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Gut Microbiota and Immunity

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: closed (31 March 2021) | Viewed by 58936

Special Issue Editor


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Guest Editor
Department of Physiology, School of Medicine and Dentistry, University of Valencia, 15 Avda. Blasco Ibanez, 46010 Valencia, Spain
Interests: effects of ethanol on TLR4 immune response; extracellular vesicles; effect of binge drinking in adolescent brain; microbiome; inflammatory response; glial cells
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Special Issue Information

The human gut hosts a wide and diverse ecosystem of microorganisms termed the microbiota or the novel name “holobiota”. The microbiota is involved in both health and disease, contributing to prevent illness by facilitating the metabolism, the immune system, cancer resistance, endocrine signaling and brain function. However, dysfunctions of the microbiota could lead to gut dysbiosis, leading to alterations of the intestinal permeability and in the immune system. Innate and adaptive immunity plays an important role in the containment and clearance of microbial pathogens, and new mechanisms have been discovered that can cause or influence systemic immunity alterations in different disorders, such as cancer, autoimmune or neurodegenerative diseases, among others. In this Special Issue, a particular emphasis will be given to the role of the microbiota–gut–brain axis, to deepen the knowledge of the mechanisms of gut microbiota–brain communication, including immune signaling and neural–enteroendocrine pathways. We will also review important advances in techniques associated with microbial research, such as DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics. Finally, this Special Issue of IJMS will also focus on advances in therapeutic applications, for instance, the usefulness of microbial or chemobiotic applications as promising therapeutic choices to palliate immune-mediated diseases, neurodegenerative disorders, and other syndromes.

Dr. Maria Pascual
Guest Editor

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Keywords

  • gut
  • microbiota
  • immune response
  • infectious disease
  • cancer
  • brain function
  • metabolism
  • endocrine signaling
  • pathological conditions
  • therapy

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Published Papers (10 papers)

