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Background <p>Gut metabolites and symbionts are indispensable for host health, yet the precise identification of keystone metabolites and construction of synthetic microbial communities (SynComs) to enhance disease resistance remains limited.</p> Results <p>Using <i>Litopenaeus vannamei</i> as a model, we identified pyruvic acid and DL-glutamine (1:2) as keystone metabolites by borrowing the microbial ecology principles of bio-indicators and driver taxa. Dietary supplementation with these metabolites sufficiently protected shrimp from white feces syndrome (WFS). Multi-omics analyses demonstrated that keystone metabolites exerted positive effects by enriching beneficial <i>Ruegeria lacuscaerulensis</i>, <i>Bacillus subtilis</i> and <i>Nioella nitratireducens</i>, strengthening the gut network stability, and&#xa0;enhancing shrimp immunity, which collectively potentiated WFS resistance. The recruited three strains were consumers and producers of the two keystone metabolites, and discriminative strains between healthy and diseased shrimp across global datasets. A SynCom constructed from the three strains (4:3:2) replicated the efficacy of keystone metabolites. Both keystone metabolites and SynCom elevated shrimp gut and hepatopancreas lipoxin A4 (LXA4) levels, which suppressed the pro-inflammatory transcription factor AP-1, as validated by in vivo inhibition assay.</p> Conclusions <p>Our findings demonstrate that precisely designed keystone metabolites enhance shrimp disease resistance through the recruitment of key symbionts–LXA4–AP-1 axis. The rationally designed keystone metabolites and SynCom are compelling biocontrol solutions in improving host disease resistance.</p> <p><MediaObject ID="MOESM2"> <VideoObject FileRef="MediaObjects/40168_2026_2418_MOESM2_ESM.mp4" VideoID="737_CjzugapEkzbPAjRAwa"> <Caption Language="En" xml:lang="en"> <CaptionContent> <p>Video Abstract</p> </CaptionContent> </Caption> </VideoObject> </MediaObject></p>

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Precisely designed keystone metabolites boost shrimp disease resistance by recruiting symbionts via the lipoxin A4–AP-1 pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月2日

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  • Haonan Sha,
  • Jiong Chen,
  • Jianguo He,
  • Bin He,
  • Jie Huang,
  • Jizhong Zhou,
  • Xuan Dong,
  • Jinbo Xiong

摘要

Background

Gut metabolites and symbionts are indispensable for host health, yet the precise identification of keystone metabolites and construction of synthetic microbial communities (SynComs) to enhance disease resistance remains limited.

Results

Using Litopenaeus vannamei as a model, we identified pyruvic acid and DL-glutamine (1:2) as keystone metabolites by borrowing the microbial ecology principles of bio-indicators and driver taxa. Dietary supplementation with these metabolites sufficiently protected shrimp from white feces syndrome (WFS). Multi-omics analyses demonstrated that keystone metabolites exerted positive effects by enriching beneficial Ruegeria lacuscaerulensis, Bacillus subtilis and Nioella nitratireducens, strengthening the gut network stability, and enhancing shrimp immunity, which collectively potentiated WFS resistance. The recruited three strains were consumers and producers of the two keystone metabolites, and discriminative strains between healthy and diseased shrimp across global datasets. A SynCom constructed from the three strains (4:3:2) replicated the efficacy of keystone metabolites. Both keystone metabolites and SynCom elevated shrimp gut and hepatopancreas lipoxin A4 (LXA4) levels, which suppressed the pro-inflammatory transcription factor AP-1, as validated by in vivo inhibition assay.

Conclusions

Our findings demonstrate that precisely designed keystone metabolites enhance shrimp disease resistance through the recruitment of key symbionts–LXA4–AP-1 axis. The rationally designed keystone metabolites and SynCom are compelling biocontrol solutions in improving host disease resistance.

Video Abstract