The growing worldwide epidemic of obesity and associated metabolic health comorbidities has resulted in an urgent need for safe and efficient nutritional solutions. The research linking obesity with gut microbiota dysbiosis has led to a hypothesis that certain bacterial strains could serve as probiotics helping in weight management and metabolic health. In the search for such strains, the effect of Bifidobacterium animalis subsp. lactis 420 (B420) on gut microbiota and metabolic health, and the mechanisms of actions, has been investigated in a variety of in vitro, pre-clinical, and clinical studies. In this review, we aim to highlight the research on B420 related to obesity, metabolic health, and the microbiota. Current research supports the hypothesis that gut dysbiosis leads to an imbalance in the inflammatory processes and loss of epithelial integrity. Bacterial components, like endotoxins, that leak out of the gut can invoke low-grade, chronic, and systemic inflammation. This imbalanced state is often referred to as metabolic endotoxemia. Scientific evidence indicates that B420 can slow down many of these detrimental processes via multiple signaling pathways, as supported by mechanistic in vitro and in vivo studies. We discuss the connection of these mechanisms to clinical evidence on the effect of B420 in controlling weight gain in overweight and obese subjects. The research further indicates that B420 may improve the epithelial integrity by rebalancing a dysbiotic state induced by an obesogenic diet, for example by increasing the prevalence of lean phenotype microbes such as Akkermansia muciniphila. We further discuss, in the context of delivering the health benefits of B420: the safety and technological aspects of the strain including genomic characterization, antibiotic resistance profiling, stability in the product, and survival of the live probiotic in the intestine. In summary, we conclude that the clinical and preclinical studies on metabolic health suggest that B420 may be a potential candidate in combating obesity; however, further clinical studies are needed.

Background/Objectives: Ergothioneine (EGT) is an effective antioxidant that animals cannot produce and has an important anti-inflammatory role in cell protection, which can help lower the risk of various diseases. In this study, we investigated the potential role of gut microbiota in the production of EGT, which was found to increase in the mouse liver after dietary supplementation with betaine (BET) or polydextrose (PDX). Methods: The effects of BET and PDX on the gut microbiota and tissue EGT content were investigated using a diet-induced obese mouse model and simulated fermentation in the human colon. Male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce obesity and related metabolic disorders, and for the last 4 weeks of this study, the mice continued on the same diet, supplemented with BET, PDX, or their combination. The potential function of BET and PDX in microbial EGT production was further studied in an in vitro human colon model. Results: The quantity of Bifidobacterium spp. and Bacteroidota were significantly higher in the feces of mice on diets supplemented with PDX or BET + PDX, and Enterobacteriaceae levels were significantly higher in PDX-supplemented mice than in HFD-fed mice. Untargeted metabolomic analysis of the liver revealed a significant increase in EGT in mice fed HFDs with BET or BET + PDX. Microbial analysis from samples collected from the human in vitro model showed significant changes in Neglecta timonensis, Blautia faecis, Lachnospiracea incertae sedis, Faecalibacillus, and Stenotrophomonas maltophilia species, along with an increase in microbial metabolites, namely, acetic, propionic and butyric acids, and a decrease in 2-methylbutyric acid. Conclusions: Although PDX and BET or their combination affected microbial composition and metabolites in the human colon simulation model, the model used was not able to detect a significant change in microbiota-based EGT production and, therefore, could not explain the increase in EGT in the liver of betaine-fed mice.