• IMMUNE NETWORK
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• v.23 no.1
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• pp.6.1-6.24
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• 2023

Intestinal microorganisms interact with various immune cells and are involved in gut homeostasis and immune regulation. Although many studies have discussed the roles of the microorganisms themselves, interest in the effector function of their metabolites is increasing. The metabolic processes of these molecules provide important clues to the existence and function of gut microbes. The interrelationship between metabolites and T lymphocytes in particular plays a significant role in adaptive immune functions. Our current review focuses on 3 groups of metabolites: short-chain fatty acids, bile acids metabolites, and polyamines. We collated the findings of several studies on the transformation and production of these metabolites by gut microbes and explained their immunological roles. Specifically, we summarized the reports on changes in mucosal immune homeostasis represented by the Tregs and Th17 cells balance. The relationship between specific metabolites and diseases was also analyzed through latest studies. Thus, this review highlights microbial metabolites as the hidden treasure having potential diagnostic markers and therapeutic targets through a comprehensive understanding of the gut-immune interaction.

• Journal of Microbiology and Biotechnology
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• v.30 no.11
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• pp.1607-1613
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• 2020

Colorectal cancer (CRC) is regarded as one of the most common and deadly forms of cancer. Gut microbiota is vital to retain and promote several functions of intestinal. Although previous researches have shown that some gut microbiota have the abilities to inhibit tumorigenesis and prevent cancer from progressing, they have not yet clearly identified associative mechanisms. This review not only concentrates on the antitumor effects of metabolites produced by gut microbiota, for example, SCFA, ferrichrome, urolithins, equol and conjugated linoleic acids, but also the molecules which constituted the bacterial cell wall have the antitumor effect in the host, including lipopolysaccharide, lipoteichoic acid, β-glucans and peptidoglycan. The aim of our review is to develop a possible therapeutic method, which use the products of gut microbiota metabolism or gut microbiota constituents to help treat or prevent colorectal cancer.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• Korean Circulation Journal
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• v.53 no.8
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• pp.499-518
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• 2023

Cardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD. In addition, increasing evidence has demonstrated the alterations in the ratio of Firmicutes to Bacteroidetes and the imbalance of microbial-dependent metabolites, including short-chain fatty acids and trimethylamine N-oxide, play a crucial role in the pathogenesis of CVD. However, the exact mechanism of action remains undefined to this day. In this review, we focus on the compositional changes in the gut microbiome and its related metabolites in various CVDs. Moreover, the potential treatment and preventive strategies targeting the gut microbiome and its metabolites are discussed.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.7.1-7.27
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• 2023

The mammalian intestines harbor trillions of commensal microorganisms composed of thousands of species that are collectively called gut microbiota. Among the microbiota, bacteria are the predominant microorganism, with viruses, protozoa, and fungi (mycobiota) making up a relatively smaller population. The microbial communities play fundamental roles in the maturation and orchestration of the immune landscape in health and disease. Primarily, the gut microbiota modulates the immune system to maintain homeostasis and plays a crucial role in regulating the pathogenesis and pathophysiology of inflammatory, neuronal, and metabolic disorders. The microbiota modulates the host immune system through direct interactions with immune cells or indirect mechanisms such as producing short-chain acids and diverse metabolites. Numerous researchers have put extensive efforts into investigating the role of microbes in immune regulation, discovering novel immunomodulatory microbial species, identifying key effector molecules, and demonstrating how microbes and their key effector molecules mechanistically impact the host immune system. Consequently, recent studies suggest that several microbial species and their immunomodulatory molecules have therapeutic applicability in preclinical settings of multiple disorders. Nonetheless, it is still unclear why and how a handful of microorganisms and their key molecules affect the host immunity in diverse diseases. This review mainly discusses the role of microbes and their metabolites in T helper cell differentiation, immunomodulatory function, and their modes of action.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.334-343
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• 2021

