Probiotic Lactobacillus rhamnosus GR-1 is a unique prophylactic agent that suppresses infection-induced myometrial cell responses.

2019-03-18
Scientific reports 9(1)

PubMed: 30886179
DOI: 10.1038/s41598-019-41133-0

Study Design

Population: human myometrial cell line, hTERT-HM
Methods: L. rhamnosus GR-1 supernatant was tested for its ability to suppress LPS-induced cytokine secretion in hTERT-HM cells; heat resistance/trypsin sensitivity was assessed, and pre-incubation with low-dose Pam3CSK prior to LPS administration was also examined

Rigorous Journal

Preterm birth (PTB) is a multifactorial syndrome affecting millions of neonates worldwide. Intrauterine infection can induce PTB through the secretion of pro-inflammatory cytokines and untimely activation of uterine contractions. In pregnant mice, prophylactic administration of probiotic Lactobacillus rhamnosus GR-1 supernatant (GR1SN) prevented lipopolysaccharide (LPS)-induced PTB and reduced cytokine expression in the uterine muscle (myometrium). In this study we sought to delineate the mechanisms by which GR1SN suppressed cytokine secretion in the myometrium. We observed that L. rhamnosus GR-1 uniquely secretes heat-resistant but trypsin-sensitive factors, which significantly suppressed LPS-induced secretion of pro-inflammatory cytokines IL-6, IL-8, and MCP-1 in the human myometrial cell line, hTERT-HM. This effect was unique to GR1SN and could not be replicated using supernatant derived from non-GR-1 commensal lactobacilli species: L. rhamnosus GG, L. lactis, L. casei, or L. reuteri RC-14. Furthermore, pre-incubation of hTERT-HM cells with low-dose Pam3CSK (a TLR1/2 synthetic agonist which mimics LPS action) prior to LPS administration also significantly decreased LPS-induced cytokine secretion. This study highlights the distinct capacity of protein-like moieties secreted by L. rhamnosus GR-1 to inhibit pro-inflammatory cytokine production by human myometrial cells, potentially through a TLR1/2-mediated mechanism.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus rhamnosus GR-1	—	Reduced Inflammation	Beneficial	Moderate	View source L. rhamnosus GR-1 uniquely secretes heat-resistant but trypsin-sensitive factors, which significantly suppressed LPS-induced secretion of pro-inflammatory cytokines IL-6, IL-8, and MCP-1 in the human myometrial cell line, hTERT-HM.
Lactobacillus rhamnosus GR-1	—	Reduced Preterm Births	Beneficial	Moderate	View source In pregnant mice, prophylactic administration of probiotic Lactobacillus rhamnosus GR-1 supernatant (GR1SN) prevented lipopolysaccharide (LPS)-induced PTB and reduced cytokine expression in the uterine muscle (myometrium).