The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment.
The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment.
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DOI：
10.3389/fcimb.2017.00167
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发表时间：
2017
影响因子：
5.7
通讯作者：
Heimesaat MM
中科院分区：
文献类型：
--
作者：
Ekmekciu I;von Klitzing E;Fiebiger U;Neumann C;Bacher P;Scheffold A;Bereswill S;Heimesaat MM
有令人信服的证据将肠道微生物群与宿主健康联系起来，进而将抗生素诱导的微生物群组成的扰动与不同的病理联系起来。尽管益生菌疗法作为有益地改变肠道微生物群的工具具有吸引力，但其免疫学作用仍不完全清楚。本研究的目的是评估益生菌制剂VSL#3的疗效，该制剂由8种不同的细菌菌种（包括嗜热链球菌、短双歧杆菌、B. longum，B.嗜酸乳杆菌（Lactobacillus acidophilus）、L. [医]植物paracasei和L.德氏与复杂鼠微生物群的再结合相比，保加利亚）在逆转微生物群耗竭的免疫效应中的作用。为了解决这一问题，对常规小鼠进行8周的广谱抗生素治疗，并经口与VSL#3细菌或复杂的鼠微生物群重新关联。VSL#3去活化导致小肠和大肠固有层中的CD 4+和CD 8+细胞数量以及小肠固有层中的B220+细胞数量恢复，而益生菌干预不足以逆转抗生素诱导的脾脏中相应细胞群的变化。然而，VSLI #3给药与复杂微生物群再结合一样有效，可降低小肠、结肠、肠系膜淋巴结和脾脏中调节性T细胞、活化树突状细胞和记忆/效应T细胞的频率。尽管广谱抗生素治疗导致相应免疫区室中CD 4+细胞产生的细胞因子（如IFN-γ、IL-17、IL-22和IL-10）减少，但VSLI #3去活化足以完全恢复抗炎细胞因子IL-10的表达，而不影响促炎介质。总之，益生菌化合物VSL#3对粘膜、外周和全身先天性以及适应性免疫具有广泛影响，在肠道和全身隔室中发挥有益的抗炎作用。因此，VSLI #3可视为抗生素治疗后的治疗性免疫调节工具。
There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus) in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and systemic innate as well as adaptive immunity, exerting beneficial anti-inflammatory effects in intestinal as well as systemic compartments. Hence, VSL#3 might be considered a therapeutic immunomodulatory tool following antibiotic therapy.