Wang, X. (2025) · Medicine · doi:10.1097/md.0000000000043239 · Cited by 7 · see citing works
“[9] Clinical studies have demonstrated that patients with type 2 diabetes who received GLP-1RAs therapy attenuated the risk of knee OA and total knee replacement compared with non-GLP-1RA-treated patients.”
Self-citationThe functional roles and mechanisms of polyamines in age-related bone diseases
Zhang, J., Cai, C., Zhang, Y., Luo, C., Huo, S., Wang, K., Shi, C., Liu, J., & Xu, G. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-06001-3 · Cited by 7 · see citing works
“Emerging insights into the “gut-joint axis” have further revealed a connection between gut microbiota composi - tion and OA progression [86].”
Self-citationFXR in bone metabolism: An emerging regulator
Rizvi, S. M. M. H., Aihemaiti, S., Kan, Y., Tao, S., & Liu, H. (2026) · iScience · doi:10.1016/j.isci.2026.114842 · Cited by 7 · see citing works
“6,11 Bile acids such as CDCA activate FXR, a nuclear receptor expressed in the liver, intestine, and bone cells.”
Kouraki, A., Franks, S. J., Vijay, A., Kurien, T., Taylor, M. A., Smith, S. L., Smith, B. E., Kelly, T., & Valdes, A. M. (2026) · Nutrients · doi:10.3390/nu18050714 · Cited by 6 · see citing works
GLP-1 and GIP: Magic bullet for musculoskeletal diseases?
Fang, Q., Gan, L., Liu, P., Ding, P., & Gao, Y. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.08.046 · Cited by 5 · see citing works
“In mouse OA models, intra-articular injection of liraglutide has been proven efficient in preventing cartilage degradation [162].”
InfluentialNot Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells
Smith, E. S. J., Burton, M. D., Heegaard, A., & Stucky, C. L. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1309-25.2025 · Cited by 5 · see citing works
The role of GLP-1 in the pathophysiology and treatment of sepsis: a narrative review
Dimić, N., Djuric, M. D., Vejapi, M., Nenadic, I. B., Bobos, M. M., Bojic, S. C., Savić, P., Milanović, M., & Stevanovic, P. D. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1612034 · Cited by 6 · see citing works
A Remote-Controlled Nanopump Delivers Oxygen to Boost Energy Production in Osteoarthritis
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“While traditionally considered as a “wear-and-tear” disorder, emerging evidence reveals that OA pathogenesis involves a complex interplay of multiple risk factors such as mechanical overloading, metabolic dysregulation, and chronic low-grade inflammation [ 5–7].”
Self-citationZhu, W., Han, L., He, L., Wei, S., Li, J., Xin, L., Zhang, H., Shen, J., Song, Y., Zhou, J., et al. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04288-3 · Cited by 5 · see citing works
“Bile acids are a major class of microbiota-modulated metabolites that function not only as digestive detergents but also as endogenous signaling molecules linking intestinal microbial activity to distal organ immunity, including the gut-heart [51] and gut-joint [52] axes.”
Self-citationThe liver-bone axis: an emerging player in disease pathogenesis and therapeutic intervention
Han, S., Wei, Y., Yu, G., Jia, W., Liao, W., He, Y., Cheng, K., Zhao, J., Xiang, S., Zhang, W., et al. (2026) · Science China Life Sciences · doi:10.1007/s11427-025-3207-5 · Cited by 5 · see citing works
“…involving UDCA supplementation or the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide effectively suppress the farnesoid X receptor signaling pathway while increasing circulating GLP-1 levels, thereby significantly attenuating osteoarthritis progression (Yang et al., 2025a).”
Self-citationUrsini, F., Ciaffi, J., & Caporali, R. (2025) · RMD Open · doi:10.1136/rmdopen-2025-006025 · Cited by 3 · see citing works
“29 This experimental pathway links bile acid metabolism to joint homeostasis and supports the concept of OA as a systemically modifiable disease, not merely a consequence of mechanical overload.”
