Srutkova Dagmar, Schwarzer Martin, Hudcovic Tomas, Zakostelska Zuzana, Drab Vladimir, Spanova Alena, Rittich Bohuslav, Kozakova Hana, Schabussova Irma
Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Novy Hradek, Czech Republic.
Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Czech Republic.
PLoS One. 2015 Jul 28;10(7):e0134050. doi: 10.1371/journal.pone.0134050. eCollection 2015.
Reduced microbial diversity has been associated with inflammatory bowel disease (IBD) and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis.
Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952) and CCDM 372 (Bl 372) were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS)-induced colitis was used to compare their beneficial effects in vivo.
The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum.
We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.
微生物多样性降低与炎症性肠病(IBD)相关,益生菌已被提议用于其预防和/或治疗。然而,针对同一亚种菌株特定健康益处的比较研究却很匮乏。在此,我们比较了两株长双歧杆菌亚种长双歧杆菌菌株预防实验性结肠炎的能力。
通过刺激小鼠脾细胞评估9种益生菌双歧杆菌的免疫调节特性。通过刺激骨髓来源的树突状细胞、HEK293/TLR2或HEK293/NOD2细胞,进一步表征对长双歧杆菌亚种长双歧杆菌CCM 7952(Bl 7952)和CCDM 372(Bl 372)的免疫反应。使用葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型比较它们在体内的有益作用。
这9种双歧杆菌表现出菌株特异性的诱导细胞因子产生的能力。与Bl 7952相比,Bl 372在脾脏和树突状细胞培养物中诱导产生更高水平的促炎和抗炎细胞因子。两株菌株均与TLR2结合并含有NOD2配体。在DSS诱导的结肠炎小鼠模型中,Bl 7952而非Bl 372减轻了临床症状并保留了紧密连接蛋白的表达。重要的是,血清中FITC-葡聚糖水平降低表明Bl 7952改善了肠道屏障功能。
我们已表明,Bl 7952而非Bl 372可保护小鼠免受实验性结肠炎的发展。我们的数据表明,尽管某些免疫调节特性可能在双歧杆菌属中广泛存在,但其他特性可能很罕见且仅为特定菌株所特有。因此,在IBD益生菌临床试验中提供有益结果时,仔细选择可能至关重要。