Kamrani Amin, Asghari Kimia Motlagh, Zafarani Yasamin, Rahmanzad Fatemeh, Soltani-Zangbar Mohammad Sadegh, Badihi Elham, Afandideh Farshid, Sedghi Aminabad Negar, Pirouzpanah Mohammadbagher, Abroon Sina, Novinbahador Tannaz, Danaii Shahla, Ahmadian Heris Javad, Aghebati-Maleki Leili, Roshangar Leila, Shekarchi Ali Akbar, Pourlak Tannaz, Zolfaghari Mohammadali, Yousefi Mehdi
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Hum Immunol. 2025 Jan;86(1):111220. doi: 10.1016/j.humimm.2024.111220. Epub 2024 Dec 19.
Among the complex causes of infertility, Recurrent Implantation Failure (RIF) stands out as a challenging condition. Immunological aberrations are closely implicated in RIF, particularly the imbalance between T helper 1 (Th1) and T helper 2 (Th2) cytokines. Interest in harnessing probiotics to enhance fertility outcomes in RIF-affected women is growing. This study aimed to investigate the potential of probiotics in restoring the Th1 to Th2 ratio and enhancing implantation outcomes in women experiencing RIF.
A double-blinded randomized controlled trial enrolled 50 women with a record of at least three RIFs and 50 women with successful pregnancies as a control group in our study. RIF patients were randomly assigned to either the probiotic intervention group (n = 25) or the placebo group (n = 25). The probiotic group administered two tablets per day for 6 months the probiotic tablets that contained prebiotic. At the same time, the placebo group received an identical-looking placebo. Flow cytometry technique was used to evaluate Th1 and Th2 cell frequencies. Gene expression of IL-4, IL-10, TNF-α and IFN-ɣ was analyzed using QRT-PCR. Serum concentrations of IL-4, IL-10, TNF-α and IFN-ɣ cytokines were evaluated using the ELISA technique.
Flow cytometry analysis revealed significantly higher Th1 cell percentages in RIF patients compared to healthy controls, while healthy controls exhibited more significant Th2 cell proportions. Probiotic intervention led to a reduction in Th1 cells and an increase in Th2 cells in RIF patients. ELISA analysis indicated higher proinflammatory and lower anti-inflammatory cytokines compared to controls. After probiotic treatment, TNF-α and IFN-ɣ levels decreased, while IL-10 and IL-4 levels increased in RIF patients. QRT-PCR analysis showed no significant differences in cytokine gene expression between RIF patients before intervention. After probiotic therapy, pro-inflammatory cytokine expression decreased, and anti-inflammatory cytokine expression increased. Placebo treatment resulted in limited changes. Probiotic intervention effectively modulated the Th1 to Th2 ratio in RIF patients, evidenced by reduced Th1 cell percentages, enhanced Th2 cell populations, and cytokine level adjustments. The probiotic intervention improved implantation outcomes in women with RIF, as evidenced by a higher clinical pregnancy rate in the treatment group compared to the placebo group (p = 0.037).
These findings highlight the potential of probiotics in restoring immune balance and improving implantation outcomes in women with RIF.
在不孕症的复杂病因中，反复种植失败（RIF）是一种具有挑战性的情况。免疫异常与RIF密切相关，尤其是辅助性T细胞1（Th1）和辅助性T细胞2（Th2）细胞因子之间的失衡。利用益生菌改善受RIF影响女性的生育结局的兴趣日益增加。本研究旨在探讨益生菌在恢复RIF女性的Th1/Th2比值和提高种植结局方面的潜力。
一项双盲随机对照试验纳入了50名有至少三次RIF记录的女性和50名成功怀孕的女性作为对照组。RIF患者被随机分为益生菌干预组（n = 25）或安慰剂组（n = 25）。益生菌组每天服用两片含益生元的益生菌片，持续6个月。同时，安慰剂组接受外观相同的安慰剂。采用流式细胞术评估Th1和Th2细胞频率。使用QRT-PCR分析IL-4、IL-10、TNF-α和IFN-γ的基因表达。采用ELISA技术评估血清中IL-4、IL-10、TNF-α和IFN-γ细胞因子的浓度。
流式细胞术分析显示，与健康对照组相比，RIF患者的Th1细胞百分比显著更高，而健康对照组的Th2细胞比例更高。益生菌干预使RIF患者的Th1细胞减少，Th2细胞增加。ELISA分析表明，与对照组相比，RIF患者的促炎细胞因子水平较高，抗炎细胞因子水平较低。益生菌治疗后，RIF患者的TNF-α和IFN-γ水平降低，而IL-10和IL-4水平升高。QRT-PCR分析显示，干预前RIF患者细胞因子基因表达无显著差异。益生菌治疗后，促炎细胞因子表达降低，抗炎细胞因子表达增加。安慰剂治疗导致的变化有限。益生菌干预有效调节了RIF患者的Th1/Th2比值，表现为Th1细胞百分比降低、Th2细胞群体增加以及细胞因子水平调整。益生菌干预改善了RIF女性的种植结局，治疗组的临床妊娠率高于安慰剂组（p = 0.037）。
这些发现凸显了益生菌在恢复RIF女性免疫平衡和改善种植结局方面的潜力。