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The role of GLP-1 receptor in pain disorders and its pharmacological properties
Jing, F., Zeng, Y., Yu, Q.-L., & Fu, C. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178345 · Cited by 4 · see citing works
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Self-citationBeyond weight loss: GLP-1 emerges as a disease-modifying signal in osteoarthritis
Berenbaum, F. (2025) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2025.06.011 · Cited by 4 · see citing works
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“Nevertheless, GLP-1r expression in articular cartilage has also been confirmed by others (43, 44).”
Bile Acids Metabolism in Symptomatic Hand Osteoarthritis
Li, J., Ye, J., Yang, T., Hunter, D. J., Zhang, W., Doherty, M., Zhang, Y., Yang, Z., Li, H., Wang, Y., et al. (2025) · Arthritis & Rheumatology · doi:10.1002/art.70048 · Cited by 3 · see citing works
“34 However, the speci fi c BAs and gut microbial species associated with knee OA differed from those identi fi ed in the current study on hand OA.”
Self-citationZhang, T., Zhang, H., Chen, X., Liu, Y., Han, X., Zhu, W., Liu, Y., Zeng, G., & Jiao, K. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-025-07615-8 · Cited by 3 · see citing works
Zhang, A., Li, S., Qiao, J., Zhong, C., Zhang, Z., Ye, X., Jin, J., Shang, S., Wu, S., Zhang, Q., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121257 · Cited by 3 · see citing works
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Self-citationMurillo‐Saich, J., Mannochio-Russo, H., Sala‐Climent, M., Argel, N., Quan, A. M., Hose, M. K., Paz-González, R., Akkati, M., Chang, E. Y., Cutuk, A., et al. (2026) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2026.02.011 · Cited by 3 · see citing works
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Self-citationZhang, H., Liu, Y., Zhang, S., Wang, Z., Zhang, X., Zhang, Y., Zhang, J., Liang, S., Li, C., Su, M., et al. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04261-0 · Cited by 3 · see citing works
“safeguarding chondrocytes from endoplasmic reticulum stress and apoptosis, and displaying anti-inflammatory and antioxidant properties [15–17].”
Self-citationLv, J., Zhou, L., Dai, X., Landberg, R., Meng, H., Tian, H., Zhang, S., Liu, T., Yin, X., Zhang, J., et al. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2668127 · Cited by 3 · see citing works
“71,73,74 This coordinated signaling through nuclear and membrane bile acid receptors synergistically promotes GLP-1 production and secretion, proving UDCA as a multifaceted modulator of enteroendocrine function.”
Lin, J., Luo, M., Tang, H., Lu, K., Mou, Y., Jiang, Q., Yuan, X., Deng, Z., Xu, W., Nie, M., et al. (2026) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2026.101166 · Cited by 3 · see citing works
“This pathway antagonizes the intestinal farnesoid X receptor (FXR), thereby promoting glucagon-like peptide-1 (GLP-1) secretion and activating GLP-1R, ultimately exerting osteoarthritis protective effects [36].”
Mo, H., Hou, Y., He, J., Ruan, Z., Liang, L., Qi, J., Wang, C., Guo, F., & Peng, C. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115096 · Cited by 2 · see citing works
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Self-citationLiang, T., Jiang, T., Liang, Z., Chen, Y., Chen, T., Wang, D., Dong, B., & Wu, Q. (2026) · Journal of Future Foods · doi:10.1016/j.jfutfo.2026.02.014 · Cited by 2 · see citing works
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Self-citationMeng, Y., Li, S., Zhou, K., Suonan, Z., Dai, Z., Shen, Q., & Xue, Y. (2026) · Food Chemistry · doi:10.1016/j.foodchem.2026.149195 · Cited by 2 · see citing works
Hu, J., Luo, P., Zhang, W., Chen, T., Yang, X., Chen, Z., Huang, S., Zhang, X., Kuang, Z., & Zhang, B. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.103113 · Cited by 2 · see citing works
Self-citationYang, W., Hao, C., Wang, N., Xie, J., Zhou, B., Yang, Z., Zheng, A., Wei, J., Li, C., Xie, C., et al. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2661854 · Cited by 2 · see citing works
“16 Second, Bacteroides species facilitate the conversion of primary BAs into secondary derivatives such as ωMCA and HCA, providing ligands for GLP-1–secreting L cells.”