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Research

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17 pages, 3569 KiB  
Article
Treatment with the Probiotic Product Aviguard® Alleviates Inflammatory Responses during Campylobacter jejuni-Induced Acute Enterocolitis in Mice
by Markus M. Heimesaat, Dennis Weschka, Soraya Mousavi and Stefan Bereswill
Int. J. Mol. Sci. 2021, 22(13), 6683; https://doi.org/10.3390/ijms22136683 - 22 Jun 2021
Cited by 4 | Viewed by 2349
Abstract
Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential [...] Read more.
Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10−/− mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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23 pages, 2864 KiB  
Article
Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice
by Macarena González-Portilla, Sandra Montagud-Romero, Francisco Navarrete, Ani Gasparyan, Jorge Manzanares, José Miñarro and Marta Rodríguez-Arias
Int. J. Mol. Sci. 2021, 22(10), 5279; https://doi.org/10.3390/ijms22105279 - 17 May 2021
Cited by 6 | Viewed by 2722
Abstract
Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In [...] Read more.
Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory response of adolescent BD when combined with a continuous or intermittent HFD and its effects on adult ethanol consumption by using a self-administration (SA) paradigm in mice. The inflammatory biomarkers IL-6 and CX3CL1 were measured in the striatum 24 h after BD, 3 weeks later and after the ethanol (EtOH) SA. Adolescent BD increased alcohol consumption in the oral SA and caused a greater motivation to seek the substance. Likewise, mice with intermittent access to HFD exhibited higher EtOH consumption, while the opposite effect was found in mice with continuous HFD access. Biochemical analyses showed that after BD and three weeks later, striatal levels of IL-6 and CX3CL1 were increased. In addition, in saline-treated mice, CX3CL1 was increased after continuous access to HFD. After oral SA procedure, striatal IL-6 was increased only in animals exposed to BD and HFD. In addition, striatal CX3CL1 levels were increased in all BD- and HFD-exposed groups. Overall, our findings show that adolescent BD and intermittent HFD increase adult alcohol intake and point to neuroinflammation as an important mechanism modulating this interaction. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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15 pages, 12564 KiB  
Article
The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine
by Peter Ergang, Karla Vagnerová, Petra Hermanová, Martin Vodička, Michal Jágr, Dagmar Šrůtková, Václav Dvořáček, Tomáš Hudcovic and Jiří Pácha
Int. J. Mol. Sci. 2021, 22(8), 4229; https://doi.org/10.3390/ijms22084229 - 19 Apr 2021
Cited by 19 | Viewed by 2851
Abstract
Glucocorticoids (GCs) are hormones that are released in response to stressors and exhibit many activities, including immunomodulatory and anti-inflammatory activities. They are primarily synthesized in the adrenal gland but are also produced in peripheral tissues via regeneration of adrenal 11-oxo metabolites or by [...] Read more.
Glucocorticoids (GCs) are hormones that are released in response to stressors and exhibit many activities, including immunomodulatory and anti-inflammatory activities. They are primarily synthesized in the adrenal gland but are also produced in peripheral tissues via regeneration of adrenal 11-oxo metabolites or by de novo synthesis from cholesterol. The present study investigated the influence of the microbiota on de novo steroidogenesis and regeneration of corticosterone in the intestine of germ-free (GF) and specific pathogen-free mice challenged with a physical stressor (anti-CD3 antibody i.p. injection). In the small intestine, acute immune stress resulted in increased mRNA levels of the proinflammatory cytokines IL1β, IL6 and Tnfα and genes involved in de novo steroidogenesis (Stard3 and Cyp11a1), as well as in regeneration of active GCs from their 11-oxo metabolites (Hsd11b1). GF mice showed a generally reduced transcriptional response to immune stress, which was accompanied by decreased intestinal corticosterone production and reduced expression of the GC-sensitive marker Fkbp5. In contrast, the interaction between stress and the microbiota was not detected at the level of plasma corticosterone or the transcriptional response of adrenal steroidogenic enzymes. The results indicate a differential immune stress-induced intestinal response to proinflammatory stimuli and local corticosterone production driven by the gut microbiota. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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17 pages, 2483 KiB  
Article
Examining the Gastrointestinal and Immunomodulatory Effects of the Novel Probiotic Bacillus subtilis DE111
by Kimberley E. Freedman, Jessica L. Hill, Yuren Wei, Allegra R. Vazquez, Diana S. Grubb, Roxanne E. Trotter, Scott D. Wrigley, Sarah A. Johnson, Michelle T. Foster and Tiffany L. Weir
Int. J. Mol. Sci. 2021, 22(5), 2453; https://doi.org/10.3390/ijms22052453 - 28 Feb 2021
Cited by 25 | Viewed by 13132
Abstract
Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the [...] Read more.
Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain-specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a pilot randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-intervention, as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an increase in anti-inflammatory immune cell populations in response to ex vivo LPS stimulation of PBMCs in the DE111 intervention group. Overall perceived gastrointestinal health, microbiota, and circulating and fecal markers of inflammation (Il-6, sIgA) and gut barrier function (plasma zonulin) were largely unaffected by DE111 intervention, although the study may have been underpowered to detect these differences. These pilot data provide information and justification to conduct an appropriately powered clinical study to further examine the immunomodulatory potential of B. subtilis DE111 in human populations. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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Review

