B. longum CKD1 enhances the efficacy of anti-diabetic medicines through upregulation of IL- 22 response in type 2 diabetic mice.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gut Microbes Pub Date : 2024-01-01 Epub Date: 2024-02-23 DOI:10.1080/19490976.2024.2319889
Won Jun Kim, Bum Ju Kil, Chaewon Lee, Tae Young Kim, Goeun Han, Yukyung Choi, Kyunghwan Kim, Chang Hun Shin, Seung-Young Park, Heebal Kim, Myunghoo Kim, Chul Sung Huh
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Abstract

The gut microbiota plays a pivotal role in metabolic disorders, notably type 2 diabetes mellitus (T2DM). In this study, we investigated the synergistic potential of combining the effects of Bifidobacterium longum NBM7-1 (CKD1) with anti-diabetic medicines, Lobeglitazone (LO), Sitagliptin (SI), and Metformin (Met), to alleviate hyperglycemia in a diabetic mouse model. CKD1 effectively mitigated insulin resistance, hepatic steatosis, and enhanced pancreatic β-cell function, as well as fortifying gut-tight junction integrity. In the same way, SI-CKD1 and Met- CKD1 synergistically improved insulin sensitivity and prevented hepatic steatosis, as evidenced by the modulation of key genes associated with insulin signaling, β-oxidation, gluconeogenesis, adipogenesis, and inflammation by qRT-PCR. The comprehensive impact on modulating gut microbiota composition was observed, particularly when combined with Metformin. This combination induced an increase in the abundance of Rikenellaceae and Alistipes related negatively to the T2DM incidence while reducing the causative species of Cryptosporangium, Staphylococcaceae, and Muribaculaceae. These alterations intervene in gut microbiota metabolites to modulate the level of butyrate, indole-3-acetic acid, propionate, and inflammatory cytokines and to activate the IL-22 pathway. However, it is meaningful that the combination of B. longum NBM7-1(CKD1) reduced the medicines' dose to the level of the maximal inhibitory concentrations (IC50). This study advances our understanding of the intricate relationship between gut microbiota and metabolic disorders. We expect this study to contribute to developing a prospective therapeutic strategy modulating the gut microbiota.

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B. longum CKD1 通过上调 2 型糖尿病小鼠对 IL- 22 的反应增强了抗糖尿病药物的疗效。
肠道微生物群在代谢紊乱,尤其是 2 型糖尿病(T2DM)中发挥着关键作用。在这项研究中,我们探讨了长双歧杆菌 NBM7-1(CKD1)与抗糖尿病药物罗格列酮Ⓡ(LO)、西格列汀Ⓡ(SI)和二甲双胍Ⓡ(Met)的协同作用,以缓解糖尿病小鼠模型的高血糖。CKD1 能有效缓解胰岛素抵抗、肝脏脂肪变性,增强胰腺 β 细胞功能,并强化肠道紧密连接的完整性。同样,SI-CKD1 和 Met- CKD1 也能协同改善胰岛素敏感性,防止肝脂肪变性,这一点可以通过 qRT-PCR 对胰岛素信号转导、β 氧化、糖代谢、脂肪生成和炎症相关的关键基因的调控得到证明。观察到了调节肠道微生物群组成的综合影响,尤其是与二甲双胍Ⓡ联合使用时。这种组合诱导增加了与 T2DM 发病率呈负相关的 Rikenellaceae 和 Alistipes 的丰度,同时减少了 Cryptosporangium、Staphylococcaceae 和 Muribaculaceae 的致病物种。这些改变干预了肠道微生物群代谢产物,从而调节了丁酸盐、吲哚-3-乙酸、丙酸盐和炎症细胞因子的水平,并激活了 IL-22 通路。然而,有意义的是,联合使用 B. longum NBM7-1(CKD1)可将药物剂量降低到最大抑制浓度(IC50)的水平。这项研究加深了我们对肠道微生物群与代谢紊乱之间错综复杂关系的理解。我们期待这项研究能为开发调节肠道微生物群的前瞻性治疗策略做出贡献。
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来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
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