Great immunosuppression session and great speakers with the best chairs 😉@LaureElens @IATDMCT

🔬 Le microbiote, un nouvel acteur dans le rejet des greffes🔬 ➡️ Lire les travaux de @Laure_Bindels, Promotrice WELBIO @welri, Promotrice @televie, et @LaureElens , Promotrice PDR @frsFNRS , épaulées par @DegraeveAl Aspirante @frsFNRS à l’ @UCLouvain_be https://t.co/VEvG4rUVhs

The gut #microbiome fosters the absorption of #tacrolimus through the transcriptional downregulation of #ABCB1 aka the Pglycoprotein. Video Abstract🎬With @DegraeveAlA and @LaureElens, made by @researchsquare 👀Full article available here https://t.co/EoWIcv7zrk

12/ 🙏Thanks to everyone involved in this 5-year project, including @DegraeveAl @LaureElens @LarsVereecke @lgatt0, our funders @frsFNRS @FWOVlaanderen, and our institutions @UCLouvain_ADRE @WELRI_asbl @VIBLifeSciences @GgigGhent

11/ Our work may be of clinical importance considering the high number of drugs with unexplained PK variability transported by ABCB1.

10/ Clinical study is ongoing to explore the association between gut microbiota and tacrolimus PK in kidney-transplanted patients, more to come soon !! @LaureElens, Michel Mourad and Vincent Haufroid

9/ Using RNAseq, we identified CAR as a factor potentially involved in the transcriptional inhibition of ABCB1 by bacterial metabolites/compounds, thanks to @lgatt0 and Axelle Loriot.

8/ Bacterial metabolites/compounds recapitulated the inhibitory effect of the gut microbiota on ABCB1 transcription in vitro. No direct effect of bacterial metabolites/compounds on ABCB1 activity was found.

7/ The promotion of tacrolimus blood exposure by the gut microbiota was blocked by the administration of zosuquidar, an ABCB1 inhibitor.

6/ Similar findings were made in germ-free mice undergoing conventionalization, thanks to @LarsVereeckeand Vanessa Andries.

5/ Mice displayed lower levels of tacrolimus upon microbiota depletion using broad-spectrum antibiotics. Looking at the various ADME enzymes and proteins involved in tacrolimus PK, we found lower levels of ABCB1 transcripts in the small intestine of ATB-treated mice.

4/ Our study thus aims to explore the contribution of the gut microbiome to tacrolimus #pharmacokinetics(PK). 🦠 We found that the gut microbiome modulates tacrolimus PK through the transcriptional regulation of intestinal #ABCB1, an efflux pump also known as the #Pglycoprotein.

3/ Success of a solid organ transplantation is insured among others by #tacrolimus, an immunosuppressive drug. 💊Tacrolimus clinical use is difficult due to the high inter- and intra-patient variability. Genetics contributes to it but does not fully explain it. 🧬

2/ Organ availability is a key issue and 40% of the patients will wait more than 1 year to get an organ transplanted. 🫀 Once the organ is transplanted, it is thus key to avoid its rejection.

Congratulations👏to @DegraeveAl for her first 1st author article in @MicrobiomeJ demonstrating that the gut #microbiome fosters the absorption of tacrolimus through the transcriptional downregulation of ABCB1 aka the Pglycoprotein. Amazing collaboration with @LaureElens A 🧵1/13

Interested to join a highly interdisciplinary EU research team? 📢We are #hiring 2 #phdstudent and 1 #postdoc to join the #BESAFE_HORIZONEU team. The research topic is #benzodiazepine #deprescribing. Can't wait to see applications coming in!