Pharmacokinetic and gut microbiota analyses revealed the effect of Lactobacillus acidophilus on the metabolism of Olsalazine in ulcerative colitis rats

Olsalazine is a typical 5-aminosalicylic acid (5-ASA) drug that depends on gut microbiota to liberate its anti-inflammatory moiety 5-ASA in the treatment of ulcerative colitis (UC). In recent decades, 5-ASA drugs combined with probiotics have achieved a better effective treatment for UC. Mechanisms of combination therapy have been widely discussed from a pharmacodynamic perspective. However, it is still unclear whether the better therapeutic efficacy of combination therapy was made by changing the metabolism of 5-ASA drugs in the colon under the regulation of probiotics. In the present study, combined with pharmacokinetic and gut microbiota analyses, we systematically evaluated the potential effect of Lactobacillus acidophilus (L. acidophilus) on the metabolism of Olsalazine at three levels (pharmacokinetic characteristics, metabolic microbiota, and metabolic enzymes) to offer some insights into this issue. As pharmacokinetic results showed, L. acidophilus barely had an influence on the pharmacokinetic parameters of Olsalazine, 5-ASA, and N-Ac-5-ASA. Notably, the colonic exposure of 5-ASA was not affected by L. acidophilus. Gut microbiota results also illustrated that L. acidophilus did not change the total abundance of azoreductase (azoR) and N-acetyltransferase (NAT) associated gut microbiota and enzymes, which are involved in the metabolism of Olsalazine. Both pharmacokinetic and gut microbiota results revealed that L. acidophilus did not increase the colonic exposure of 5-ASA to improve the efficacy of combination therapy. L. acidophilus played its role in UC treatment by regulating gut microbiota composition and amino acid, phenolic acid, oligosaccharide, and peptidoglycan metabolic pathways. There was no potential medication risk of combination therapy of Olsalazine and L. acidophilus. In summary, this research provided strong evidence of medication safety and a comprehensive understanding of therapeutic advantages for combination therapy of probiotics and 5-ASA drugs from the pharmacokinetic and gut microbiota perspectives.