Background and aims: Non-alcoholic fatty liver disease (NAFLD) is characterized by the presence of fat in hepatocytes because of decreased β-oxidation and increased lipogenesis. Prebiotics, probiotics, and synbiotic have modulatory effects on intestinal microbiota and may influence the gut-liver axis. Our aim was to evaluate the effects of prebiotic, probiotics, and synbiotic on liver histopathology and gene expression related to β-oxidation and lipogenesis after hypercholesterolemia.Methods: Wistar male adult rats (n = 40) were submitted to hypercholesterolemic conditions (HPC) (60 days). On Day 30 of HPC, rats were subdivided in 5 groups: negative control (NC): without HPC + Gv (distilled water); positive control (PC): with HPC + Gv (distilled water); prebiotic (PRE): HPC + Gv with prebiotic (Fiber FOS®); probiotic (PRO): HPC + Gv with probiotic strains Gv (Probiatop®); and synbiotic (SYN): HPC + Gv with synbiotic (Simbioflora®). All rats were sacrificed on Day 30 post-treatment. Blood was collected to verify total serum cholesterol, and liver tissue was sampled to verify histopathological changes and gene expression. Gene expression related to ß-oxidation (PPAR-α and CPT-1) and lipogenesis (SREBP-1c, FAS and ME) was evaluated in liver tissue using RT-qPCR.Results: PC had higher cholesterol levels when compared to NC. PRE and SYN rats had lower cholesterol levels than PC. PC rats showed more histopathological changes than NC rats; PRE and SYN rats showed fewer alterations than PC rats. PPAR-α was expressed at higher levels in SYN and PC rats compared with PRE and PRO rats. CPT-1 expression was similar in all groups. SREBP-1c was expressed at higher levels in PC rats compared with NC rats; levels were lower in SYN rats compared with PRO rats; levels were lower in PRE rats compared with PC and PRO rats. FAS was expressed at lower levels in PRE rats compared with SYN rats. ME expression was lower in PC rats compared with NC rats.Conclusion: Prebiotic and synbiotic supplementation improve hepatic alterations related to hypercholesterolemia. These changes appear to be mediated by altered expression of genes related to β-oxidation and lipogenesis.

In recent decades, special attention has been given to the potential association between the gut ecosystem and chronic diseases. Several features and complications of chronic kidney disease (CKD) may induce an unbalanced gut environment, leading to unfavorable consequences for a patient's health. The first section of this review is dedicated to a description of some aspects of gut microbiota and intestinal barrier physiology. The following section explores the impact of CKD on the gut ecosystem and intestinal barrier, particularly the association with uremic toxins, inflammation, and immunodeficiency. Finally, the review describes the state of the art of potential therapies with prebiotics, probiotics, and synbiotics employed to modulate the gut environment and to reduce the generation of colon-derived uremic toxins in CKD.

In chronic kidney disease (CKD), the accumulation of gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole 3-acetic acid (IAA), has been associated with the burden of the disease. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating the gut microbiota and production of their metabolites. The aim of this study was to evaluate the effect of unripe banana flour (UBF—48% resistant starch, a prebiotic) on serum concentrations of IS, pCS, and IAA in individuals undergoing peritoneal dialysis (PD). A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch—12 g/day) for 4 weeks, or vice versa (4-week washout). The primary outcomes were total and free serum levels of IS, pCS, and IAA. Secondary outcomes were 24 h urine excretion and dialysis removal of IS, pCS, and IAA, serum inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α)], serum lipopolysaccharide LPS, and dietary intake. Of the 43 individuals randomized, 26 completed the follow-up (age = 55 ± 12 years; 53.8% men). UBF did not promote changes in serum levels of IS (p = 0.70), pCS (p = 0.70), and IAA (p = 0.74). Total serum IS reduction was observed in a subgroup of participants (n = 11; placebo: median 79.5 μmol/L (31–142) versus UBF: 62.5 μmol/L (31–133), p = 0.009) who had a daily UBF intake closer to that proposed in the study. No changes were observed in other secondary outcomes. UBF did not promote changes in serum levels of IS or pCS and IAA; a decrease in IS was only found in the subgroup of participants who were able to take 21g/day of the UBF.

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The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.