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This research was funded by Ministerio de Ciencia, Innovacion y Universidades Exp. RTC-2017-5959-1 and by ISCIII Exp. PI18/01041 and co-financed by Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa". MP holds a contract (IFI20/00034) from the Carlos III National Health Institute, cofunded by the European Social Fund 2014-2020 "The FSE invests in your future". The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Modulation of miR-29a and miR-29b Expression and Their Target Genes Related to Inflammation and Renal Fibrosis by an Oral Nutritional Supplement with Probiotics in Malnourished Hemodialysis Patients

Publicated to:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 25 (2): 1132- - 2024-01-01 25(2), DOI: 10.3390/ijms25021132

Authors: Sasso, Corina Veronica; Lhamyani, Said; Hevilla, Francisco; Padial, Marina; Blanca, Maria; Barril, Guillermina; Jimenez-Salcedo, Tamara; Martinez, Enrique Sanz; Nogueira, Angel; Lago-Sampedro, Ana Maria; Olveira, Gabriel

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Abstract

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 TNF alpha. 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.

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