Thursday, March 23, 2017

#NephMadness 2017: The Gut Microbiota and Kidney Disease- Will it Survive the Hype? #NutritionRegion

I was very excited to see delightful topics in the Nutrition Region of this year’s #NephMadness, especially the Gut Microbiome and Kidney Disease. Before starting my Ph.D., I was aware that the colonic microbiota existed, but I acquired a very different perspective by being in contact with many researchers investigating the effects of our microbial friends in animal models of certain diseases (e.g., obesity, inflammatory bowel disease, and menopause), but also in humans (e.g., changes throughout the life cycle, autism-spectrum disorder, effects of exercise). I began to read about the topic and was amazed by the data linking metabolites of microbial origin and kidney disease progression, cardiovascular disease, mineral and bone disorder, and mortality.

Despite all of the aforementioned convincing studies, data on the gut microbiota structure (what microbes are there?) and their function (what are they doing?) is very scarce among patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). In 2013, Vaziri et al. showed that the bacterial species richness is decreased in patients undergoing hemodialysis (HD). Specifically, bacterial families that have been traditionally associated with positive outcomes, such as Lactobacillaceae and Prevotellaceae, were decreased. Also, it was revealed that bacterial families that have been associated with detrimental effects are enriched in hemodialysis (HD) patients. Then, the same group later showed in an in silico analysis that bacterial families that possess the enzymes needed for two of the most famous bacteria-derived uremic toxins (indoxyl sulfate and p-cresyl sulfate, which are derived from the fermentation of tryptophan and tyrosine, respectively) are enriched in the microbiota of HD patients. In 2016, in a very elegant study, Devlin et al. showed that by knocking out the tryptophanase gene in Bacteroides thetaiotaomicron, the production of indoxyl sulfate was eliminated in mice.

These studies are remarkable, but how can we modulate the presence/absence of specific bacteria in CKD and ESKD? Several studies have demonstrated that fermentable dietary fiber (bacteria’s favorite food), may be beneficial. Bacteria that have been traditionally considered beneficial, degrades these carbohydrates. Meijers et al. supplemented 20g of oligofructose-enriched inulin (the adequate intake of fiber recommended for healthy females and males is 25g/d and 38g/d, respectively) to HD patients and found out that after four weeks of treatment, the levels of p-cresyl sulfate were reduced by 20%, but there was no change in indoxyl sulfate. Poesen et al., similarly supplemented 20g of arabinoxylans and found a small decrease in trimethylamine N-oxide (TMAO), another unwanted bacteria-derived metabolite, but not p-cresyl sulfate or indoxyl sulfate. Other researchers have used synbiotics (pro + prebiotics) with the thought that, by providing “beneficial” bacteria and the food for these bacteria, a shift in the microbiota would occur. Rossi et al. supplemented 15g/d of a mixture of fermentable dietary fibers (inulin, fructooligosaccharides, and galactooligosaccharides) and 90 billion CFU probiotic strains/d from the Bifidobacterium, Lactobacillus, and Streptococcus genera to CKD patients. The authors concluded that the synbiotic decreased p-cresyl sulfate, but not indoxyl sulfate. In addition, it was revealed that there was an increase in the relative abundance of Bifidobacterium and a decrease in Ruminococcaceae. Given these findings, the supplementation of prebiotics and synbiotics has resulted in certain positive outcomes; however, these results have been inconsistent.

Therefore, what should researchers do next? In my opinion, we should be looking into what patients are eating, instead of just supplementing them. Diet is one of the main determinants of the gut microbiota. CKD and ESKD patients have very distinctive diets characterized by a restriction of dietary phosphorus, sodium, and potassium. This approach may lead patients to limit their intake of foods that are high in dietary fiber, such as fruits, vegetables, legumes, whole grains, and nuts. These food groups additionally contain other compounds, such as phytochemicals, which may also affect the gut microbiota. To date, however, no studies are assessing the effects of the traditionally restrictive renal diet in comparison to a more “liberal” diet on the gut microbiota structure and function of CKD and ESRD patients.

In conclusion, will the gut microbiome in kidney disease survive the hype? In my opinion it WILL. There are several ongoing studies and many studies to be performed since we already know that metabolites that are produced by our microbial friends (or enemies?) affect the progression of kidney disease in addition to outcomes in this population. Additionally, newly high throughput technologies will enable us to perform it into more detail, not only to find out who is there, but also what they are doing and how are they doing it.

Annabel Biruete
Ph.D. student in Nutritional Sciences at the University of Illinois at Urbana-Champaign
#NSMC intern
follow her @anniebelch

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