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Metabolites
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Targeting Microbiota and Metabolites for Prevention and Treatment of Human...
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Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 11041

Special Issue Editors

Dr. Zhipeng Tao

E-Mail Website
Guest Editor
Department of Nutrition and Food Sciences, Texas Woman’s University, Denton, TX 76209, USA
Interests: molecular nutrition; target therapy
Special Issues, Collections and Topics in MDPI journals
Dr. Danhui Wang

E-Mail Website
Guest Editor
Department of Nutrition and Food Sciences, Texas Woman’s University, Denton, TX 76209, USA
Interests: food safety; food microbiology; microbial metabolomics; biosensor
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut microbiota, a spectrum of bacteria that reside in the gastrointestinal system, supplies essential signaling metabolites that are vital to the hosts’ physiological processes. Gut microbiota metabolites support basic host functions at healthy stage, while their production can be disrupted to cause a variety of diseases, including cancer, neurological disorders, gastrointestinal disorders, metabolic diseases, and cardiovascular diseases. By targeting the microbiota and/or microbial metabolites can lead to dietary interventions or therapeutic options for human diseases. The current issue will cover the topics,

  • Optimization of fermentation conditions (exogenous microbial fermentation and endogenous gut microbiota fermentation) to maximize the production of healthy metabolites;
  • Targeting microbiota for the prevention and treatments of these pathological processes;
  • Microbial metabolites based target therapies.

Dr. Zhipeng Tao
Dr. Danhui Wang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbiota
  • metabolites
  • metabolic diseases
  • cancer
  • cardiovascular diseases
  • liver diseases

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Published Papers (7 papers)