InfluentialSelf-citationMultiple roles of bile acids in ferroptosis regulation: Opportunities for disease therapy
Wu, N., Yu, S., Wei, X., Yang, L., & Zhang, X. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108224 · Cited by 2 · see citing works
He, J., Qin, L., & Sun, X. (2026) · Metabolites · doi:10.3390/metabo16060366 · Cited by 2 · see citing works
“X axis framework, illustrating how the GM profoundly influences distant organ systems and establishing the gut as a master regulator of systemic homeostasis [4–7].”
Hu, H., Yin, H., Liu, Y.-W., Wang, Z., & Xie, H. (2026) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2026.101139 · Cited by 2 · see citing works
“The STEP-9 trial and several cohort studies have shown that patients receiving GLP-1 RA treatment not only experience significant relief in joint pain but also have a markedly lower risk of total knee replacement (TKR) [265,266,273].”
Mechanical Activation of Piezo1 Drives Osteoarthritis Through Kdm5c‐Mediated Epigenetic Silencing
Kan, T., Li, X., Wang, H. Y., Sun, L., Wang, Y., Wu, J., Cui, J., Yang, Y., Yuan, K., Chu, L., et al. (2026) · Advanced Science · doi:10.1002/advs.76089 · Cited by 2 · see citing works
Self-citationEffects of Weight-lowering Medications in People With Obesity and Rheumatic Diseases
Karacabeyli, D., & Lacaille, D. V. (2025) · Current Treatment Options in Rheumatology · doi:10.1007/s40674-025-00232-y · Cited by 3 · see citing works
“To our knowledge, since 2021, two RCTs and three controlled cohort studies have examined the effects of GLP-1 RAs on OA-related outcomes [ 45–49 ].”
InfluentialGan, D., Qin, L., & Xiao, G. (2026) · Research · doi:10.34133/research.1319 · Cited by 1 · see citing works
“Gut dysbiosis has been implicated in RA-associated immune activation, whereas modulation of microbial BA metabolism and glucagon-like peptide-1 secretion has emerged as a potential therapeutic route in OA [ 130 ].”
Zheng, H., He, W., Tian, B., Xu, Z., Su, D., Lü, H., Li, X., Ni, H., Wei, L., Mo, X., et al. (2025) · Medicine · doi:10.1097/md.0000000000044666 · Cited by 1 · see citing works
“[5] Concurrently, microbial dysbiosis undermines the integrity of the intestinal mucosal barrier, resulting in endotoxin translocation and systemic low-grade inflammation, which creates a “synergistic effect” with local joint damage and accelerates the progression of OA.”
Resta, S., Bardi, E., D’Arrigo, D., Favaro, A., Bondi, A., & Bonanzinga, T. (2025) · Journal of Functional Foods · doi:10.1016/j.jff.2025.107078 · Cited by 1 · see citing works
Li, C., Wang, Y., Zhang, Q., Liang, H., Li, J., Zhang, S., Duan, J., & Guo, J. (2025) · Microbiome · doi:10.1186/s40168-025-02246-z · Cited by 1 · see citing works
“In osteoarthritis patients, the abundance of C. bolteae decreased, and colonization of C. bolteae alleviated osteoarthritis in mice through an FXR-mediated gut–joint axis [21].”
