Fast-Growing Broilers Pay a Bone Price Through the Gut-Bone Axis

Broiler chickens bred to pack on weight at extraordinary speed are paying a hidden price in their legs, and a new study suggests the damage may travel through an unexpected route: the gut. In a controlled experiment with 300 Arbor Acres broilers raised for 21 days, researchers found that birds gaining weight fastest showed measurably worse tibial health than slower-growing flockmates, with structural bone damage, disrupted bone-remodeling signals, and shifts in both cecal microbes and blood metabolites that track with the injury. The work, published in the journal Animal Diseases, frames rapid growth not just as a skeletal problem but as a whole-body one, mediated in part by the gut–bone axis.

The team, led by Wenli Ding and Shucheng Huang, sorted the birds on day 14 by extreme phenotype sampling: the heaviest 35% formed a high body weight group and the lightest 35% formed a low body weight group, with 30 broilers sampled per group. By days 14 and 21, the heavy birds had growth rates 20.93% and 40.51% above the low group, and their feed intake area under the curve was substantially greater. The heavier birds also had heavier, longer, and thicker tibiae, which might at first glance look like better bone development. But the relationship between body weight and tibial morphology told a different story. Pearson correlation analysis showed that tibial weight, length, diameter, and growth plate width were negatively correlated with body weight within the high group, with tibial weight and growth plate width showing significant negative associations (R = 0.2203, p = 0.002 and R = 0.1637, p = 0.012, respectively). In other words, as these birds grew faster, their tibiae were not keeping proportional pace.

Histology sharpened that picture. Hematoxylin and eosin staining of tibial sections revealed that the trabecular structure in the high-weight group was incomplete, marked by fractures, expansions, void enlargements, and a reduced trabecular area, while the low group retained a complete trabecular network with closely connected bone trabeculae merging into larger pieces; the trabecular area was significantly larger in the low group (p = 0.0015). Safranin-O/Fast Green staining showed that new bone formation in the trabeculae of the high group was absent or reduced, and quantitative analysis confirmed the proportion of new bone formation was significantly lower than in the low group (p < 0.01). Toluidine blue staining revealed severe disorganization of chondrocyte arrangement in the fast-growing birds, with some chondrocytes showing blurred morphology, nuclear dissolution, and degeneration that left small, vacuole-filled cartilage cavities, although the tibial cartilage area itself did not differ significantly between groups (p = 0.142). Goldner’s trichrome staining added the final piece: the relative area of mineralized bone was substantially decreased in the high group (p = 0.0028). Together, the stains indicate that rapid weight gain is associated with reduced trabecular bone and mineralization in the tibia.

The molecular signature of that damage centers on the RANKL/RANK/OPG system, the core regulatory circuit that balances osteoblast-mediated bone formation against osteoclast-mediated resorption. In the tibial growth plate, RANKL and RANK expression were increased in the high group, particularly on day 21, while the OPG/RANKL ratio was significantly lower at both time points (p = 0.02 and p < 0.001). Osteogenic markers told a consistent story: mRNA levels of BMP-2, RUNX2, and VEGF, key regulators of osteoblast differentiation, bone matrix formation, and angiogenesis, were consistently higher in the low group, with significant differences for BMP-2 and VEGF (p = 0.019 and p < 0.001). Inflammatory markers shifted in parallel. Pro-inflammatory cytokines TNF-α and IL-1β were higher in the high group, whereas the anti-inflammatory cytokine IL-10 was significantly elevated in the low group at both time points. Western blotting at day 21 confirmed that protein levels of OPG, VEGF, and RUNX2 were significantly increased in the low group, while RANKL protein showed no significant difference. Immunohistochemistry for osteocalcin, an osteoblast-derived protein involved in mineralization, revealed significantly higher OCN-positive areas in the low group at both magnifications tested (p < 0.001 for both), pointing to enhanced osteoblast maturation and bone matrix deposition under slower growth.

To probe the mechanisms behind the damage, the researchers turned to transcriptome sequencing of the tibial growth plate. Principal component analysis separated the two groups clearly, and 477 differentially expressed genes emerged, 332 upregulated and 145 downregulated, using a threshold of |Log2FC| > 2 and p < 0.05. Gene Ontology analysis linked these genes to myofibrils, contractile fibers, sarcomeres, muscle system processes, muscle contraction, and striated muscle cell development, while KEGG analysis flagged adrenergic signaling in cardiomyocytes, cardiac muscle contraction, calcium signaling pathways, and, notably, focal adhesion. Among the top 40 differentially expressed genes, three muscle-related regulators stood out: phospholamban (PLN), myosin light-chain kinase 2 (MYLK2), and calcium voltage-gated channel subunit alpha1 S (CACNA1S). Their expression was significantly negatively correlated with RANKL and positively correlated with OPG, and excessive weight gain reduced their expression, a result the authors validated by qPCR for MYLK2 and CACNA1S (p = 0.003 and p = 0.002). The pattern suggests potential muscle–bone communication during rapid growth, with muscle-support functions weakening as body mass accelerates.

