허철성 (서울대학교)

한빛사논문

조회191

서울대학교

Gut Microbes, 23 Feb 2024 | https://doi.org/10.1080/19490976.2024.2319889 B. longum CKD1 enhances the efficacy of anti-diabetic medicines through upregulation of IL- 22 response in type 2 diabetic mice

Won Jun Kim ^a, Bum Ju Kil ^a, Chaewon Lee ^a, Tae Young Kim ^b, Goeun Han ^b, Yukyung Choi ^c, Kyunghwan Kim ^c, Chang Hun Shin ^c, Seung-Young Park ^d, Heebal Kim^a,e, Myunghoo Kim ^b,*and Chul Sung Huh ^d,f,*

^aDepartment of Agricultural Biotechnology, College of Agriculture Sciences, Seoul National University, Seoul, South Korea
^bDepartment of Animal Science, Pusan National University, Miryang, South Korea
^cResearch Institute, Chong Kun Dang Bio Co Ltd, Ansan, South Korea
^dInstitute of Green-Bio Science & Technology, Seoul National University, Pyeongchang, South Korea
^eDepartment of Animal Science and Biotechnology, Seoul National University, Seoul, South Korea
^fGraduate School of International Agricultural Technology, Seoul National University, Seoul, South Korea

^*Corresponding authors: correspondence to Myunghoo Kim or Chul Sung Huh

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.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-27)
연구진국내 연구진
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