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The Development of Metabolites from the Gut Microbiome via In Silico Strategy

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 18186

Special Issue Editors


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Guest Editor
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Korea
Interests: network pharmacology; drug repurposing; protein–protein interaction; bioinformatics
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Guest Editor
1. Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
2. Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Republic of Korea
Interests: hepatitis; liver diseases; liver cirrhosis; hepatocellular carcinoma; liver diseases and immunology; gastrointestinal diseases; hepatitis B; hepatitis C

Special Issue Information

Dear Colleagues,

Gut microbiota diversity has potential as a diagnostic tool for unraveling intestinal disorders, and may contribute to the maintenance of digestive health and overall wellbeing.

At present, a great deal of microbiome data have been reported concerning the development of several diseases (e.g., obesity, type 1 diseases, cancer, cirrhosis, and Alzheimer’s, among others).

Recently, prebiotics, probiotics and postbiotics have been utilized as therapeutics to alleviate diverse body disorders. In particular, metabolites produced by postbiotics play significant roles in the human gut, directly or indirectly. They have pleiotropic efficacy against diverse diseases, including anti-inflammation, immunomodulation, anti-tumor, and even anti-psychiatry. The therapeutic benefits of the cross-communication between organs and the gut microbiota can not only be identified in local areas, but also distant organs, because the metabolites exert bidirectional communication from the gut. This is defined as the gut–organ axis, which can be differentiated into the gut–brain, gut–liver, gut–lung, and gut–skin axes, and so on.

However, the detailed roles of metabolites from the gut microbiota are not well documented; therefore, researchers have had difficulty in proving their in vitro or in vivo effects. In particular, an in silico strategy for identifying the mechanism of metabolite(s) from the gut microbiota may be an essential tool in investigating their health benefits.

This Special Issue will concentrate on current issues in molecular biology based on computational methods, merged networks (microbiota–mechanisms–targets–metabolites) and new insights regarding metabolites from the gut microbiota.

The submission of original articles, reviews, and hypotheses is welcome. Topics of interest for this Special Issue include, but are not limited to:

  • The gut–organ axis from metabolites in human (e.g., gut–liver, gut–brain, gut–skin axis, and so on);
  • Networks of microbiota–mechanisms–targets–metabolites to alleviate human diseases;
  • Systemic insights to identify potential therapeutic metabolites or gut microbiota;
  • Microbiome-based analysis for human therapeutics, by either dry-based or wet-based experiments.

Dr. Ki Kwang Oh
Prof. Dr. Ki Tae Suk
Guest Editors

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Keywords

  • gut microbiota
  • in silico strategy
  • metabolites
  • gut–organ axis
  • human therapeutics
  • prebiotics, probiotics and postbiotics
  • computational methods

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Published Papers (6 papers)

