Abstract
Since alterations of the gut microbiota have been shown to play a major role in obesity, probiotics have attracted attention. Our aim was to identify probiotic candidates for the management of obesity using a combination of in vitro and in vivo approaches. We evaluated in vitro the ability of 23 strains to limit lipid accumulation in adipocytes and to enhance the secretion of satiety-promoting gut peptide in enteroendocrine cells. Following the in vitro screening, selected strains were further investigated in vivo, single, or as mixtures, using a murine model of diet-induced obesity. Strain Bifidobacterium longum PI10 administrated alone and the mixture of B. animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 limited body weight gain and reduced obesity-associated metabolic dysfunction and inflammation. These protective effects were associated with changes in the hypothalamic gene expression of leptin and leptin receptor as well as with changes in the composition of gut microbiota and the profile of bile acids. This study provides crucial clues to identify new potential probiotics as effective therapeutic approaches in the management of obesity, while also providing some insights into their mechanisms of action.
Highlights
The impact of B. longum PI10 and L. salivarius PI2 on adipocyte lipid accumulation was further confirmed by the increased expression of genes encoding key regulators of adipose lipid metabolism: the peroxisome proliferator-activated receptor (PPAR) gamma and the lipoprotein lipase in treated adipocytes, compared to untreated cells (Figure 1B)
The multi-criteria in vitro screening strategy we used was successful to identify at least one high-potential strain, B. longum PI10, able to significantly impact obesity as a single strain, as well as a high-potential mixture composed of a strain of B. animalis subsp
Lactis and a strain of L. gasseri. These potential probiotic treatments may act through multiple mechanisms, including a decrease in the inflammatory status and improvement of fasting glycemia and leptin resistance
Summary
Obesity is linked to chronic low-grade inflammation, and a disruption in the integrity of the intestinal barrier, notably characterized by a reduction of tight junction proteins and mucus production This increased permeability may allow the translocation of pro-inflammatory bacterial compounds, such as lipopolysaccharides (LPS), responsible for metabolic endotoxemia and leading gradually to chronic low-grade inflammation and insulin resistance [6]. SCFAs have been shown to serve as a source of energy for colonocytes, reducing permeability and increasing mucus production [8], thereby, improving gut barrier function Another important class of metabolites, bile acids synthesized in the liver from cholesterol and metabolized by the gut microbiota, can regulate several host functions, including energy metabolism [9]
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