Self-citationGonzalez-Garcia, B., Plaza, M., Fresco, M., Aparicio, C., Rocio, A., Muriana, F. J. G., & Jaramillo-Carmona, S. M. (2026) · iScience · doi:10.1016/j.isci.2026.114813 · Cited by 1 · see citing works
A Novel FXR-Targeted DUBTAC and Its Applications in Cholestasis Therapy
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Song, H., Wang, J., Hao, Y., Li, X., Yan, S., Han, S., Zhao, J., Han, Y., Sun, S., Chen, X., et al. (2026) · Poultry Science · doi:10.1016/j.psj.2026.106927 · Cited by 1 · see citing works
Self-citationHu, D., Sun, Y., Lu, Q., Zhang, Y., Li, J., Hou, H., Wang, H., Tang, H., Zhang, Y., Zheng, X., et al. (2026) · Advanced Science · doi:10.1002/advs.202523949 · Cited by 1 · see citing works
“GLP-1 recently was also reported to alleviate osteoarthritis inflammation through the gut-joint axis [ 29 , 30 ].”
Self-citationFeng, H., Nan, J., Wu, R. Y., Zhang, B., Liu, Q., Ma, T., Zhang, Z., Hu, Y., Xie, J., & Yang, Y. (2026) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-026-00960-6 · Cited by 1 · see citing works
“However, these interventions fail to reverse disease progression or repair damaged cartilage [14], highlighting the urgent need for disease-modifying therapies.”
Self-citationYu, T., Liu, Z., Liu, Y., Gao, M., Guo, F., Liu, Y., Xiong, J., Jiang, Y., & Yan, S. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158363 · Cited by 1 · see citing works
Wang, W., Fortuna, R., Mayengbam, S., Seerattan, R. A., Mu, C., Rios, J. L., Abughazaleh, N., Vaghef‐Mehrabany, E., Tuplin, E. W. N., Hart, D. A., et al. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2679516 · Cited by 1 · see citing works
“2 In mice, farnesoid X receptor (FXR) inhibition and/or intra-articular injection of the GLP-1 receptor agonist liraglutide mitigate cartilage degradation.”
InfluentialHeading Toward a Different Future: The Microbiome, Dysbiosis, Microbial Translocation, and Beyond.
He, M.-C., Ferrini, A., Chisari, E., Kolhoff, F., Sehgal, P., & Parvizi, J. (2026) · Journal of Bone and Joint Surgery. American volume · doi:10.2106/jbjs.25.01100 · Cited by 1 · see citing works
Jiang, Y., Qin, W., Wei, L., Liao, Y., & Wei, G. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1862397 · Cited by 1 · see citing works
“Accumulating studies have verified that gut microbiota participates in the initiation and progression of OA (12, 13).”
The oral–gut microbiome axis in systemic bone-related diseases
Zhang, Z., Sun, L., Lou, F., & Xiao, J. (2026) · Oral Science and Homeostatic Medicine · doi:10.26599/oshm.2026.9610069 · Cited by 1 · see citing works
Immunomodulatory mechanisms of bile acids in autoimmune diseases along the gut-liver axis
Zhang, S., Xiong, X., Wei, S., Meng, R., An, H., & Chen, L. (2026) · Autoimmunity Reviews · doi:10.1016/j.autrev.2026.104183 · Cited by 1 · see citing works
Makarczyk, M. J., Zhang, Y., Aguglia, A. M., Bartholomew, O., Hines, S. E., Li, K., Sinkar, S., Liu, S., Duvall, C. L., & Lin, H. (2025) · eLife · doi:10.7554/elife.106224.2 · Cited by 1 · see citing works
Self-citationMakarczyk, M. J., Zhang, Y., Aguglia, A. M., Bartholomew, O., Hines, S. E., Li, K., Sinkar, S., Liu, S., Duvall, C. L., & Lin, H. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.18.643933
Self-citationMicrobiome variations in osteoarthritis reflect aging and metabolic factors, not the diseasePreprint
Bevc, K., Malfertheiner, L., Neuenschwander, S., Tran, V. D. T., Pagni, M., Pantiukh, K., Jaagura, M., Niiranen, T., Knight, R. D., Salomaa, V. V., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.24.661261
“Interestingly, one study also reported a lower abundance of Clostridium boltae and suggests that this alters microbial bile acid formation and affects OA progression 30 .”
