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Huang et al. Microbiome Res Rep 2024;3:30  https://dx.doi.org/10.20517/mrr.2024.14  Page 11 of 13

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               serotonylation, influencing chromatin accessibility and gene transcription . In addition, gut microbial
               metabolites can directly bind G-protein coupled receptors [3,35]  and trigger downstream signaling pathways
               such as the activation of transcription factor NF-κB. It is worth noting that only 169 metabolites were
               included in the target metabolomic analysis, which is a limitation of this study. Hence, including more
               metabolites and other bacterial components such as proteins, lipids, and cell wall components in the
               analysis will provide a more comprehensive view of how F. prausnitzii impacts TF transcription.

               DECLARATIONS
               Acknowledgment
               We thank Olena Fedoniuk at the Metabolite Profiling Core Facility of the Whitehead Institute for assistance
               on metabolomics analysis. We thank H. Lee for lab management.


               Authors’ contributions
               Research conception and design, data analysis and figure configuration, manuscript writing: Zhang J
               Experiments: Zhang J, Huang YJ, Wright C, Schneider K, Kemmitt J
               Data acquisition: Zhang J, Lewis CA
               Funding acquisition: Griffith LG, Trumper DL, Breault DT, Yilmaz O, Zhang J
               All authors reviewed and commented the manuscript.

               Availability of data and materials
               The data supporting this study’s findings are available in the Supplementary Materials or from the
               corresponding authors upon request.


               Financial support and sponsorship
               This study was supported by the NIH R01EB021908 and the Boehringer Ingelheim SHINE Program. Zhang
               J is funded by the University of Amsterdam Research Priority Area Systems Biology Host-Microbiome
               Interactions, Personal Microbiome Health, and NWA-ORC project 1389.20.080. The funding body has no
               interference with the research design, data collection, analysis and interpretation, and manuscript writing.


               Conflicts of interest
               All authors declared that there are no conflicts of interest.

               Ethical approval and consent to participate
               The organoid was derived from patients following the protocol approved by the Institutional Review Board
               of Boston Children’s Hospital (protocol number IRB-P00000529), the Koch Institute Institutional Review
               Board Committee, and the Massachusetts Institute of Technology Committee, and informed consent was
               obtained from the patients.

               Consent for publication
               Not applicable.

               Copyright
               © The Author(s) 2024.

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