瑞士乳杆菌和钝顶螺旋藻对克罗恩病相关大肠杆菌引发炎症的结肠细胞的抗炎作用。
Anti-Inflammatory effects of Lactobacillus helveticus and Arthrospira platensis on colonic cells inflamed by Crohn's disease-associated Escherichia coli.
作者信息
Alipour Samira, Halimi Hossein, Asri Nastaran, Rostami-Nejad Mohammad, Pishkar Leila, Houri Hamidreza
机构信息
Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St., P.O. BOX: 1985717411, Velenjak, Tehran, Iran.
Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
BMC Mol Cell Biol. 2025 Jun 11;26(1):20. doi: 10.1186/s12860-025-00545-9.
BACKGROUND
Adherent-invasive Escherichia coli (AIEC) is linked to intestinal inflammation in inflammatory bowel disease (IBD). Arthrospira platensis and Lactobacillus helveticus exhibit anti-inflammatory properties individually, yet their effects remain underexplored in IBD-associated inflammation. We aimed to investigate the anti-inflammatory potential of L. helveticus and the hydroalcoholic extract of A. platensis (HA-A. platensis) in Caco-2 cells inflamed by IBD-associated E. coli.
METHODS
Caco-2 cells inflamed by a Crohn's disease (CD)-associated E. coli strain (MOI 10) were treated with HA-A. platensis (2 mg/mL) and/or L. helveticus (MOI 50) in live (LBC), heat-killed (HKC), or cell-free supernatant (CFS) forms. The anti-invasion/adhesion properties of L. helveticus and/or HA-A. platensis were investigated by assessing the CD-associated E. coli invasion/adhesion rate (%). Signaling molecules (NF-κB, STAT3, NOD2) were analyzed via qPCR to capture pathway activation dynamics, while cytokines (TNF-α, IL-1β, IL-8, IL-10) were quantified by ELISA to assess secreted functional proteins.
RESULTS
HA-A. platensis reduced E. coli adhesion by 68% (P < 0.001) and completely inhibited invasion. L. helveticus (live form) decreased adhesion by 88% and invasion by 90%. Combined treatment showed synergistic effects, reducing adhesion by 89% and fully blocking invasion. HA-A. platensis downregulated STAT3 expression by 0.4-fold (P < 0.01), while L. helveticus (heat-killed form) reduced NF-κB by 0.51-fold (P < 0.05) and increased NOD2 by 1.8-fold (P < 0.01). Cytokine analysis revealed that HA-A. platensis decreased IL-1β by 0.61-fold (P < 0.001), and L. helveticus (heat-killed) reduced TNF-α (0.51-fold) and IL-8 (0.23-fold) while elevating anti-inflammatory IL-10 (4.39-fold; P < 0.001).
CONCLUSIONS
L. helveticus and HA-A. platensis synergistically inhibit CD-associated E. coli pathogenicity and modulate inflammatory responses in vitro. These findings highlight their potential as adjunctive therapies for CD, warranting further preclinical validation.
背景
粘附侵袭性大肠杆菌（AIEC）与炎症性肠病（IBD）中的肠道炎症有关。钝顶螺旋藻和瑞士乳杆菌各自具有抗炎特性，但它们在IBD相关炎症中的作用仍未得到充分研究。我们旨在研究瑞士乳杆菌和钝顶螺旋藻水醇提取物（HA-钝顶螺旋藻）对IBD相关大肠杆菌诱导炎症的Caco-2细胞的抗炎潜力。
方法
用HA-钝顶螺旋藻（2mg/mL）和/或瑞士乳杆菌（感染复数50）的活菌体（LBC）、热灭活菌体（HKC）或无细胞上清液（CFS）形式处理被克罗恩病（CD）相关大肠杆菌菌株（感染复数10）诱导炎症的Caco-2细胞。通过评估CD相关大肠杆菌的侵袭/粘附率（%）来研究瑞士乳杆菌和/或HA-钝顶螺旋藻的抗侵袭/粘附特性。通过qPCR分析信号分子（NF-κB、STAT3、NOD2）以捕捉信号通路激活动态，同时通过ELISA定量细胞因子（TNF-α、IL-1β、IL-8、IL-10）以评估分泌的功能蛋白。
结果
HA-钝顶螺旋藻使大肠杆菌的粘附减少68%（P<0.001）并完全抑制侵袭。瑞士乳杆菌（活菌体形式）使粘附减少88%，侵袭减少90%。联合处理显示出协同作用，使粘附减少89%并完全阻断侵袭。HA-钝顶螺旋藻使STAT3表达下调0.4倍（P<0.01），而瑞士乳杆菌（热灭活形式）使NF-κB减少0.51倍（P<0.05）并使NOD2增加1.8倍（P<0.01）。细胞因子分析显示，HA-钝顶螺旋藻使IL-1β减少0.61倍（P<0.001），瑞士乳杆菌（热灭活）使TNF-α（0.51倍）和IL-8（0.23倍）减少，同时使抗炎性IL-10升高（4.39倍；P<0.001）。
结论
瑞士乳杆菌和HA-钝顶螺旋藻在体外协同抑制CD相关大肠杆菌的致病性并调节炎症反应。这些发现突出了它们作为CD辅助治疗方法潜在价值，值得进一步进行临床前验证。
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