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Heat-Killed Lactobacillus reuteri GMNL-263 Inhibits Systemic Lupus Erythematosus–Induced Cardiomyopathy in NZB/W F1 Mice

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Abstract

It has been increasingly recognized that accelerated atherosclerosis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus, a multisystem autoimmune disease. In this study, we investigated the anti-apoptotic effects of heat-killed Lactobacillus reuteri GMNL-263 on the cardiac tissue of NZB/W F1 mice. The myocardial architecture of the mice heart was observed and evaluated using different staining techniques such as hematoxylin and eosin, TUNEL assay, Masson’s trichrome, and fluorescent immunohistochemistry. Additionally, the probiotics-related pathway proteins were analyzed via western blot analysis. Our results showed prevention of enlarged interstitial spaces and abnormal myocardial structures in the hearts of NZB/W F1 mice with L. reuteri GMNL-263 feeding. Significant reduction in TUNEL-positive cells, Fas death receptor–related components, and apoptosis was also detected in the cardiac tissues of the NZB/W F1 mice after L. reuteri GMNL-263 feeding compared with the control group. These findings are the first to reveal the protective effects of L. reuteri GMNL-263 against cardiac abnormalities in NZB/W F1 mice and suggest the potential clinical applications of L. reuteri GMNL-263 in the treatment of SLE-related cardiovascular diseases.

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Abbreviations

FADD:

Fas-associated protein with death domain

L. reuteri GMNL-263:

Lactobacillus reuteri GMNL-263

MMP-9:

Matrix metallopeptidase 9

SLE:

Systemic lupus erythematosus

TNF-R1:

Tumor necrosis factor receptor 1

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Acknowledgments

We thank the help provided by Dr. Marthandam Asokan Shibu.

Funding

This work is supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019) and in part by grants from China Medical University, Asia University, and China Medical University Hospital (CMU102-ASIA-02 and ASIA-105-CMUH-01).

Author information

Author notes

  1. Peng Xiang and Chih-Yang Huang contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan

    Yu-Lan Yeh

  2. Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Taipei, Taiwan

    Yu-Lan Yeh

  3. Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

    Min-Chi Lu

  4. Department of Microbiology and Immunology, School of Medicine, China Medical University, Taichung, Taiwan

    Min-Chi Lu

  5. Graduate Institute of Aging Medicine, China Medical University, Taichung, Taiwan

    Bruce Chi-Kang Tsai & Chih-Yang Huang

  6. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

    Bor-Show Tzang

  7. Department of Healthcare Administration, Asia University, Taichung, Taiwan

    Shiu-Min Cheng

  8. Department of Cardiology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, China

    Xiaoyong Zhang

  9. Department of Physiology, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Liang-Yo Yang

  10. Institute of Research and Development, Duy Tan University, Da Nang, Vietnam

    B. Mahalakshmi

  11. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo

  12. Nephrology Center, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital , Qingyuan, Guangdong, China

    Peng Xiang

  13. Department of Biotechnology, Asia University, Taichung, Taiwan

    Chih-Yang Huang

  14. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Chih-Yang Huang

  15. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan

    Chih-Yang Huang

Authors
  1. Yu-Lan Yeh
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  2. Min-Chi Lu
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  6. Xiaoyong Zhang
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  9. Wei-Wen Kuo
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  10. Peng Xiang
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  11. Chih-Yang Huang
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Contributions

Conceptualization, Yu-Lan Yeh, Min-Chi Lu, and Chih-Yang Huang; data curation, Yu-Lan Yeh, Bruce Chi-Kang Tsai, and Bor-Show Tzang; formal analysis, Min-Chi Lu, Bruce Chi-Kang Tsai, and Chih-Yang Huang; funding acquisition, Wei-Wen Kuo and Chih-Yang Huang; project administration, Wei-Wen Kuo and Peng Xiang; resources, Bor-Show Tzang, Shiu-Min Cheng, Xiaoyong Zhang, and Liang-Yo Yang; supervision, Chih-Yang Huang; writing—original draft, Yu-Lan Yeh, Bruce Chi-Kang Tsai, and Bharath Mahalakshmi; writing—review and editing, Wei-Wen Kuo, Peng Xiang, and Chih-Yang Huang.

Corresponding author

Correspondence to Chih-Yang Huang.

Ethics declarations

The Institutional Animal Care and Use Committee at Chung Shan Medical University approved the animal study (approval no. 847), and the Institutional Review Board (IRB) reviewed and approved the IACUC protocols of The Animal Care and Use Committee of the Chung Shan Medical University, Taichung, Taiwan.

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The authors declare that they have no competing interests.

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Yeh, YL., Lu, MC., Tsai, B.CK. et al. Heat-Killed Lactobacillus reuteri GMNL-263 Inhibits Systemic Lupus Erythematosus–Induced Cardiomyopathy in NZB/W F1 Mice. Probiotics & Antimicro. Prot. 13, 51–59 (2021). https://doi.org/10.1007/s12602-020-09668-1

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