School of Biological Sciences and Technology, Chonnam National University, 77 Yongbong-Ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
Department of Nursing, Nambu University, 23 Chumdan Jungang-Ro, Gwangsan-Gu, Gwangju, 62271, Republic of Korea.
Sci Rep. 2023 Apr 1;13(1):5371. doi: 10.1038/s41598-023-32527-2.
Axl is a tyrosine kinase receptor, a negative regulator for innate immune responses and inflammatory bowel disease (IBD). The gut microbiota regulates intestinal immune homeostasis, but the role of Axl in the pathogenesis of IBD through the regulation of gut microbiota composition remains unresolved. In this study, mice with DSS-induced colitis showed increased Axl expression, which was almost entirely suppressed by depleting the gut microbiota with antibiotics. Axl mice without DSS administration exhibited increased bacterial loads, especially the Proteobacteria abundant in patients with IBD, significantly consistent with DSS-induced colitis mice. Axl mice also had an inflammatory intestinal microenvironment with reduced antimicrobial peptides and overexpression of inflammatory cytokines. The onset of DSS-induced colitis occurred faster with an abnormal expansion of Proteobacteria in Axl mice than in WT mice. These findings suggest that a lack of Axl signaling exacerbates colitis by inducing aberrant compositions of the gut microbiota in conjunction with an inflammatory gut microenvironment. In conclusion, the data demonstrated that Axl signaling could ameliorate the pathogenesis of colitis by preventing dysbiosis of gut microbiota. Therefore, Axl may act as a potential novel biomarker for IBD and can be a potential candidate for the prophylactic or therapeutic target of diverse microbiota dysbiosis-related diseases.
Axl 是一种酪氨酸激酶受体，是先天免疫反应和炎症性肠病 (IBD) 的负调节剂。肠道微生物群调节肠道免疫稳态，但 Axl 通过调节肠道微生物群组成在 IBD 发病机制中的作用仍未解决。在这项研究中，DSS 诱导结肠炎的小鼠表现出 Axl 表达增加，而抗生素耗尽肠道微生物群几乎完全抑制了 Axl 表达。未给予 DSS 处理的 Axl 小鼠表现出细菌负荷增加，特别是在 IBD 患者中丰富的变形菌，与 DSS 诱导的结肠炎小鼠非常一致。Axl 小鼠还具有炎症性肠道微环境，抗菌肽减少，炎症细胞因子表达过度。与 WT 小鼠相比，Axl 小鼠中变形菌的异常扩张导致 DSS 诱导的结肠炎更快发作。这些发现表明，缺乏 Axl 信号通过诱导肠道微生物群的异常组成以及炎症性肠道微环境来加重结肠炎。总之，数据表明 Axl 信号可以通过防止肠道微生物群的失调来改善结肠炎的发病机制。因此，Axl 可能作为 IBD 的潜在新型生物标志物，并可作为多种与微生物群失调相关疾病的预防或治疗靶点的潜在候选物。
