Abstract
This study investigates the role of trehalose in modulating gut microbiota metabolism and alleviating symptoms of severe acute pancreatitis (SAP). Here, we found that gut microbial metabolism was imbalanced in SAP. In particular, we observed increased lipid metabolism and decreased carbohydrate and amino acid metabolism, which were reversed by gut microbiota depletion. Moreover, the production of trehalose was significantly increased after gut microbiota depletion. Interestingly, trehalose treatment effectively reduced pancreatic injury and ameliorated the SAP-induced microbial metabolism imbalance by promoting carbohydrate metabolism and suppressing lipid metabolism. The effect of trehalose was depend on the gut microbiota, especially the expansion of Muribaculaceae. Mechanistically, trehalose-remodelled gut microbiota suppressed SAP-induced increases in serum TG, IL-6, IL-17A, and TNF-α levels, inhibited caspase-3-mediated apoptosis, and reduced macrophage infiltration into the pancreas. Overall, our study revealed that trehalose ameliorates SAP by modulating gut microbial metabolism homeostasis, providing new insights into the “microbial metabolism‒gut‒pancreatic axis”.
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Data availability
All the gene sequence data were obtained from the National Genomics Data Center (NGDC), which is part of the China National Center for Bioinformation (CNCB) database under accession code PRJCA026291.
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Acknowledgements
We would like to thank Prof. Yangchao Chen for technical assistance. This work was funded by the National Natural Science Foundation of China (82270678, 82102275, and 82070669), and Postdoctoral Fellowship Project (97157).
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W.Q.L. and Z.H.T.: Conceptualization, funding acquisition, and methodology. S.W.S.: Conceptualization, visualization, and methodology. H.B.H. and D.R.D.: Conceptualization, project administration, writing—original draft, and writing— review and editing. H.L.: Data curation, methodology, and Writing—review and editing. W.L. and Y.Z.L.: Data curation and methodology. G.H.H.: Data curation and Writing—review and editing. Y.X.L. and C.L.S.: Software, data curation, and investigation. L.L.L.: Resources and Supervision. L.K.: Conceptualization, supervision, and writing–review and editing. A.K.F.: Conceptualization and writing—review and editing.
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Hao, H., Du, D., Lin, H. et al. Trehalose ameliorates severe acute pancreatitis by modulating gut microbial metabolism. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-00950-8
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DOI: https://doi.org/10.1038/s41522-026-00950-8


