Lactobacillus acidophilus Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model

Author:

O-Sullivan InSugORCID,Natarajan Anbazhagan Arivarasu,Singh GurjitORCID,Ma KaigeORCID,Green Stefan J.,Singhal Megha,Wang Jun,Kumar Anoop,Dudeja Pradeep K.,Unterman Terry G.,Votta-Velis Gina,Bruce Benjamin,van Wijnen Andre J.ORCID,Im Hee-Jeong

Abstract

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).

Funder

National Institute of Health

United States Department of Defense

United States Department of Veterans Affairs

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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