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Research

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16 pages, 2448 KiB  
Article
Lactobacillus johnsonii N6.2 Phospholipids Induce T Cell Anergy upon Cognate Dendritic Cell Interactions
by Alexandra E. Cuaycal, Monica F. Torrez Lamberti, Graciela L. Lorca and Claudio F. Gonzalez
Metabolites 2025, 15(5), 284; https://doi.org/10.3390/metabo15050284 - 22 Apr 2025
Viewed by 350
Abstract
Background/Objectives: Lactobacillus johnsonii N6.2 is a gut symbiont with probiotic properties. L. johnsonii N6.2 delayed the progression of type 1 diabetes (T1D) in diabetic-prone rats. The probiotic intake demonstrated immune cell modulation in healthy volunteers, leading to improved wellness and fewer reported [...] Read more.
Background/Objectives: Lactobacillus johnsonii N6.2 is a gut symbiont with probiotic properties. L. johnsonii N6.2 delayed the progression of type 1 diabetes (T1D) in diabetic-prone rats. The probiotic intake demonstrated immune cell modulation in healthy volunteers, leading to improved wellness and fewer reported symptoms like headaches and abdominal pain. These systemic immune-modulating benefits are attributed to L. johnsonii N6.2’s bioactive fractions, including extracellular vesicles (EVs) and purified phospholipids (PLs). We have previously shown that L. johnsonii N6.2 PLs modulate dendritic cell (DC) function towards a regulatory-like phenotype. Here, we further characterize the immune regulatory effects of L. johnsonii N6.2 PLs on adaptive immunity, specifically upon DC and T cell interactions. We hypothesized that PL-stimulated DCs suppress T cell-mediated responses to maintain tolerance in intra- and extra-intestinal sites. Methods: Bone marrow-derived dendritic cells (BMDCs) were generated from Sprague-Dawley rats and stimulated with L. johnsonii N6.2 PLs. Isogenic T cells were isolated from PBMCs obtained via terminal exsanguination. In vitro cellular assays, co-culture experiments, gene expression analysis by qRT-PCR, and flow cytometry assays were conducted to assess the immune regulatory effects of L. johnsonii N6.2 PLs. Results: The PL-stimulated BMDCs upregulated DC regulatory markers and exhibited an immature-like phenotype with reduced surface expression of maturation markers but increased surface migratory molecules (ICAM-1). These BMDCs presented immunosuppressive functions upon cognate T cell interactions and in the presence of TCR stimulation. Specifically, PL-stimulated BMCDs suppressed Th1 effector function and induced the expression of T cell anergy-related genes after co-culturing for 72 h. Conclusions: This study highlights the immune regulatory capacity of L. johnsonii N6.2’s bioactive components on adaptive immunity, specifically that of purified PLs on DC:T cell-mediated responses leading to immunosuppression. Our findings suggest that L. johnsonii N6.2-purified PLs play a role in regulating adaptive immunity, offering potential benefits for managing immune-related diseases like T1D. Full article
(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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21 pages, 21358 KiB  
Article
Didymin Ameliorates Dextran Sulfate Sodium (DSS)-Induced Ulcerative Colitis by Regulating Gut Microbiota and Amino Acid Metabolism in Mice
by Zhongxing Chu, Zuomin Hu, Feiyan Yang, Yaping Zhou, Yiping Tang and Feijun Luo
Metabolites 2024, 14(10), 547; https://doi.org/10.3390/metabo14100547 - 14 Oct 2024
Viewed by 3484
Abstract
Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative [...] Read more.
Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative colitis. Methods and Results: Our results indicated that didymin could alleviate the symptoms of ulcerative colitis, as it inhibited the expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Didymin also promoted the expressions of claudin-1 and zona occludens-1(ZO-1), which are closely related with restoring colon barrier function. Didymin also increased the abundance of Firmicutes and Verrucomicobiota, while decreasing the abundance of Bacteroidota and Proteobacteria. Meanwhile, didymin significantly altered the levels of metabolites related to arginine synthesis and metabolism, and lysine degradation in the colitis mice. Utilizing network pharmacology and molecular docking, our results showed that the metabolites L-ornithine and saccharin could interact with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB). In this in vitro study, L-ornithine could reduce the expressions of transcription factors STAT3 and NF-κB, and it also inhibited the expressions of IL-6 and IL-1β in the lipopolysaccharides (LPS) induced in RAW264.7 cells, while saccharin had the opposite effect. Conclusions: Taken together, didymin can regulate gut microbiota and alter metabolite products, which can modulate STAT3 and NF-κB pathways and inhibit the expressions of inflammatory factors and inflammatory response in the DSS-induced colitis mice. Full article
(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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12 pages, 840 KiB  
Article
Association of Firmicutes/Bacteroidetes Ratio with Body Mass Index in Korean Type 2 Diabetes Mellitus Patients
by Kainat Ahmed, Ha-Neul Choi, Sung-Rae Cho and Jung-Eun Yim
Metabolites 2024, 14(10), 518; https://doi.org/10.3390/metabo14100518 - 26 Sep 2024
Cited by 5 | Viewed by 1803
Abstract
Background: The gut microbiome, which is the collection of microorganisms living in the gastrointestinal tract, has been shown to play a significant role in the development of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Studies have found that the [...] Read more.
