New research in rats shows a direct link between spinal cord injury, gut microbiome disruption, and altered metabolism—offering a potential pathway for therapeutic interventions.
Understanding Spinal Cord Injury and Its Systemic Impact
Spinal cord injury (SCI) is a severe neurological condition that affects over 25,000 to 50,000 people annually across the globe. Beyond the obvious loss of motor and sensory functions, SCI often leads to complications in multiple body systems. These include cardiovascular, respiratory, urinary, and gastrointestinal dysfunctions—all of which significantly complicate rehabilitation and long-term care.
Notably, the gut is one of the organs most affected. The injury disrupts communication between the central nervous system (CNS) and the digestive tract, which leads to significant changes in the gut microbiome—the vast community of bacteria that live in the intestines. These changes can in turn worsen the body’s inflammatory responses, metabolism, and even neurological recovery.
Emerging research suggests that this gut–brain relationship is bidirectional: changes in the brain or spinal cord influence the gut, and vice versa. Similar gut microbiome alterations have been observed in people with other CNS conditions, such as traumatic brain injury and Alzheimer’s disease. This highlights a critical connection that scientists are only beginning to understand.
Study Overview: Linking Gut Microbiome to SCI Recovery
To investigate this further, researchers at Zhejiang Chinese Medical University in China examined the gut microbiome and blood serum metabolites in a rat model of SCI. Using advanced metagenomic and metabolomic techniques, the team compared SCI rats with a sham-operated control group.
The goal was to determine how changes in gut bacteria might correlate with metabolic changes in the body—and whether these interactions could play a role in recovery.
Significant Microbiome Shifts After SCI
The researchers found that SCI significantly altered the composition and diversity of gut bacteria. Two genera, Ligilactobacillus and Staphylococcus, increased in abundance following injury, while beneficial bacteria such as Lactobacillus and Limosilactobacillus decreased.
An increase in bacterial diversity (measured through Chao1 and ACE indices) was also observed. Although higher diversity is often considered beneficial, in this case it indicated an unstable microbial environment, with many rare or previously undetected species emerging—likely in response to stress or inflammation.
Notably, the species Romboutsia, associated with the production of short-chain fatty acids that support gut health and immune function, was reduced in the SCI group. Conversely, genera like Corynebacterium and Macrococcus, which are potentially pro-inflammatory, were more prevalent in SCI rats.
“These shifts likely reflect the influence of gastrointestinal environmental changes on microbial community composition after SCI,” the authors noted.
Disrupted Metabolism and Oxidative Stress
To understand how these microbiome changes affect the body, the team analyzed serum metabolites. They found elevated levels of pyruvate and lactic acid in SCI rats, suggesting that energy metabolism was disrupted and that tissue hypoxia (lack of oxygen) was present.
Meanwhile, a decrease in the antioxidant compound carnosine pointed to increased oxidative stress—a condition that can further damage neurons. Higher levels of aspartic acid may indicate alterations in neurotransmitter signaling, while reductions in other compounds suggested that fatty acid metabolism was also affected.
Pathway analysis showed enrichment in several biological routes related to energy, amino acid, and SCFA metabolism. These are all critical in supporting recovery and maintaining immune balance.
Microbiome–Metabolite Interactions: Correlation Insights
The team then looked at how specific bacteria correlated with metabolic changes. Using Spearman’s correlation analysis, they found:
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Limosilactobacillus was positively associated with carnosine and 3-hydroxyisovaleric acid, both involved in amino acid metabolism and oxidative stress reduction.
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Lactococcus correlated with isocitric acid, a key molecule in the TCA cycle (a central energy-producing pathway).
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Romboutsia was linked with metabolites associated with short-chain fatty acid pathways.
These associations suggest that certain microbes may help regulate key metabolic functions, especially those related to energy balance, inflammation, and nerve repair.
Functional Shifts in Microbiota
Although broad functional differences in the microbiome were subtle, specific pathways did change. The researchers identified enrichment in areas related to carbohydrate, lipid, and amino acid metabolism. These functional shifts may relate to observed issues in energy use and fat processing after SCI.
The study also reported increased activity in secondary metabolite biosynthesis pathways, which are often activated during stress responses. These could include both harmful (pro-inflammatory) and beneficial (anti-inflammatory) microbial products.
Potential Therapeutic Implications
The findings support the idea that the gut microbiome is not just a passive bystander in SCI but may actively shape recovery outcomes.
By targeting specific bacterial populations—either by increasing beneficial strains like Limosilactobacillus or decreasing harmful ones like Corynebacterium—it may be possible to reduce inflammation, support metabolic balance, and improve neurological recovery.
This approach could complement current therapies focused on physical rehabilitation and medication. While these findings are still in the preclinical stage, they provide a strong foundation for future therapeutic strategies.
Limitations and Future Directions
The researchers acknowledged several limitations. While strong associations were found, causal relationships remain to be established. The team plans to investigate this further through fecal microbiota transplantation and metabolite supplementation in future studies.
They also emphasized the need for clinical validation before these results can be applied to human patients.
Conclusion
This study offers new insight into the complex relationship between spinal cord injury, gut microbiota, and host metabolism. It suggests that modulating the gut microbiome could be a novel strategy to support recovery after SCI.
By integrating metagenomic and metabolomic data, the research opens up new paths for both basic science and potential clinical applications—highlighting the gut as a critical player in neurological injury and healing.
