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The Interplay of Microbiome and Immune Response in Health and Diseases 3.0

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: closed (15 July 2023) | Viewed by 13535

Special Issue Editor

Dr. Amedeo Amedei

E-Mail Website
Guest Editor
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
Interests: microbiota-immunity axis; autoimmunity; cancers; inflammation; T cells; micro and nanoplastic effects on human
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Increasing evidence suggests that microbiota plays a key role in human physiology, spanning from intestinal to brain activities and directly influencing several molecular pathways. Recent findings indicate how dysbiosis, a disproportion in the composition and organization of microbial populations, could severely impact in the development of different medical conditions (from metabolic to mood disorders), providing new insight for the comprehension of diverse diseases, such as IBD, obesity, asthma, autism spectrum disorders, stroke, diabetes, and cancer. Given that microbial cells in the gut outnumber cells of the host, microbiota influences human physiology functionally and structurally. Microbial metabolites bridge various, even distant, areas of the organism, by way of the immune and hormone system. For instance, it is now clear that the mutual interaction between the gastrointestinal tract and the brain, the so called gut-brain axis, often involves gut microbiota, indicating that the crosstalk between the organism and its microbial residents represents a fundamental aspect of both establishment and maintenance of healthy conditions. Moreover it is crucial to recognize that microbiota is not localized only in the gut. Both commensal and pathogenic organisms populate, beyond the intestinal tract, other organs and tissues (e.g., skin and oral mucosa) of the “host”. This Special Issue will be dedicated to the impact of microbiota on human health physiology and pathology, welcoming all those studies that will help to clarify how microorganisms interact with their hosts, if there are tissue-specific interactions and what are the effects of their presence, absence or imbalance.

Dr. Amedeo Amedei
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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • dysbiosis
  • inflammatory
  • immune system
  • gut-brain axis
  • probiotics
  • microbial metabolites

Published Papers (4 papers)

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Research

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17 pages, 1687 KiB  
Article
Exploratory Transcriptomic Profiling Reveals the Role of Gut Microbiota in Vascular Dementia
by Navdeep Kaur, Geneva LaForce, Deepthi P. Mallela, Prasenjit Prasad Saha, Jennifer Buffa, Xinmin S. Li, Naseer Sangwan, Kasia Rothenberg and Weifei Zhu
Int. J. Mol. Sci. 2023, 24(9), 8091; https://doi.org/10.3390/ijms24098091 - 30 Apr 2023
Cited by 1 | Viewed by 2173
Abstract
Stroke is the second most common cause of cognitive impairment and dementia. Vascular dementia (VaD), a cognitive impairment following a stroke, is common and significantly impacts the quality of life. We recently demonstrated via gut microbe transplant studies that the gut microbe-dependent trimethylamine-N-oxide [...] Read more.
Stroke is the second most common cause of cognitive impairment and dementia. Vascular dementia (VaD), a cognitive impairment following a stroke, is common and significantly impacts the quality of life. We recently demonstrated via gut microbe transplant studies that the gut microbe-dependent trimethylamine-N-oxide (TMAO) pathway impacts stroke severity, both infarct size and long-term cognitive outcomes. However, the molecular mechanisms that underly the role of the microbiome in VaD have not been explored in depth. To address this issue, we performed a comprehensive RNA-sequencing analysis to identify differentially expressed (DE) genes in the ischemic cerebral cortex of mouse brains at pre-stroke and post-stroke day 1 and day 3. A total of 4016, 3752 and 7861 DE genes were identified at pre-stroke and post-stroke day 1 and day 3, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated pathways of neurodegeneration in multiple diseases, chemokine signaling, calcium signaling, and IL-17 signaling as the key enriched pathways. Inflammatory response genes interleukin-1 beta (Il-1β), chemokines (C–X–C motif chemokine ligand 10 (Cxcl10), chemokine ligand 2 (Ccl2)), and immune system genes (S100 calcium binding protein 8 (S100a8), lipocalin-2 (Lcn2)) were among the most significantly upregulated genes. Hypocretin neuropeptide precursor (Hcrt), a neuropeptide, and transcription factors such as neuronal PAS domain protein 4 (Npas4), GATA binding protein 3 (Gata3), and paired box 7 (Pax7) were among the most significantly downregulated genes. In conclusion, our results indicate that higher plasma TMAO levels induce differential mRNA expression profiles in the ischemic brain tissue in our pre-clinical stroke model, and the predicted pathways provide the molecular basis for regulating the TMAO-enhanced neuroinflammatory response in the brain. Full article
(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases 3.0)
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17 pages, 3527 KiB  
Article
Gut Microbiome and Metabolome Modulation by Maternal High-Fat Diet and Thermogenic Challenge
by Henry A. Paz, Anna-Claire Pilkington, Ying Zhong, Sree V. Chintapalli, James Sikes, Renny S. Lan, Kartik Shankar and Umesh D. Wankhade
Int. J. Mol. Sci. 2022, 23(17), 9658; https://doi.org/10.3390/ijms23179658 - 25 Aug 2022
Cited by 1 | Viewed by 2163
Abstract
The gut microbiota plays a critical role in energy homeostasis and its dysbiosis is associated with obesity. Maternal high-fat diet (HFD) and β-adrenergic stimuli alter the gut microbiota independently; however, their collective regulation is not clear. To investigate the combined effect of these [...] Read more.
The gut microbiota plays a critical role in energy homeostasis and its dysbiosis is associated with obesity. Maternal high-fat diet (HFD) and β-adrenergic stimuli alter the gut microbiota independently; however, their collective regulation is not clear. To investigate the combined effect of these factors on offspring microbiota, 20-week-old offspring from control diet (17% fat)- or HFD (45% fat)-fed dams received an injection of either vehicle or β3-adrenergic agonist CL316,243 (CL) for 7 days and then cecal contents were collected for bacterial community profiling. In a follow-up study, a separate group of mice were exposed to either 8 °C or 30 °C temperature for 7 days and blood serum and cecal contents were used for metabolome profiling. Both maternal diet and CL modulated the gut bacterial community structure and predicted functional profiles. Particularly, maternal HFD and CL increased the Firmicutes/Bacteroidetes ratio. In mice exposed to different temperatures, the metabolome profiles clustered by treatment in both the cecum and serum. Identified metabolites were enriched in sphingolipid and amino acid metabolism in the cecum and in lipid and energy metabolism in the serum. In summary, maternal HFD altered offspring’s response to CL and altered microbial composition and function. An independent experiment supported the effect of thermogenic challenge on the bacterial function through metabolome change. Full article
(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases 3.0)
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Review

