## 8 Disease Management Options within the Context of a Disturbed Gastrointestinal Barrier
### The Effects of Dietary Intervention on the Microbiome and GI Barrier  
Recently, plant-based diets have emerged as a modifier of the microbiome. Increased dietary fiber promotes carbohydrate fermentation and the growth of _Bifidobacteria_ and _Lactobacillus_. This decreases protein fermentation and could improve CKD-induced dysbiosis [100]. Dietary addition of fiber led to a decrease of renal marker creatinine in patients with CKD [101; 102]. Association between improved survival and higher dietary fiber intake in CKD patients may be due to lowering inflammatory markers [103]. In HD patients, the dietary addition of high-amylase maize resistant starch type 2 (HAM-RS2) significantly decreased serum urea and creatinine as well as inflammatory markers TNF-\(\alpha\) and interleukin-6 [104]. HAM-RS2 altered the composition of the microbiome by increasing _Faecalibacterium_[105]. Further analysis was carried out in adenine-induced CKD in rats, focusing on microbial changes and gut-derived uremic toxins. After three weeks of additional HAM-RS2, decreased serum and urinary IS levels and an increased _Bacteroidetes/Firmicutes_ ratio were noted [106]. Gum arabica (GA), a tree exudate, has also been named a potential candidate to increase renal function. In an adenine-induced mouse model, GA significantly decreased duodenal TNF-\(\alpha\), II-6 and TGF\(\beta\)[107]. Unfortunately, no parameters of renal function were published [107]. Patients with CKD stage 2 or 3 or progressive renal disease benefited from the long-term application of GA [108]. GA generally preserved or even increased estimated GFR [108]. Unfortunately, this study lacked a placebo group as a control. Furthermore, dietary fiber activates peristaltic movements, decreases gut transition time, and reduces the time for protein fermentation [102; 104]. This leads to a decrease in uremic toxin load [102]. A higher intake of fruits and vegetables can also be advantageous as it improves metabolic acidosis, a common symptom of CKD [109]. Phosphate uptake is automatically reduced on a plant-based diet because of low bioavailability [110]. Even short-term dietary modification results in lower serum phosphorus levels and decreased phosphaturic hormone FGF23 [110]. Conversely, evidence in clinical trials suggests that prescribed dietary phosphorus restriction is not associated with survival benefits among HD patients [111] and that the correspondence of phosphate intake with adverse outcomes is speculative [81; 82; 101]. On the other hand, a low-protein diet, often prescribed in CKD patients to achieve neutral phosphorous balance, has recently emerged as the potential modulator of Nrf2 expression. The longitudinal study that recruited 30 non-dialysis CKD patients investigated the effects of dietary protein restriction for six months. It was demonstrated that a low-protein diet increased Nrf2 mRNA expression and Nrf2/NF-\(\kappa\)B ratio in peripheral blood mononuclear cells [112]. However, more clinical evidence is necessary to confirm that a protein-reducing diet is associated with a decline in ROS production and pro-inflammatory cytokines. The high potassium content of plant-based diets seems counterintuitive. However, so far, there is no experimental evidence suggesting that dietary potassium restriction is beneficial for CKD patients [113]. Taken together, a vegetarian diet could likely be beneficial for CKD patients. Prebiotic supplementation of oligofructose-enriched inulin induced a significant reduction of uremic toxins, urea and PCS in rats with adenine-induced kidney injury [114]. Histological assessment of renal injury revealed less tubular and glomerular damage and interstitial fibrosis than in untreated CKD rats. No effects on the production levels of colonic TJ proteins claudin-1 and occludin could be observed [114]. In a randomized controlled trial, inulin supplementation in HD patients did not change fecal or plasma uremic toxins levels but increased _Akkermansia_ in the fecal microbiota [115].