Humoral immune responses against gut bacteria In dogs with inflammatory bowel disease

Inflammatory bowel disease (IBD) in dogs is associated with clinical signs of intestinal dysfunction, as well as abnormal lymphocytic and myeloid cell infiltrates in the small and/or large intestine. Thus, in many respects IBD in dogs resembles IBD in humans. However, the factors that trigger intestinal inflammation in dogs with IBD are not well understood and have been variously attributed to immune responses against dietary antigens or intestinal antigens. Previous studies in humans with IBD have documented increased production of IgG and IgA antibodies specific to intestinal bacteria, and this abnormal immune response has been linked to disease pathogenesis. Therefore, we investigated the humoral immune response against gut bacteria in dogs with IBD, using flow cytometry to quantitate IgG and IgA binding. Studies were also done to investigate the source of these antibodies (locally produced versus systemic production) and whether greater antibody binding to bacteria is associated with increased inflammatory responses. We found that dogs with IBD had significantly higher percentages and overall amounts of IgG bound to their intestinal bacteria compared to healthy dogs. Similarly, significantly higher percentages of bacteria were IgA+ bacteria were also found in dogs with IBD. Serum antibody recognition of gut bacteria was not different between healthy dogs and dogs with IBD, suggesting that anti-bacterial antibodies were primarily produced locally in the gut rather than systemically. Importantly, bacteria in the Actinobacteria phylum and in particular the genus Collinsella had significantly greater levels of antibody binding in dogs with IBD. Based on these findings, we concluded that antibody binding to commensal gut bacteria was significantly increased in dogs with IBD, that particular phyla were preferential targets for gut antibodies, and that anti-bacterial antibody responses may play an important role in regulating gut inflammation.

犬类炎症性肠病（Inflammatory Bowel Disease, IBD）以肠道功能障碍的临床症状为主要表现，同时伴随小肠和/或大肠内异常淋巴细胞与髓系细胞浸润。因此，犬类IBD在诸多方面与人类炎症性肠病相似。然而，目前对于犬类IBD诱发肠道炎症的具体机制尚未完全阐明，现有假说多将其归咎于针对膳食抗原或肠道自身抗原的免疫应答。既往针对人类IBD的研究已证实，肠道细菌特异性免疫球蛋白G（Immunoglobulin G, IgG）与免疫球蛋白A（Immunoglobulin A, IgA）抗体的产生水平升高，且这种异常免疫应答与疾病发病机制密切相关。基于此，本研究针对犬类IBD展开肠道细菌靶向体液免疫应答的相关研究，采用流式细胞术对IgG与IgA的结合水平进行定量分析。本研究同时开展了相关实验，以明确此类抗体的产生来源（肠道局部产生与全身系统性产生），以及抗体与细菌的结合水平升高是否与炎症反应增强存在关联。研究结果显示，相较于健康犬，犬类IBD个体肠道细菌结合的IgG抗体百分比与总含量均显著升高。类似地，犬类IBD个体中IgA阳性细菌的占比同样显著升高。健康犬与犬类IBD个体的血清抗体对肠道细菌的识别水平并无显著差异，这提示抗菌抗体主要由肠道局部产生，而非经由全身系统合成。尤为重要的是，在犬类IBD个体中，放线菌门（Actinobacteria）尤其是柯林斯菌属（Collinsella）的细菌，其抗体结合水平显著升高。基于上述研究结果，本研究得出如下结论：犬类IBD个体与共生肠道细菌的抗体结合水平显著升高；特定菌门是肠道抗体的优先靶向目标；抗菌抗体应答或许在调控肠道炎症过程中发挥关键作用。