Background: Gut microbiota mainly function in the biotransformation of primary ginsenosides into bioactive metabolites. Herein, we investigated the effects of three prebiotic fibers by targeting gut microbiota on the metabolism of ginsenoside Rb1 in vivo. Methods: Sprague Dawley rats were administered with ginsenoside Rb1 after a two-week prebiotic intervention of fructooligosaccharide, galactooligosaccharide, and fibersol-2, respectively. Pharmacokinetic analysis of ginsenoside Rb1 and its metabolites was performed, whilst the microbial composition and metabolic function of gut microbiota were examined by 16S rRNA gene amplicon and metagenomic shotgun sequencing. Results: The results showed that peak plasma concentration and area under concentration time curve of ginsenoside Rb1 and its intermediate metabolites, ginsenoside Rd, F2, and compound K (CK), in the prebiotic intervention groups were increased at various degrees compared with those in the control group. Gut microbiota dramatically responded to the prebiotic treatment at both taxonomical and functional levels. The abundance of Prevotella, which possesses potential function to hydrolyze ginsenoside Rb1 into CK, was significantly elevated in the three prebiotic groups (P < 0.05). The gut metagenomic analysis also revealed the functional gene enrichment for terpenoid/polyketide metabolism, glycolysis, gluconeogenesis, propanoate metabolism, etc. Conclusion: These findings imply that prebiotics may selectively promote the proliferation of certain bacterial stains with glycoside hydrolysis capacity, thereby, subsequently improving the biotransformation and bioavailability of primary ginsenosides in vivo.

• Journal of Microbiology and Biotechnology
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• v.34 no.6
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• pp.1214-1221
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• 2024

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. β-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.12
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• pp.1948-1956
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• 2020

Objective: The purpose of this study was to reveal the metabolic shift in the fungus cocultured with the methanogen (Methanobrevibacter thaueri). Methods: Gas chromatography-mass spectrometry was used to investigate the metabolites in anaerobic fungal (Pecoramyces sp. F1) cells and the supernatant. Results: A total of 104 and 102 metabolites were detected in the fungal cells and the supernatant, respectively. The partial least squares-discriminant analysis showed that the metabolite profiles in both the fungal cell and the supernatant were distinctly shifted when co-cultured with methanogen. Statistically, 16 and 30 metabolites were significantly (p<0.05) affected in the fungal cell and the supernatant, respectively by the co-cultured methanogen. Metabolic pathway analysis showed that co-culturing with methanogen reduced the production of lactate from pyruvate in the cytosol and increased metabolism in the hydrogenosomes of the anaerobic fungus. Citrate was accumulated in the cytosol of the fungus co-cultured with the methanogen. Conclusion: The co-culture of the anaerobic fungus and the methanogen is a good model for studying the microbial interaction between H₂-producing and H₂-utilizing microorganisms. However, metabolism in hydrogenosome needs to be further studied to gain better insight in the hydrogen transfer among microorganisms.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.31 no.3
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• pp.131-145
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• 2020

The microbiota-gut-brain axis, which refers to the bidirectional communication pathway between gut bacteria and the central nervous system, has a profound effect on important brain processes, from the synthesis of neurotransmitters to the modulation of complex behaviors such as sociability and anxiety. Previous studies have revealed that the gut microbiota is potentially related to not only gastrointestinal disturbances, but also social impairment and repetitive behavior-core symptoms of autism spectrum disorder (ASD). Although studies have been conducted to characterize the microbial composition in patients with ASD, the results are heterogeneous. Nevertheless, it is clear that there is a difference in the composition of the gut microbiota between ASD and typically developed individuals, and animal studies have repeatedly suggested that the gut microbiota plays an important role in ASD pathophysiology. This possibility is supported by abnormalities in metabolites produced by the gut microbiota and the association between altered immune responses and the gut microbiota observed in ASD patients. Based on these findings, various attempts have been made to use the microbiota in ASD treatment. The results reported to date suggest that microbiota-based therapies may be effective for ASD, but largescale, well-designed studies are needed to confirm this.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1111-1118
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• 2023

As a long-term condition that affects the airways and lungs, chronic obstructive pulmonary disease (COPD) is characterized by inflammation, emphysema, breathlessness, chronic cough, and sputum production. Currently, the bronchodilators and anti-inflammatory drugs prescribed for COPD are mostly off-target, warranting new disease management strategies. Accumulating research has revealed the gut-lung axis to be a bidirectional communication system. Cigarette smoke, a major exacerbating factor in COPD and lung inflammation, affects gut microbiota composition and diversity, causing gut microbiota dysbiosis, a condition that has recently been described in COPD patients and animal models. For this review, we focused on the gut-lung axis, which is influenced by gut microbial metabolites, bacterial translocation, and immune cell modulation. Further, we have summarized the findings of preclinical and clinical studies on the association between gut microbiota and COPD to provide a basis for using gut microbiota in therapeutic strategies against COPD. Our review also proposes that further research on probiotics, prebiotics, short-chain fatty acids, and fecal microbiota transplantation could assist therapeutic approaches targeting the gut microbiota to alleviate COPD.