Lactobacillus (LA-1) and butyrate inhibit osteoarthritis by controlling autophagy and inflammatory cell death of chondrocytes

Abstract

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated Lactobacillus (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of Faecalibacterium which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA.

Gold nanoparticles exhibit anti-osteoarthritic effects via modulating interaction of the “microbiota-gut-joint” axis

“…Notably, the genus Lactobacillus has been widely proved to ameliorate OA and protect cartilage by modulating inflammation progression [ 64 ]. Keun Hyung Cho et al demonstrated that Lactobacillus supplement increased the level of Faecalibacterium that produces butyrate, thereby improving OA progression [ 29 ]. The InSug O Sullivan group also revealed that Lactobacillus treatment could effectively alleviate OA-related joint pain, protect against cartilage degradation, and reverse gut microbiota dysbiosis [ 65 ].…”

“…Previous studies demonstrated that the gut microbiota dominating in ACLT GNPs group such as Lactobacillus , Akkermansia , and Muribaculum were involved in the production of SCFAs [ 69 – 72 ]. In consideration of the key role of SCFAs in maintaining the homeostatic balance of intestine flora and the beneficial effects of SCFAs on alleviating OA progression, we investigated the alteration in the SCFAs concentration in fecal samples via a targeted metabolomics assay [ 29 , 73 ]. Consistent with the alteration in gut microbiota structure and composition, the PCA score plot and Orthogonal partial least-squares discriminant analysis (OPLS-DA) score plot demonstrated distinct clustering patterns, indicating a pronounced dissimilarity in the SCFA metabolism between the two groups (Fig.…”

“…Recent evidence has indicated that the levels of SCFAs (especially butyric acid) is negatively correlated with the progression of the articular cartilage matrix destruction in the context of OA [ 28 ]. Moreover, inactivated Lactobacillus (LA-1) ingestion could contribute to an increase in the abundance of SCFA (butyrate)-producing bacteria Faecalibacterium , which increases SCFA (butyric acid) levels and relieves OA-related pain by inhibiting the production of pro-inflammatory cytokines as well as reducing cartilage degradation [ 29 ]. Although the underlying pathogenesis of OA has not been entirely elucidated, accumulating research indicates that excessive inflammatory responses and immune disorders act as important factors in the destruction of cartilage and joint pain in OA.…”

Bioactives and their roles in bone metabolism of osteoarthritis: evidence and mechanisms on gut-bone axis

“…Quercetin, an antioxidant used in the treatment of osteoarthritis, influenced rat metabolome and gut microbial composition by increasing Lactobacillus species and levels of SCFAs ( 125 ). The presence of Peptostreptococcaceae and Desulfovibrio , both of which hurt the intestine, and the absence of lactic acid-producing bacteria have been shown in rat models of osteoarthritis ( 126 ). Orally supplemented butyrate and Lactobacillus acidophillus (LA-1) ameliorated osteoarthritis in rats by downregulating inflammatory cytokines and improved autophagy by reducing necroptosis factors ( 126 ).…”

Dietary fiber may benefit chondrocyte activity maintenance

“…In contrast, ablation of SESN2 masked the benefits of exercise on gut microbiota ( Yu et al., 2023 ). Factors that influence the composition of the gut microbiota, such as exercise and aging, also influence the development of OA, and SESN2 has been implicated in all of these factors, perhaps as a central mediator linking the gut-bone axis ( O'Toole and Jeffery, 2015 ; Cho et al., 2022 ).…”