Background: The gut microbiome, which is the collection of microorganisms living in the gastrointestinal tract, has been shown to play a significant role in the development of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Studies have found that the ratio of Firmicutes to Bacteroidetes (F/B) is higher in obese individuals compared to lean individuals and tends to decrease with weight loss. However, the relationship between the F/B ratio and T2DM in Korean individuals, with or without obesity, is not fully understood. Objective: The objective of this study is to compare the F/B ratios and metabolic profiles of lean and obese Korean individuals with T2DM. Methods: In this study, 36 individuals with type 2 diabetes mellitus (T2DM) were recruited and classified into four groups (I, II, III, and IV) based on their body mass index (BMI). Group I had a BMI of less than 23.0, group II had a BMI between 23.0 and 24.9, group III had a BMI between 25.0 and 29.9, and group IV had a BMI of 30 kg/m2 or greater. Fecal samples were collected from all participants and sent to Chunlab Inc. (located in Seoul, Republic of Korea) for analysis. The changes in the major microbial phyla within the samples were investigated using quantitative real-time PCR. The collected data were then statistically analyzed using the SPSS program. Results: The levels of triglycerides and alanine transaminase in group I were significantly lower than in the other three groups. The amount of Actinobacteria in group IV was the highest among all four groups. The ratio of Firmicutes to Bacteroidetes increased as BMI increased, and this ratio was positively correlated with AST activity. Conclusions: Our study showed that there is a correlation between the degree of obesity in individuals with diabetes and their gut microbiome. Additionally, the ratio of Firmicutes to Bacteroidetes (F/B ratio) may play a role in the metabolic effects of fatty liver disease, as it may contribute to obesity. Full article
(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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12 pages, 2012 KiB  
Article
Synergistic Fermentation of Pichia kluyveri and Saccharomyces cerevisiae Integrated with Two-Step Sugar-Supplement for Preparing High-Alcohol Kiwifruit Wine
by Qiang Wu, Qiaoling Yuan, Xi Wang, Lingying Chen, Senlin Yi, Xiaodan Huang, Jun Wang and Xutong Wang
Metabolites 2024, 14(6), 310; https://doi.org/10.3390/metabo14060310 - 28 May 2024
Viewed by 1150
Abstract
Wild yeast suitable for kiwifruit wine fermentation was isolated and purified, and the fermentation process was optimized to increase the alcohol content of the kiwifruit wine. Pichia kluyveri was isolated from kiwifruit pulp by lineation separating, screened by morphological characteristics in Wallerstein Laboratory [...] Read more.
Wild yeast suitable for kiwifruit wine fermentation was isolated and purified, and the fermentation process was optimized to increase the alcohol content of the kiwifruit wine. Pichia kluyveri was isolated from kiwifruit pulp by lineation separating, screened by morphological characteristics in Wallerstein Laboratory Nutrient Agar (WL) medium and microscope observation, and further identified by 26S rDNA D1/D2 domain sequence analysis. Taking alcohol content and sensory evaluation as two indexes, the fermentation condition for kiwifruit wine was optimized by single factor and response surface experiment. The optimal fermentation conditions were optimized as follows: the fermentation temperature was at 24 °C, the initial pH was 3.8, the sugar dosage in second step was 8% (w/w), and the inoculating quantity of Pichia kluyveri and Saccharomyces cerevisiae was 0.15 g/L at equal proportion. Under these optimal conditions, the maximum estimated alcohol content was 15.6 vol%, and the kiwifruit wine was light green in color with strong kiwifruit aroma and mellow taste. Full article
(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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14 pages, 6095 KiB  
Article
Identification and Free Radical Scavenging Activity of Oligopeptides from Mixed-Distillate Fermented Baijiu Grains and Soy Sauce Residue
by Yunhao Zhao, Xiangyue Liu, Sijie Zhang, Zhengwei Wang, Shanlin Tian and Qiang Wu
Metabolites 2024, 14(6), 298; https://doi.org/10.3390/metabo14060298 - 24 May 2024
Cited by 4 | Viewed by 1464
Abstract
This study aimed to explore the potential antioxidant activity and mechanism of oligopeptides from sauce-aroma Baijiu. The oligopeptides of Val-Leu-Pro-Phe (VLPF), Pro-Leu-Phe (PLF), Val-Gly-Phe-Cys (VGFC), Leu-Tyr-Pro (LYP), Leu-Pro-Phe (LPF), and Phe-Thr-Phe (FTF) were identified by liquid chromatography–mass spectrometry (LC–MS) from the mixed-distillate of [...] Read more.
This study aimed to explore the potential antioxidant activity and mechanism of oligopeptides from sauce-aroma Baijiu. The oligopeptides of Val-Leu-Pro-Phe (VLPF), Pro-Leu-Phe (PLF), Val-Gly-Phe-Cys (VGFC), Leu-Tyr-Pro (LYP), Leu-Pro-Phe (LPF), and Phe-Thr-Phe (FTF) were identified by liquid chromatography–mass spectrometry (LC–MS) from the mixed-distillate of Baijiu fermented grains and soy sauce residue (MDFS). The antioxidant mechanism of these oligopeptides on scavenging DPPH•, ABTS•+, and hydroxide radicals was investigated, respectively. Among them, VGFC had the strongest potential antioxidant activity, which was responsible for its hydrogen bonds with these radicals with high affinity. The binding energies between VGFC and these radicals were −1.26 kcal/mol, −1.33 kcal/mol, and −1.93 kcal/mol, respectively. Additionally, free radicals prefer to bind the oligopeptide composed of hydrophobic amino acid residues such as Leu, Val, Phe, and Pro, thus being scavenged for exerting antioxidant activity. It provided a new idea for the development and utilization of bioactive oligopeptides in sauce-aroma Baijiu. Full article
(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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Review