The focal adhesion pathway proved to be a central thread. Focal adhesion kinase (FAK) regulates the PI3K/Akt signaling pathway and promotes osteoblast differentiation and maturation, and western blotting showed that rapid weight gain significantly reduced protein expression of FAK, PI3K, and Akt in the tibiae (p = 0.019, p = 0.005, and p < 0.001, respectively). Because FAK-mediated PI3K/Akt signaling is known to promote osteoblast differentiation, extracellular matrix deposition, and bone regeneration, the authors argue that its suppression in fast-growing broilers may contribute to impaired osteoblast function and defective trabecular formation. The transcriptomic and protein-level findings converge on a single mechanism: rapid growth appears to dampen a signaling route that bone cells need to build and maintain the trabecular scaffold that carries the bird’s weight.

The gut side of the gut–bone axis showed its own rearrangements. Using full-length 16S rRNA gene sequencing on the PacBio Sequel II platform, the team profiled cecal contents from six birds per group. Alpha diversity indices, including Chao1, observed species, Shannon, and Simpson, did not differ significantly between groups, though all four values trended lower in the high group. But community composition told a sharper story: the PCA plot revealed differences in microbiological profiles (ANOSIM, R2 = 0.1908, p = 0.008), and the number of group-specific OTUs was 15,425 in the low group versus 10,065 in the high group, with 4,372 core OTUs shared. At the phylum level, Bacteroidetes accounted for 6.8% of the low group’s cecal community but only 2.6% of the high group’s, and the high group also showed significantly lower levels of Acidobacteria, Euryarchaeota, and Planctomycetes. At the species level, Ligilactobacillus aviarius_B was significantly less abundant in the high group (p = 0.007), whereas L. salivarius and Limosilactobacillus reuteri were significantly more abundant (p = 0.02 and p = 0.023, respectively). Linear discriminant analysis effect size analysis found the low group characterized by significantly increased abundance of L. salivarius.

Blood metabolomics connected those microbial shifts to circulating chemistry. Untargeted LC–MS/MS analysis identified 134 differentially abundant metabolites, 91 upregulated and 43 downregulated, and KEGG pathway analysis pointed to ABC transporters, biosynthesis of amino acids, and 2-oxocarboxylic acid metabolism as the major enriched pathways. Random forest analysis ranked succinic acid as the most important metabolite, and overlap between differential abundance and importance rankings highlighted six key metabolites. Among them, rapid weight gain significantly increased the abundance of 3-pyridylacetic acid, Indaziflam, hyodeoxycholic acid, and chenodeoxycholic acid (all p = 0.004), while decreasing didehydrooxayohimban-16-carboxylate and palmitoylglycine. The bile acids are the striking part: hyodeoxycholic acid and chenodeoxycholic acid were negatively correlated with tibial development in the study’s correlations, and previous research has shown that excessive bile acid accumulation can disrupt bone remodeling by affecting osteoblast activity and osteoclast function. In this study, increased bile acid levels coincided with reduced OCN expression and impaired tibial structure, suggesting that microbiota-derived metabolites may serve as a mediator connecting intestinal dysbiosis with bone dysfunction.

Correlation analysis wove the threads together. Limosilactobacillus reuteri was negatively correlated with BMP-2, while L. aviarius_B was positively correlated with RUNX2 and significantly associated with didehydrooxayohimban-16-carboxylate and Indaziflam. These associations, the authors write, support the possibility that rapid weight gain impairs tibial health through coordinated changes in gut microbiota composition, circulating metabolites, and bone remodeling processes. The context matters: over the past 60 years, commercial broiler weight gain has more than quadrupled, rising from 25 g/day in the 1950s to 100 g/day in 2008, and recent surveys of commercial flocks have found that approximately 30% of birds exhibit mobility problems, with 3.3% nearly incapable of movement. Fast muscle growth that outpaces bone development is a recognized driver of lameness and welfare compromise in poultry, and this study adds a molecular and microbial dimension to that well-documented problem.

The authors are careful about what the data can and cannot show. The multi-omics results are primarily correlational, so a direct causal relationship between the gut microbiota, bile acid metabolism, and tibial damage cannot be established from this study alone. Key metabolites such as deoxycholic acid and chenodeoxycholic acid require validation through targeted quantitative methods, and functional validation is needed to determine whether the identified microorganisms or metabolites directly regulate osteoblast and osteoclast activity. The team also acknowledges that extreme phenotype sampling may enhance inter-individual variation and limit generalizability, and they call for future work including fecal microbiota transplantation, targeted probiotic or bile acid interventions, and in vitro osteocyte experiments to test causality. Even so, the study offers poultry producers a concrete lead: managing growth rate, and potentially the gut microbes and bile acid profiles that accompany it, may help protect the skeletal health of birds bred for speed.

Subject of Research: Associations between rapid weight gain, tibial bone health, the gut microbiota, and blood metabolites in broiler chickens

Article Title: Rapid weight gain as a factor compromising tibial health via the gut‒bone axis in broiler chickens

Article References: Ding, W., Zhang, Z., Guo, F., Sun, A., Iqbal, M. K., Shaukat, A., & Huang, S. (2026). Rapid weight gain as a factor compromising tibial health via the gut‒bone axis in broiler chickens. Animal Diseases, 6(1), Article 61. https://doi.org/10.1186/s44149-026-00280-4

Image Credits: AI Generated

DOI: 10.1186/s44149-026-00280-4

Keywords: broiler chickens, tibial health, gut-bone axis, RANKL/RANK/OPG, FAK/PI3K/Akt, cecal microbiota, bile acids, bone remodeling, transcriptomics, 16S rRNA sequencing, metabolomics, poultry welfare