ArticleThe Journal of clinical investigation2016
Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 409 papers, 5 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
409 citing papers in PubMed, 5 syntheses or guidelines pooled it, 605 citations in OpenAlex.
- The Health Benefits of Probiotic Lactiplantibacillus plantarum: A Systematic Review and Meta-Analysis.Probiotics and antimicrobial proteins · 2025Pooled it
- Gut microbiome and bone health: update on mechanisms, clinical correlations, and possible treatment strategies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Pooled it
- A systematic review and meta-analysis of the effects of probiotics on bone outcomes in rodent models.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Pooled it
- Causal effects of specific gut microbiota on bone mineral density: a two-sample Mendelian randomization study.Frontiers in endocrinology · 2023Pooled it
- A two-cohort study on the association between the gut microbiota and bone density, microarchitecture, and strength.Frontiers in endocrinology · 2023Pooled it
- Using probiotic supplementation to support bone health in postmenopausal women: a randomized, double-blind, parallel, placebo-controlled, multi-center study.Archives of osteoporosis · 2025Trial
- Limosilactobacillus reuteri 6475 and Prevention of Early Postmenopausal Bone Loss: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Trial
- Targeting the gut-bone axis in osteoporosis: probiotic interventions and other microbiota-based therapeutic strategies.Gut microbes · 2026Review
- Article
- The gut-bone axis: microbial metabolism and nutritional interventions for bone health.Gut microbes · 2026Review
- Article
- Bacterial small RNAs and extracellular vesicles in inflammatory and osteoimmune diseases: regulatory mechanisms and host-microbe communication.Archives of microbiology · 2026Review
- Targeting the Gut-Bone Axis with Prebiotics, Probiotics, Synbiotics, and Postbiotics: From Mechanistic Plausibility to Clinical Bone Outcomes.Nutrients · 2026Review
- Markers of compromised gut epithelial barrier integrity increase during the menopause transition.The Journal of clinical investigation · 2026Article
- Article
- Article
- Gut microbiota transmits osteoimmune dysregulation and exacerbates trabecular bone loss in tristetraprolin-deficient mice.Journal of bone and mineral metabolism · 2026Article
- Therapeutic zinc targets dysregulated GC-C signaling and restores ileal defects in a preclinical model of familial diarrheal disease.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Supplementation with the probiotic Bifidobacterium lactis BB-12 improves the efficacy of alendronate sodium/vitamin D₃ therapy on skeletal health in stage 3 CKD.Journal of endocrinological investigation · 2026Article
349 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency-induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid-deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.