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Molecular Mechanisms of Bioactive Nutrients Promoting Health Through Gut Microbiota: 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 20 February 2026 | Viewed by 5650

Special Issue Editors

Prof. Dr. Baojun Xu

E-Mail Website
Guest Editor
Food Science and Technology Program, Department of Life Sciences, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China
Interests: phytochemicals; natural products; functional foods; human health
Special Issues, Collections and Topics in MDPI journals
Dr. Matteo Bordiga

E-Mail Website
Guest Editor
Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale “A. Avogadro”, Largo Donegani 2, 28100 Novara, Italy
Interests: food chemistry; gas chromatography; liquid chromatography; mass spectrometry; polyphenols; volatile compounds; wine chemistry; extraction; fermentation; prebiotic compounds
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of the 2020 Special Issue “Molecular Mechanisms of Bioactive Nutrients Promoting Health Through Gut Microbiota” and the 2023 Special Issue “Molecular Mechanisms of Bioactive Nutrients Promoting Health Through Gut Microbiota 2.0”.

It is becoming clear that the human gut microbiota plays a critical role in human health. The human gut microbiota, depending on dietary intake and consequently nutrient availability within the gut, can produce either harmful metabolites, leading to human diseases, or beneficial compounds that protect against host diseases. Abnormal gut microbiota can produce endotoxins, which enhance chronic inflammation and metabolic disorders. Modification of gut microbiota by bioactive food components to balance its compositions has grown to be seen as a promising strategy for the management of colon health and host health. Bioactive components can be obtained from dietary sources designed and characterized to meet human nutritional and immunological needs as well as balance the gut microbiota. The goal of this Special Issue is to collect the latest research findings on the interrelationship among bioactive food components (such as phytochemicals and complex carbohydrates), gut microbiota, colon stem cells, and chronic metabolic diseases. Health benefits of small molecular phytochemicals and large biopolymer polysaccharides have been reported in different disciplines; however, it is not clear how gut microbiota metabolize these dietary phytochemicals and polymers; it is also not clear how the gut metabolites from these dietary compounds further affect the host.

Prof. Dr. Baojun Xu
Dr. Matteo Bordiga
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • phytochemicals
  • complex carbohydrates
  • gut microbiota
  • prebiotics
  • probiotics
  • inflammation
  • molecular mechanisms
  • human health

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Published Papers (3 papers)

