ArticleProceedings of the National Academy of Sciences of the United States of America2016
Gut microbiota induce IGF-1 and promote bone formation and growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04015999 (Microbiota-directed Complementary Food), which is not on this map. Cited by 450 papers, 3 of them syntheses that pooled it.
What it found
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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.
Microbiota-directed Complementary Food (MDCF) Trial
Who cites it
450 citing papers in PubMed, 3 syntheses or guidelines pooled it, 710 citations in OpenAlex.
- 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
- Effectiveness of low-fat diet on the levels of insulin-like growth factor-1 and insulin-like growth factor binding proteins: a systematic review and meta-analysis of randomized controlled clinical trials.Journal of health, population, and nutrition · 2024Pooled it
- Effects of Heat-KilledNutrients · 2026Trial
- Enhancement of Lower Limb Muscle Strength and Reduction of Inflammation in the Elderly: A Randomized, Double-Blind Clinical Trial ComparingNutrients · 2025Trial
- Trial
- Trial
- Targeting the gut-bone axis in osteoporosis: probiotic interventions and other microbiota-based therapeutic strategies.Gut microbes · 2026Review
- HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation.Gut microbes · 2026Article
- The gut-bone axis: microbial metabolism and nutritional interventions for bone health.Gut microbes · 2026Review
- Effects of anti-aging diets and exercise on age-related musculoskeletal diseases via gut microbiota modulation.Annals of medicine · 2026Review
- Chondroitin sulfate modulates gut microbiota to improve bone metabolism and reduce locomotion problems in yellow-feathered broilers.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Multi-omics insights into growth impairment mechanisms in children with persistent diarrhea.Microbiology spectrum · 2026Article
- Diffuse Idiopathic Skeletal Hyperostosis (DISH): Potential Links Between Gut Microbiota and Spinal Degenerative Diseases.Nutrients · 2026Review
- Fermented protein foods as modulators of the gut-muscle axis: mechanisms, evidence, and future directions.Communications biology · 2026Review
- The Tryptophan-Kynurenine Pathway as a Key Mediator of the Gut-Brain Axis in Depression and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Probiotic supplementation promotes bone development, immune maturation, and cognitive function in growing mice.Journal of the science of food and agriculture · 2026Article
- Article
- Osteoporosis from the perspective of the gut-bone axis: gut microbiota, metabolites, and multi-system synergistic regulation.Journal of endocrinological investigation · 2026Review
- Deficiency of Natural Plant-Derived Gut Metabolites Is a Potential Cause of Skeletal Deformities in Captive-Bred Green Peafowl (Animals : an open access journal from MDPI · 2026Article
390 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.
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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.