@article {70184,
	title = {Chemical modulation of gut bacterial metabolism induces colanic acid and extends the lifespan of nematode and mammalian hosts.},
	journal = {PLoS Biol},
	volume = {23},
	year = {2025},
	month = {2025 Nov 11},
	pages = {e3002749},
	abstract = {<p>Microbiota-derived metabolites have emerged as key regulators of longevity. The metabolic activity of the gut microbiota, influenced by dietary components and ingested chemical compounds, profoundly impacts host fitness. While the benefits of dietary prebiotics are well-known, chemically targeting the gut microbiota to enhance host fitness remains largely unexplored. Here, we report a novel chemical approach to induce a pro-longevity bacterial metabolite in the host gut. We discovered that wild-type Escherichia coli strains overproduce colanic acids (CAs) when exposed to a low dose of cephaloridine, leading to an increased life span in the host organism Caenorhabditis elegans. In the mouse gut, oral administration of low-dose cephaloridine induced transcription of the capsular polysaccharide synthesis (cps) operon responsible for CA biosynthesis in commensal E. coli at 37 {\textdegree}C, and attenuated age-related metabolic changes. We also found that low-dose cephaloridine overcomes the temperature-dependent inhibition of CA biosynthesis and promotes its induction through a mechanism mediated by the membrane-bound histidine kinase ZraS, independently of cephaloridine{\textquoteright}s known antibiotic properties. Our work lays a foundation for microbiota-based therapeutics through chemical modulation of bacterial metabolism and highlights the promising potential of leveraging bacteria-targeting drugs in promoting host longevity.</p>
},
	keywords = {Animals, Caenorhabditis elegans, Escherichia coli, Gastrointestinal Microbiome, Longevity, Mice, Polysaccharides},
	issn = {1545-7885},
	doi = {10.1371/journal.pbio.3002749},
	url = {https://doi.org/10.1371/journal.pbio.3002749},
	author = {Hu, Guo and Savini, Marzia and Cooke, Matthew Brandon and Wei, Xin and Deng, Dinghuan and Gao, Shihong M and Xia, Ruyue Alps and Guan, Youchen and Wen, Alice X and Yu, Xin and Wang, Jin and Jiang, Chao and Herman, Christophe and Li, Jiefu and Wang, Meng C}
}
@article {69755,
	title = {Quantitative Profiling pH Heterogeneity of Acidic Endolysosomal Compartments using Fluorescence Lifetime Imaging Microscopy.},
	journal = {Mol Biol Cell},
	year = {2025},
	month = {2025 Jan 29},
	pages = {mbcE23060220},
	abstract = {<p>The endo-lysosomal system plays a crucial role in maintaining cellular homeostasis and promoting organism fitness. The pH of its acidic compartments is a crucial parameter for proper function, and it is dynamically influenced by both intracellular and environmental factors. Here, we present a method based on fluorescence lifetime imaging microscopy (FLIM) for quantitatively analyzing the pH profiles of acidic endolysosomal compartments in diverse types of primary mammalian cells and in live organism . This FLIM-based method exhibits high sensitivity in resolving subtle pH differences, thereby revealing heterogeneity within a cell and across cell types. This method enables rapid measurement of pH changes in the acidic endolysosomal system in response to various environmental stimuli. Furthermore, the fast FLIM measurement of pH-sensitive dyes circumvents the need for transgenic reporters and mitigates potential confounding factors associated with varying dye concentrations or excitation light intensity. This FLIM approach offers absolute pH quantification and highlights the significance of pH heterogeneity and dynamics, offering a valuable tool for investigating lysosomal functions and their regulation in various physiological and pathological contexts.</p>
},
	issn = {1939-4586},
	doi = {10.1091/mbc.E23-06-0220},
	author = {Deng, Dinghuan and Guan, Youchen and Mutlu, Ayse Sena and Wang, Baiping and Gao, Shihong Max and Zheng, Hui and Wang, Meng C}
}
