Trillions of microbial cells harbor at the human intestine as one part of our physiological ecosystem. These communities of bacteria, fungi, archaea, and viruses are collectively referred as “microbiota,” and their genome as the “microbiome.” 4 The microbial colonization of the gastrointestinal tract initiates at birth and the composition of the species-level phylotypes differs individually. 5 Approximately 99% of human gut microbiota are composed by the four phyla of bacterial species, including Firmicutes, Bacteroides, Actinobacteria, and Proteobacteria. 6 Among them, Firmicutes and Bacteroidetes phyla are the two major species accounting for almost 90% of bacterial species in the human intestines. 7
The gut microbiota plays an important role in the immune support and host metabolism. Abnormal changes of the gut flora might affect host health by inducing immune response. 7 From the previous studies, the gut microbiota could code various enzymes, synthesize vitamins, produce amino acids, and digest various nondigestible dietary components (e.g., large polysaccharides, resistant starch, pectin, cellulose, hemicellulose, alcohols, and sugars, etc. ). 5
The interindividual variabilities of the microbial communities are interfered by host-microbial interactions, host genetics, host diets, host life-style, and environmental conditions (e.g., PH gradient, gastric motility, oxygen content, and nutrition, etc.). 4 The diverse, and various metabolites from gut microbiota also affect the host physiology vice versa. 6
The Main Findings of This Study
In this study, the DNAs of the gut microbiota were extracted from the fecal samples of the subjects, and the DNA libraries were constructed by 16S rRNA gene sequencing on the MiSeq (Illumina) platform. The highly similar sequences were grouped into the OTUs. After alpha diversity analysis, the OTUs and faith phylogenetic diversity (PD) were noted to be different between AMI and control groups (p-value = 0.01 and < 0.001, individually). Therefore, the abundance of gut microbiota was different between the AMI and control groups.
The taxonomic cladogram reported all clades of the gut microbiota, and there was less abundance of Selenomonadales in the AMI group relative to the control group at the Family, Genus, and Species levels. The KEGG database resource was comparing for evaluating the possibly metabolic pathways involved with the AMI episodes. After the metagenome functional analysis, the seleno-compound wa noted to be more abundant in the AMI group.
From the current studies, there was relatively increasing abundance of Ruminococcus gnavus in the patients with CAD. 8 In addition to coronary atherosclerosis, the Ruminococcus gnavus was also linked to specific inflammatory process, production of inflammatory polysaccharide, and inflammatory bowel disease. 8 On the contrary, the abundances of Lachnospiraceae and Ruminococcus gauvreauii were decreasing in the subjects with CAD. 8 This is the first study to demonstrate “another distinct” gut microbiome- Selenomonadales and seleno-compound to be associated with the occurrence of AMI. The possible mechanisms for altering microbiota, and the potential metabolome in association with the AMI episodes are discussed in the following paragraphs.
The Possibly Metabolic Pathways of Selenomonadales in Correlation with AMI Episodes
1. Selenomonadales and short-chain free fatty acids (SCFAs)
Generally, the primary products of anaerobic fermentation of undigested nutrients (e.g., resistant starch, dietary fiber, and various complex polysaccharides) after bacterial hydrolysis are monosaccharides. Those monosaccharides are further fermented to various fatty acids ranging from 1 to 6 carbon chains, commonly referred as short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate. 4 Acetate is utilized by butyrate producers to produce butyrate while the butyryl- CoA: acetate-CoA-transferase pathway is the main process for the biosynthesis of butyrate.9 Butyrate acts as histone deacetylases inhibitor, and involves in epigenetic regulation of T-cell development and maintenance. 10
Those SCFAs (e.g., acetate, butyrate, and propionate) are transported by the monocarboxylate transporters on the mucosal epithelium of the intestines, and into the systemic circulation. Although 5–10% SCFAs, particularly butyrate serves as energy substrates for epithelial cells of the intestines, SCFAs also serve as signaling molecules. SCFAs interact with G-protein receptor (e.g., GPR41 and GPR43), and olfactory receptor 78 (Olfr78), which exhibit various physiological functions (e.g., histone deacetylases inhibition, chemotaxis, phagocytosis modulation, reactive oxygen species induction, regulating immune cell proliferation, lipid, and glucose metabolism, etc.). 4
Additionally, both GRP41 and Olfr78 are expressed in smooth muscle cells of small vessels, where they differentially mediate vascular tone. The 3-carbon SCFA propionate may stimulate GRP41 to lower blood pressure, whereas stimulation of Olfr78 can increase blood pressure. 4 These signal mechanisms have been proved by the animal models. For instance, Olfr78 knock-out mice are hypotensive, whereas GRP41 knock-out mice are hypertensive. 4 Therefore, SCFAs could modulate several physiological effects associated with cardiovascular diseases in addition to energy metabolism (e.g., autonomic systems, blood pressure, immune function, inflammatory responses, and other cellular functions, etc.). 4 Besides, SCFAs have been shown to be beneficial for increasing insulin sensitivity, keeping glucose homeostasis, and body weight control as well. 6
Selenomonadales are the members of Firmicutes, and the class of Negativicutes which are Gram-negative. Selenomonadales have been reported to ferment carbohydrates into acetate and lactate. 9 Therefore, those SCFAs metabolites generated by the Selenomonadales might lead to the downstream metabolic alterations, and affect coronary atherosclerosis in correlation with AMI episodes.
