Cellular components, surface layer protein (SLP) and exopolysaccharides (EPS) of postbiotic lactic bacteria (PLAB) can rehabilitate high-fat diet-induced dysbiosis and obese characteristic gut microbiome. However, it is not clear whether and how PLAB components affect gut microbiota and specifically adipocyte gene expression. Furthermore, SLP and EPS of PLAB in combination with polyphenolics of prebiotic wine grape seed flour (GSF) may have greater benefit on high-fat diet (HFD)-induced obesity and gut microbiota imbalance. To investigate interactions, C57BL/6 mice were fed a HFD and orally administered saline (CON), 250 mg/Kg EPS, or 120 mg/Kg SLP or saline with fed 2% GSF (GSF) or combination (42 mg/Kg EPS + 20 mg/Kg SLP + 0.5% GSF; ALL). There were significant reductions of HFD-induced body weight gain, adipose weight, serum triglyceride, and insulin resistance by the SLP and ALL diets compared to CON, with the most profound effect by ALL. ALL significantly affected the distribution of intestinal bacterial genus and species particularly those involved in production of short chain fatty acid (SCFA) and anti-obesogenic action. Microarray analysis from adipose tissue showed that ALL significantly affected expression of genes related to fatty acid biosynthesis, autophagy, inflammatory response, immune response, brown adipose tissue development and response to lipoteichoic acid and peptidoglycan (p < 0.05). Interestingly, expression of Akp13 (A-kinase anchoring protein 13) gene, which is related to body mass index and immune response, was negatively associated with the abundance of obesogenic and SCFAs producing gut bacteria. These data suggest that a combination of postbiotic kefir LAB cellular components and prebiotic GSF establishes a healthy intestinal microbiota that in part was associated with the prevention of obesity and obesity-related diseases.

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