Helmholtz Institute for Pharmaceutical Research Saarland, Department of Pharmacy, Saarland University, Campus E8 1, 66123 Saarbrücken, Germany.
INM - Leibniz Institute for New Materials, Campus D2 2, 66123 Saarbrücken, Germany.
ACS Appl Bio Mater. 2021 May 17;4(5):3739-3748. doi: 10.1021/acsabm.0c01136. Epub 2021 Jan 5.
During infection, inflammation is an important contributor to tissue regeneration and healing, but it may also negatively affect these processes should chronic overstimulation take place. Similar issues arise in chronic inflammatory gastrointestinal diseases such as inflammatory bowel diseases or celiac disease, which show increasing incidences worldwide. For these dispositions, probiotic microorganisms, including lactobacilli, are studied as an adjuvant therapy to counterbalance gut dysbiosis. However, not all who are affected can benefit from the probiotic treatment, as immunosuppressed or hospitalized patients can suffer from bacteremia or sepsis when living microorganisms are administered. A promising alternative is the treatment with bacteria-derived membrane vesicles that confer similar beneficial effects as the progenitor strains themselves. Membrane vesicles from lactobacilli have shown anti-inflammatory therapeutic effects, but it remains unclear whether the stimulation of probiotics induces vesicles that are more efficient. Here, the influence of culture conditions on the anti-inflammatory characteristics of membrane vesicles was investigated. We reveal that the culture conditions of two strains, namely, and , can be optimized to increase the anti-inflammatory effect of their vesicles. Five different cultivation conditions were tested, including pH manipulation, agitation rate, and oxygen supply, and the produced membrane vesicles were characterized physico-chemically regarding size, yield, and zeta potential. We furthermore analyzed the anti-inflammatory effect of the purified vesicles in macrophage inflammation models. Compared to standard cultivation conditions, vesicles obtained from cultured at pH 6.5 and agitation induced the strongest interleukin-10 release and tumor necrosis factor-α reduction. For , medium adjusted to pH 5 had the most pronounced effect on the anti-inflammatory activity of their vesicles. Our results reveal that the anti-inflammatory effect of probiotic vesicles may be potentiated by expanding different cultivation conditions for lactobacilli. This study creates an important base for the utilization of probiotic membrane vesicles to treat inflammation.
在感染过程中，炎症是组织再生和修复的重要贡献者，但如果发生慢性过度刺激，它也可能对这些过程产生负面影响。类似的问题也出现在慢性炎症性胃肠道疾病中，如炎症性肠病或乳糜泻，这些疾病在全球的发病率不断上升。对于这些疾病，包括乳杆菌在内的益生菌微生物被研究作为辅助治疗方法，以平衡肠道菌群失调。然而，并非所有受影响的人都能从益生菌治疗中受益，因为免疫抑制或住院的患者在给予活菌时可能会发生菌血症或败血症。一种有前途的替代方法是使用细菌衍生的膜泡进行治疗，这些膜泡具有与原始菌株本身相似的有益效果。乳杆菌的膜泡已显示出抗炎治疗效果，但仍不清楚刺激益生菌是否会诱导更有效的泡囊。在这里，研究了培养条件对膜泡抗炎特性的影响。我们揭示了两种菌株，即 和 ，的培养条件可以优化，以增加其膜泡的抗炎效果。测试了五种不同的培养条件，包括 pH 操作、搅拌速度和氧气供应，并对大小、产量和 ζ 电位等物理化学特性进行了膜泡的特征分析。我们还在巨噬细胞炎症模型中分析了纯化膜泡的抗炎效果。与标准培养条件相比，在 pH 6.5 和搅拌下培养的 产生的膜泡诱导的白细胞介素-10 释放和肿瘤坏死因子-α减少最强。对于 ，将培养基调整至 pH 5 对其膜泡抗炎活性的影响最为显著。我们的结果表明，通过扩大乳杆菌的不同培养条件，可以增强益生菌泡囊的抗炎效果。这项研究为利用益生菌膜泡治疗炎症奠定了重要基础。
