Abstract
A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)—with or without oral inulin supplementation as a prebiotic—modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case–control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus (p ≤ 0.01) and serum uric acid (p ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, p ≤ 0.01; base excess, p ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin (p = 0.008) and fasting glucose levels (p = 0.022), HOMA-IR (p = 0.004), as well as lower total serum cholesterol (p = 0.012), triglycerides (p = 0.016), C-reactive protein (p = 0.044) and homocysteine (p = 0.044) and higher HDL (p < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.
Highlights
The gut microbiota contributes to host metabolism, nutritional status and immunity, and carries out a protective action against different type of infections [1], being represented by saccharolytic bacteria, that are predominant in healthy conditions and produce most of short chain fatty acids (SCFA), whose beneficial effects consist in regulating glycemic and lipid metabolism, maintaining intact the intestinal barrier and the intestinal pH, and regulating immune system and inflammatory response [2,3]
A total of 41 chronic kidney disease (CKD) patients (25 males) with a mean age of 61.38 ± 12.36 years were enrolled, 18 patients were treated with low-protein diet (LPD) (0.6 g/kg/day) plus inulin (19 g/day) (LPD + Inulin Group) and 23 patients, serving as controls, were treated only with
We showed a reduction of waist circumference (WC) without a significant reduction of body mass index (BMI) and a significant improvement of metabolic acidosis, which in turn could decrease muscle protein catabolism, insulin resistance, mineral metabolism disorders and inflammation [14]
Summary
The gut microbiota contributes to host metabolism, nutritional status and immunity, and carries out a protective action against different type of infections [1], being represented by saccharolytic bacteria, that are predominant in healthy conditions and produce most of short chain fatty acids (SCFA), whose beneficial effects consist in regulating glycemic and lipid metabolism, maintaining intact the intestinal barrier and the intestinal pH, and regulating immune system and inflammatory response [2,3]. Several acute and chronic diseases—including chronic kidney disease (CKD), as we recently observed—may determine dysbiosis [3], increasing inflammation and oxidative stress, favoring. The main cause of intestinal dysbiosis in CKD patients remains unknown, several hypotheses have been formulated, i.e. the increased transit of urea transformed into ammonia and ammonium hydroxide, the increased intestinal pH and altered intestinal barrier with bacterial translocation and subsequent endotoxemia, determining inflammation [4,5]. Microbiota modulation may represent a novel therapeutic strategy, that may be achieved by nutritional intervention with low protein diet (LPD), which was able to lower uremic toxins produced by gut microbiota in non-dialysis CKD patients [2], and by oral administration of prebiotics, such as inulin [3,11]. Inulin has a neutral taste, little side effects and has shown to increase the growth of saccharolytic bacteria [1,12,13]
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