Immunosuppressive therapy after solid organ transplantation and the gut microbiota: Bidirectional interactions with clinical consequences

Abstract

The gut microbiota (GM) is the total microbial mass that colonizes the digestive tract of a host. It is composed of trillions of bacteria, viruses, archaea, and fungi that are distributed throughout the digestive tract with different abundances. 1,2 Our knowledge of the GM has dramatically increased over the last few decades principally because of the development of new genetic tools. 3 Solid organ transplantation (SOT) can only be considered medically when accompanied by the long-term use of immunosuppressive treatments (IST) to avoid graft rejection. However, ISTs are

Alterations of gut bacteria Akkermansia muciniphila and Faecalibacterium prausnitzii in late post-transplant period after liver transplantation

“…Most studies have been performed on mouse models of LT and immunosuppressive treatment. Same as us, some authors indicate a reduction in the load of this bacterium after tacrolimus treatment [22], in contrast others report that tacrolimus increases the amount of AKM [10]. It has been found in mice that the medium dose of tacrolimus increased the amount of FAEP, while both low and high dose of immunosuppressant reduced the bacteria [11].…”

“…However, it should be noted that there are age related changes in the gut microbiota with infant microbiota being relatively volatile [9]. Calcineurin inhibitors (CNI), including tacrolimus and cyclosporine A (CsA), are the main immunosuppressive drugs used in the treatment of patients after LT [10]. Optimal dosing is extremely important for a better allograft outcome.…”

“…Mycophenolate mofetil (MMF) is potent immunosuppressive agent used as adjunctive therapy in prevention of allograft rejection. MMF has been shown to be associated with frequent diarrhea and dysbiosis, as well as a reduction in some beneficial bacteria including AKM [10]. The mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus, have a favorable adverse event profile and are effective in protecting kidney function in LT patients.…”

Is Intestinal Dysbiosis-Associated With Immunosuppressive Therapy a Key Factor in the Pathophysiology of Post-Transplant Diabetes Mellitus?

“…The faecal microbial diversity was decreased in some patients with post-transplant complications (diarrhoea, acute rejection, urinary tract infection) ( 37 ). In addition, the diversity of the gut microbiota was significantly lower and the levels of Proteobacteria higher with abundant Escherichia coli in kidney transplant recipients compared to healthy control ( 38 ). In liver transplant recipients, this diversity transiently decreased two weeks after transplantation and then gradually increased back to reach the pre-transplantation levels after 5 weeks ( 39 ).…”

“…A recent review from Gabarre et al has provided a thorough overview of the bidirectional interaction between the immunosuppressants and the gut microbiota ( 8 ). The use of the anti-proliferative agent, mycophenolic acid, initially known for its antibacterial, antifungal and antiviral properties, is associated to a decrease in the diversity of the gut microbiota in kidney transplant recipients ( 38 , 41 ). Further investigations in preclinical models have revealed an alteration of the intestinal microbiota in mycophenolic acid-treated mice with an expansion of bacteria belonging to the Proteobacteria phylum ( 42 , 43 ).…”