Isolated from Different Hosts Modifies the Intestinal Microbiota and Displays Differential Metabolic and Immunomodulatory Properties in Mice Fed a High-Fat Diet.

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 modification of the intestinal microbiota composition has been developed as a strategy for the treatment of obesity. In this study, we selected four strains isolated from the feces of newborn and elderly humans to investigate whether supplementation with 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) N4_N3, (ii) Z25, (iii) 17_3, (iv) 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 strains isolated from the feces of elderly humans ( Z25, 17_3, and 2016_7_2) decreased the body weight or weight gain of mice, whilst the strain isolated from the newborn ( N4_N3) increased the body weight of mice. The 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 strains alleviated inflammations in the spleen and brain and modified the cecal and colonic microbiota. Particularly, all strains reversed the HFD-induced depletion of and reduced the development of beta-lactam resistance. In addition, the strains isolated from the elderly increased the relative abundances of potentially beneficial genera, such as , and . We speculate that such increased abundance of commensal bacteria may have mediated the alleviation of obesity, as supplementation decreased the intestinal production of SCFAs, thereby reducing energy delivery to the host mice. Our results revealed that certain strains of can alleviate obesity and modify the gut microbiota of mice. The tested strains of 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 from different sources may have disparate effects on host health possibly due to the transmission of origin-specific functions to the host.