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Research

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27 pages, 5846 KB  
Article
Agrocybe cylindracea Polysaccharides Ameliorate DSS-Induced Colitis by Restoring Intestinal Barrier Function and Reprogramming Immune Homeostasis via the Gut–Liver Axis
by Aamna Atta, Muhammad Naveed, Mujeeb Ur Rahman, Yamina Alioui, Immad Ansari, Sharafat Ali, Eslam Ghaleb, Nabeel Ahmed Farooqui, Mohammad Abusidu, Yi Xin and Bin Feng
Int. J. Mol. Sci. 2025, 26(14), 6805; https://doi.org/10.3390/ijms26146805 - 16 Jul 2025
Viewed by 826
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by immune dysregulation, microbiota imbalance, and intestinal barrier dysfunction. Despite its global burden, effective therapies remain limited. This study explores the therapeutic potential of Agrocybe cylindracea polysaccharides (ACP) in a dextran sulfate sodium [...] Read more.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by immune dysregulation, microbiota imbalance, and intestinal barrier dysfunction. Despite its global burden, effective therapies remain limited. This study explores the therapeutic potential of Agrocybe cylindracea polysaccharides (ACP) in a dextran sulfate sodium (DSS)-induced murine colitis model. High-performance liquid chromatography (HPLC)-characterized ACP was administered orally to BALB/c mice following colitis induction. ACP treatment significantly reduced Disease Activity Index (DAI) scores, preserved colon length, and restored intestinal barrier integrity by upregulating tight junction proteins. Mechanistically, ACP modulated immune homeostasis, suppressing pro-inflammatory cytokines (IL-17, IL-23, CRP) while enhancing anti-inflammatory mediators (IL-4, TGF-β). Furthermore, ACP inhibited hepatic TLR4/MyD88/NF-κB signaling, attenuated systemic inflammation, and reshaped gut microbiota composition by enriching beneficial taxa and reducing pathogenic Bacteroides. These findings demonstrate ACP multi-target efficacy in colitis, positioning it as a promising natural therapeutic for UC. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Health Through Gut Microbiota: 3rd Edition)
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18 pages, 1517 KB  
Article
A Randomized Controlled Trial Evaluating the Effects of a Probiotic Containing Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on Gastrointestinal Symptoms and Metabolomic Profiles in Female Dancers
by Jakub Wiącek, Karolina Skonieczna-Żydecka, Igor Łoniewski, Daniel Styburski, Mariusz Kaczmarczyk and Joanna Karolkiewicz
Int. J. Mol. Sci. 2025, 26(12), 5823; https://doi.org/10.3390/ijms26125823 - 18 Jun 2025
Viewed by 3583
Abstract
Dancers experience physical and psychological stressors that can impact gut health. We hypothesized that a three-month supplementation with Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 would result in measurable alterations in the fecal metabolomic profile and improve gastrointestinal symptomatology in dancers. Of the [...] Read more.
Dancers experience physical and psychological stressors that can impact gut health. We hypothesized that a three-month supplementation with Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 would result in measurable alterations in the fecal metabolomic profile and improve gastrointestinal symptomatology in dancers. Of the 51 volunteers, 26 female dancers were randomized to a 12-week trial (NCT05567653). A homogenous group of 16 (probiotic: n = 5; placebo: n = 11) was analyzed. The participants received L. helveticus R0052 and B. longum R0175 (3 × 109 colony-forming units/day) or a placebo. Baseline dietary intake and body composition were recorded. Fecal samples were analyzed using liquid chromatography–mass spectrometry, and gastrointestinal symptoms were assessed with the Rome IV questionnaire. Statistical methods included principal component analysis, mixed-effects models, and analysis of variance–simultaneous component analysis (ASCA). The study revealed shifts in the probiotic group’s fecal metabolome (permutation test p = 0.026), including a reduction in (2RS)-2-(4-hydroxyphenyl)propionic acid (p = 0.023). No improvement in gastrointestinal symptoms was observed. No adverse events occurred. L. helveticus R0052 and B. longum R0175 may alter the gut metabolome, notably (2RS)-2-(4-hydroxyphenyl)propionic acid, but small sample size and absent symptom improvement limit the conclusions. Larger studies with varied doses and blood metabolite analysis are needed to confirm relevance. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Health Through Gut Microbiota: 3rd Edition)
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Review

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45 pages, 2358 KB  
Review
A Comprehensive Review of the Triangular Relationship Among Diet, Gut Microbiota, and Aging
by Chapa Ramasinghe, Matteo Bordiga and Baojun Xu
Int. J. Mol. Sci. 2025, 26(18), 8785; https://doi.org/10.3390/ijms26188785 - 9 Sep 2025
Viewed by 572
Abstract
Aging is a complex biological process influenced by internal and external factors, with diet and gut microbiota emerging as pivotal, interconnected modulators. This review explores their triangular relationship, emphasizing how they dynamically interact to shape health across the lifespan. Aging involves notable shifts [...] Read more.
Aging is a complex biological process influenced by internal and external factors, with diet and gut microbiota emerging as pivotal, interconnected modulators. This review explores their triangular relationship, emphasizing how they dynamically interact to shape health across the lifespan. Aging involves notable shifts in gut microbiota, including reduced diversity, increased pro-inflammatory taxa, and impaired production of key metabolites, like short-chain fatty acids. These changes contribute to systemic inflammation, immune-senescence, and age-related conditions, such as cognitive decline and metabolic disorders. Diet, particularly Mediterranean and plant-based patterns, plays a critical role in modulating gut microbiota by enhancing beneficial microbes and their metabolic functions. In contrast, Western-style diets rich in saturated fats and processed foods promote dysbiosis and accelerate aging. The review synthesizes evidence from human studies, animal models, and interventions to show how microbiota mediates diet-driven effects on aging. It also explores the role of specific nutrients, fiber, omega-3 fatty acids, and polyphenols in influencing microbial and host aging biology. Emerging therapies, including probiotics, prebiotics, and precision nutrition, show promise for promoting healthy aging by restoring microbial balance. However, gaps remain, including the need for long-term, age-specific studies, standardized microbiome protocols, and integrated omics approaches to support targeted longevity strategies. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Bioactive Nutrients Promoting Health Through Gut Microbiota: 3rd Edition)
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