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Metabolites
Special Issues
Insights into How Gut Microbial Metabolites Regulate Innate Immune Responses
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Insights into How Gut Microbial Metabolites Regulate Innate Immune Responses

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 7144

Special Issue Editor

Dr. Agnieszka M. Smolinska

E-Mail Website
Guest Editor
1. Department Pharmacology and Toxicology, Maastricht University, 6229ER Maastricht, The Netherlands
2. NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229ER Maastricht, The Netherlands
Interests: volatile metabolite; exhaled breath; fecal headspace analysis; machine learning; gut microbiome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut microbiota and their metabolites have been receiving a lot of attention in terms of their regulatory effects on the immune system in the past decade. Major microbial metabolites include the carbohydrate metabolites short-chain fatty acids, amino acid metabolites, and secondary bile acid metabolites. These metabolites function through host-receptor-dependent and independent mechanisms to regulate cells of the innate immune system, which include epithelial cells, NK cells, innate lymphoid cells, dendritic cells, macrophages, and granulocytes. Major host receptors for these microbial metabolites include G protein-coupled receptors (GPR43, GPR41, GPR109A, Olfr78 and TGR5) for fast regulatory actions in the cytoplasm and nuclear receptors (PXR, LXR, VDR, and FXR) and other receptors such as aryl hydrocarbon receptor (AHR) for gene expression regulation in the nucleus. Recent advances indicate that these metabolites regulate innate immunity, host metabolism, inflammation, cancer, tissue repair and even regulation of adaptive immune responses.

Despite the recent advances in this area, I feel that we have only scratched the surface so far of the important functions of these metabolites in the immune system and host physiology. This special issue of Metabolites will be dedicated for publishing current advances on the functions of gut microbial metabolites in regulating the innate immune system, which encompasses not only immune cells but also barrier tissue cells.

Dr. Agnieszka M. Smolinska
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. 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

  • Microbial metabolites
  • Short-chain fatty acids
  • Tryptophan metabolites
  • Secondary bile acid metabolites
  • Epithelial cells
  • Dendritic cells
  • Innate lymphoid cells
  • NK cells
  • Macrophages
  • Inflammation
  • Infection
  • Barrier function
  • Wound repair
  • Metabolism
  • Cancer

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Published Papers (2 papers)

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19 pages, 5605 KiB  
Article
Flavin-Containing Monooxygenase 3 (FMO3) Is Critical for Dioxin-Induced Reorganization of the Gut Microbiome and Host Insulin Sensitivity
by William Massey, Lucas J. Osborn, Rakhee Banerjee, Anthony Horak, Kevin K. Fung, Danny Orabi, E. Ricky Chan, Naseer Sangwan, Zeneng Wang and J. Mark Brown
Metabolites 2022, 12(4), 364; https://doi.org/10.3390/metabo12040364 - 18 Apr 2022
Cited by 7 | Viewed by 3940
Abstract
Exposure to some environmental pollutants can have potent endocrine-disrupting effects, thereby promoting hormone imbalance and cardiometabolic diseases such as non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiorenal diseases. Recent evidence also suggests that many environmental pollutants can reorganize the gut microbiome to potentially [...] Read more.
Exposure to some environmental pollutants can have potent endocrine-disrupting effects, thereby promoting hormone imbalance and cardiometabolic diseases such as non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiorenal diseases. Recent evidence also suggests that many environmental pollutants can reorganize the gut microbiome to potentially impact these diverse human diseases. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most potent endocrine-disrupting dioxin pollutants, yet our understanding of how TCDD impacts the gut microbiome and systemic metabolism is incompletely understood. Here, we show that TCDD exposure in mice profoundly stimulates the hepatic expression of flavin-containing monooxygenase 3 (Fmo3), which is a hepatic xenobiotic metabolizing enzyme that is also responsible for the production of the gut microbiome-associated metabolite trimethylamine N-oxide (TMAO). Interestingly, an enzymatic product of FMO3 (TMAO) has been associated with the same cardiometabolic diseases that these environmental pollutants promote. Therefore, here, we examined TCDD-induced alterations in the gut microbiome, host liver transcriptome, and glucose tolerance in Fmo3+/+ and Fmo3−/− mice. Our results show that Fmo3 is a critical component of the transcriptional response to TCDD, impacting the gut microbiome, host liver transcriptome, and systemic glucose tolerance. Collectively, this work uncovers a previously underappreciated role for Fmo3 in integrating diet–pollutant–microbe–host interactions. Full article
(This article belongs to the Special Issue Insights into How Gut Microbial Metabolites Regulate Innate Immune Responses)
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25 pages, 2241 KiB  
Systematic Review
Systematic Review: Contribution of the Gut Microbiome to the Volatile Metabolic Fingerprint of Colorectal Neoplasia
by Robert van Vorstenbosch, Hao Ran Cheng, Daisy Jonkers, John Penders, Erik Schoon, Ad Masclee, Frederik-Jan van Schooten, Agnieszka Smolinska and Zlatan Mujagic
Metabolites 2023, 13(1), 55; https://doi.org/10.3390/metabo13010055 - 30 Dec 2022
Cited by 17 | Viewed by 2555
Abstract
Colorectal cancer (CRC) has been associated with changes in volatile metabolic profiles in several human biological matrices. This enables its non-invasive detection, but the origin of these volatile organic compounds (VOCs) and their relation to the gut microbiome are not yet fully understood. [...] Read more.
Colorectal cancer (CRC) has been associated with changes in volatile metabolic profiles in several human biological matrices. This enables its non-invasive detection, but the origin of these volatile organic compounds (VOCs) and their relation to the gut microbiome are not yet fully understood. This systematic review provides an overview of the current understanding of this topic. A systematic search using PubMed, Embase, Medline, Cochrane Library, and the Web of Science according to PRISMA guidelines resulted in seventy-one included studies. In addition, a systematic search was conducted that identified five systematic reviews from which CRC-associated gut microbiota data were extracted. The included studies analyzed VOCs in feces, urine, breath, blood, tissue, and saliva. Eight studies performed microbiota analysis in addition to VOC analysis. The most frequently reported dysregulations over all matrices included short-chain fatty acids, amino acids, proteolytic fermentation products, and products related to the tricarboxylic acid cycle and Warburg metabolism. Many of these dysregulations could be related to the shifts in CRC-associated microbiota, and thus the gut microbiota presumably contributes to the metabolic fingerprint of VOC in CRC. Future research involving VOCs analysis should include simultaneous gut microbiota analysis. Full article
(This article belongs to the Special Issue Insights into How Gut Microbial Metabolites Regulate Innate Immune Responses)
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