| 摘要: |
| 细菌是线虫的天然食物来源，其代谢多样性为解析饮食调控寿命的机制提供了理想模型。然而，但海洋细菌作为饮食因素调控海洋线虫寿命的机制尚不清楚有待探讨。本研究以大肠杆菌 Escherichia coli OP50 为对照，以 73 株海洋细菌作为海洋线虫 Litoditis marina 的饮食，开展了海洋线虫 14 天存活率初筛及全生命周期寿命验证。相较于对照组，初筛中发现太平洋芽孢杆菌 Bacillus pacificus 可显著提高 14 天存活率，但该效应未能在全生命周期寿命实验中验证，本研究未发现可显著延长 L. marina 寿命的海洋细菌；相反，发现多种海洋细菌（如高空芽孢杆菌 Bacillus altitudinis、坎贝氏弧菌 Vibrio campbellii 和海藻希瓦氏菌 Shewanella algae）可显著降低 L. marina 14天存活率，并显著缩短线虫寿命。发现多种海洋细菌，如高空芽孢杆菌 Bacillus altitudinis、坎贝氏弧菌 Vibrio campbellii 和海藻希瓦氏菌 Shewanella algae，可显著降低 L. marina 14 天存活率，并显著缩短线虫寿命。通过随机森林分析发现，与 L. marina 14 天存活相关联的通路为 2-氨基乙基膦酸降解途径 II、厌氧萘降解途径和砷酸盐解毒途径 Ⅳ。对 OP50、B. altitudinis、V. campbellii 和 S. algae 的菌体进行非靶向代谢组学分析，发现3 株减寿细菌在代谢层面具有共同特征，也存在差异。三株菌共有的显著上调代谢物包括甲硫氨酰-色氨酸、天冬氨酰-谷氨酸、色胺、吲哚-3-乙酰胺和 3-甲基吲哚等；共有的显著下调代谢物包括 2,3-二羟基-N-苯甲酰丝氨酸、溶血磷脂酰乙醇胺类代谢物［LysoPE(0:0/14:1(9Z))、LysoPE(0:0/16:0)］等。三株菌上调代谢物共同富集的通路为包括色氨酸代谢以及丙氨酸、天冬氨酸和谷氨酸代谢通路等，未发现一致下调的代谢通路。进一步分析发现，B. altitudinis 与 V. campbellii 中泛酸和辅酶 A 生物合成通路显著下调；B. altitudinis 与 S. algae 中 β-丙氨酸代谢显著下调；V. campbellii 与 S. algae 中萘降解、苯丙氨酸代谢和酪氨酸代谢显著下调。不同菌株还表现出各自特异性的代谢特征：B. altitudinis 的上调通路为半胱氨酸和蛋氨酸代谢等，下调通路为嘌呤代谢、组氨酸代谢等；V. campbellii 的上调通路为 D-氨基酸代谢、精氨酸生物合成等，下调通路为酪氨酸代谢以及泛酸和辅酶 A 生物合成；S. algae 的上调通路为 ABC 转运蛋白、精氨酸和脯氨酸代谢，下调通路为苯丙氨酸代谢和 β-丙氨酸代谢。本研究为阐明海洋细菌饮食调控线虫宿主衰老调控机制提供了新的实验依据，为开发基于海洋微生物资源的健康衰老干预策略提供了新思路。 |
| 关键词: 海洋线虫 Litoditis marina 细菌饮食 14 天存活率 寿命 代谢组学 |
| DOI： |
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| Metabolomic Analysis of the Effects of Diets on Lifespan Regulation in the Marine Nematode Litoditis marina |
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Zhao xiaotian,Xue beining,Zhang Liusuo
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Institute of Oceanology, Chinese Academy of Sciences
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| Abstract: |
| Bacteria are natural food sources for nematodes, and their metabolic diversity provides an ideal model for elucidating the mechanisms underlying mechanisms by which diet regulates animal lifespan. However, the mechanisms by which marine bacteria, as dietary factors, regulate the lifespan of marine nematodes remain unclear. Using Escherichia coli OP50 as the control diet, 73 marine bacterial strains were tested as food sources for the marine nematode Litoditis marina through an initial 14-day survival screening followed by full-lifespan validation. Compared with the control group, Bacillus pacificus significantly increased the 14-day survival rate in the initial screening, but this effect was not reproduced in the full-lifespan assay. No marine bacterial strain capable of stably extending the lifespan of L. marina was identified. In contrast, several marine bacterial strains, including Bacillus altitudinis, Vibrio campbellii, and Shewanella algae, significantly reduced the 14-day survival rate of L. marina and markedly shortened its lifespan. Random forest analysis showed that the major metabolic pathways associated with the 14-day survival rate of L. marina included 2-aminoethylphosphonate degradation pathway II, anaerobic naphthalene degradation and arsenate detoxification IV. Untargeted metabolomic analysis of the bacterial cells of OP50, B. altitudinis, V. campbellii, and S. algae revealed that the three lifespan-shortening strains shared common metabolic features while also exhibiting distinct differences. The commonly upregulated metabolites among the three strains included methionyl-tryptophan,methionyl-tryptophan, aspartyl-glutamate, tryptamine, indole-3-acetamide, and 3-methylindole, whereas the commonly downregulated metabolites included 2,3-dihydroxy-N-benzoylserine and lysophosphatidylethanolamines [LysoPE(0:0/14:1(9Z)) and LysoPE(0:0/16:0)]. The shared upregulated metabolites were mainly enriched in tryptophan metabolism and alanine, aspartate and glutamate metabolism, whereas no downregulated pathway was identified. Further analysis showed that pantothenate and coenzyme A biosynthesis was significantly downregulated in B. altitudinis and V. campbellii; β-alanine metabolism was significantly downregulated in B. altitudinis and S. algae; and naphthalene degradation, phenylalanine metabolism, and tyrosine metabolism were significantly downregulated in V. campbellii and S. algae. Each bacterial strain also exhibited distinct metabolic characteristics: the upregulated pathways in B. altitudinis included cysteine and methionine metabolism, whereas the downregulated pathways included purine metabolism and histidine metabolism; the upregulated pathways in V. campbellii included D-amino acid metabolism and arginine biosynthesis, whereas the downregulated pathways included tyrosine metabolism and pantothenate and coenzyme A biosynthesis; the upregulated pathways in S. algae included ABC transporters and arginine and proline metabolism, whereas the downregulated pathways included phenylalanine metabolism and β-alanine metabolism. These findings provide an important foundation for further elucidating the metabolic and molecular mechanisms by which diet regulates survival and aging in nematode animals, and offer new insights for developing healthy aging intervention strategies based on marine microbial resources. |
| Key words: marine nematode Litoditis marina bacterial diet 14-day survival rate lifespan metabolomics |