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Gut Microbiota-Derived Metabolites in Human Health and Disease

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

Deadline for manuscript submissions: 30 April 2026 | Viewed by 1339

Special Issue Editor


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Guest Editor
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
Interests: microbiome; cardiovascular research; analytical biochemistry; mass spectrometry; metabolomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut microbiota, composed of trillions of microorganisms residing in the human gut, are often regarded as a “virtual organ” with extensive digestive, metabolic, and endocrine functions. They play a pivotal role in maintaining health but can also contribute to the onset and progression of disease. Many of these effects are mediated through metabolites produced by gut microbes, which influence diverse aspects of human physiology and pathology. Continued investigation of these metabolites will provide a strong theoretical foundation for strategies to promote human health.

The Special Issue, “Gut Microbiota-Derived Metabolites in Human Health and Disease”, aims to stimulate comprehensive research that adopts a holistic perspective. We welcome articles on topics including the biosynthesis of gut microbiota-derived metabolites (such as specific bacterial strains, relevant substrates, and regulatory strategies) as well as the roles of these metabolites in chronic diseases, ranging from inflammatory bowel disease and cardiovascular disorders to neurodegenerative conditions.

Dr. Zeneng Wang
Guest Editor

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Keywords

  • microbiome
  • microbiota
  • gut
  • metabolomics
  • health
  • disease
  • inflammation

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Published Papers (2 papers)

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Research

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26 pages, 1872 KB  
Article
A Combined Probiotic-Morus alba Strategy Enhances Glucose Homeostasis in an In Vitro Gut-Pancreas-Liver Axis Model: A Preliminary Mechanistic Screening Study
by Francesca Parini, Rebecca Galla, Simone Mulè, Matteo Musu and Francesca Uberti
Int. J. Mol. Sci. 2026, 27(5), 2375; https://doi.org/10.3390/ijms27052375 - 4 Mar 2026
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Abstract
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder linked to gut microbiota dysbiosis and impaired inter-organ metabolic signalling. This study investigated the combined effects of the probiotic Lactiplantibacillus plantarum TJA7 and Mulberry Leaf extract (Morus alba) on cellular processes [...] Read more.
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder linked to gut microbiota dysbiosis and impaired inter-organ metabolic signalling. This study investigated the combined effects of the probiotic Lactiplantibacillus plantarum TJA7 and Mulberry Leaf extract (Morus alba) on cellular processes relevant to T2DM-related metabolic dysfunction. An advanced in vitro gut–pancreas–liver axis model, using Caco-2, EndoC-βH5, and HepG2 cells, was employed under hyperglycemic and oxidative stress conditions. The combined treatment consistently outperformed the individual components by improving intestinal barrier integrity, as indicated by increased transepithelial electrical resistance (TEER), and by enhancing butyrate translocation across the intestinal layer. Metabolites derived from the combination attenuated pancreatic β-cell dysfunction, reducing reactive oxygen species (ROS) levels and increased insulin secretion (1.7-fold compared with Mulberry Leaf extract alone). At the hepatic level, co-administration modulated key glucose metabolism pathways, including Insulin Receptor Substrate 1 (IRS1), Protein Kinase B (AKT), AMP-Activated Protein Kinase (AMPK), and Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha (PGC-1α), suggesting improved cellular glucose handling. Collectively, these findings support a positive dose-specific interaction under the tested conditions and provide a biologically plausible, hypothesis-generating framework for probiotic–phytochemical cooperation along the gut–pancreas–liver axis. Further in vivo and clinical studies are required to establish causality and translational relevance. Full article
(This article belongs to the Special Issue Gut Microbiota-Derived Metabolites in Human Health and Disease)
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Review

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16 pages, 768 KB  
Review
Anticancer Potential of Lacticaseibacillus rhamnosus in Colorectal Cancer—A Systematic Review of In Vitro Cell Culture Evidence
by Arshiya Nasreen Bint Shajahan, Sakina Mustafa Vakhariya, Malak Moones Abedi, Syeda Nishaat Fatima, Liyan Khadeeja, Elham Hassan Nazari Fard, Abshina Shajahan, Vijaya Paul Samuel, Grisilda Vidya Bernhardt and Suresh Kumar Srinivasamurthy
Int. J. Mol. Sci. 2026, 27(7), 2944; https://doi.org/10.3390/ijms27072944 - 24 Mar 2026
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Abstract
This systematic review aimed to synthesize experimental evidence on the anticancer effects of Lacticaseibacillus rhamnosus (L. rhamnosus) and its derivatives against colorectal cancer (CRC) cell models. Eligible studies investigated probiotics, postbiotics, or bioactive compounds derived from L. rhamnosus with an in [...] Read more.
This systematic review aimed to synthesize experimental evidence on the anticancer effects of Lacticaseibacillus rhamnosus (L. rhamnosus) and its derivatives against colorectal cancer (CRC) cell models. Eligible studies investigated probiotics, postbiotics, or bioactive compounds derived from L. rhamnosus with an in vitro component; studies relying solely on in vivo animal models, clinical trials, or observational designs were excluded. PubMed and Scopus were searched to identify relevant studies. Risk of bias was assessed using a modified QUIN tool, and extracted data were tabulated. Owing to incomplete numerical data, meta-analysis was not feasible, and the results were synthesized accordingly. Seventeen studies were included. L. rhamnosus and its derivatives reduced CRC cell proliferation, induced apoptosis, and caused cell cycle arrest. Reported mechanisms included upregulation of Bax, caspase-3/9, and p53; downregulation of Bcl-2/Bcl-xl; inhibition of Wnt/β-catenin signaling; reduced invasion and migration; increased reactive oxygen species; and immunomodulatory effects. Key limitations were heterogeneity in interventions, dosages, exposure periods, and cell lines, along with incomplete reporting, which precluded quantitative synthesis. Overall, preclinical evidence indicates multimodal anticancer effects of L. rhamnosus in CRC models; however, standardized reporting and translational research are required. Full article
(This article belongs to the Special Issue Gut Microbiota-Derived Metabolites in Human Health and Disease)
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