Innovative Food Intervention Containing Probiotics and Policosanols Counteracts Gut Barrier Breakdown and Inflammation Associated With Obesity via Butyrate‐glial‐IL1β Axis

ABSTRACT The combined use of probiotics and policosanols has emerged as a promising therapeutic strategy for the management of obesity. Here, we investigated the efficacy of an innovative mixture, containing probiotics ( Bifidobacterium infantis GM‐21, Bifidobacterium bifidum GM‐25, Lactobacillus rhamnosus GM‐28) and policosanols in counteracting and preventing body weight gain, intestinal epithelial barrier (IEB) dysfunction, and enteric inflammation in a mouse model of high‐fat diet (HFD)‐induced obesity, also characterizing its molecular mechanism of action. C57BL/6J mice were fed with HFD or standard diet for 8 weeks. Supplementation with the mixture or each individual component was starting from the first day of the study (preventive) or from the fifth week (curative). Body weight gain, BMI, metabolic parameters, circulating lipopolysaccharide binding protein (LBP), colonic interleukin (IL)‐1β, tight junction (TJ) protein expression and distribution, fecal butyrate, and butyrate SMCT1 transporter were analyzed. Enteric gliosis was assessed by glial fibrillary acidic protein (GFAP) + cells. After 8 weeks, HFD mice showed increased body weight and BMI, metabolic alterations, IEB disruption with elevated LBP levels and reduced TJ molecules, decreased colonic SMCT1 and butyrate bioavailability, increased GFAP + cells, and intestinal inflammation characterized by increased colonic IL‐1β and GFAP + /IL‐1β + cells. Supplementation with the mixture improved all above‐mentioned parameters, in both preventive and curative protocol, by enhancing butyrate bioavailability and reducing IL‐1β release from reactive glial cells. Of note, each individual component only partially improved these parameters. Overall, our results suggest that mixture exerts anti‐obesity properties, improving the IEB and blunting gut inflammation, likely through the modulation of the butyrate‐glia‐IL‐1β axis.