Exploring the interactions of gut microbiome and metabolites in polycystic ovary syndrome: a review
Li, J., Jia, Y., Xu, H., Bing, H., Ling, Q., Wang, S., Wang, Y., Zhang, X., & Zhao, L. (2025) · Microbiological Research · doi:10.1016/j.micres.2025.128309
Self-citationMetformin for Treatment of Knee Osteoarthritis in Patients With Overweight or Obesity
Yen, H., Fu, S., & Chiang, C. (2025) · JAMA · doi:10.1001/jama.2025.10717
Makarczyk, M. J., Zhang, Y., Aguglia, A. M., Bartholomew, O., Hines, S. E., Li, K., Sinkar, S., Liu, S., Duvall, C. L., & Lin, H. (2025) · eLife · doi:10.7554/elife.106224.3
Self-citationHong, L., Zhu, X., Zhu, J., Chen, N., & Bao, W. (2025) · Transboundary and Emerging Diseases · doi:10.1155/tbed/2422900
“…in fl uence osteoarthritis progression and intestinal far-nesoid X receptor is a viable therapeutic target to ameliorate osteoarthritis by increasing intestinal L cell-secreted glucagon-like peptide 1, which uncovered the existence of a functional and targetable gut-joint axis in human [12].”
Wen, H., Li, J., Yin, J., Hu, Y., Wang, R., Li, H., & Zhou, S. (2025) · Journal of Future Foods · doi:10.1016/j.jfutfo.2025.12.005
Self-citationGuan, S., & Mei, Y. (2026) · International Journal of Rheumatic Diseases · doi:10.1111/1756-185x.70535
The local-mechanical and systemic-metabolic dialogue: A new dawn in osteoarthritis treatment
Wang, D., Bao, B., Hu, B., Zhang, J., Zhou, J., Zuo, J., Wang, Z., & Suo, J. (2026) · The Innovation · doi:10.1016/j.xinn.2026.101269
“Two seminal studies published in 2025, one in Cell by Zhu et al. 4 and another in Science by Yang et al., 5 have risen to this challenge.”
Wang, W., Fortuna, R., Mayengbam, S., Seerattan, R. A., Mu, C., Rios, J. L., Abughazaleh, N., Mehrabany, E. V., Tuplin, E. W. N., Hart, D. A., et al. (2026) · medRxiv · doi:10.64898/2026.01.21.26344540
Advanced Biomaterials Revolutionize Gout Therapy: From Uric Acid Degradation to Pain Alleviation
Cao, J., Gong, F., Han, Z., Qiao, X., Cui, X., & Cheng, L. (2026) · Advanced Functional Materials · doi:10.1002/adfm.202530174
“Conversely, dysbiosis of the microbiota may affect the production of these beneficial metabolites, negatively impact bone health, and trigger various types of bone inflammation [148, 149].”
Yuan, H., Wang, J., Wang, Q., Jiang, L., Liu, L., Shen, W., Li, P., Liu, W., Liu, Z., Hu, F., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.02.703430
“Recent advances in antibody engineering enable precise, instructive modulation of immune cells— particularly macrophages— in vivo [29–34].”
Intra-articular GLP-1 analogues: A new disease-modifying strategy for osteoarthritis?
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Wang, J., Shi, Y., Jia, Y., & Peng, J. (2026) · The FASEB Journal · doi:10.1096/fj.202503650rrr
“A reduced abundance of E. bolteae has been documented in patients with osteoarthritis, and its colonization has been shown to alleviate disease progression via the gut FXR-joint GLP-1 axis [46].”
