María Blanca

Background/Objectives: The prevalence of depression and anxiety symptoms is remarkably high in malnourished individuals undergoing hemodialysis. The goal of this project was to evaluate the impact of administering an oral nutritional supplement combined with a probiotic blend on the microbiota, intestinal permeability, and depression symptoms in malnourished hemodialysis patients. Methods: With this aim, a randomized trial was conducted with three parallel groups: a control group with individualized diet, a supplement–placebo (SU-PL) group with oral nutritional supplementation (ONS), and a supplement–probiotic (SU-PR) group with ONS in conjunction with a probiotic blend. Blood and fecal samples were collected at basal time, and at 3 and 6 months. Several blood biomarkers, like zonulin, lipopolysaccharide-binding protein (LBP), lipopolysaccharide (LPS), and brain-derived neurotrophic factor (BDNF), were measured, and the fecal microbiome was sequenced with the Illumina platform. The Hospital Anxiety and Depression Scale (HADS) was used for the estimation of depression (HADS-D) and anxiety (HADS-A) symptoms, along with the standardized mental health index SF12-MH from the general health questionnaire SF-12. Results: The results showed that patients who consumed the probiotic blend maintained the LPS levels from their baseline readings and decreased their BDNF levels compared to the SU-PL or control groups. Moreover, a significant decrease in HADS-D scores (less depressive symptoms) and an increase in SF12-MH scores (higher quality of life) were found in that group in comparison to the other groups. The intervention produced an impact on the microbiome population, where the SU-PR group had reduced Akkermansia abundance with respect to the other groups, while their Acidaminococcus abundance decreased and their Barnesiella abundance increased with respect to the SU-PL group. Conclusions: Overall, the results indicate that the probiotic with the nutritional supplement could reduce the intestinal permeability biomarkers and improve depressive symptoms and quality of life in malnourished hemodialysis patients.

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS), specifically designed for malnourished (or at risk) hemodialysis patients with a “similar to the Mediterranean diet” pattern, improved caloric-protein intake, nutritional status and biomarkers of inflammation and oxidation. Our aim in this study was to evaluate whether the new ONS, associated with probiotics or not, may produce changes in miRNA’s expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We performed a randomized, multicenter, parallel-group trial in malnourished hemodialysis patients with three groups (1: control (C) individualized diet (n = 11); 2: oral nutritional supplement (ONS) + placebo (ONS-PL) (n = 10); and 3: ONS + probiotics (ONS-PR) (n = 10)); the trial was open regarding the intake of ONS or individualized diet recommendations but double-blinded for the intake of probiotics. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for RUNX2 and TNFα. TGFB1 expression was decreased in the ONS-PR group compared to baseline in the third month. PTEN gene expression was significantly elevated in the ONS-PR group at 3 months in comparison with baseline. LEPTIN expression was significantly increased in the ONS-PL group at the 3-month intervention compared to baseline. The new oral nutritional supplement associated with probiotics increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this oral nutritional supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS) for malnourished (or at-risk) hemodialysis patients with a "similar to the Mediterranean diet" model, improved caloric and protein intake, nutritional status and inflammation and oxidation biomarkers. Our aim in this study was to evaluate whether the new ONS, including probiotics, may produce changes in miRNAs expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We conducted a randomized, multicenter, parallel-group study in malnourished hemodialysis patients divided in 3 groups (1: Control -C- individualized diet 2: Oral nutritional supplement -ONS- + placebo -ONS-PL- and 3: ONS + probiotics -ONS-PR). Study registration: NCT03924089. The trial was open to the ONS diet or individual dietary advice, but double-blind for the intake of probiotics supplements. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for RUNX2 and TNFα. TGFB1 expression was decreased in the ONS-PR group compared to baseline in the third month. PTEN gene expression was significantly elevated in the ONS-PR group at 3-months in comparison with baseline. LEPTIN expression was significantly increased in ONS-PL group at 3-month intervention compared to baseline. The new Oral Nutritional Supplement associated with probiotics; increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this Oral Nutritional Supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.