This study investigated the effects of Lactobacillus delbrueckii and Lacticaseibacillus rhamnosus (LD+LR) on the pharmacokinetics (PK) and withdrawal time (WDT) of florfenicol (FF) and the relationship of these effects to the gut microbiota in Nile tilapia. After 10 days of LD+LR or saline administration, fish received either a single dose of FF at 10 mg/kg body weight for PK analysis or five consecutive days of medication for WDT assessment. In the PK study, pretreatment with LD+LR reduced the elimination half-life (t₁/₂_β) by 5.1 hours, decreased the maximum serum concentration (C_max) by 40%, decreased the area under the concentration–time curve (AUC) by 49%, and increased clearance (CL/F) by 2.1-fold compared with controls. Under multiple-dose conditions, LD+LR pretreatment increased florfenicol amine (FFA) concentrations and FFA/FF ratios and reduced the WDT by two days. Next-generation sequencing of the gut microbiota revealed that LD+LR administration increased overall microbial richness and the relative abundance of Bacilli, coinciding with upregulation of the Cyp3A40 gene and enhanced hepatic CYP3A activity. The results suggest that the Lactobacilli mixture may influence FF disposition, potentially in part involving microbiota-associated regulation of CYP3A activity, which may warrant consideration in dosage optimization.

To Cite This Article: Wu CM, Rairat T, Lu YP, Chen PW, Faqir M, Rodkhum C and Chou CC, 2026. Effects of a lactobacillus mixture on florfenicol disposition, cyp3a activity and gut microbiota in Nile tilapia (Oreochromis niloticus). Pak Vet J, 46(5): 1167-1176. http://dx.doi.org/10.29261/pakvetj/2026.104