TY - JOUR
T1 - In vitro models to detect in vivo bile acid changes induced by antibiotics
AU - Zhang, Nina
AU - Wang, Jingxuan
AU - Bakker, Wouter
AU - Zheng, Weijia
AU - Baccaro, Marta
AU - Murali, Aishwarya
AU - van Ravenzwaay, Bennard
AU - Rietjens, Ivonne M.C.M.
PY - 2022/12
Y1 - 2022/12
N2 - Bile acid homeostasis plays an important role in many biological activities through the bile–liver–gut axis. In this study, two in vitro models were applied to further elucidate the mode of action underlying reported in vivo bile acid changes induced by antibiotics (colistin sulfate, tobramycin, meropenem trihydrate, and doripenem hydrate). 16S rRNA analysis of rat fecal samples anaerobically incubated with these antibiotics showed that especially tobramycin induced changes in the gut microbiota. Furthermore, tobramycin was shown to inhibit the microbial deconjugation of taurocholic acid (TCA) and the transport of TCA over an in vitro Caco-2 cell layer used as a model to mimic intestinal bile acid reuptake. The effects induced by the antibiotics in the in vitro model systems provide novel and complementary insight explaining the effects of the antibiotics on microbiota and fecal bile acid levels upon 28-day in vivo treatment of rats. In particular, our results provide insight in the mode(s) of action underlying the increased levels of TCA in the feces upon tobramycin exposure. Altogether, the results of the present study provide a proof-of-principle on how in vitro models can be used to elucidate in vivo effects on bile acid homeostasis, and to obtain insight in the mode(s) of action underlying the effect of an antibiotic, in this case tobramycin, on bile acid homeostasis via effects on intestinal bile acid metabolism and reuptake.
AB - Bile acid homeostasis plays an important role in many biological activities through the bile–liver–gut axis. In this study, two in vitro models were applied to further elucidate the mode of action underlying reported in vivo bile acid changes induced by antibiotics (colistin sulfate, tobramycin, meropenem trihydrate, and doripenem hydrate). 16S rRNA analysis of rat fecal samples anaerobically incubated with these antibiotics showed that especially tobramycin induced changes in the gut microbiota. Furthermore, tobramycin was shown to inhibit the microbial deconjugation of taurocholic acid (TCA) and the transport of TCA over an in vitro Caco-2 cell layer used as a model to mimic intestinal bile acid reuptake. The effects induced by the antibiotics in the in vitro model systems provide novel and complementary insight explaining the effects of the antibiotics on microbiota and fecal bile acid levels upon 28-day in vivo treatment of rats. In particular, our results provide insight in the mode(s) of action underlying the increased levels of TCA in the feces upon tobramycin exposure. Altogether, the results of the present study provide a proof-of-principle on how in vitro models can be used to elucidate in vivo effects on bile acid homeostasis, and to obtain insight in the mode(s) of action underlying the effect of an antibiotic, in this case tobramycin, on bile acid homeostasis via effects on intestinal bile acid metabolism and reuptake.
KW - 16S rRNA analysis
KW - Antibiotics
KW - Bile acid homeostasis
KW - Bile acid reuptake
KW - Tobramycin, fecal incubations
U2 - 10.1007/s00204-022-03373-4
DO - 10.1007/s00204-022-03373-4
M3 - Article
C2 - 36074177
AN - SCOPUS:85137584465
SN - 0340-5761
VL - 96
SP - 3291
EP - 3303
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 12
ER -