Novel insights on the effects of potential probiotic strains on acenocoumarol

FRAGOMENO MELISA; MINNAARD, JESSICA; PÉREZ, PABLO FERNANDO

Los Cocos, Cordoba

Congreso; Congreso de la Sociedad Argentina de Microbiolgía General; 2022

SAMIGE

Bifidobacterium and Lactobacillus are two probiotic bacteria genera and exhibit beneficial properties on the host. In this context, we have previously demonstrated, in vitro, the ability of strains CIDCA 5310, CIDCA 5317 and ATCC 314 to biomodify acenocoumarol, a widely used oral anticoagulant in Argentina. Since patients undergoing anticoagulant treatment have certain dietary restrictions and considering that the consumption of probiotic based foods is growing steadily; we focus our studies in deepening the knowledge regarding the interaction of these probiotic bacteria and acenocoumarol.The aim of the present work was to evaluate the effect of the bacteria on drug transport and internalisation in Caco-2/TC7 epithelial cells. For transport experiments, transwell systems were used. Bacteria were added to the apical compartment containing or not AC in culture medium (DMEM/15 % bovine fetal serum) and incubated for 18 h. The basolateral compartment contained only culture medium. Integrity of the monolayers was monitored by measurement of transepithelial electrical resistance (TEER) value. To assess internalisation, cells were lysed by incubation with distilled water (1hr-37°C/5% CO2). Acenocoumarol was determined by HPLC.Regarding the transport assays, we notice that the drug’s concentration on the apical side of the system was substantially lower in the presence of the strain CIDCA 5310 as compared with controls without bacteria (0,007 ± 0,002 mg/ml vs 0,033 ± 0,004 mg/ml). The values of AC in the apical compartment containing strains 5317 and 314 were 0,0330 ± 0,0008 mg/ml and 0,017 ± 0,007 mg/ml respectively. No differences were detected in the concentration of AC in the basolateral compartment when all three strains and control were compared (5310: 0,0203 ± 0,0007 mg/ml, 5317: 0,0228± 0,0008 mg/ml, 314: 0,017± 0,007 mg/ml, AC: 0,025 ± 0,002 mg/ml)Internalisation analysis also showed that the concentration of AC inside the cells coincubated with strain CIDCA 5310 was lower than the AC control (0,0019 ± 0,0001 mg/ml vs 0,00271 ± 0,00004 mg/ml, respectively). For strains 5317 and 314 intracellular AC concentration values were 0,00320 ± 0,00007 mg/ml and 0,003163 ± 0,000009 mg/ml respectively. Our results show a strain-dependent effect of bacteria on the acenocoumarol concentration across epithelial monolayers. Even though the effect of strain 5310 could be ascribed to its demonstrated ability to biomodify the drug, other effects on drug transport and metabolism (e. g. induction of the cytochrome system) cannot be ruled out. Findings of the present study are relevant to delineate the diet of individuals under anticoagulant therapy.