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26 pages, 1147 KiB  
Review
Implication of the Gut Microbiome and Microbial-Derived Metabolites in Immune-Related Adverse Events: Emergence of Novel Biomarkers for Cancer Immunotherapy
by David Dora, Syeda Mahak Zahra Bokhari, Kenan Aloss, Peter Takacs, Juliane Zsuzsanna Desnoix, György Szklenárik, Patrick Deniz Hurley and Zoltan Lohinai
Int. J. Mol. Sci. 2023, 24(3), 2769; https://doi.org/10.3390/ijms24032769 - 01 Feb 2023
Cited by 8 | Viewed by 4579
Abstract
Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy have become the standard of care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, the mechanism of action [...] Read more.
Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy have become the standard of care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, the mechanism of action of immune checkpoint inhibitors (ICIs) exposes a new toxicity profile known as immune-related adverse effects (irAEs). This novel toxicity can damage any organ, but the skin, digestive and endocrine systems are the most frequently afflicted. Most ICI-attributed toxicity symptoms are mild, but some are severe and necessitate multidisciplinary side effect management. Obtaining knowledge on the various forms of immune-related toxicities and swiftly changing treatment techniques to lower the probability of experiencing severe irAEs has become a priority in oncological care. In recent years, there has been a growing understanding of an intriguing link between the gut microbiome and ICI outcomes. Multiple studies have demonstrated a connection between microbial metagenomic and metatranscriptomic patterns and ICI efficacy in malignant melanoma, lung and colorectal cancer. The immunomodulatory effect of the gut microbiome can have a real effect on the biological background of irAEs as well. Furthermore, specific microbial signatures and metabolites might be associated with the onset and severity of toxicity symptoms. By identifying these biological factors, novel biomarkers can be used in clinical practice to predict and manage potential irAEs. This comprehensive review aims to summarize the clinical aspects and biological background of ICI-related irAEs and their potential association with the gut microbiome and metabolome. We aim to explore the current state of knowledge on the most important and reliable irAE-related biomarkers of microbial origin and discuss the intriguing connection between ICI efficacy and toxicity. Full article
(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases 3.0)
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17 pages, 1432 KiB  
Review
Gut Microbial-Derived Metabolites as Immune Modulators of T Helper 17 and Regulatory T Cells
by Laura Calvo-Barreiro, Longfei Zhang, Somaya A. Abdel-Rahman, Shivani Paritosh Naik and Moustafa Gabr
Int. J. Mol. Sci. 2023, 24(2), 1806; https://doi.org/10.3390/ijms24021806 - 16 Jan 2023
Cited by 10 | Viewed by 3665
Abstract
The gut microbiota and its derived metabolites greatly impact the host immune system, both innate and adaptive responses. Gut dysbiosis and altered levels of microbiota-derived metabolites have been described in several immune-related and immune-mediated diseases such as intestinal bowel disease, multiple sclerosis, or [...] Read more.
The gut microbiota and its derived metabolites greatly impact the host immune system, both innate and adaptive responses. Gut dysbiosis and altered levels of microbiota-derived metabolites have been described in several immune-related and immune-mediated diseases such as intestinal bowel disease, multiple sclerosis, or colorectal cancer. Gut microbial-derived metabolites are synthesized from dietary compounds ingested by the host or host-produced metabolites, and additionally, some bacterial products can be synthesized de novo. In this review, we focus on the two first metabolites families including short-chain fatty acids, indole metabolites, polyamines, choline-derived compounds, and secondary bile acids. They all have been described as immunoregulatory molecules that specifically affect the adaptive immune system and T helper 17 and regulatory T cells. We discuss the mechanisms of action and the consequences in health and diseases related to these gut microbial-derived metabolites. Finally, we propose that the exogenous administration of these molecules or other compounds that bind to their immunoregulatory receptors in a homologous manner could be considered therapeutic approaches. Full article
(This article belongs to the Special Issue The Interplay of Microbiome and Immune Response in Health and Diseases 3.0)
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