Bjerkhaug, A. U., Jakobsson, J. E., Ahmed, A. S., Carlsson, H., Erngren, I., Al-Grety, A., Farinotti, A. B., Svensson, C. I., Kultima, K., & Kosek, E. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101227
“Given the availability of FDA-approved drugs that modulate bile acid metabolism (e.g., UDCA, FXR agonists/antagonists, and GLP-1R agonists), these insights may inform future personalized treatment strategies for OA that integrate metabolic and microbiota-focused approaches (Yang et al., 2025).”
InfluentialPekary, A. E., & Sattin, A. (2026) · Research Square · doi:10.21203/rs.3.rs-9162755/v1
Targeting Bifidobacterium animalis alleviates high-fluoride exposure-induced kidney injury in mice
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“Microbiome research increasingly follows a discovery-to-validation pipeline: microbiome profiling identifies candidate taxa, which are then tested in vivo using defined strains to evaluate effects beyond the gut (Gui et al. 2024; Routy et al. 2018; Yuan et al. 2019; Yang et al. 2025).”
ASSOCIATION BETWEEN HAND SYNOVITIS AND ALL-CAUSE MORTALITY: A GENERAL POPULATION-BASED STUDY
Liu, K., Weng, Q., Zhang, Y., Zhang, W., Doherty, M., Yang, T., Yang, Z., Chen, Q., Su, C., Wang, Y., et al. (2026) · Arthritis Care & Research · doi:10.1002/acr.80141
Self-citationZhang, Y., Gao, B., Zhu, X., Chen, Y., Huang, C., & Wang, G. (2025) · Archives of Clinical Rheumatology · doi:10.33696/rheumatology.1.004
Self-citationBeaulieu, M. L., Patel, N. B., & Wojtys, E. M. (2026) · Osteoarthritis and Cartilage Open · doi:10.1016/j.ocarto.2026.100807
“Notably, a recently published PTOA study provides a more specific mechanistic example of gut-joint axis [53].”
Yang, Y., Liu, X., Wang, M., Zhu, X., Yang, B., Cao, J., Song, Y., & Jiang, G. (2026) · Environment & Health · doi:10.1021/envhealth.5c00852
Self-citation
- Authors
- Yang, Y., Hao, C., Jiao, T., Yang, Z., Li, H., Zhang, Y., Zhang, W., Doherty, M., Sun, C., Yang, T., Li, J., Wu, J., Zhang, M., Wang, Y., Xie, D., Wang, T., Wang, N., Huang, X., Li, C., Gonzalez, F. J., Wei, J., Xie, C., Zeng, C., & Lei, G.
- Affiliations
- Central South University (CN)
- Chinese Academy of Sciences (CN)
- Harvard University (US)
- University of Nottingham (GB)
- Nanjing University of Chinese Medicine (CN)
- University of Toronto (CA)
- National Institutes of Health (US)
- Corresponding author
- Yang, Yuanheng
- Hao, Cong
- Jiao, Tingying
- Yang, Zidan
- Li, Hui
- Wei, Jie
- Xie, Cen
- Zeng, Chao
- Lei, Guanghua
- ORCID
- Venue
- Science
- Published
- 2025-04-04
- Volume
- 388
- Issue
- 6742
- Pages
- eadt0548-eadt0548
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4409176469
- Cited by
- 160
- References
- 91
- Citations by year
- 2026: 110 · 2025: 50
- FWCI
- 47.42
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (82 372 474, 2022YFC2505500, 81930071, 2022YFC3601900)
- Peking University
- Xiangya Hospital, Central South University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- osteoarthritis, gut-joint axis, glucagon-like peptide-1, farnesoid X receptor, glycoursodeoxycholic acid, bile acid metabolism, gut microbiota, Clostridium bolteae, ursodeoxycholic acid, GLP-1 receptor, joint replacement, microbiota-targeted therapy
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Gastrointestinal Microbiome, Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Clostridium, Female, Humans, Male, Mice, Inbred C57BL, Osteoarthritis, Ursodeoxycholic Acid, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Mice, Glucagon-Like Peptide 1
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