Targeted Modulation of Gut Microbiota: A New Perspective on Acupuncture for the Treatment of Knee Osteoarthritis

The gut microbiota and its metabolites play a key role in the pathological progression of knee osteoarthritis (KOA). Acupuncture may reshape gut‑microbiota profiles, repair intestinal barrier integrity and regulate immune system. Elucidating such biological effects would facilitate a systematic comprehension of the gut‑joint axis as a mediating factor in the pathogenesis and progression of KOA, as well as further mechanistic exploration of acupuncture acting through this gut‑joint axis. In recent years, a growing body of in vivo and in vitro studies has begun to offer insights into the potential mechanisms by which acupuncture may affect KOA through modulation of the gut microbiota. Therefore, it would be valuable to synthesize the existing literature on the possible role of the gut microbiota in acupuncture's effects on KOA. This will deepen our understanding of the biological effects underlying acupuncture‑based interventions. In this review, we emphasize that the regulation of acupuncture on the gut-joint axis involves multiple targets, including the types of intestinal flora, intestinal barrier function, intestinal flora metabolites, immune response, and the role of acupuncture at its own acupoints and clinical program design. Nevertheless, our review of the relevant literature indicates that the current evidence remains primarily at the preclinical stage. And there is still a lack of conclusive clinical evidence to support the hypothesis that modulating the gut microbiota is one of the mechanisms by which acupuncture exerts its therapeutic effects. Accordingly, we discuss future research directions focusing on acupoint compatibility and acupuncture parameters protocol design to decipher potential mechanisms of acupuncture modulating the gut‑joint axis interfere with KOA. This review may provide references for ongoing and future studies of acupuncture for KOA as well as for developing gut-joint-axis-centred acupuncture therapeutic strategies.