2. Dysbiosis of gut microbiota in AMI subjects
An abnormal imbalance of the gut microbiota is called “dysbiosis”. Foods are important to maintain the integrity of the diversity, and keep balance of microbiota for producing SCFAs efficiently. However, high fat, and modern diets tend to hamper the gut microbiota ecosystem, which may explain the increasing incidence of metabolic diseases recently. 10 Shifts from the animal-based diets to be plant-based diets could alter, and modify the production of SCFAs. 4 An increase in Firmicutes has been related to increase enzymes for disintegrating polysaccharides from food, and produce SCFAs as well. 7 Those SCFAs are critical for repairing the cardiac structure after AMI episodes from the animal models. 4 The intestinal microbiota, and their metabolites might stimulate the immune system via intestinal lymphoid tissues. 4 The relative less abundance of Selenomonadales in the AMI subjects might be associated with deprivation of SCFAs in the intestine, and resulting in the loss of benefits from SCFAs mentioned above. Therefore, it might be speculated that propagation or sterilization of bacterial species specific for augmenting SCFAs generation, might prevent inflammatory process including coronary atherosclerosis, and could be beneficial for the treatment of AMI subjects.
Intervention of Selenomonadales with probiotic
In addition to changing dietary habits, probiotic is another possible method to modulate gut microbiota profiles. In a rat myocardial infarction model, administration of either Lactobacillus plantarum or Lactobacillus rhamnosus GR-1 is associated with attenuation of cardiac remodeling after AMI. 4 As Selenomonadales are considered, Clostridium butyricum, which is an oral diet-added probiotic, has been demonstrated to promote the abundance of Selenomonadales dramatically. Clostridium. butyricum is an anaerobic, Gram-positive, butyric acid-producing bacillus, and has a protective role after intestinal injury by modulating gut microbial metabolites, such as SCFAs.9 After using Clostridium butyricum probiotic for two weeks, Selenomonadales replace Clostridiales to be the major and dominant bacteria in the intestines. 9
Seleno-compound Metabolism with the Association of AMI
We are the first to find the relationship between seleno-compound and AMI episodes by metabolomic analysis. Selenium (Se) is a naturally occurring, and essential trace element necessary for activation of specific enzymes (e.g. glutathione peroxidases and thioredoxin reductase) after oxidative stress. 11 Se-containing enzymes, especially glutathione peroxidase, are involved in regulating the redox balance in almost all tissues 12 and very important for the detoxification of reactive oxygen species (e.g., peroxides and hydroperoxides). 11 While the human body is under stress, for instanced, oxidative stress caused by the intense growth activity of the fetus during pregnancy, the first line of defense against the oxidative stress are the endogenous antioxidants, such as the Se containing compounds. During pregnancy, the placenta also plays an important role for activating seleno-compounds such as glutathione-peroxidase and thioredoxinreductase. 12 Therefore, it is reasonable that the increasing abundance of seleno-compound in the AMI subjects might be correlated with the reaction of oxidative stress after AMI episodes.
The Interaction of Selenomonadales, Seleno-compound, and Dietary Se
At present, the Selenomonadales have not been reported to be associated with the bioavailable Se-protein compound for supplying selenium to the organisms. 13 The relationship between the Selenomonadales, and the seleno-compound needs to be clarified in the future. However, the dietary Se has been proved to be cardioprotective for reducing oxidative stress, lowering connexin-43 dephosphorylation, and decreasing TNF-α expression from the rat models. 14 For the patients with cardiac dysfunction, the Se intake might be helpful for improving cardiac remodeling even when the provided Se is within the normal range of physiological values. 14
For the dietary Se, the Se-enriched plants (e.g., onion, broccoli, wild leek, and garlic) possess protective effects on the anti-inflammation, ant-cancer, and anti-oxidant activities via Se-methyl selenocysteine or gamma-glutamyl-Se-methyl selenocysteine. 15,16 Additionally, the combination treatment with Vit E, Se, and anthocyanin from purple carrots shows greater antioxidant activities against D-galactose-induced oxidative damage in rats than those of individual treatments, suggesting the synergistic antioxidant effects of these antioxidants. 17 The protection from Vit E against the adverse effects of nitrites/nitrates is attributed to its ability to reduce ONOO- formation, while Se exerts its protective effects via seleno-enzymes/compounds, which reduce ONOO- formed. 18
Whether data collected for the study, including participant data and a data dictionary defining each field in the set, will be made available to others after publication. These data will be made available after approval of a proposal and a signed data access agreement by e-mail request (e-mail: [email protected]).