Abstract
BackgroundLactobacillus mucosae DPC 6426 has previously demonstrated potentially cardio-protective properties, in the form of dyslipidaemia and hypercholesterolemia correction in an apolipoprotein-E deficient mouse model. This study aims to characterise the manner in which this microbe may modulate host bile pool composition and immune response, in the context of cardiovascular disease. Lactobacillus mucosae DPC 6426 was assessed for bile salt hydrolase activity and specificity. The microbe was compared against several other enteric strains of the same species, as well as a confirmed bile salt hydrolase-active strain, Lactobacillus reuteri APC 2587.ResultsQuantitative bile salt hydrolase assays revealed that enzymatic extracts from Lactobacillus reuteri APC 2587 and Lactobacillus mucosae DPC 6426 demonstrate the greatest activity in vitro. Bile acid profiling of porcine and murine bile following incubation with Lactobacillus mucosae DPC 6426 confirmed a preference for hydrolysis of glyco-conjugated bile acids. In addition, the purified exopolysaccharide and secretome of Lactobacillus mucosae DPC 6426 were investigated for immunomodulatory capabilities using RAW264.7 macrophages. Gene expression data revealed that both fractions stimulated increases in interleukin-6 and interleukin-10 gene transcription in the murine macrophages, while the entire secretome was necessary to increase CD206 transcription. Moreover, the exopolysaccharide elicited a dose-dependent increase in nitric oxide and interleukin-10 production from RAW264.7 macrophages, concurrent with increased tumour necrosis factor-α secretion at all doses.ConclusionsThis study indicates that Lactobacillus mucosae DPC 6426 modulates both bile pool composition and immune system tone in a manner which may contribute significantly to the previously identified cardio-protective phenotype.
Highlights
Lactobacillus mucosae DPC 6426 has previously demonstrated potentially cardio-protective properties, in the form of dyslipidaemia and hypercholesterolemia correction in an apolipoprotein-E deficient mouse model
These enzymes are produced primarily as a defence against the harsh enteric environment and act in cleaving the amino group off a bile acid (BA), rendering the molecule amenable to further degradation by other bacterial enzymes, such as 7-α-dehydroxylases [7,8,9]. This process reduces BA reabsorption in the ileum and in turn can up-regulate de novo synthesis of BA, of which cholesterol is a major component. This effect is the result of the suppression of the ileal farnesoid X receptor-fibroblast growth factor (FXR-FGF)15/19 axis, which impacts through the hepatocyte membrane FGFR4/ß-klotho complex primarily on CYP7A1-expression downstream in the cascade; improving the host lipid profile and metabolic health [10, 11], potentially leading to a reduced risk of cardiovascular disease (CVD)
Lactobacillus mucosae DPC 6426 secretome and EPS induce macrophage phenotypes that share features of both classically and alternatively activated macrophages Recently, it was posited that ingestion of Lb. mucosae DPC 6426 alters lipid metabolism due to the production of a complex polysaccharide [5]
Summary
Lactobacillus mucosae DPC 6426 has previously demonstrated potentially cardio-protective properties, in the form of dyslipidaemia and hypercholesterolemia correction in an apolipoprotein-E deficient mouse model. The gut microbiome is a complex ecosystem of diverse metabolic pathways which is central to the progression and prevention of host cardiovascular disease (CVD) and other closely related metabolic dysfunctions such as obesity and type-2 diabetes [1] These microorganisms are capable of contributing to atherogenesis through a number of pathways, with the potential to alter gut hormone signalling, bile and lipid metabolism. One mechanism through which gut microbes are known to impact on host lipid profile is through a set of enzymes, termed bile salt hydrolases (BSH), which function in deconjugating bile salt to bile acid (BA) [6] These enzymes are produced primarily as a defence against the harsh enteric environment and act in cleaving the amino group off a BA, rendering the molecule amenable to further degradation by other bacterial enzymes, such as 7-α-dehydroxylases [7,8,9]. This effect is the result of the suppression of the ileal farnesoid X receptor-fibroblast growth factor (FXR-FGF)15/19 axis, which impacts through the hepatocyte membrane FGFR4/ß-klotho complex primarily on CYP7A1-expression downstream in the cascade; improving the host lipid profile and metabolic health [10, 11], potentially leading to a reduced risk of CVD
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