School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China; Postdoctoral Research Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China.
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
Phytomedicine. 2024 Dec;135:156151. doi: 10.1016/j.phymed.2024.156151. Epub 2024 Oct 16.
Type 2 diabetes mellitus (T2DM) is a worldwide public health problem characterized by a progressive decline in β cell function. In traditional Chinese medicine (TCM) theory, 'fire' and 'healthy qi deficiency' are important pathogeneses of T2DM, and purging 'fire' and reinforcing the 'healthy qi' (Pinyin name: Xiehuo-Guzheng, XHGZ) are important method of treatment. Over the years, we have observed its benefit for diabetes. However, the underlying mechanisms remain unclear.
To investigate the mechanism of XHGZ granules against β cell dedifferentiation in T2DM based on gut microbiota.
Rats with T2DM, induced by intraperitoneal injection of streptozotocin after eight weeks of high-fat diet, were randomly allocated to receive XHGZ granules, metformin, or distilled water for eight consecutive weeks. Changes in metabolic parameters, β cell dedifferentiation, inflammatory cytokines, gut microbiota, and microbial metabolites (lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs)), were detected. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the anti-diabetic effect of XHGZ granule-regulated gut microbiota in pseudo-germ-free T2DM rats.
XHGZ granules significantly ameliorated hyperglycaemia, improved islet function and pathology, and reduced β cell dedifferentiation and pro-inflammatory cytokines in T2DM rats. 16S rRNA sequencing revealed that XHGZ granules decreased the LPS-containing microbiota (e.g., Colidextribacter, Desulfovibrionaceae, and Morganella) and increased the SCFAs-producing bacteria (e.g., Prevotella, Alloprevotella, and Muribaculaceae) and Lactobacillus_intestinalis. Correspondingly, it strengthened intestinal barrier, lowered LPS, and elevated acetic and butyric acids. Tax4Fun analysis indicated that XHGZ granules restored abnormal metabolism, lipopolysaccharide biosynthesis, and pantothenate and CoA biosynthesis. Moreover, the XHGZ granule-regulated microbiota also exhibited the effects of anti-diabetes, anti-β cell dedifferentiation, and anti-inflammation along with the reduction of LPS and the increase of SCFAs in pseudo-germ-free T2DM rats.
Our results show that XHGZ granules alleviate β cell dedifferentiation via regulating gut microbiota and their metabolites in T2DM, suggesting its potential as a promising complementary treatment for T2DM. As far as we know, there are very few studies on the alleviation of β cell dedifferentiation by TCM, and investigations into the mechanism from the perspective of intestinal flora and microbial metabolites are yet to be reported.
2 型糖尿病（T2DM）是一种全球性的公共卫生问题，其特征是β细胞功能逐渐下降。在中医理论中，“火”和“气虚”是 T2DM 的重要发病机制，“泻火”和“补气”（拼音名称：Xiehuo-Guzheng，XHGZ）是重要的治疗方法。多年来，我们观察到它对糖尿病有好处。然而，其潜在机制尚不清楚。
基于肠道微生物群研究 XHGZ 颗粒对 T2DM 中β细胞去分化的作用机制。
8 周高脂饮食后腹腔注射链脲佐菌素诱导 T2DM 大鼠，随机分为 XHGZ 颗粒组、二甲双胍组和蒸馏水组，连续 8 周。检测代谢参数、β细胞去分化、炎症细胞因子、肠道微生物群和微生物代谢物（脂多糖（LPS）和短链脂肪酸（SCFAs））的变化。此外，进行粪便微生物群移植（FMT）以确认 XHGZ 颗粒调节肠道微生物群对无菌 T2DM 大鼠的抗糖尿病作用。
XHGZ 颗粒显著改善了 T2DM 大鼠的高血糖，改善了胰岛功能和病理学，并减少了β细胞去分化和促炎细胞因子。16S rRNA 测序显示，XHGZ 颗粒减少了 LPS 含量丰富的微生物群（例如，Colidextribacter、Desulfovibrionaceae 和 Morganella），增加了产生 SCFAs 的细菌（例如，Prevotella、Alloprevotella 和 Muribaculaceae）和 Lactobacillus_intestinalis。相应地，它增强了肠道屏障，降低了 LPS，并升高了乙酸和丁酸。Tax4Fun 分析表明，XHGZ 颗粒恢复了异常代谢、脂多糖生物合成以及泛酸和辅酶 A 生物合成。此外，XHGZ 颗粒调节的微生物群也表现出抗糖尿病、抗β细胞去分化和抗炎作用，同时降低 LPS 和增加 SCFAs 在无菌 T2DM 大鼠中。
我们的结果表明，XHGZ 颗粒通过调节 T2DM 中的肠道微生物群及其代谢物来减轻β细胞去分化，提示其作为 T2DM 有前途的辅助治疗方法的潜力。据我们所知，中医对β细胞去分化的缓解作用研究很少，从肠道菌群和微生物代谢物的角度进行的机制研究尚未报道。
