Gut Microbiome
The effect of gut microbiome on human immune system is widely known, but it has never been utilized in the practice of kidney transplantation. Reducing the incidents of infectious disease is one of the most critical challenges of post-transplant kidney care. Such incidents can be directly linked to the change in gut microbiome diversity. Gene sequencing of the gut microbiome has shed light on some previously unexplainable dynamics of immunosuppressive medication effectiveness. All investigations point out to the fact that gut microbiota has a critical role in the development of post-transplant complications (Xiao et. al; 2018).
There are 1000 different types of microbiota in the human gut (Gin et. al; 2010) and the composition of the gut microbiome differs from person to person (Lynch et. al; 2016). Imbalance in the gut microbiome is associated with inflammatory bowel disease, obesity, diabetes, colorectal cancer, cardiovascular disease and nervous system disease (Xiao et. al; 2018). Several studies have looked into the change of the microbiome composition after a kidney transplant operation (Lee et.al, 2014; Zaza et al., 2017). All studies have observed:
1) a decrease in the baseline predominant organisms;
2) a decrease of diversity;
3) emergence of new dominant bacterial population after transplantation (Xiao et. al; 2018).
All studies conclude that the above changes lead to an increased risk of post-transplant infection (ibid). Imbalance in the gut microbiota is associated with increased risk of graft failure in renal transplants by influencing the dosing of immunosuppressants (Zaza et al., 2017). For example, Fecal Faecalibacterium Prausnitzii abundance in the first week of transplantation is positively associated with higher tacrolimus dosing at 1 month (Lee et al., 2014). Other studies have also observed the role of gut microbiome in the prognosis of kidney transplant outcomes (Ardalan et al., 2017; Ahmad et al., 2016; Fricke et al., 2014). Ardalan et al. reported that gut dysbiosis causes accumulation of uremic toxins, systemic inflammation, and infection that influence the pathogenesis of acute kidney injury, chronic kidney disease, emergence of infection, changes in drug metabolism and graft rejection (Ardalan et al., 2017). Dysbiosis can be caused by immunosuppression and antimicrobial therapies, ischemia-reperfusion (I/R) injury, and dietary restrictions (ibid).
Studies are still in their infancy stage and results are somehow mixed due to small sample sizes. This project aims to be the very first attempt in incorporating gut microbiome as a factor in determining immunosuppressive medication dosage. Studies on gut microbiome have been limited to extremely small sample sizes, 19 and 20 (Lee et al., 2014; Zaza et al., 2017). Our project will include 400 patients, which will be the largest study in the field to explore the effect of gut microbiome on the optimum dosage selection of immunosuppressive medication. The final aspect that makes this novel dataset extremely valuable is the pairing of gut microbiome data of individuals with their gene markers information.