Conjunctival Sac‐Derived Lactobacillus mucosae MM‐1 Metabolite Indole‐3‐Lactic Acid Attenuates Lens‐Induced Myopia in Mice via AHR Activation and TGF‐β/Smad Inhibition

ABSTRACT

Emerging research has revealed a diverse microbiota in the high myopia (HM) conjunctival sac, highlighting the therapeutic potential of modulating this community to influence disease outcomes. However, current research on targeted modulation of this microbiota for myopia intervention lacks in‐depth investigation and definitive conclusions regarding its efficacy and underlying mechanisms. In this study, high‐throughput sequencing and culturomics were first used to screen the conjunctival sac microbiota of healthy people, identifying Lactobacillus mucosae MM‐1 as a potential probiotic for myopia control. Then, animal studies further confirmed that L. mucosae MM‐1 significantly attenuated lens‐induced myopia, improved COL1A1 expression and scleral integrity and elevated Lactobacillus abundance. Furthermore, untargeted metabolomics analysis suggested that indole‐3‐lactic acid (ILA) may be a key substance for L. mucosae MM‐1 to exert its effects for myopia control. Mechanistically, pharmacological ILA supplementation supports the involvement of AHR in TGF‐β/Smad pathway inhibition, accompanied by altered COL1A1 and α‐SMA expression and attenuation of lens‐induced myopia in mice. Therefore, these findings suggest that L. mucosae MM‐1 may attenuate lens‐induced myopia in mice, at least in part, through ILA‐mediated regulation of the TGF‐β/Smad pathway, and offer a theoretical foundation for future therapeutic strategies based on conjunctival sac microbiome manipulation.