Bacterial small RNAs and extracellular vesicles in inflammatory and osteoimmune diseases: regulatory mechanisms and host-microbe communication.

Bacterial small RNAs (sRNAs) functions as post-transcriptional regulators that influnce microbial adaptation, pathobiont behavior, and host-microbe communication. This review analyzes bacterial sRNAs and vesicle-associated RNA signals in inflammatory and osteoimmune diseases, with a focus on gastrointestinal and oral microbial communities. Major sRNA classes and mechanisms are summarized, followed by an evaluation of evidence in gastrointestinal inflammation, periodontitis, rheumatoid arthritis, osteoarthritis, and postmenopausal osteoporosis. Direct disease-related evidence is currently limited. The most robust mechanistic example is Porphyromonas gingivalis vesicle-associated sRNA45033, which targets the 3' untranslated region (UTR) of CBX5 and regulates apoptosis in periodontal ligament cell, P. gingivalis outer membrane vesicles also promote alveolar bone resorption in vivo. Human studies in rheumatoid arthritis provide emerging associative evidence, while evidence in osteoarthritis and osteoporosis remains primarily indirect. Future research integrating small RNA sequencing, metatranscriptomics, extracellular vesicle profiling, and functional validation is required to establish causal roles and biomarker potential.