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Research

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17 pages, 5193 KiB  
Article
Microbiomic and Metabolomic Analyses Unveil the Protective Effect of Saffron in a Mouse Colitis Model
by Gulshan Singh, Hassan Brim, Yeneneh Haileselassie, Sudhir Varma, Aida Habtezion, Mudasir Rashid, Sidhartha R. Sinha and Hassan Ashktorab
Curr. Issues Mol. Biol. 2023, 45(7), 5558-5574; https://doi.org/10.3390/cimb45070351 - 30 Jun 2023
Cited by 3 | Viewed by 3097
Abstract
Despite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) [...] Read more.
Despite the existence of effective drugs used to treat inflammatory bowel disease (IBD), many patients fail to respond or lose response over time. Further, many drugs can carry serious adverse effects, including increased risk of infections and malignancies. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD and how the microbiome and metabolome play a role has not been explored extensively. We aimed to establish whether saffron treatment modulates the host microbiome and metabolic profile in experimental colitis. Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron in a dose of 20 mg/kg body weight or vehicle through daily gavage. On day 10, stool pellets from mice were collected and analyzed to assess saffron’s effect on fecal microbiota and metabolites through 16S rRNA sequencing and untargeted primary metabolite analysis. Saffron treatment maintained gut microbiota homeostasis by counter-selecting pro-inflammatory bacteria and maintained Firmicutes/Bacteroides ratio, which was otherwise disturbed by DSS treatment. Several metabolites (uric acid, cholesterol, 2 hydroxyglutaric acid, allantoic acid, 2 hydroxyhexanoic acid) were altered significantly with saffron treatment in DSS-treated mice, and this might play a role in mediating saffron’s colitis-mitigating effects. These data demonstrate saffron’s therapeutic potential, and its protective role is modulated by gut microbiota, potentially acting through changes in metabolites. Full article
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10 pages, 306 KiB  
Article
Effect of Radium-223 on the Gut Microbiota of Prostate Cancer Patients: A Pilot Case Series Study
by Ana Fernandes, Ana Oliveira, Carla Guedes, Rúben Fernandes, Raquel Soares and Pedro Barata
Curr. Issues Mol. Biol. 2022, 44(10), 4950-4959; https://doi.org/10.3390/cimb44100336 - 16 Oct 2022
Cited by 8 | Viewed by 2090
Abstract
Radium-223 (Ra-223) is a targeted nuclear medicine therapy for castration-resistant prostate cancer with bone metastases. Its major route of elimination is the intestine. There is overwhelming evidence that the gut microbiota is altered by ionizing radiation (IR) from radiotherapy treatments. Nevertheless, it is [...] Read more.
Radium-223 (Ra-223) is a targeted nuclear medicine therapy for castration-resistant prostate cancer with bone metastases. Its major route of elimination is the intestine. There is overwhelming evidence that the gut microbiota is altered by ionizing radiation (IR) from radiotherapy treatments. Nevertheless, it is known that extrapolation of outcomes from radiotherapy to nuclear medicine is not straightforward. The purpose of this study was to prospectively determine the effect of Ra-223 on selected important bacteria from the gut microbiota. Stool samples from three prostate cancer patients and two healthy individuals were obtained, processed, and analysed. We specifically measured the relative change of the abundance of important bacteria, determined by the 2−ΔΔC method. We found that Ra-223 influenced the gut microbiota composition. The most relevant changes were increases of Proteobacteria and Atopobacter; and decreases of Bacteroidetes, Prevotella, Lactobacillus, Bifidobacterium, Clostridium coccoides, and Bacteroides fragilis. Additionally, our experiment confirms that the composition of gut microbiota from prostate cancer patients is altered. No significant correlation was found between each subject’s gut microbiome profile and their clinical indices. Despite its limited sample, the results of this pilot study suggest that ionizing radiation from Ra-223 alters the gut microbiota composition and that the gut microbiota of prostate cancer patients has an increase of the bacteria with known prejudicial effects and a decrease of the ones with favorable effects. Full article
13 pages, 1214 KiB  
Article
Identification of Gut Microbiota Affecting Fiber Digestibility in Pigs
by Qing Niu, Guang Pu, Lijuan Fan, Chen Gao, Tingxu Lan, Chenxi Liu, Taoran Du, Sung Woo Kim, Peipei Niu, Zongping Zhang, Pinghua Li and Ruihua Huang
Curr. Issues Mol. Biol. 2022, 44(10), 4557-4569; https://doi.org/10.3390/cimb44100312 - 30 Sep 2022
Cited by 9 | Viewed by 1999
Abstract
Dietary fiber plays an important role in porcine gut health and welfare. Fiber is degraded by microbial fermentation in the intestine, and most gut microbiota related to fiber digestibility in pigs are worth pursuing. The aim of this study was to identify gut [...] Read more.
Dietary fiber plays an important role in porcine gut health and welfare. Fiber is degraded by microbial fermentation in the intestine, and most gut microbiota related to fiber digestibility in pigs are worth pursuing. The aim of this study was to identify gut microbiota associated with the apparent total tract digestibility (ATTD) of neutral detergent fiber (NDF) and of acid detergent fiber (ADF) in pigs. Large phenotypic variations in the ATTD of NDF and of ADF were separately found among 274 Suhuai pigs. Microbial community structures were significantly different between high and low fiber digestibility groups. Fourteen genera separately dominated the communities found in the high ATTD (H-AD) of NDF and ADF samples and were in very low abundance in the low ATTD (L-AD) of NDF and ADF samples. In conclusion, norank_f__Bacteroidales_S24-7_group (p < 0.05), Ruminococcaceae_UCG-005 (p < 0.05), unclassified_f__Lachnospiraceae (p < 0.05), Treponema_2 (p < 0.01), and Ruminococcaceae_NK4A214_group (p < 0.01) were the main genera of gut microbiota affecting the ATTD of NDF in pigs. Christensenellaceae_R-7_group (p < 0.01), Treponema_2 (p < 0.05), Ruminococcaceae_NK4A214_group (p < 0.05), Ruminococcaceae_UCG-002 (p < 0.05), and [Eubacterium]_coprostanoligenes_group (p < 0.05) were the main genera of gut microbiota affecting the ATTD of ADF in pigs. The most important functions of the above different potential biomarkers were: carbohydrate transport and metabolism, general function prediction only, amino acid transport and metabolism, cell wall/membrane/envelope biogenesis, translation, transcription, replication, energy production and conversion, signal transduction mechanisms, and inorganic ion transport and metabolism. The most important metabolic pathways of the above different potential biomarkers were: membrane transport, carbohydrate metabolism, amino acid metabolism, replication and repair, translation, cell motility, energy metabolism, poorly characterized, nucleotide metabolism, metabolism of cofactors and vitamins, and cellular processes and signaling. Full article
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Review

