Cited by 354Gut microbiota and healthCardiac Fibrosis and RemodelingCongenital heart defects research

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Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair

Tang, Tony W.H., Chen, Hung-Chih, Chen, Chen-Yun, Yen, Christopher Y.T., Lin, Chen-Ju, Prajnamitra, Ray P., Chen, Li-Lun, Ruan, Shu-Chian, Lin, Jen-Hao, Lin, Po-Ju, Lu, Hsueh-Han, Kuo, Chiung-Wen, Chang, Cindy M., Hall, Alexander D., Vivas, Eugenio I., Shui, Jr-Wen, Chen, Peilin, Hacker, Timothy A., Rey, Federico E., Kamp, Timothy J., Hsieh, Patrick C.H.·2019·Circulation

DOI 10.1161/circulationaha.118.035235

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Abstract

Background: The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated. Methods: To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI. Results: Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate. Conclusions: Gut microbiota–derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.

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Authors: Tang, T. W. H., Chen, H.-C., Chen, C.-Y., Yen, C. Y. T., Lin, C.-J., Prajnamitra, R. P., Chen, L.-L., Ruan, S.-C., Lin, J.-H., Lin, P.-J., Lu, H.-H., Kuo, C.-W., Chang, C. M., Hall, A. D., Vivas, E. I., Shui, J.-W., Chen, P., Hacker, T. A., Rey, F. E., Kamp, T. J., & Hsieh, P. C. H.
Affiliations: Institute of Biomedical Sciences, Academia Sinica (TW)
Research Center for Applied Science, Academia Sinica (TW)
University of Wisconsin–Madison (US)
ORCID: Chen, Hung-Chih
Yen, Christopher Y.T.
Lin, Chen-Ju
Prajnamitra, Ray P.
Chen, Li-Lun
Ruan, Shu-Chian
Lu, Hsueh-Han
Chang, Cindy M.
Shui, Jr-Wen
Chen, Peilin
Hacker, Timothy A.
Rey, Federico E.
Kamp, Timothy J.
Hsieh, Patrick C.H.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2019-01-29
Volume: 139
Issue: 5
Pages: 647-659
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.118.035235
OpenAlex: W2896600834
Cited by: 348
References: 43
Citations by year: 2026: 29 · 2025: 56 · 2024: 67 · 2023: 51 · 2022: 46 · 2021: 57 · 2020: 32 · 2019: 10
FWCI: 12.00
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords: gut microbiota, myocardial infarction, cardiac repair, short-chain fatty acids, myeloid cells, Lactobacillus, probiotics, antibiotic depletion, fecal microbiota transplantation, cardioprotection
MeSH terms: RAW 264.7 Cells, Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Anti-Bacterial Agents, Bacteria, Disease Models, Animal, Fatty Acids, Female, Lactobacillus, Male, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Myocardial Infarction, Myocardium, Probiotics, Mice, Host-Pathogen Interactions, Dysbiosis

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Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair

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