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New Insights into the Effects of Microbiome-Derived Metabolites on Health and Disease

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

Deadline for manuscript submissions: 20 July 2025 | Viewed by 9713

Special Issue Editor


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Guest Editor
Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Pawinskiego 3c Street, 02-106 Warsaw, Poland
Interests: bacterial metabolites; short-chain fatty acids; trimethylamine N-oxide; gut microbiome; molecular pathways; intestinal barrier

Special Issue Information

Dear Colleagues,

The biological impacts of molecules derived from gut bacteria are apparent in diverse tissues, constituting a crucial facet of the gut microbiome’s impact on our health. Metabolites such as short-chain fatty acids, methylamines, and various others intricately modulate carbohydrate metabolism and cardiovascular homeostasis and influence the course of numerous diseases. Furthermore, factors such as gut–blood barrier permeability, liver metabolism, and kidney clearance may influence metabolite concentrations, thereby limiting their effects.

This Special Issue endeavours to establish a platform for research on the molecular biological effects of bacterial metabolites and the pathways responsible for these impacts. Additionally, we extend an invitation for studies elucidating disease-associated mechanisms that shape the manifestations of bacterial metabolites.

Dr. Kinga Jaworska
Guest Editor

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Keywords

  • bacterial metabolites
  • short-chain fatty acids
  • trimethylamine N-oxide
  • gut microbiome
  • molecular pathways
  • intestinal barrier

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Published Papers (5 papers)

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Research

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25 pages, 8696 KiB  
Article
Effects of Deoxynivalenol Contamination on Growth Performance, Blood Biochemistry, Histology, Metabolomics, and the Microbiota: A Subacute Dose Oral Toxicity Study in Rats
by Jinyoung Jeong, Junsik Kim, Minji Kim, Boram Lee, Cheolju Park and Minseok Kim
Int. J. Mol. Sci. 2025, 26(7), 3086; https://doi.org/10.3390/ijms26073086 - 27 Mar 2025
Cited by 1 | Viewed by 380
Abstract
Deoxynivalenol (DON), one of the most common mycotoxins, is frequently found in foods. This study investigated the effects of orally administered DON on the blood biochemical parameters, growth performance, histology, microbial composition, and metabolism of rats. After a 1-week adaptation period, 4-week-old rats [...] Read more.
Deoxynivalenol (DON), one of the most common mycotoxins, is frequently found in foods. This study investigated the effects of orally administered DON on the blood biochemical parameters, growth performance, histology, microbial composition, and metabolism of rats. After a 1-week adaptation period, 4-week-old rats were administered 0.9% saline (control), 1 mg/L DON (T1), 10 mg/L DON (T2), or 50 mg/L DON (T3) by gavage for 49 days. The DON-treated groups had significantly lower body weights than the control group (p < 0.05). Blood alkaline phosphatase, phosphate, cholesterol, amylase, and creatinine levels differed significantly between the DON-treated and control groups (p < 0.05). With increasing DON doses, fibrosis and apoptosis were observed in several tissues. In terms of metabolites, the bile acid biosynthesis pathway emerged as a potential biomarker, while the tryptophan metabolism pathway was found to be the most affected. The fecal microbiota showed significant differences in both alpha and beta diversity between the DON-treated and control groups (p < 0.05). In the cecal and fecal microbiota, the relative abundance of Firmicutes increased in the control and T1 groups, whereas Bacteroidota and Campylobacterota were more abundant in the T2 and T3 groups. In conclusion, our results showed that high DON exposure induces several dose-dependent adverse effects on rats. Full article
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15 pages, 4199 KiB  
Article
Exposure of Colon-Derived Epithelial Monolayers to Fecal Luminal Factors from Patients with Colon Cancer and Ulcerative Colitis Results in Distinct Gene Expression Patterns
by Maria K. Magnusson, Anna Bas Forsberg, Alexandra Verveda, Maria Sapnara, Julie Lorent, Otto Savolainen, Yvonne Wettergren, Hans Strid, Magnus Simrén and Lena Öhman
Int. J. Mol. Sci. 2024, 25(18), 9886; https://doi.org/10.3390/ijms25189886 - 13 Sep 2024
Viewed by 1427
Abstract
Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) [...] Read more.
Microbiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) on the colonic epithelium using a standardized colon-derived two-dimensional epithelial monolayer. The complex primary human stem cell-derived intestinal epithelium model, termed RepliGut® Planar, was expanded and passaged in a two-dimensional culture which underwent stimulation for 48 h with fecal supernatants (FS) from CC patients (n = 6), UC patients with active disease (n = 6), and healthy subjects (HS) (n = 6). mRNA sequencing of monolayers was performed and cytokine secretion in the basolateral cell culture compartment was measured. The addition of fecal supernatants did not impair the integrity of the colon-derived epithelial monolayer. However, monolayers stimulated with fecal supernatants from CC patients and UC patients presented distinct gene expression patterns. Comparing UC vs. CC, 29 genes were downregulated and 33 genes were upregulated, for CC vs. HS, 17 genes were downregulated and five genes were upregulated, and for UC vs. HS, three genes were downregulated and one gene was upregulated. The addition of FS increased secretion of IL8 with no difference between the study groups. Fecal luminal factors from CC patients and UC patients induce distinct colonic epithelial gene expression patterns, potentially reflecting the disease pathophysiology. The culture of colonic epithelial monolayers with fecal supernatants derived from patients may facilitate the exploration of IBD- and CC-related intestinal microenvironmental and barrier interactions. Full article
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Review

