Cetobacterium somerae-derived argininosuccinic acid promotes intestinal and liver ureagenesis to alleviate ammonia intoxication.

IF 13.8 1区 生物学 Q1 MICROBIOLOGY
Shidong Wang, Xue Li, Muzi Zhang, Ming Li
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引用次数: 0

Abstract

Background: 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.

Results: 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.

Conclusion: 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.

精氨酸琥珀酸促进肠道和肝脏的尿变性,以减轻氨中毒。
背景:氨基酸代谢产生的氨是一种细胞毒素,可对细胞功能和整体健康产生不利影响,并可能因其积累而导致细胞毒性和死亡。先前的研究表明,急性氨中毒(AI)可增加肠道中somerc .的丰度,提示somerc .可能参与了宿主对AI的反应。然而,梭状芽孢杆菌减轻人工智能影响的确切机制尚不确定。结果:本研究阐明了移植索窝鲸杆菌(Cetobacterium somerae ceto, CSC)辅助宿主控制AI的代谢机制。我们的研究结果表明(I) AI导致尿源通路受损。这表现在血液、肝脏和肠道中的氨水平升高,同时尿素水平降低。(II)口服补充活CSC有助于其在肠道内定植,通过逆转肠道精氨酸琥珀酸(ARA)的消耗和促进尿原作用来减轻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从环境中吸收富马酸和苹果酸,抑制了CSC的fuma - bumb - argh基因簇对ARA的降解。(IV)活体CSC为伪不育黄颡鱼肠道和肝脏的尿素发生提供ARA支持,降低了黄颡鱼内源氨水平。(V)补充ARA可通过促进尿源作用降低全身氨水平。通过RNA干扰抑制肝脏精氨酸琥珀酸裂解酶的表达,可以阻碍精氨酸的合成,从而消除ARA的降氨作用。结论:综上所述,本研究发现益生菌增强宿主抗AI能力的作用依赖于CSC产生的ARA的功能。AI可导致ARA耗竭并中断脲原作用,而csc产生的ARA可补充肝脏和肠道中的脲原作用,促进氨解毒为尿素。视频摘要。
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来源期刊
Microbiome
Microbiome MICROBIOLOGY-
CiteScore
21.90
自引率
2.60%
发文量
198
审稿时长
4 weeks
期刊介绍: Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.
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