Wang Shidong, Li Xue, Zhang Muzi, Li Ming
School of Marine Sciences, Ningbo University, Ningbo, 315211, China.
College of Animal Science, Guizhou University, Guiyang, 550025, China.
Microbiome. 2025 Jul 12;13(1):163. doi: 10.1186/s40168-025-02152-4.
Ammonia generated from amino acid metabolism is a cytotoxin that can adversely affect cell function and overall health and potentially lead to cellular toxicity and death due to its accumulation. Previous studies have shown that acute ammonia intoxication (AI) can increase the intestinal C. somerae abundance, hinting at a possible involvement of C. somerae in the host's reaction to AI. Nonetheless, the precise mechanism through which C. somerae mitigates the effects of AI is uncertain.
This research elucidated the metabolic mechanism of transplanting Cetobacterium somerae ceto (CSC) to assist the host in managing AI. Our results suggest that (I) AI resulted in impaired ureagenesis pathway. This was manifested by elevated levels of ammonia in the blood, liver, and intestines, along with decreased urea levels. (II) Supplementing orally with live CSC facilitated its colonization in the intestines, mitigating AI by reversing depletion of intestinal argininosuccinic acid (ARA) and promoting ureagenesis. (III) CSC synthesized ARA from aspartate and asparagine through the asnA-ansA/B-argG gene cluster. Additionally, CSC assimilated fumaric acid and malic acid from the environment, dampening the degradation of ARA by CSC's fumA-fumB-argH gene cluster. (IV) Live CSC provided ARA support for ureagenesis in the intestine and liver, reducing endogenous ammonia levels of pseudo-sterile yellow catfish. (V) Supplementation of ARA decreased systemic ammonia levels by promoting ureagenesis. Inhibiting the expression of argininosuccinate lyase in the liver through RNA interference can impede arginine synthesis, thereby eliminating the ammonia-lowering effect of ARA.
In summary, this study found that the role of probiotics in enhancing the host's resistance to AI depends on the function of ARA generated by CSC. AI can lead to depletion of ARA and interrupting ureagenesis, while CSC-produced ARA supplements ureagenesis in the liver and intestines, facilitating ammonia detoxification into urea. Video Abstract.
氨基酸代谢产生的氨是一种细胞毒素，会对细胞功能和整体健康产生不利影响，并可能因其积累导致细胞毒性和死亡。先前的研究表明，急性氨中毒（AI）会增加肠道中索氏梭菌（C. somerae）的丰度，这暗示索氏梭菌可能参与宿主对AI的反应。然而，索氏梭菌减轻AI影响的确切机制尚不清楚。
本研究阐明了移植索氏梭菌ceto（CSC）以协助宿主应对AI的代谢机制。我们的结果表明：（I）AI导致尿素生成途径受损。这表现为血液、肝脏和肠道中氨水平升高，同时尿素水平降低。（II）口服补充活的CSC促进其在肠道内定殖，通过逆转肠道中精氨琥珀酸（ARA）的消耗并促进尿素生成来减轻AI。（III）CSC通过asnA-ansA/B-argG基因簇从天冬氨酸和天冬酰胺合成ARA。此外，CSC从环境中同化富马酸和苹果酸，抑制CSC的fumA-fumB-argH基因簇对ARA的降解。（IV）活的CSC为肠道和肝脏中的尿素生成提供ARA支持，降低无菌黄颡鱼的内源性氨水平。（V）补充ARA通过促进尿素生成降低全身氨水平。通过RNA干扰抑制肝脏中精氨琥珀酸裂解酶的表达会阻碍精氨酸合成，从而消除ARA的降氨作用。
总之，本研究发现益生菌增强宿主对AI抗性的作用取决于CSC产生的ARA的功能。AI可导致ARA耗竭并中断尿素生成，而CSC产生的ARA补充肝脏和肠道中的尿素生成，促进氨解毒为尿素。视频摘要。
