Lactobacillus plantarum NCHBL-004 modulates high-fat diet–induced weight gain and enhances GLP-1 production for blood glucose regulation

•Oral administration of NCHBL-004 improves obesity in HFD-fed mice.•NCHBL-004 induces the production of serum GLP-1 and increases SCFAs levels in feces.•Administration of NCHBL-004 increases the proportion of SCFA-producing microbes. This study investigated the therapeutic potential of Lactobacillus plantarum NCHBL-004 (NCHBL-004) in the treatment of obesity and associated metabolic disorders. Mice were fed either a normal diet (ND) or a high-fat diet (HFD) with oral administration of NCHBL-004. After euthanasia, blood, liver and adipose tissue were collected. Furthermore, the microbiome and short-chain fatty acids (SCFAs) were analyzed from feces. Oral administration of live NCHBL-004 to mice fed a HFD resulted in notable reductions in weight gain, improvements in glucose metabolism, and maintenance of balanced lipid levels. A comparative analysis with other Lactobacillus strains highlighted the superior efficacy of NCHBL-004. Moreover, heat-killed NCHBL-004 demonstrated beneficial effects similar to those of live NCHBL-004. Additionally, administration of live NCHBL-004 induced glucagon-like peptide 1 (GLP-1) production and increased the levels of short-chain fatty acids (SCFAs), including acetate and propionate, in feces, positively influencing liver lipid metabolism and mitigating inflammation. Consistent with this, analysis of the gut microbiome following NCHBL-004 administration showed increases in SCFA-producing microbes with increased proportions of Lactobacillus spp. and a significant increase in the proportion of microbes capable of promoting GLP-1 secretion. These findings underscore the potential of both live and inactivated NCHBL-004 as potential therapeutic approaches to managing obesity and metabolic disorders, suggesting avenues for further investigation and clinical applications.