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17 pages, 925 KiB  
Review
Microbiome-Derived Trimethylamine N-Oxide (TMAO) as a Multifaceted Biomarker in Cardiovascular Disease: Challenges and Opportunities
by Kinga Jaworska, Wojciech Kopacz, Mateusz Koper and Marcin Ufnal
Int. J. Mol. Sci. 2024, 25(23), 12511; https://doi.org/10.3390/ijms252312511 - 21 Nov 2024
Viewed by 2037
Abstract
Biomarkers play a crucial role in various stages of disease management, including screening, diagnosis, prediction, prognosis, treatment, and safety monitoring. Although they are powerful tools in disease diagnosis, management, and drug development, identifying and validating reliable biomarkers remains a significant challenge. Among potential [...] Read more.
Biomarkers play a crucial role in various stages of disease management, including screening, diagnosis, prediction, prognosis, treatment, and safety monitoring. Although they are powerful tools in disease diagnosis, management, and drug development, identifying and validating reliable biomarkers remains a significant challenge. Among potential microbiome-derived biomarkers, trimethylamine N-oxide (TMAO) has gained notable attention for its link to atherosclerosis and cardiovascular risk. However, despite the growing body of research on TMAO, its practical application in clinical settings for disease management and patient outcome enhancement is still not a reality. This paper presents recent data on the utility of TMAO as a cardiovascular biomarker, categorized by its various roles: diagnostic, prognostic, susceptibility/risk, monitoring, pharmacodynamic/response, predictive, and safety. It also briefly discusses research on TMAO’s potential role in cardiovascular disease development. While TMAO shows promise, particularly in prognostic applications, its reliability as a biomarker has been inconsistent across studies. These variances may result from several confounding factors that affect TMAO plasma levels, including diet, kidney function, and demographic variables. The review aims to elucidate the specific contexts in which TMAO can be valuable, potentially leading to more personalized and effective management of cardiovascular disease. Full article
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24 pages, 343 KiB  
Review
The Microbiome–Genetics Axis in Autism Spectrum Disorders: A Probiotic Perspective
by Marija Mihailovich, Maja Tolinački, Svetlana Soković Bajić, Sanja Lestarevic, Milica Pejovic-Milovancevic and Nataša Golić
Int. J. Mol. Sci. 2024, 25(22), 12407; https://doi.org/10.3390/ijms252212407 - 19 Nov 2024
Cited by 3 | Viewed by 2365
Abstract
Autism spectrum disorder (commonly known as autism) is a complex and prevalent neurodevelopmental condition characterized by challenges in social behavior, restricted interests, and repetitive behaviors. It is projected that the annual cost of autism spectrum disorder in the US will reach USD 461 [...] Read more.
Autism spectrum disorder (commonly known as autism) is a complex and prevalent neurodevelopmental condition characterized by challenges in social behavior, restricted interests, and repetitive behaviors. It is projected that the annual cost of autism spectrum disorder in the US will reach USD 461 billion by 2025. However, despite being a major public health problem, effective treatment for the underlying symptoms remains elusive. As numerous literature data indicate the role of gut microbiota in autism prognosis, particularly in terms of alleviating gastrointestinal (GI) symptoms, high hopes have been placed on probiotics for autism treatment. Approximately twenty clinical studies have been conducted using single or mixed probiotic cultures. However, unequivocal results on the effect of probiotics on people with autism have not been obtained. The small sample sizes, differences in age of participants, choice of probiotics, dose and duration of treatment, outcome measures, and analytical methods used are largely inconsistent, making it challenging to draw distinctive conclusions. Here, we discuss the experimental evidence for specific gut bacteria and their metabolites and how they affect autism in light of the phenotypic and etiological complexity and heterogeneity. We propose a personalized medicine approach for using probiotics to increase the quality of life of individuals with autism by selecting specific probiotics to improve particular features of the condition. Full article
25 pages, 1511 KiB  
Review
Cutting-Edge iPSC-Based Approaches in Studying Host—Microbe Interactions in Neuropsychiatric Disorders
by Marija Mihailovich, Svetlana Soković Bajić, Miroslav Dinić, Jelena Đokić, Milica Živković, Dušan Radojević and Nataša Golić
Int. J. Mol. Sci. 2024, 25(18), 10156; https://doi.org/10.3390/ijms251810156 - 21 Sep 2024
Cited by 2 | Viewed by 2340
Abstract
Gut microbiota (GM), together with its metabolites (such as SCFA, tryptophan, dopamine, GABA, etc.), plays an important role in the functioning of the central nervous system. Various neurological and psychiatric disorders are associated with changes in the composition of GM and their metabolites, [...] Read more.
Gut microbiota (GM), together with its metabolites (such as SCFA, tryptophan, dopamine, GABA, etc.), plays an important role in the functioning of the central nervous system. Various neurological and psychiatric disorders are associated with changes in the composition of GM and their metabolites, which puts them in the foreground as a potential adjuvant therapy. However, the molecular mechanisms behind this relationship are not clear enough. Therefore, before considering beneficial microbes and/or their metabolites as potential therapeutics for brain disorders, the mechanisms underlying microbiota–host interactions must be identified and characterized in detail. In this review, we summarize the current knowledge of GM alterations observed in prevalent neurological and psychiatric disorders, multiple sclerosis, major depressive disorder, Alzheimer’s disease, and autism spectrum disorders, together with experimental evidence of their potential to improve patients’ quality of life. We further discuss the main obstacles in the study of GM–host interactions and describe the state-of-the-art solution and trends in this field, namely “culturomics” which enables the culture and identification of novel bacteria that inhabit the human gut, and models of the gut and blood–brain barrier as well as the gut–brain axis based on induced pluripotent stem cells (iPSCs) and iPSC derivatives, thus pursuing a personalized medicine agenda for neuropsychiatric disorders. Full article
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