Abstract: Several studies report the important role of an altered gut microbiota in the development of
obesity, highlighting the potential use of probiotics in the treatment of obesity. The aim of this study
is to investigate the effect of a novel probiotic approach on the expression of specific miRNAs and
mRNAs associated with obesity in combination with the hypocholesterolemic octacosanol. Twenty
overweight/obese women participated in a randomized, placebo-controlled, double-blind study
and were randomly divided into two groups: the intervention group (daily one capsule containing
Lactobacillus plantarum 299v (DSM9843), Saccharomyces cerevisiae var. boulardii, and 40 mg octacosanol;
N = 12) and the placebo group (N = 8). Changes in lipid parameters and expression of miRNAs and
mRNAs were assessed before (T0) and after the 12-week intervention (T1). After the intervention,
the expression of miR-155-5p (9.38 0.85 vs. 8.38 1.06, p = 0.05) and miR-24-3p (3.42 0.38 vs.
2.71 0.97, p = 0.031) showed significant decreases in the intervention group when compared to
the control group. At T1, the expression of miR-155-5p (8.69 1.31 vs. 9.3 0.85, p = 0.04), miR-
125b-5p (5.41 1.18 vs. 5.99 1.36, p = 0.049), and TNF-a (10.24 1.66 vs. 11.36 1.12, p = 0.009)
were significantly decreased in the intervention group. No changes in lipids and anthropometric
parameters were observed. The novel probiotic approach had a positive effect on regulating the
expression of certain miRNAs and mRNAs important for regulating inflammation and adipogenesis,
which are essential for obesity onset and control.