biostudies-literatureUnknown15(3)Guo MNational Natural Science Foundation of ChinaThe liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of <i>Parabacteroides distasonis</i> (<i>P. distasonis</i>) post-PHx, correlating with hepatocyte proliferation. Treatment with live <i>P. distasonis</i> significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between <i>P. distasonis</i> and <i>β</i>-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenyActa pharmaceutica Sinica. B1430-1446https://www.ebi.ac.uk/biostudies/studies/S-EPMC12069244biostudies-literature&lt;i&gt;Parabacteroides distasonis&lt;/i&gt; promotes liver regeneration by increasing &lt;i&gt;β&lt;/i&gt;-hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.PMC12069244Chen PZhou WZhang SFan SYang XBi HGuo MBi GWang PLiang FOuyang HJiang XZhang XWu TFang JHfalse&lt;i&gt;Parabacteroides distasonis&lt;/i&gt; promotes liver regeneration by increasing &lt;i&gt;β&lt;/i&gt;-hydroxybutyric acid (BHB) production and BHB-driven STAT3 signals.The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of <i>Parabacteroides distasonis</i> (<i>P. distasonis</i>) post-PHx, correlating with hepatocyte proliferation. Treatment with live <i>P. distasonis</i> significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between <i>P. distasonis</i> and <i>β</i>-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxypheny2025-01-01T00:00:00Z2025 Mar2026-06-03T02:45:24.146Z2026-04-23T03:11:16.389ZS-EPMC120692444037053310.1016/j.apsb.2025.01.024