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20 pages, 3292 KiB  
Review
The Effect of Probiotic Supplementation on the Gut–Brain Axis in Psychiatric Patients
by Hussein Sabit, Areej Kassab, Donia Alaa, Shaza Mohamed, Shaimaa Abdel-Ghany, Mohamed Mansy, Osama A. Said, Mona A. Khalifa, Halah Hafiz and Asmaa M. Abushady
Curr. Issues Mol. Biol. 2023, 45(5), 4080-4099; https://doi.org/10.3390/cimb45050260 - 6 May 2023
Cited by 13 | Viewed by 4582
Abstract
The pathophysiology of several psychiatric diseases may entail disturbances in the hypothalamic–pituitary–adrenal (HPA) axis and metabolic pathways. Variations in how these effects present themselves may be connected to individual variances in clinical symptoms and treatment responses, such as the observation that a significant [...] Read more.
The pathophysiology of several psychiatric diseases may entail disturbances in the hypothalamic–pituitary–adrenal (HPA) axis and metabolic pathways. Variations in how these effects present themselves may be connected to individual variances in clinical symptoms and treatment responses, such as the observation that a significant fraction of participants do not respond to current antipsychotic drugs. A bidirectional signaling pathway between the central nervous system and the gastrointestinal tract is known as the microbiota–gut–brain axis. The large and small intestines contain more than 100 trillion microbial cells, contributing to the intestinal ecosystem’s incredible complexity. Interactions between the microbiota and intestinal epithelium can alter brain physiology and affect mood and behavior. There has recently been a focus on how these relationships impact mental health. According to evidence, intestinal microbiota may play a role in neurological and mental illnesses. Intestinal metabolites of microbial origin, such as short-chain fatty acids, tryptophan metabolites, and bacterial components that might stimulate the host’s immune system, are mentioned in this review. We aim to shed some on the growing role of gut microbiota in inducing/manipulating several psychiatric disorders, which may pave the way for novel microbiota-based therapies. Full article
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34 pages, 797 KiB  
Review
The Effects of Ionizing Radiation on Gut Microbiota: What Can Animal Models Tell Us?—A Systematic Review
by Ana Fernandes, Ana Oliveira, Raquel Soares and Pedro Barata
Curr. Issues Mol. Biol. 2023, 45(5), 3877-3910; https://doi.org/10.3390/cimb45050249 - 2 May 2023
Cited by 6 | Viewed by 2257
Abstract
Background: The gut microbiota is relatively stable; however, various factors can precipitate an imbalance that is known to be associated with various diseases. We aimed to conduct a systematic literature review of studies reporting the effects of ionizing radiation on the composition, richness, [...] Read more.
Background: The gut microbiota is relatively stable; however, various factors can precipitate an imbalance that is known to be associated with various diseases. We aimed to conduct a systematic literature review of studies reporting the effects of ionizing radiation on the composition, richness, and diversity of the gut microbiota of animals. Methods: A systematic literature search was performed in PubMed, EMBASE, and Cochrane library databases. The standard methodologies expected by Cochrane were utilized. Results: We identified 3531 non-duplicated records and selected twenty-nine studies after considering the defined inclusion criteria. The studies were found to be heterogeneous, with significant differences in the chosen populations, methodologies, and outcomes. Overall, we found evidence of an association between ionizing radiation exposure and dysbiosis, with a reduction of microbiota diversity and richness and alterations in the taxonomic composition. Although differences in taxonomic composition varied across studies, Proteobacteria, Verrucomicrobia, Alistipes, and Akkermancia most consistently reported to be relatively more abundant after ionizing radiation exposure, whereas Bacteroidetes, Firmicutes, and Lactobacillus were relatively reduced. Conclusions: This review highlights the effect of ionizing exposure on gut microbiota diversity, richness, and composition. It paves the way for further studies on human subjects regarding gastrointestinal side effects in patients submitted to treatments with ionizing radiation and the development of potential preventive, therapeutic approaches. Full article
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Other

