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Page 14 of 23 Poznyak et al. Microbiome Res Rep. 2026;5:3

strategies in preventing arthritis onset. While oral antibiotics may alleviate arthritis symptoms, their
preventive use could disrupt the delicate balance of the intestinal microbiota and potentially trigger RA
development. Moreover, FMT has shown promise in restoring intestinal bacterial balance and barrier
function in CIA models, but applying FMT before arthritis onset poses risks, including potential infections
and further disruption of gut microbiota .
[213]

Innovative strategies for managing gut microbiota in the early stages of RA are emerging, including the use
of probiotics, natural compounds, autophagy modulation, miRNA therapies, and vitamin D
supplementation. Natural compounds commonly used in RA treatment can effectively alleviate gut dysbiosis
while maintaining safety. Furthermore, optimizing gut microbiota could enhance the efficacy of these natural
compounds in slowing RA progression and influencing immune cell behavior. Modulating autophagy in
IECs has the potential to rebalance gut microbiota and restore intestinal barrier integrity, thereby preventing
early RA advancement, though further research is warranted in this area [214] . The ability of miRNAs and
vitamin D to influence microbiota highlights their potential roles in preventing early-stage RA. Previous
studies have indicated that probiotics can modify gut microbiota and provide symptomatic relief from RA.
Given the strong preventive effects of probiotics on RA development demonstrated in animal studies, further
investigation into their application for gut microbiota management in early RA appears promising [215] .
Additionally, combining probiotics with dietary modifications could enhance preventive measures against
RA. Therefore, a comprehensive approach that incorporates probiotics, dietary changes, natural compounds,
and vitamin D therapy to manage microbiota and prevent RA progression is a valuable avenue for future
research.

This summary underscores groundbreaking insights into how changes in microbiota during early RA can
enhance our understanding of immune dysfunctions at this stage. Several potential therapeutic strategies
have been identified that could ultimately aid in preventing RA progression and improving disease remission
during the pre-clinical phase .
[216]

CONCLUSION
The strong connection between gut microbiota and the onset of RA highlights the urgent need for early
intervention strategies targeting the preclinical phase of the disease. As emerging evidence increasingly
points to dysbiosis as a key factor in RA development, it becomes evident that understanding the dynamics
of microbiota offers a promising path for both prevention and treatment. Current therapeutic approaches
primarily focus on managing established disease, which often results in adverse side effects. In contrast,
targeting gut microbiota through dietary modifications, probiotics, and other microbiome-centered
strategies may not only restore balance but also reduce inflammation and potentially halt RA progression.

Research into specific microbial species such as P. copri and Collinsella, along with advancements in
therapies such as FMT and autophagy modulation, presents exciting opportunities for intervention.
Furthermore, investigating miRNA modulation offers valuable insights into the complex relationship
between gut health and immune function. However, additional clinical studies are necessary to validate these
strategies and assess their effectiveness in preclinical populations.

In conclusion, enhancing our understanding of the gut-joint axis creates new opportunities for RA
prevention. A proactive, multifaceted approach that combines nutritional, microbial, and immunological
insights will be essential for transforming therapeutic paradigms, ultimately leading to better outcomes for
individuals at risk for RA.

DECLARATIONS
Authors’ contributions
Writing - original draft preparation: Poznyak AV