Protective effect of a combination of multiple strains of <i>Lactobacillus acidophilus</i> on collagen-induced arthritis

Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease. Many studies have shown that microorganisms may be an important pathological factor leading to the onset of RA. Some infectious or non-infectious pathogenic microorganisms and their metabolites may be the initiating factors of the early onset of RA. The aim of this study was to alleviate RA by regulating the imbalance of the gut microbiota in the early stage of RA using mixed bacterial strains. The mixed strains of <i>Lactobacillus acidophilus</i> (BD18, NCFM, BD1802, BD3545, BD5032) significantly reduced the clinical score and swelling thickness of the paws of collagen-induced arthritis (CIA) rats. The expression of TNF-α and MMP-13 proteins in the joints of CIA rats was also inhibited. The levels of specific antibodies (anti-CII IgG, anti-CII IgG1, anti-CII IgG2a, and anti-CII IgG2b) and inflammatory factor IL-6 in the serum of CIA rats were also significantly reduced. The relative abundance of <i>Lactobacillus</i>, <i>Clostridia</i>_UCG-014, <i>Ruminococcus</i>, <i>Candidatus</i>_<i>Saccharimonas</i>, <i>Romboutsia</i>, <i>Turicibacter</i>, and <i>Clostridium</i>_<i>sensu</i>_<i>stricto</i>_1 in the gut microbiota of CIA rats receiving oral administration of the mixed strains of <i>L. acidophilus</i> was significantly reduced, bringing their microbiota closer to that of healthy rats. Moreover, the levels of intestinal metabolites of short chain fatty acids in CIA rats, acetic acid and butyric acid, were significantly increased. The mixed strains of <i>L. acidophilus</i> could recover the relative abundance of <i>Ligilactobacillus</i>, <i>Clostridia</i>_UCG-014_unclassified, <i>Ruminococcus</i>, <i>Candidatus_Saccharimonas</i>, <i>Romboutsia</i> and <i>Turicibacter</i>, affecting purine metabolism, transcription factors and alanine metabolism, and reducing the levels of specific antibodies and inflammatory factors in the blood, finally slowing the development of experimental arthritis induced by CII, which exerts the protective effect of probiotics. Mixed <i>L. acidophilus</i> strains are more effective than a single strain, and the effect is not the result of a single strain, but of a combination of strains.