2. Academic Validation
  3. Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles

Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles

  • Life Sci. 2023 Aug 23;122001. doi: 10.1016/j.lfs.2023.122001.
Jintao Wei 1,  Zehua Li 2,  Ying Fan 1,  Liyun Feng 2,  Xinglong Zhong 3,  Weirun Li 1,  Tingting Guo 2,  Xiaodong Ning 1,  Zhenhua Li 4,  Caiwen Ou 5
Affiliations

Affiliations

  • 1 The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China.
  • 2 Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.
  • 3 Department of Cardiology, The Fourth Affiliated Hospital of Guangxi Medical University/Liuzhou Workers' Hospital, Liuzhou, PR China.
  • 4 The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China. Electronic address: zhenhuali@hbu.edu.cn.
  • 5 The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Dongguan 523018, PR China. Electronic address: oucaiwen@smu.edu.cn.
PMID: 37625519 DOI: 10.1016/j.lfs.2023.122001
Abstract

Aims: Lactobacillus rhamnosus GG (LGG) is a probiotic with great promise in future clinical application, which can significantly promote bone formation. However, the effect of LGG on CKD-related vascular calcification is unclear. In this study, we aimed to investigate the effect of LGG on CKD-related vascular calcification.

Materials and methods: After 2 weeks of 5/6 nephrectomy, CKD rats received a special diet (4 % calcium and 1.8 % phosphate) combined with 1,25-dihydroxyvitamin D3 to induce vascular calcification. Meanwhile, CKD rats in the LGG group were gavaged orally with LGG (1 × 109 CFU bacteria/day). 16S RNA amplicon Sequencing was performed to analyze the effect of LGG treatment on gut microbiota composition. Furthermore, differential ultracentrifugation was utilized to extract EVs. The effects of EVs on vascular calcification were evaluated in rat VSMCs, rat aortic rings, and CKD rat calcification models. In this study, vascular calcification was assessed by microcomputed tomography analysis, alizarin red staining, calcium content determination, and the expression of osteogenic transcription factors RUNX2 and BMP2.

Key findings: LGG remarkably aggravated vascular calcification. LGG supplementation significantly altered gut microbiota composition in CKD rats, particularly increasing Lactobacillus. Interestingly, EVs presented a significant promoting effect on the development of calcification. Finally, mechanistic analysis proved that EVs aggravated vascular calcification through PI3K/Akt signaling.

Significance: These results do not support the supplementation of LGG in CKD-associated vascular calcification patients. Our study presented a fresh perspective on LGG with potential risks and adverse effects. CKD patients should use specific probiotic strains cautiously.

Keywords

Bacterial extracellular vesicles; Chronic kidney disease; Lactobacillus rhamnosus GG; Probiotic; Vascular calcification.

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