Bifidobacterium adolescentis isolated from different hosts modifies the intestinal microbiota and displays differential metabolic and immunomodulatory properties in mice fed a high-fat diet

Abstract

The incidence of obesity, which is closely associated with the gut microbiota and chronic inflammation, has rapidly increased in the past 40 years. Therefore, the probiotic-based modifica-tion of the intestinal microbiota composition has been developed as a strategy for the treatment of obesity. In this study, we selected four Bifidobacterium adolescentis strains isolated from the feces of newborn and elderly humans to investigate whether supplementation with B. adolescentis of various origins could alleviate obesity in mice. Male C57BL/6J mice fed a high-fat diet (HFD, 60% energy as fat) received one of the following 14-week interventions: (i) B. adolescentis N4_N3, (ii) B. adolescentis Z25, (iii) B. adolescentis 17_3, (iv) B. adolescentis 2016_7_2, and (v) phosphate-buffered saline. The metabolic parameters, thermogenesis, and immunity of all treated mice were measured. Cecal and colonic microbial profiles were determined by 16S rRNA gene sequencing. Intestinal concentrations of short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The B. adolescentis strains isolated from the feces of elderly humans (B. adolescentis Z25, 17_3, and 2016_7_2) decreased the body weight or weight gain of mice, whilst the strain isolated from the newborn (B. adolescentis N4_N3) increased the body weight of mice. The B. adolescentis strains isolated from the elderly also increased serum leptin concentrations and induced the expression of thermogenesis-and lipid metabolism-related genes in brown adipose tissue. All the B. adolescentis strains alleviated inflammations in the spleen and brain and modified the cecal and colonic microbiota. Particularly, all strains reversed the HFD-induced depletion of Bifidobacterium and reduced the development of beta-lactam resistance. In addition, the B. adolescentis strains isolated from the elderly increased the relative abundances of potentially beneficial genera, such as Bacteroides, Parabacteroides, and Faecalibaculum. We speculate that such increased abundance of commensal bacteria may have mediated the alleviation of obesity, as B. adolescentis supplementation decreased the intestinal production of SCFAs, thereby reducing energy delivery to the host mice. Our results revealed that certain strains of B. adolescentis can alleviate obesity and modify the gut microbi-ota of mice. The tested strains of B. adolescentis showed different effects on lipid metabolism and immunity regulation, with these effects related to whether they had been isolated from the feces of newborn or elderly humans. This indicates that B. adolescentis from different sources may have dis-parate effects on host health possibly due to the transmission of origin-specific functions to the host.