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In silico method to maximise the biological potential of understudied metabolomic biomarkers: a study in pre-eclampsia
  1. Huimin Zheng1,
  2. Feihong Mai2,
  3. Siyou Zhang1,
  4. Zixin Lan3,
  5. Zhang Wang2,
  6. Shanwei Lan3,
  7. Renfang Zhang4,
  8. Dong Liang1,
  9. Guoqiang Chen5,
  10. Xia Chen1,
  11. Yinglin Feng6
  1. 1 Department of Obstetrics and Gynecology, The First People's Hospital of Foshan, Foshan, Guangdong, China
  2. 2 Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou, China
  3. 3 The Second Clinical Medical College, Southern Medical University, Guangzhou, China
  4. 4 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, China
  5. 5 Department of Rheumatology and Immunology, The First People's Hospital of Foshan, Foshan, Guangdong, China
  6. 6 Institute of Translational Medicine, The First People's Hospital of Foshan, Foshan, Guangdong, China
  1. Correspondence to Dr Xia Chen, Department of Obstetrics and Gynecology, The First People's Hospital of Foshan, Foshan, Guangdong, China; chenx_fsyyy{at}163.com; Dr Guoqiang Chen, Department of Rheumatology and Immunology, The First People's Hospital of Foshan, Foshan, Guangdong, China; 13929981788{at}139.com; Dr Yinglin Feng, Institute of Translational Medicine, The First People's Hospital of Foshan, Foshan, Guangdong, China; doctorlynn{at}126.com

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We read with interest the study by Adam et al reporting a textbook-level pipeline for biomarker identification in metabolomic datasets.1 2 This study pointed to a long-standing issue in metabolomic studies. The lack of robust strategies for biomarker discovery would leave readers with the impression that ‘the biomarker is out-of-nowhere but works’, especially in those scarcely studied biomarkers. Herein, we provided a strategy that infers the potential of understudied biomarkers for further investigation.

A previous study has shown that gut bacterial dysbiosis can cause pre-eclampsia (PE) symptoms through the gut–placenta axis.3 However, the role and potential therapeutic effect of gut metabolites as key mediators between bacteria and host remain elusive in PE. Thus, we assessed the faecal metabolome in an age-matched case–control study to complete the theory of the gut–placenta axis and identify metabolites with therapeutic potential for PE. For metabolites depleted in PE, the variable importance in projection score indicated that ononetin contributed the most to group separation (figure 1A). However, little is known about ononetin, except for it being a plant-based deoxybenzoin and a potent TRPM3 antagonist,4 let alone its links with PE. Thus, we designed a two-arms strategy to predict the potential association between ononetin and PE (figure 1B, methods detailed in online supplemental material).

Supplemental material

[gutjnl-2022-329312supp001.pdf]

Figure 1

Ononetin, a plant-derived metabolite, was significantly depleted in patients with pre-eclampsia (PE) and may interact with pathways involved in PE. Faecal samples from patients with PE or age-matched normotensive pregnant women in the third trimester were subjected to metabolomics analysis. (A) Results indicated 97 differential metabolites between patients with PE and control subjects. The height of bars indicates variable importance in projection (VIP) scores of metabolites. (B) There is limited information on ononetin, aside from it being a natural product from fabaceae and citrus …

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Footnotes

  • Twitter @HuiMinZheng2

  • HZ, FM and SZ contributed equally.

  • Contributors HZ, YF and XC designed the study and prepared the manuscript. YF, FM, ZL, SL, RZ, SZ, DL and GC collected the samples and conducted the experiments. HZ, YF, XC, FM and ZL analysed the data. ZW provided crucial advice in analysing and interpreting the data.

  • Funding This work was supported by the Natural Science Foundation of Guangdong Province (2022A1515110278 (HZ), 2021A1515110183 (YF), 2020A1515110321 (XC)); the National Natural Science Foundation of China (8210063004 (XC) and 82201812 (HZ)); the China Postdoctoral Science Foundation (2022M710696 (HZ)) and the Medical Scientific Research Foundation of Guangdong Province (A2022277 (XC)). The funding bodies had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.