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14 pages, 3983 KiB  
Hypothesis
Identification of Gut Microbiome Metabolites via Network Pharmacology Analysis in Treating Alcoholic Liver Disease
by Ki-Kwang Oh, Ye-Rin Choi, Haripriya Gupta, Raja Ganesan, Satya Priya Sharma, Sung-Min Won, Jin-Ju Jeong, Su-Been Lee, Min-Gi Cha, Goo-Hyun Kwon, Dong-Joon Kim and Ki-Tae Suk
Curr. Issues Mol. Biol. 2022, 44(7), 3253-3266; https://doi.org/10.3390/cimb44070224 - 19 Jul 2022
Cited by 2 | Viewed by 3346
Abstract
Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the pathogenesis of ALD [...] Read more.
Alcoholic liver disease (ALD) is linked to a broad spectrum of diseases, including diabetes, hypertension, atherosclerosis, and even liver carcinoma. The ALD spectrum includes alcoholic fatty liver disease (AFLD), alcoholic hepatitis, and cirrhosis. Most recently, some reports demonstrated that the pathogenesis of ALD is strongly associated with metabolites of human microbiota. AFLD was the onset of disease among ALDs, the initial cause of which is alcohol consumption. Thus, we analyzed the significant metabolites of microbiota against AFLD via the network pharmacology concept. The metabolites from microbiota were retrieved by the gutMGene database; sequentially, AFLD targets were identified by public databases (DisGeNET, OMIM). The final targets were utilized for protein–protein interaction (PPI) networks and signaling pathway analyses. Then, we performed a molecular docking test (MDT) to verify the affinity between metabolite(s) and target(s) utilizing the Autodock 1.5.6 tool. From a holistic viewpoint, we integrated the relationships of microbiota-signaling pathways-targets-metabolites (MSTM) using the R Package. We identified the uppermost six key targets (TLR4, RELA, IL6, PPARG, COX-2, and CYP1A2) against AFLD. The PPI network analysis revealed that TLR4, RELA, IL6, PPARG, and COX-2 had equivalent degrees of value (4); however, CYP1A2 had no associations with the other targets. The bubble chart showed that the PI3K-Akt signaling pathway in nine signaling pathways might be the most significant mechanism with antagonistic functions in the treatment of AFLD. The MDT confirmed that Icaritin is a promising agent to bind stably to RELA (known as NF-Κb). In parallel, Bacterium MRG-PMF-1, the PI3K-Akt signaling pathway, RELA, and Icaritin were the most significant components against AFLD in MSTM networks. In conclusion, we showed that the Icaritin–RELA complex on the PI3K-Akt signaling pathway by bacterial MRG-PMF-1 might have promising therapeutic effects against AFLD, providing crucial evidence for further research. Full article
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