{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T03:54:55Z","timestamp":1781495695199,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Province agricultural science and technology basic scientific research business fee","award":["KYJF2023JJ103"],"award-info":[{"award-number":["KYJF2023JJ103"]}]},{"name":"Jilin Province agricultural science and technology basic scientific research business fee","award":["KYJF2026ZY015"],"award-info":[{"award-number":["KYJF2026ZY015"]}]},{"name":"Jilin Province Agricultural Science and Technology Innovation Project","award":["CXGC2025ZD012"],"award-info":[{"award-number":["CXGC2025ZD012"]}]},{"name":"Jilin Province Agricultural Science and Technology Innovation Project","award":["CXGC2025RCY038"],"award-info":[{"award-number":["CXGC2025RCY038"]}]},{"name":"Jilin Province Agricultural Science and Technology Innovation Project","award":["CXGC2023RCY026"],"award-info":[{"award-number":["CXGC2023RCY026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Natto, a well-known fermented soybean product beneficial for bone health, remains unclear in its mechanism. Methods: This study investigated its effect on secondary osteoporosis (OP) in mice. Results: Natto significantly inhibited weight loss, bone quality deterioration, and bone morphological damage, and regulated OPG\/RANKL pathway protein expression (p &lt; 0.05) in OP mice. Analysis of 16S rRNA revealed that natto increased gut microbiota \u03b1-diversity and the abundance of Sutterella, Roseburia, and Coprococcus, while reducing harmful bacteria such as Streptococcus, Shigella, and Helicobacter. These microbial changes positively correlated with body weight, bone size, and serum osteogenic metabolism in OP mice. Serum metabolomics showed differential metabolites of the natto group enriched in PPAR signaling and primary bile acid biosynthesis. Verification by mRNA and ELISA indicated that the upregulated liver and circulating PPAR\u03b1 by natto may regulate downstream bile acid pathways, linking gut microbiota to multi-organ metabolic functions. Conclusions: In summary, natto may act on gut microbiota to alleviate bone loss via the \u201cgut microbiota\u2013bile acid\u2013OPG\/RANKL\u201d network, targeting multiple organs including gut, liver, and bone. This provides a theoretical basis for natto dietary intervention in osteoporosis prevention through the gut\u2013bone axis.<\/jats:p>","DOI":"10.3390\/nu18121927","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T03:01:27Z","timestamp":1781492487000},"page":"1927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natto May Alleviate Retinoic Acid-Induced Osteoporosis by Activating Gut Microbiota\u2013Bile Acid Axis and OPG\/RANKL Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Bimi","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, China"},{"name":"Food and Drug Engineering Institute, Jilin Provincial Institute of Economic Management and Administration, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubai","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfu","family":"Liu","sequence":"additional","affiliation":[{"name":"Jilin Province Agricultural Product Processing Promotion Center, Changchun 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7880-8337","authenticated-orcid":false,"given":"Tong","family":"Pan","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuecong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguang","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuetong","family":"Gan","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghong","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-8065","authenticated-orcid":false,"given":"Mei","family":"Hua","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3125-2107","authenticated-orcid":false,"given":"Jinghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China), 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