Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe

Paul M. Ryan, Ellen H. Stolte, Lis E.E. London, Jerry M. Wells, Sarah L. Long, Susan A. Joyce, Cormac G.M. Gahan, Gerald F. Fitzgerald, R.P. Ross, Noel M. Caplice, Catherine Stanton*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Background: 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. 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. Results: Quantitative 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. Conclusions: This 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.

Original languageEnglish
Article number33
JournalBMC Microbiology
Volume19
Issue number1
DOIs
Publication statusPublished - 8 Feb 2019

Fingerprint

choloylglycine hydrolase
Lactobacillus
Bile
Mucous Membrane
Lactobacillus reuteri
Macrophages
Bile Acids and Salts
Interleukin-10
Enzyme Assays
Apolipoproteins E
Dyslipidemias
Hypercholesterolemia
Immune System
Interleukin-6
Nitric Oxide
Hydrolysis
Cardiovascular Diseases
Swine
Tumor Necrosis Factor-alpha
Phenotype

Keywords

  • Bile acid
  • Bile salt hydrolase (BSH)
  • CVD
  • Exopolysaccharide
  • Hypercholesterolaemia

Cite this

Ryan, Paul M. ; Stolte, Ellen H. ; London, Lis E.E. ; Wells, Jerry M. ; Long, Sarah L. ; Joyce, Susan A. ; Gahan, Cormac G.M. ; Fitzgerald, Gerald F. ; Ross, R.P. ; Caplice, Noel M. ; Stanton, Catherine. / Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe. In: BMC Microbiology. 2019 ; Vol. 19, No. 1.
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title = "Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe",
abstract = "Background: 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. 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. Results: Quantitative 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. Conclusions: This 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.",
keywords = "Bile acid, Bile salt hydrolase (BSH), CVD, Exopolysaccharide, Hypercholesterolaemia",
author = "Ryan, {Paul M.} and Stolte, {Ellen H.} and London, {Lis E.E.} and Wells, {Jerry M.} and Long, {Sarah L.} and Joyce, {Susan A.} and Gahan, {Cormac G.M.} and Fitzgerald, {Gerald F.} and R.P. Ross and Caplice, {Noel M.} and Catherine Stanton",
year = "2019",
month = "2",
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Ryan, PM, Stolte, EH, London, LEE, Wells, JM, Long, SL, Joyce, SA, Gahan, CGM, Fitzgerald, GF, Ross, RP, Caplice, NM & Stanton, C 2019, 'Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe', BMC Microbiology, vol. 19, no. 1, 33. https://doi.org/10.1186/s12866-019-1403-0

Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe. / Ryan, Paul M.; Stolte, Ellen H.; London, Lis E.E.; Wells, Jerry M.; Long, Sarah L.; Joyce, Susan A.; Gahan, Cormac G.M.; Fitzgerald, Gerald F.; Ross, R.P.; Caplice, Noel M.; Stanton, Catherine.

In: BMC Microbiology, Vol. 19, No. 1, 33, 08.02.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe

AU - Ryan, Paul M.

AU - Stolte, Ellen H.

AU - London, Lis E.E.

AU - Wells, Jerry M.

AU - Long, Sarah L.

AU - Joyce, Susan A.

AU - Gahan, Cormac G.M.

AU - Fitzgerald, Gerald F.

AU - Ross, R.P.

AU - Caplice, Noel M.

AU - Stanton, Catherine

PY - 2019/2/8

Y1 - 2019/2/8

N2 - Background: 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. 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. Results: Quantitative 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. Conclusions: This 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.

AB - Background: 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. 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. Results: Quantitative 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. Conclusions: This 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.

KW - Bile acid

KW - Bile salt hydrolase (BSH)

KW - CVD

KW - Exopolysaccharide

KW - Hypercholesterolaemia

UR - https://doi.org/10.6084/m9.figshare.c.4395449

U2 - 10.1186/s12866-019-1403-0

DO - 10.1186/s12866-019-1403-0

M3 - Article

VL - 19

JO - BMC Microbiology

JF - BMC Microbiology

SN - 1471-2180

IS - 1

M1 - 33

ER -