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Review
. 2025 Dec;17(1):2545417.
doi: 10.1080/19490976.2025.2545417. Epub 2025 Aug 28.

Interactions between the gut microbiota and immune cell dynamics: novel insights into the gut-bone axis

Yanghao You  1 , Tingwen Xiang  1 , Chuan Yang  1   2 , Shiyu Xiao  1 , Yong Tang  1 , Gang Luo  3 , Zhiguo Ling  4 , Fei Luo  1 , Yueqi Chen  1   5
Affiliations
Review

Interactions between the gut microbiota and immune cell dynamics: novel insights into the gut-bone axis

Yanghao You et al. Gut Microbes. 2025 Dec.

Abstract

Over the past few decades, accumulating evidence has demonstrated that gut microbiota engages in a sustained dialog with the immune system, leading to microbiota-driven immune responses that mediate the regulation of bone-related diseases. Despite the complexity of the dynamic interactions within the gut-immune-bone axis, advancements in high-throughput multi-omics sequencing have significantly facilitated the detailed exploration of this intricate network, thereby providing the potential to develop novel therapeutic strategies for bone-related diseases. In this review, we first summarize the variations in gut microbiota composition observed in patients with bone-related diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and osteoporosis (OP), in comparison to healthy controls, along with the factors influencing these changes. The review that follows synthesize evidences highlighting the profound effects of gut microbial dysbiosis on immune homeostasis and bone microenvironment, respectively. We further elaborate that the gut-immune axis and gut-bone axis are not independent but three-dimensional networks, emphasizing gut microbial dysbiosis as a pivotal driver of immune dysregulation and subsequent bone homeostasis imbalance. Therapeutic strategies to manipulate the gut-immune-bone axis based on the use of probiotics as well as prebiotics, fecal microbiota transplantation, dietary modifications, and pharmacological interventions are also discussed. Finally, we discuss the challenges of current research on the gut-immune-bone axis and propose future directions for identifying novel therapeutic targets based on this axis to treat these diseases.

Keywords: Gut microbiota; bone homeostasis; bone-related diseases; gut-immune-bone axis.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Association between gut dysbiosis and bone-related diseases.
Figure 2.
Figure 2.
Immunomodulatory mechanisms of gut microbiota.
Figure 3.
Figure 3.
Gut microbiota-mediated modulation of the bone microenvironment.
Figure 4.
Figure 4.
Gut-immune-bone axis regulatory mechanisms.
Figure 5.
Figure 5.
Therapeutic strategies targeting the gut-immune-bone axis.
See this image and copyright information in PMC

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