Journal of reproductive immunology · 2026
NLRP3 inflammasome activation and impaired Treg-mediated immune tolerance are associated with spontaneous preterm birth: A case-control study with in vitro probiotic metabolite intervention.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Xuemei, Zhuang Lin, Huang Heying, Chen Jin, Xu Jiao, Wang Xiaoyin
Аннотация
BACKGROUND: Spontaneous preterm birth (sPTB) is a leading cause of neonatal morbidity and mortality worldwide. Excessive NLRP3 inflammasome activation coupled with impaired regulatory T cell (Treg)-mediated immune tolerance may be associated with sPTB; however, whether probiotic-derived metabolites can modulate this immunological imbalance under in vitro conditions remains unclear.
METHODS: A case-control study enrolled 45 women with sPTB and 50 term controls. Peripheral blood and fetal membrane/decidual tissues were collected to assess NLRP3 pathway activation (NLRP3, caspase-1, and IL-1β) and immune tolerance markers (Treg proportion, IL-10, and TGF-β). Multivariable logistic regression was performed to evaluate independent associations with sPTB. In vitro experiments used paired samples from six donors, and data were analysed with linear mixed-effects models treating donor as a random effect. Fetal membrane explants and peripheral blood mononuclear cells (PBMCs) were cultured in vitro under lipopolysaccharide-stimulated conditions and treated with sodium butyrate or Lactobacillus rhamnosus GG culture supernatant to evaluate effects on NLRP3 pathway markers and the proportion of CD4⁺CD25⁺Foxp3⁺ cells. An uninoculated, identically processed MRS broth control was included.
RESULTS: The sPTB group exhibited significantly elevated NLRP3, caspase-1, and IL-1β expression alongside reduced Treg proportions and decreased IL-10 and TGF-β levels compared with term controls (all P < 0.001). Tissue NLRP3 expression (adjusted OR = 2.74) and Treg proportion (adjusted OR = 0.61) were independently associated with sPTB status. Under in vitro conditions, both interventions attenuated LPS-induced NLRP3 pathway marker expression and increased the proportion of CD4⁺CD25⁺Foxp3⁺ cells with higher anti-inflammatory cytokine concentrations in fetal membrane explants and PBMCs, whereas the MRS broth control produced no significant change.
CONCLUSIONS: NLRP3 pathway overactivation and reduced Treg proportion coexisted and were each independently associated with sPTB. Probiotic-derived metabolites modulated NLRP3-related and Treg-related measurements at the maternal-fetal interface under in vitro conditions. These cross-sectional and in vitro findings describe associations only and do not establish causality or a preventive effect.
METHODS: A case-control study enrolled 45 women with sPTB and 50 term controls. Peripheral blood and fetal membrane/decidual tissues were collected to assess NLRP3 pathway activation (NLRP3, caspase-1, and IL-1β) and immune tolerance markers (Treg proportion, IL-10, and TGF-β). Multivariable logistic regression was performed to evaluate independent associations with sPTB. In vitro experiments used paired samples from six donors, and data were analysed with linear mixed-effects models treating donor as a random effect. Fetal membrane explants and peripheral blood mononuclear cells (PBMCs) were cultured in vitro under lipopolysaccharide-stimulated conditions and treated with sodium butyrate or Lactobacillus rhamnosus GG culture supernatant to evaluate effects on NLRP3 pathway markers and the proportion of CD4⁺CD25⁺Foxp3⁺ cells. An uninoculated, identically processed MRS broth control was included.
RESULTS: The sPTB group exhibited significantly elevated NLRP3, caspase-1, and IL-1β expression alongside reduced Treg proportions and decreased IL-10 and TGF-β levels compared with term controls (all P < 0.001). Tissue NLRP3 expression (adjusted OR = 2.74) and Treg proportion (adjusted OR = 0.61) were independently associated with sPTB status. Under in vitro conditions, both interventions attenuated LPS-induced NLRP3 pathway marker expression and increased the proportion of CD4⁺CD25⁺Foxp3⁺ cells with higher anti-inflammatory cytokine concentrations in fetal membrane explants and PBMCs, whereas the MRS broth control produced no significant change.
CONCLUSIONS: NLRP3 pathway overactivation and reduced Treg proportion coexisted and were each independently associated with sPTB. Probiotic-derived metabolites modulated NLRP3-related and Treg-related measurements at the maternal-fetal interface under in vitro conditions. These cross-sectional and in vitro findings describe associations only and do not establish causality or a preventive effect.