{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:11:02Z","timestamp":1786565462123,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Polish National Science Centre\/Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2021\/41\/N\/NZ9\/00838"],"award-info":[{"award-number":["2021\/41\/N\/NZ9\/00838"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Osteoporosis in menopausal women requires alternatives to current medications, considering their adverse effects. In this context, probiotics and isoflavone products are promising dietary interventions. The objective of our study was to examine the impacts of Lactobacillus acidophilus and its combination with daidzein and tempeh on calcium status, calcium transporters, and bone metabolism biomarkers in a post-menopausal osteoporotic rat model. A total of 48 female Wistar rats were exposed to a two-stage experiment involving calcium deficit induction and subsequent dietary interventions across six groups. Calcium levels, the gene expression of TRPV5 and TRPV6 calcium transporters, bone histopathology, serum bone metabolism markers, and blood biochemistry were evaluated. The results revealed that, while decreasing serum calcium levels, the groups that received the probiotic L. acidophilus and isoflavone combination exhibited increased bone metabolism biomarkers and decreased calcium transporter expressions, akin to the effects of bisphosphonate. Additionally, significant improvements in bone histopathology were observed in these groups. However, the group receiving probiotic L. acidophilus alone did not exhibit significant changes in bone resorption biomarkers, calcium transporter expression, or various blood parameters. Meanwhile, the combination of probiotic L. acidophilus with tempeh positively influenced hematological parameters and reduced cholesterol and triglyceride levels, but it led to elevated blood glucose levels. Correlation analyses highlighted associations between serum calcium levels, calcium transporter expression, and bone metabolism biomarkers. In conclusion, our findings suggest that the daily consumption of probiotic L. acidophilus in combination with isoflavone products may improve bone health in ovariectomized rats, warranting further research to elucidate potential interactions with other nutrients.<\/jats:p>","DOI":"10.3390\/nu16152524","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T09:34:17Z","timestamp":1722591257000},"page":"2524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Impact of Lactobacillus acidophilus and Its Combination with Isoflavone Products on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in a Post-Menopausal Osteoporotic Rat Model"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4914-9514","authenticated-orcid":false,"given":"Iskandar Azmy","family":"Harahap","sequence":"first","affiliation":[{"name":"Department of Human Nutrition and Dietetics, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, 60-624 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8417-2245","authenticated-orcid":false,"given":"Marcin","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Microbiology, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-6905","authenticated-orcid":false,"given":"Ewa","family":"Pruszy\u0144ska-Oszma\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, Biochemistry and Biostructure, Faculty of Veterinary Medicine and Animal Science, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Sassek","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, Biochemistry and Biostructure, Faculty of Veterinary Medicine and Animal Science, Poznan University of Life Sciences, 60-637 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0937-8427","authenticated-orcid":false,"given":"Joanna","family":"Suliburska","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition and Dietetics, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, 60-624 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106020","DOI":"10.1016\/j.phrs.2021.106020","article-title":"Lactobacillus acidophilus ameliorates obesity in mice through modulation of gut microbiota dysbiosis and intestinal permeability","volume":"175","author":"Kang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.nutres.2008.02.002","article-title":"Growth of preschool children was improved when fed an iron-fortified fermented milk beverage supplemented with Lactobacillus acidophilus","volume":"28","author":"Silva","year":"2008","journal-title":"Nutr. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhou, J., Cheng, J., Liu, L., Luo, J., and Peng, X. (2023). Lactobacillus acidophilus (LA) Fermenting Astragalus Polysaccharides (APS) Improves Calcium Absorption and Osteoporosis by Altering Gut Microbiota. Foods, 12.","DOI":"10.3390\/foods12020275"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"115317","DOI":"10.1016\/j.bone.2020.115317","article-title":"The role of gut microbiota in bone homeostasis","volume":"135","author":"Behera","year":"2020","journal-title":"Bone"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/cei.12474","article-title":"Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota","volume":"179","author":"Peterson","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"McCabe, L.R. (2017). Understanding the Gut-Bone Signaling Axis, Springer.","DOI":"10.1007\/978-3-319-66653-2"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Harahap, I.A., and Suliburska, J. (2021). Probiotics and Isoflavones as a Promising Therapeutic for Calcium Status and Bone Health: A Narrative Review. Foods, 10.","DOI":"10.3390\/foods10112685"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1007\/s00198-020-05476-z","article-title":"Effects of isoflavone interventions on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials","volume":"31","author":"Sansai","year":"2020","journal-title":"Osteoporos. Int."