A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders

作者：Lingru Li, Tianxing Li, Xue Liang, Linghui Zhu, Yini Fang, Ling Dong, Yifeng Zheng, Yi Zheng, Xiaoxue Xu, Mingrui Li, Tianqi Cai, Fufangyu Zhao, Meiling Xin, Mingyan Shao, Yuanyuan Guan, Fangli Li, Fangli Li, Chenhong Zhang, Qi Wang, Wenlong Sun, Yanfei Zheng, Yanfei Zheng · 发表于：Cell Discovery · 年份：2025 · DOI：10.1038/s41421-025-00789-x · 被引用次数：112 · 研究领域：Ginseng Biological Effects and Applications、Gut microbiota and health、Cancer-related molecular mechanisms research

According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to...