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

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.

KEYWORDS:

• Bifidobacterium longum CKD1
• anti-diabetic medicines
• IL-22 signaling
• insulin resistance
• hepatic steatosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

WJK, CHS, and CSH conceived and designed the experiments; WJK, YKC, and KHK performed the experiments; WJK, BJK, and CWL analyzed the data; TYK and GEH contributed data or analysis tools; WJK, SYP, MHK, and CSH wrote the paper; SYP, HBK, MHK, and CSH reviewed and edited the paper.

Data availability statement

The 16s rRNA sequencing data for CKD1(SUB12927731) was registered in the NCBI sequence Read Archive (SRA) database.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2319889

Additional information

Funding

The work was supported by the Chong Kun Dang Bio Co. Ltd.