},{"key":"ref_10","first-page":"651","article-title":"The physiological actions of isoflavone phytoestrogens","volume":"59","author":"Jagla","year":"2010","journal-title":"Physiol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ejphar.2014.07.057","article-title":"Phytoestrogens and their effects","volume":"741","author":"Alexander","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s13318-012-0112-y","article-title":"Isoflavones: Estrogenic activity, biological effect and bioavailability","volume":"38","author":"Vitale","year":"2013","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hooshiar, S.H., Tobeiha, M., and Jafarnejad, S. (2022). Soy Isoflavones and Bone Health: Focus on the RANKL\/RANK\/OPG Pathway. Biomed Res. Int., 2022.","DOI":"10.1155\/2022\/8862278"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1080\/10408398.2014.989958","article-title":"An updated review of dietary isoflavones: Nutrition, processing, bioavailability and impacts on human health","volume":"57","author":"Zaheer","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1016\/j.foodchem.2013.05.017","article-title":"Effect of soybean processing on content and bioaccessibility of folate, vitamin B12 and isoflavones in tofu and tempe","volume":"141","author":"Moa","year":"2013","journal-title":"Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s00198-005-2035-9","article-title":"The role of collagen in bone strength","volume":"17","author":"Garnero","year":"2006","journal-title":"Osteoporos. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.ctrv.2008.05.001","article-title":"Bone markers and their prognostic value in metastatic bone disease: Clinical evidence and future directions","volume":"34","author":"Coleman","year":"2008","journal-title":"Cancer Treat. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s11033-021-06794-z","article-title":"The role of TRPV channels in osteoporosis","volume":"49","author":"Liu","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e16801","DOI":"10.1016\/j.heliyon.2023.e16801","article-title":"Isoflavones and probiotics effect on bone calcium and bone cells in rats","volume":"9","author":"Harahap","year":"2023","journal-title":"Heliyon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1002\/fsn3.3571","article-title":"Effects of isoflavone and probiotic intake on calcium transport and bone metabolism biomarkers in female rats","volume":"11","author":"Harahap","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Harahap, I.A., Kuligowski, M., Cieslak, A., Ko\u0142odziejski, P.A., and Suliburska, J. (2024). Effect of Tempeh and Daidzein on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in Ovariectomized Rats. Nutrients, 16.","DOI":"10.3390\/nu16050651"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1080\/10408398.2011.621169","article-title":"Lactobacillus acidophilus: Characterization of the Species and Application in Food Production","volume":"54","author":"Anjum","year":"2014","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.anaerobe.2012.03.002","article-title":"The prebiotic source influences the growth, biochemical features and survival under simulated gastrointestinal conditions of the probiotic Lactobacillus acidophilus","volume":"18","author":"Nazzaro","year":"2012","journal-title":"Anaerobe"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ijos.2014.52","article-title":"Probiotics to counteract biofilm-associated infections: Promising and conflicting data","volume":"6","author":"Vuotto","year":"2014","journal-title":"Int. J. Oral Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/ilar.43.4.202","article-title":"Practical aspects of experimental design in animal research","volume":"43","author":"Johnson","year":"2002","journal-title":"ILAR J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/ilar\/ilu043","article-title":"The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies","volume":"55","author":"Wever","year":"2014","journal-title":"ILAR J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.nbd.2013.10.014","article-title":"Mesenchymal stem cells improve locomotor recovery in traumatic spinal cord injury: Systematic review with meta-analyses of rat models","volume":"62","author":"Oliveri","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1017\/S0007114512001195","article-title":"Magnesium and calcium deficiencies additively increase zinc concentrations and metallothionein expression in the rat liver","volume":"109","author":"Kotani","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1263\/jbb.100.685","article-title":"Analysis of isoflavone content in tempeh, a fermented soybean, and preparation of a new isoflavone-enriched tempeh","volume":"100","author":"Nakajima","year":"2005","journal-title":"J. Biosci. Bioeng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/aps.2012.170","article-title":"Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats","volume":"34","author":"Fu","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bonr.2018.02.001","article-title":"Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance","volume":"8","author":"Dar","year":"2018","journal-title":"Bone Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Szuli\u0144ska, M., \u0141oniewski, I., Skrypnik, K., Sobieska, M., Korybalska, K., Suliburska, J., and