Probiotic Lactobacillus rhamnosus GR-1 supernatant prevents lipopolysaccharide-induced preterm birth and reduces inflammation in pregnant CD-1 mice.
OBJECTIVE
The objective of this study was to determine the effect of probiotic Lactobacillus rhamnosus GR-1 supernatant (GR-1 SN) on lipopolysaccharide-induced preterm birth (PTB) and outputs of cytokines, chemokines, and progesterone in pregnant CD-1 mice.


METHODS
We compared PTB rates after intrauterine injection of lipopolysaccharide with and without previous GR-1 SN treatment. Cytokines and chemokines in the maternal plasma, myometrium, placenta, and amniotic fluid were examined with multiplex assay, and circulating maternal progesterone was measured with enzyme-linked immunoassay. Statistical significance was assessed with 2-tailed 1-way analysis of variance or analysis of variance on ranks. Fetal sex ratios in mice that delivered preterm were compared with those that delivered at term after lipopolysaccharide and GR-1 SN treatments.


RESULTS
GR-1 SN reduced lipopolysaccharide-induced PTB by 43%. GR-1 SN significantly decreased the lipopolysaccharide-induced production of interleukin (IL)-1β, -6, and -12p40, tumor necrosis factor-α, CCL4, and CCL5 in maternal plasma; IL-6, -12p70, -17, and -13 and tumor necrosis factor-α in myometrium; IL-6, -12p70, and -17 in placenta; and IL-6, tumor necrosis factor-α, CCL3, and CCL4 in amniotic fluid. Maternal plasma progesterone was reduced significantly after lipopolysaccharide injection with and without GR-1 SN pretreatment. There was no difference in fetal sex ratios between mice that delivered preterm and those that did not after lipopolysaccharide and GR-1 SN treatments.


CONCLUSIONS
The supernatant of probiotic L rhamnosus GR-1 attenuated lipopolysaccharide-induced inflammation and PTB in vivo. GR-1 SN may confer therapeutic benefits in the prevention of infection-associated PTB by controlling systemic and intrauterine inflammation.
Departments of Physiology and Obstetrics and Gynecology, University of Toronto Faculty of Medicine, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Siwen
S
Yang
Departments of Physiology and Obstetrics and Gynecology, University of Toronto Faculty of Medicine, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Wei
W
Li
Departments of Physiology and Obstetrics and Gynecology, University of Toronto Faculty of Medicine, Toronto, ON, Canada; Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada.
John R G
JR
Challis
Department of Microbiology and Immunology, Western University Faculty of Medicine, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada.
Gregor
G
Reid
Department of Microbiology and Immunology, Western University Faculty of Medicine, London, ON, Canada.
Sung O
SO
Kim
Departments of Physiology and Obstetrics and Gynecology, University of Toronto Faculty of Medicine, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. Electronic address: abocking@mtsinai.on.ca.
Alan D
AD
Bocking
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D052201:Lacticaseibacillus rhamnosus; D008070:Lipopolysaccharides; D051379:Mice; D008813:Mice, Inbred ICR; D060885:Multiplex Polymerase Chain Reaction; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D047928:Premature Birth / Q000209:etiology / Q000517:prevention & control*; D019936:Probiotics / Q000627:therapeutic use*; D011374:Progesterone / Q000378:metabolism; D011897:Random Allocation; D012744:Sex Ratio
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5; D011374:Progesterone
Lactobacillus rhamnosus GR-1; chemokine; cytokine; preterm birth; progesterone