Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA.
Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
NPJ Biofilms Microbiomes. 2024 Aug 29;10(1):75. doi: 10.1038/s41522-024-00556-y.
Spinal cord injury (SCI) results in numerous systemic dysfunctions, including intestinal dysmotility and enteric nervous system (ENS) atrophy. The ENS has capacity to recover following perturbation, yet intestinal pathologies persist. With emerging evidence demonstrating SCI-induced alterations to gut microbiome composition, we hypothesized that microbiome modulation contributes to post-injury enteric recovery. Here, we show that intervention with the dietary fiber, inulin, prevents SCI-induced ENS atrophy and dysmotility in mice. While SCI-associated microbiomes and specific injury-sensitive gut microbes are not sufficient to modulate intestinal dysmotility after injury, intervention with microbially-derived short-chain fatty acid (SCFA) metabolites prevents ENS dysfunctions in injured mice. Notably, inulin-mediated resilience is dependent on IL-10 signaling, highlighting a critical diet-microbiome-immune axis that promotes ENS resilience post-injury. Overall, we demonstrate that diet and microbially-derived signals distinctly impact ENS survival after traumatic spinal injury and represent a foundation to uncover etiological mechanisms and future therapeutics for SCI-induced neurogenic bowel.
脊髓损伤（SCI）导致多种全身功能障碍，包括肠道动力障碍和肠神经系统（ENS）萎缩。ENS 在受到干扰后有恢复的能力，但肠道病理学仍然存在。有新的证据表明，SCI 会引起肠道微生物组组成的改变，我们假设微生物组的调节有助于损伤后的肠内恢复。在这里，我们表明，膳食纤维菊粉的干预可以防止 SCI 诱导的小鼠 ENS 萎缩和运动障碍。虽然与 SCI 相关的微生物组和特定的损伤敏感肠道微生物不足以调节损伤后的肠道动力障碍，但微生物衍生的短链脂肪酸（SCFA）代谢物的干预可以防止受伤小鼠的 ENS 功能障碍。值得注意的是，菊粉介导的恢复依赖于 IL-10 信号，突出了一个关键的饮食-微生物-免疫轴，促进了损伤后 ENS 的恢复。总的来说，我们证明饮食和微生物衍生的信号在创伤性脊髓损伤后明显影响 ENS 的存活，并为 SCI 诱导的神经源性肠道的病因机制和未来治疗方法的研究提供了基础。
