Lipoteichoic acid from Bifidobacterium animalis subsp. lactis BPL1: a novel postbiotic that reduces fat deposition via IGF-1 pathway

Abstract

Obesity and its related metabolic disorders, such as diabetes and cardiovascular disease, are major risk factors for morbidity and mortality in the world population. In this context, supplementation with the probiotic strain Bifidobacterium animalis subsp. lactis BPL1 (CECT8145) has been shown to ameliorate obesity biomarkers. Analyzing the basis of this observation and using the pre-clinical model Caenorhabditis elegans, we have found that lipoteichoic acid (LTA) of BPL1 is responsible for its fat-reducing properties and that this attribute is preserved under hyperglycaemic conditions. This fat-reducing capacity of both BPL1 and LTA-BPL1 is abolished under glucose restriction, as a result of changes in LTA chemical composition. Moreover, we have demonstrated that LTA exerts this function through the IGF-1 pathway, as does BPL1 strain. These results open the possibility of using LTA as a novel postbiotic, whose beneficial properties can be applied therapeutically and/or preventively in metabolic syndrome and diabetes-related disorders.

Fig. 1

Lipoteichoic acid (LTA) from BPL1 strain demonstrates fat‐reducing activity. A. Fat‐reducing effect of purified LTA at different doses. B. Representative images of Nile red staining of lipid content in live young adult C. elegans in a wild‐type N2 animal under fluorescence microscopy. Nematodes were fed with BPL1 cells, heat‐treated BPL1 cells (HT‐BPL1) or LTA (10 µg ml^‐1). Scale bar 250 µm. Original image taken by the authors for this paper with a Nikon‐SMZ18 Fluorescence Stereomicroscope. C. Quantification of triglyceride content (mM TG/mg protein) in C. elegans fed with purified LTA from BPL1. D. Analysis of fat‐reducing activity of LTAs from B. longum ES1 and B. animalis subsp. lactis BB12. For a, b percentage of fluorescence in bacterial and LTA‐fed nematodes (wild‐type strain N2) is represented. Nile red was quantified at young adult stage. Orlistat (6 µg ml^‐1) was used as positive control. Data are mean ± SD. and were calculated from two biological independent experiments. For A, B, C, D *P < 0.05; **P < 0.01; ***P < 0.001; NS, not significant.

Fig. 2

LTA from BPL1 functionality is modified by glucose. Purified LTA obtained from BPL1 in standard MRS‐Cys (20 g l⁻¹) and from BPL1 cells grown in low glucose MRS‐Cys (10 g l⁻¹). BPL1 cells grown in excess or restriction of glucose were included. ***P < 0.001; NS: not significant.

Fig. 3

Lipoteichoic acid (LTA) from BPL1 strain requires the Insulin‐like signalling pathway (IGF‐I) to exert its fat‐reducing effect, and has functional activity in hyperglycaemic conditions. A. Feeding worms with LTA in mutant daf‐2 and daf‐16 strains; the same as with the live BPL1 cells and the heat‐treated BPL1 cells. B. Fat content in C. elegans mutant for SKN‐1 transcription factor treated with LTA from BPL1. C. Effect of treatments on a C. elegans hyperglycaemic model. Nematodes of wild‐type strain N2 grown in high glucose (100 mM). Metformin was used as positive control. For A, B, C percentage of fluorescence in LTA‐fed nematodes (wild‐type strain N2, GR1307, daf‐16 (mgDf50), CB1370, daf‐2 (e1370), or LG333 Skn‐1 (zu 135)). Nile red staining was quantified at young adult stage. Orlistat (6 µg ml⁻¹) was used as positive control. Data are mean ± SD. and were calculated from two independent biological experiments. ***P < 0.001, NS: not significant.