PDF(Pubmed)
Abstract：
Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling.
摘要：
泪液基质金属蛋白酶(MMP)-9是干眼(DE)患者的炎性信号。在本研究中,了解益生菌LB101（植物乳杆菌NK151和双歧杆菌NK175[4:1]混合物）对DE的作用机制，我们研究了其对单侧眶外泪腺切除术/阿托品-苯扎氯铵（EB）或EB小鼠粪便微生物群移植（eFMT）小鼠泪液量和炎症标志物表达水平的影响。口服灌胃LB101可增加EB抑制的泪液量并减少EB诱导的眨眼次数。此外，LB101降低EB诱导的TNF-α，IL-1β,和MMP-9表达，TNF-α+和NF-κB+CD11c+细胞群，结膜水肿,而EB抑制的IL-10和occludin表达增加。LB101还降低EB诱导的TNF-α和IL-1β表达以及结肠中NF-κB+CD11c+细胞群。eFMT还减少了移植小鼠的泪液量并增加了眨眼次数。eFMT增加TNF-α，IL-1β,结膜中MMP-9表达和TNF-α+和NF-κB+CD11c+细胞群,结肠中TNF-α和IL-1β表达和NF-κB+CD11c+细胞群。LB101的口服管饲法增加了eFMT抑制的泪液量，并减少了eFMT诱导的眨眼次数。此外，LB101降低TNF-α，IL-1β,和MMP-9表达，TNF-α+和NF-κB+CD11c+细胞群，结膜水肿、结肠中TNF-α和IL-1β表达和NF-κB+CD11c+细胞群，而eFMT抑制IL-10和occludin表达降低。此外，LB101增加了eFMT抑制的Muribaculaceae，Prevotellaceae，和肠道微生物群中的乳杆菌科种群，而eFMT诱导的拟杆菌科种群减少。这些发现表明，DE可能会导致肠道菌群失调，这可能是DE的风险因素，LB101可能通过抑制MMP-9和促炎细胞因子TNF-α和IL-1β的表达，并调节肠道菌群参与的NF-κB信号来减轻肠道炎症。
