Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis.
While some probiotic strains might have adjuvant effects in the therapy for inflammatory bowel diseases (IBD), these effects remain controversial and cannot be generalized. In this study, a dltD mutant of the model probiotic Lactobacillus rhamnosus GG (LGG), having a drastic modification in its lipoteichoic acid (LTA) molecules, was analysed for its effects in an experimental colitis model. Dextran sulphate sodium (DSS) was used to induce either moderate to severe or mild chronic colitis in mice. Mice received either phosphate-buffered saline (PBS), LGG wild-type or the dltD mutant via the drinking water. Macroscopic parameters, histological abnormalities, cytokine and Toll-like receptor (TLR) expression were analysed to assess disease activity. LGG wild-type did not show efficacy in the different experimental colitis set-ups. This wild-type strain even seemed to exacerbate the severity of colitic parameters in the moderate to severe colitis model compared to untreated mice. In contrast, mice treated with the dltD mutant showed an improvement of some colitic parameters compared to LGG wild-type-treated mice in both experimental models. In addition, treatment with the dltD mutant correlated with a significant down-regulation of Toll-like receptor-2 expression and of downstream proinflammatory cytokine expression in the colitic mice. These results show that molecular cell surface characteristics of probiotics are crucial when probiotics are considered for use as supporting therapy in IBD.
Claes
I J J
IJ
Centre of Microbial and Plant Genetics, University Hospital, K. U. Leuven, Belgium.
Lebeer
Sarah
S
Shen
C
C
Verhoeven
T L A
TL
Dilissen
E
E
De Hertogh
G
G
Bullens
D M A
DM
Ceuppens
J L
JL
Van Assche
G
G
Vermeire
S
S
Rutgeerts
P
P
Vanderleyden
J
J
De Keersmaecker
S C J
SC
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001835:Body Weight; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015169:Colony Count, Microbial; D016264:Dextran Sulfate / Q000494:pharmacology; D005260:Female; D005750:Gastric Juice / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology; D015870:Gene Expression / Q000235:genetics; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D052201:Lacticaseibacillus rhamnosus / Q000235:genetics*; D008070:Lipopolysaccharides / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000235:genetics; D023421:Models, Animal; D019936:Probiotics / Q000627:therapeutic use*; D013682:Teichoic Acids / Q000235:genetics*; D013869:Thiolester Hydrolases / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics; D016896:Treatment Outcome
D001426:Bacterial Proteins; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051193:Toll-Like Receptors; C009900:lipoteichoic acid; D007371:Interferon-gamma; D016264:Dextran Sulfate; C408973:DltD protein, bacteria; D013869:Thiolester Hydrolases