Bifidobacterium animalis subsp. lactis 420 for Metabolic Health: Review of the Research

Abstract

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.

Keywords: B420; Bifidobacterium lactis; gut microbiota; metabolic health; metabolic syndrome.

Figure 1

Schematic proposal of how B420 and/or its metabolites presumably affect cellular signaling via downregulation of TLR pathways, indicated as light green arrows in the figure, as well as the inflammatory IKKα-NF-κB pathways or p38 MAPK-ELK-1 pathways. B420 has been shown to enhance epithelial integrity in vitro [22] and to decrease the levels of circulating LPS in mice [27]. LPS triggers inflammation through upregulation of IKKα-NF-κB pathways and p38 MAPK-ELK-1 pathways [72], indicated as dark green arrows in the figure. Downregulation of these pathways by B420 reduces the transcription of pro-inflammatory cytokines in the nucleus. As proinflammatory cytokines are excreted out of the cell, and affect insulin receptor activity, this cascade can serve as one mechanistic route via which B420 exerts its metabolic effects through affecting epithelial integrity and cytokine levels. LPB = lipopolysaccharide binding protein; MD-2 = lymphocyte antigen 96, a protein associated with toll-like receptor 4; CD14 = cluster of differentiation 14; TLR4 = toll-like receptor 4; MYD88 = myeloid differentiation primary response protein 88; TIRAP = toll-interleukin 1 receptor (TIR) domain containing adaptor protein, IRAK = interleukin-1 receptor associated kinases; TICAM2 = toll-like receptor adaptor molecule 2; TICAM1 = toll-like receptor adaptor molecule 1; TRAP6 = thrombin receptor activator peptide 6; TAB2 = TAK1-binding protein 2; TAB1 = TAK1-binding protein 1; TAK1 = TGF-β activated kinase 1; MKK3/5 = mitogen-activated protein kinase kinase 3/5; p38 MAPK = p38 mitogen-activated protein kinase; MKK4 = mitogen-activated protein kinase kinase 4; JNK1 c-Jun N-terminal kinase 1; ELK-1 = ETS-like gene 1 (coding for ETS like protein Elk-1); c-FOS = Fos proto-oncogene, which is an AP-1 transcription factor subunit; c-JUN = Jun proto-oncogene, AP-1 transcription factor subunit; NF-κB = nuclear factor kappa B; TNF-α = tumor necrosis factor alpha; IL-12 = interleukin 12; IL-6 = interleukin 6; IL-1 = interleukin 1; MEKK1 = mitogen-activated protein kinase kinase kinase 1; IKKβ = I kappa B kinase beta; IKKα = I kappa B kinase alpha; IKKγ = I kappa B kinase gamma; TLR5 = toll-like receptor 5; TOLLIP = toll interacting protein; IL1β = interleukin 1β; INSR = insulin receptor. The schematic networks were generated through the use of IPA (QIAGEN Inc., https://www.qiagenbioinformatics.com/products/ingenuity-pathway-analysis).