<i>Lactobacillus acidophilus</i> Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model
InSug O-Sullivan,
Arivarasu Natarajan Anbazhagan,
Gurjit Singh,
Kaige Ma,
Stefan J. Green,
Megha Singhal,
Jun Wang,
Anoop Kumar,
Pradeep K. Dudeja,
Terry G. Unterman,
Gina Votta-Velis,
Benjamin Bruce,
Andre J. van Wijnen,
Hee-Jeong Im
Affiliations
InSug O-Sullivan
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA
Arivarasu Natarajan Anbazhagan
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA
Gurjit Singh
Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60612, USA
Kaige Ma
Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60612, USA
Stefan J. Green
Genomic Research Core, Research Resources Center, University of Illinois Chicago, Chicago, IL 60612, USA
Megha Singhal
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA
Jun Wang
Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60612, USA
Anoop Kumar
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA
Pradeep K. Dudeja
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA
Terry G. Unterman
Department of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA
Gina Votta-Velis
Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA
Benjamin Bruce
Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA
Andre J. van Wijnen
Biochemistry, University of Vermont, Burlington, VT 05405, USA
Hee-Jeong Im
Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60612, USA
To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia and distal colon by Safranin O/fast green staining, immunofluorescence microscopy and RT-qPCR. LA acutely reduced inflammatory knee joint pain and prevented further OA progression. The therapeutic efficacy of LA was supported by a significant reduction of cartilage-degrading enzymes, pain markers and inflammatory factors in the tissues we examined. This finding suggests a likely clinical effect of LA on OA. The effect of LA treatment on the fecal microbiome was assessed by 16S rRNA gene amplicon sequencing analysis. LA significantly altered the fecal microbiota compared to vehicle-treated mice (PERMANOVA p < 0.009). Our pre-clinical OA animal model revealed significant OA disease modifying effects of LA as reflected by rapid joint pain reduction, cartilage protection, and reversal of dysbiosis. Our findings suggest that LA treatment has beneficial systemic effects that can potentially be developed as a safe OA disease-modifying drug (OADMD).
