Dr. Patrick C.H. Hsieh, the lead author and a research fellow at the Institute of Biomedical Sciences (IBMS), Academia Sinica (AS) and his research team found that overuse of antibiotics causes alteration in gut microbial composition. The imbalanced microbiome affects the host immune system and impairs its function in cardiac repair after myocardial infarction. This increases myocardial infarction mortality. However, according to the researchers, the administration of Lactobacillus-based probiotics is able to enhance the post-infarction myocardial repair.

The study uncovers the adverse effects of antibiotics on survival after myocardial infarction and addresses a promising therapeutic strategy that involves modulation of gut microbial composition through probiotics supplementation.

The number of human microbiota reside within and on human bodies is many-folds more than the number of cells comprising human bodies. These microbes co-exist with human from birth. The use of antibiotics suppresses some species and those favor the altered environment grow and flourish. The resulting dysbiosis, i.e. the altered microbial composition, cripples the immune response.

The gut microbiome comprises several species which are in certain proportion at normal status. Literatures indicated that dysbiosis is associated with the course of disease. Dr. Hsieh’s team further reveals the mechanism of the gut-heart axis.

After depleting gut microbiota with antibiotics treatment, the researchers observed drastically increased mortality in mouse myocardial infarction (MI) model. Most of these mice died with rupture in the left ventricle. The researchers found that the lack of short-chain fatty acids (SCFAs), one of the gut microbial metabolites, leads to the findings.

SCFAs are the metabolites produced by gut microbiota through anaerobic fermentation of carbohydrates. They also serve as an important factor to modulate the function of immune cells. The injured myocardium stimulates the recruitment of macrophage and remove necrotic debris and apoptotic cells, followed by fibrosis to maintain cardiac structure. In the absence of SCFAs, cardiac repair mediated by immune cells is impaired and this increased the chance of cardiac rupture.

The team also suggests the supplementary of common Lactobacillus-based probiotics, alters the gut microbial community in a favorable way that would enhance the function of cardiac repair.

In fact, gut microbiome is associated with not only cardiovascular diseases, but also obesity, diabetes, autoimmune diseases, cancer, and neuropsychiatric disorders.

The study entitled “Loss of Gut Microbiota Alters Immune System Composition and Cripples Post-Infarction Cardiac Repair” was published online in Circulation last Monday (8th Oct). The research team is led by Dr. Patrick Hsieh at IBMS, in collaboration with Peilin Chen at the Research Center for Applied Sciences, AS; Dr. Timothy J. Kamp at The Dept. of Cell and Regenerative Biology, University of Wisconsin-Madison (UW-Madison); Dr. Timothy A. Hacker at UW-Madison Stem Cell and Regenerative Medicine Center; and Dr. Federico E. Rey at the Dept. of Bacteriology. The study is funded by the Ministry of Science and Technology, Academia Sinica, National Health Research Institutes, and the University of Wisconsin–Madison.

Image: Schematic diagram showing the importance of gut microbiota-derived short chain fatty acids for maintaining immune composition and repair capacity during homeostasis.
A, In untreated mice, gut microbiota-derived SCFAs modulate immune composition and repair capacity during homeostasis. B, Upon antibiotic-mediated dysbiosis, the depletion of the gut microbiota and their SCFA products is associated with changes in immune composition, and an abolishment of repair response leading to exacerbated mortality after MI. Restoration of the system across each level through either fecal reconstitution of the gut microbiota, dietary supplementation of SCFAs or immune cell transplantation results in improved survival.