Bogda\u0144ski, P. (2018). Multispecies probiotic supplementation favorably affects vascular function and reduces arterial stiffness in obese postmenopausal women\u2014A 12-week placebo-controlled and randomized clinical study. Nutrients, 10.","DOI":"10.3390\/nu10111672"},{"key":"ref_34","first-page":"149","article-title":"Food or fluid restriction in common laboratory animals: Balancing welfare considerations with scientific inquiry","volume":"57","author":"Rowland","year":"2007","journal-title":"Comp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/aps.2012.160","article-title":"Assessment of the estrogenic activities of chickpea (Cicer arietinum L.) sprout isoflavone extract in ovariectomized rats","volume":"34","author":"Ma","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1016\/j.clnu.2017.11.002","article-title":"Novel effects of phytoestrogenic soy isoflavones on serum calcium and chloride in premenopausal women: A 2-year double-blind, randomized, placebo-controlled study","volume":"37","author":"Lu","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100336","DOI":"10.1016\/j.phanu.2023.100336","article-title":"Can probiotics decrease the risk of postmenopausal osteoporosis in women?","volume":"24","author":"Harahap","year":"2023","journal-title":"PharmaNutrition"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1248\/jhs.48.209","article-title":"Isoflavone and bone metabolism: Its cellular mechanism and preventive role in bone loss","volume":"48","author":"Yamaguchi","year":"2002","journal-title":"J. Heal. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jff.2018.07.008","article-title":"Beneficial changes of gut microbiota and metabolism in weaned rats with Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 supplementation","volume":"48","author":"Wang","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature10098","article-title":"Global quantification of mammalian gene expression control","volume":"473","author":"Busse","year":"2011","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.2215\/CJN.09750913","article-title":"Renal Control of Calcium, Phosphate, and Magnesium Homeostasis","volume":"10","author":"Blaine","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1210\/endrev\/bnac017","article-title":"Estrogen Receptor Signaling in the Immune System","volume":"44","author":"Chakraborty","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Harahap, I.A., Kuligowski, M., Schmidt, M., and Suliburska, J. (2023). The impact of soy products, isoflavones, and Lactobacillus acidophilus on iron status and morphological parameters in healthy female rats. J. Trace Elem. Med. Biol., 78.","DOI":"10.1016\/j.jtemb.2023.127183"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1021\/jf00053a028","article-title":"Ferrous iron oxidation by Lactobacillus acidophilus and its metabolic products","volume":"43","author":"Kot","year":"1995","journal-title":"J. Agric. Food Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3177\/jnsv.40.613","article-title":"Effect of Lactobacillus acidophilus on Iron Bioavailability in Rats","volume":"40","author":"Oda","year":"1994","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1182\/blood-2006-08-019083","article-title":"New agents that stimulate erythropoiesis","volume":"109","author":"Bunn","year":"2007","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1002\/fsn3.3319","article-title":"The effects of using Tempeh as a supplement for type 2 diabetes","volume":"11","author":"Su","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Huang, Y.C., Wu, B.H., Chu, Y.L., Chang, W.C., and Wu, M.C. (2018). Effects of tempeh fermentation with lactobacillus plantarum and rhizopus oligosporus on streptozotocin-induced type II diabetes mellitus in rats. Nutrients, 10.","DOI":"10.20944\/preprints201807.0613.v1"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9961","DOI":"10.1080\/10408398.2022.2076651","article-title":"Dietary regulations for microbiota dysbiosis among post-menopausal women with type 2 diabetes","volume":"63","author":"Singh","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/j.1365-2672.2007.03438.x","article-title":"Endogenous \u03b2-glucosidase and \u03b2-galactosidase activities from selected probiotic micro-organisms and their role in isoflavone biotransformation in soymilk","volume":"103","author":"Otieno","year":"2007","journal-title":"J. Appl. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Reamtong, O., Thiangtrongjit, T., Kosoltanapiwat, N., Panbangred, W., and Prangthip, P. (2021). Potential benefits of L. acidophilus in dyslipidemic rats. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85427-8"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9931","DOI":"10.1080\/07391102.2022.2148752","article-title":"Understanding hypocholesterolemic activity of soy isoflavones: Completing the puzzle through computational simulations","volume":"41","author":"Hermanto","year":"2023","journal-title":"J. Biomol. Struct. Dyn."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/15\/2524\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:28:45Z","timestamp":1760110125000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/15\/2524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,2]]},"references-count":52,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["nu16152524"],"URL":"https:\/\/doi.org\/10.3390\/nu16152524","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,2]]}}}