The translation of the preceding English text in Chinese:
新研究发现：脊髓损伤与肠道微生物群紊乱和代谢改变之间存在直接关联，为治疗干预提供潜在新路径
了解脊髓损伤及其系统性影响
脊髓损伤（SCI）是一种严重的神经系统疾病，每年在全球范围内影响约2.5万至5万人。除了明显的运动和感觉功能丧失外，SCI还常导致多系统并发症，包括心血管、呼吸、泌尿和胃肠功能障碍，这些都会显著增加康复和长期护理的难度。
尤其值得注意的是，肠道是受影响最严重的器官之一。损伤破坏了中枢神经系统（CNS）与消化道之间的通信，导致肠道微生物群——肠道内居住的大量细菌群落——发生显著变化。这些变化进而可能加重炎症反应、扰乱代谢，甚至影响神经功能恢复。
新兴研究表明，肠—脑之间的联系是双向的：脑部或脊髓的变化会影响肠道，反之亦然。类似的肠道微生物群变化也见于其他中枢神经系统疾病患者，如创伤性脑损伤和阿尔茨海默病。这揭示了一种科学家刚刚开始深入研究的重要联系。
研究概述：探索肠道微生物群与SCI恢复之间的关系
为了进一步探究其中机制，中国浙江中医药大学的研究人员在大鼠SCI模型中分析了肠道微生物群和血清代谢物。研究团队利用先进的宏基因组和代谢组学技术，将SCI大鼠与假手术组进行对比。
研究目标是确定肠道菌群的变化是否与体内代谢改变相关联，并评估这种相互作用是否可能影响恢复过程。
SCI后肠道微生物群发生显著变化
研究发现，SCI显著改变了肠道细菌的组成和多样性。Ligilactobacillus 和 Staphylococcus 两个属在损伤后丰度增加，而有益细菌如 Lactobacillus 和 Limosilactobacillus 则显著减少。
研究还观察到菌群多样性（通过Chao1和ACE指数衡量）上升。尽管菌群多样性通常被视为有益，但在本研究中，这反映出微生物环境不稳定，许多稀有或先前未检测到的菌株出现，可能是对压力或炎症的反应。
值得注意的是，Romboutsia 属在SCI组中减少，该属与短链脂肪酸的产生有关，有助于肠道健康和免疫功能。相反，Corynebacterium 和 Macrococcus 等可能促炎的菌属在SCI大鼠中更常见。
作者指出：“这些变化可能反映了SCI后胃肠环境变化对微生物群组成的影响。”
代谢紊乱与氧化应激
为了进一步了解微生物变化如何影响机体功能，研究团队分析了血清代谢物。结果显示，SCI大鼠中丙酮酸和乳酸水平升高，提示能量代谢受损，组织存在缺氧状态。
与此同时，抗氧化物肌肽（carnosine）水平下降，提示氧化应激增加，而天冬氨酸水平升高可能反映神经递质信号传导改变。此外，其他代谢物的降低也表明脂肪酸代谢受影响。
代谢通路分析显示，与能量、氨基酸和短链脂肪酸（SCFA）代谢相关的多个生物通路富集，这些通路对恢复和免疫平衡至关重要。
肠道菌群与代谢物之间的相关性
研究人员进一步分析了特定细菌与代谢物之间的关系。通过Spearman相关性分析发现：
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Limosilactobacillus 与肌肽和3-羟基异戊酸呈正相关，这些代谢物参与氨基酸代谢并可缓解氧化应激；
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乳酸球菌（Lactococcus）与三羧酸循环中的关键分子异柠檬酸呈正相关；
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Romboutsia 与短链脂肪酸代谢相关代谢物有关。
这些相关性表明，某些菌株可能有助于调节关键代谢功能，尤其是在能量平衡、炎症调节和神经修复方面。
微生物功能的改变
虽然整体微生物群功能差异不显著，但某些代谢通路确实发生变化。研究人员发现与碳水化合物、脂质和氨基酸代谢相关的功能区域存在富集。这些变化可能与SCI后能量利用和脂肪处理能力下降有关。
此外，研究还发现继发代谢物生物合成路径活性增强，而这些通常在应激反应中被激活，可能包括促炎或抗炎的微生物产物。
潜在的治疗意义
研究结果支持这样一种观点：肠道微生物群不仅是SCI的“旁观者”，更可能积极参与康复过程。
通过靶向特定菌群——比如增加有益菌如Limosilactobacillus，减少有害菌如Corynebacterium——可能有助于降低炎症、改善代谢平衡并促进神经功能恢复。
这种方法可以作为物理康复和药物治疗的补充手段。尽管目前仍处于临床前阶段，但该研究为未来的治疗策略奠定了坚实基础。
研究局限与未来方向
研究人员也承认存在一些局限性。虽然发现了显著相关性，但因果关系尚未明确。他们计划通过粪菌移植和代谢物补充实验进一步验证这些结果。
此外，研究团队强调，在将这些成果应用于人类之前，还需进行临床验证。
结论
本研究揭示了脊髓损伤、肠道微生物群和宿主代谢之间复杂的相互关系。研究表明，调节肠道菌群可能成为SCI康复的新策略。
通过整合宏基因组学和代谢组学数据，该研究为基础科学和潜在临床应用开辟了新路径，强调肠道在神经损伤与修复过程中的关键作用。
Reference:
Jieqi Zhang, Xihan Ying, Rong Hu, Yi Huang, Ruoqi Wang, Lei Wu, Dexiong Han, Ruijie Ma, Kelin He
Metagenomic and metabolomic analysis of gut microbiome’s role in spinal cord injury recovery in rats.
Biomol Biomed [Internet]. 2025 Mar. 26 [cited 2025 May 19];
Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/12164
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