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15 pages, 1023 KiB  
Review
The Functions of Major Gut Microbiota in Obesity and Type 2 Diabetes
by Siman Liu, Zhipeng Tao, Mingyu Qiao and Limin Shi
Metabolites 2025, 15(3), 167; https://doi.org/10.3390/metabo15030167 - 1 Mar 2025
Cited by 1 | Viewed by 833
Abstract
Background: Gut microbiomes play a vital role in maintaining whole-body metabolic homeostasis. It has gained significant attention in recent years due to advancements in genome sequencing technologies and a deeper understanding of its relationship with obesity. However, the specific ways in which different [...] Read more.
Background: Gut microbiomes play a vital role in maintaining whole-body metabolic homeostasis. It has gained significant attention in recent years due to advancements in genome sequencing technologies and a deeper understanding of its relationship with obesity. However, the specific ways in which different microorganisms directly or indirectly influence host obesity, as well as the underlying mechanisms, remain uncertain because of the complexity of gut microbiota composition. Methods: In this review, we summarize the roles of the major gut microbiota phyla such as Bacteroidetes, Firmicutes, Proteobacteria, and Verrucomicrobia in obesity and type 2 diabetes based on studies published in the past five years on PubMed and Google Scholar. The current therapeutic strategies associated with gut microbiota are also explored from clinical trials, and challenges and future directions are discussed. Results and Conclusions: This review will provide a deeper understanding of the functions of major gut microbiota in obesity and type 2 diabetes, which could lead to more individualized and effective treatments for metabolic diseases. Full article
(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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146 pages, 1390 KiB  
Review
Therapeutic Strategies to Modulate Gut Microbial Health: Approaches for Chronic Metabolic Disorder Management
by Mariangela Rondanelli, Sara Borromeo, Alessandro Cavioni, Clara Gasparri, Ilaria Gattone, Elisa Genovese, Alessandro Lazzarotti, Leonardo Minonne, Alessia Moroni, Zaira Patelli, Claudia Razza, Claudia Sivieri, Eugenio Marzio Valentini and Gaetan Claude Barrile
Metabolites 2025, 15(2), 127; https://doi.org/10.3390/metabo15020127 - 13 Feb 2025
Cited by 1 | Viewed by 1195
Abstract
Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between [...] Read more.
Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and metabolic disorders, as well as the role of probiotics in the modulation of the intestinal microbiota. The aim of this review was to summarize the reviews and individual articles on the state of the art regarding ideal therapy with probiotics and prebiotics in order to obtain the reversion of dysbiosis (alteration in microbiota) to eubiosis during metabolic diseases, such as diabetes, prediabetes, obesity, hyperhomocysteinemia, dyslipidemia, sarcopenia, and non-alcoholic fatty liver diseases. This review includes 245 eligible studies. In conclusion, a condition of dysbiosis, or in general, alteration of the intestinal microbiota, could be implicated in the development of metabolic disorders through different mechanisms, mainly linked to the release of pro-inflammatory factors. Several studies have already demonstrated the potential of using probiotics and prebiotics in the treatment of this condition, detecting significant improvements in the specific symptoms of metabolic diseases. These findings reinforce the hypothesis that a condition of dysbiosis can lead to a generalized inflammatory picture with negative consequences on different organs and systems. Moreover, this review confirms that the beneficial effects of probiotics on metabolic diseases are promising, but more research is needed to determine the optimal probiotic strains, doses, and administration forms for specific metabolic conditions. Full article
(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)
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