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12 pages, 2867 KiB  
Review
Association between Microbiota and Nasal Mucosal Diseases in terms of Immunity
by Junhu Tai, Mun Soo Han, Jiwon Kwak and Tae Hoon Kim
Int. J. Mol. Sci. 2021, 22(9), 4744; https://doi.org/10.3390/ijms22094744 - 29 Apr 2021
Cited by 24 | Viewed by 7417
Abstract
The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development [...] Read more.
The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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17 pages, 2505 KiB  
Review
Role of Microbiota-Derived Extracellular Vesicles in Gut-Brain Communication
by Carlos M. Cuesta, Consuelo Guerri, Juan Ureña and María Pascual
Int. J. Mol. Sci. 2021, 22(8), 4235; https://doi.org/10.3390/ijms22084235 - 19 Apr 2021
Cited by 59 | Viewed by 6653
Abstract
Human intestinal microbiota comprise of a dynamic population of bacterial species and other microorganisms with the capacity to interact with the rest of the organism and strongly influence the host during homeostasis and disease. Commensal and pathogenic bacteria coexist in homeostasis with the [...] Read more.
Human intestinal microbiota comprise of a dynamic population of bacterial species and other microorganisms with the capacity to interact with the rest of the organism and strongly influence the host during homeostasis and disease. Commensal and pathogenic bacteria coexist in homeostasis with the intestinal epithelium and the gastrointestinal tract’s immune system, or GALT (gut-associated lymphoid tissue), of the host. However, a disruption to this homeostasis or dysbiosis by different factors (e.g., stress, diet, use of antibiotics, age, inflammatory processes) can cause brain dysfunction given the communication between the gut and brain. Recently, extracellular vesicles (EVs) derived from bacteria have emerged as possible carriers in gut-brain communication through the interaction of their vesicle components with immune receptors, which lead to neuroinflammatory immune response activation. This review discusses the critical role of bacterial EVs from the gut in the neuropathology of brain dysfunctions by modulating the immune response. These vesicles, which contain harmful bacterial EV contents such as lipopolysaccharide (LPS), peptidoglycans, toxins and nucleic acids, are capable of crossing tissue barriers including the blood-brain barrier and interacting with the immune receptors of glial cells (e.g., Toll-like receptors) to lead to the production of cytokines and inflammatory mediators, which can cause brain impairment and behavioral dysfunctions. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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33 pages, 1346 KiB  
Review
Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions
by Svetlana Kononova, Ekaterina Litvinova, Timur Vakhitov, Maria Skalinskaya and Stanislav Sitkin
Int. J. Mol. Sci. 2021, 22(8), 3854; https://doi.org/10.3390/ijms22083854 - 8 Apr 2021
Cited by 25 | Viewed by 4850
Abstract
The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic [...] Read more.
The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic microbiota, and not pathogens. The interaction of the human immune system with symbionts is not accompanied by inflammation, but is a physiological norm. This is achieved via microbiota control by the immune system through a complex balance of pro-inflammatory and suppressive responses, and only a disturbance of this balance can trigger pathophysiological mechanisms. This review discusses the establishment of homeostatic relationships during immune system development and intestinal bacterial colonization through the interaction of milk glycans, mucins, and secretory immunoglobulins. In particular, the role of fucose and fucosylated glycans in the mechanism of interactions between host epithelial and immune cells is discussed. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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15 pages, 754 KiB  
Review
The Interplay between Immune System and Microbiota in Inflammatory Bowel Disease: A Narrative Review
by Laila Aldars-García, Alicia C. Marin, María Chaparro and Javier P. Gisbert
Int. J. Mol. Sci. 2021, 22(6), 3076; https://doi.org/10.3390/ijms22063076 - 17 Mar 2021
Cited by 41 | Viewed by 5009
Abstract
The importance of the gut microbiota in human health is currently well established. It contributes to many vital functions such as development of the host immune system, digestion and metabolism, barrier against pathogens or brain–gut communication. Microbial colonization occurs during infancy in parallel [...] Read more.
The importance of the gut microbiota in human health is currently well established. It contributes to many vital functions such as development of the host immune system, digestion and metabolism, barrier against pathogens or brain–gut communication. Microbial colonization occurs during infancy in parallel with maturation of the host immune system; therefore, an adequate cross-talk between these processes is essential to generating tolerance to gut microbiota early in life, which is crucial to prevent allergic and immune-mediated diseases. Inflammatory bowel disease (IBD) is characterized by an exacerbated immune reaction against intestinal microbiota. Changes in abundance in the gut of certain microorganisms such as bacteria, fungi, viruses, and archaea have been associated with IBD. Microbes that are commonly found in high abundance in healthy gut microbiomes, such as F. prausnitzii or R. hominis, are reduced in IBD patients. E. coli, which is usually present in a healthy gut in very low concentrations, is increased in the gut of IBD patients. Microbial taxa influence the immune system, hence affecting the inflammatory status of the host. This review examines the IBD microbiome profile and presents IBD as a model of dysbiosis. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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15 pages, 1392 KiB  
Review
Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic
by Negin Kazemian, Dina Kao and Sepideh Pakpour
Int. J. Mol. Sci. 2021, 22(6), 3004; https://doi.org/10.3390/ijms22063004 - 16 Mar 2021
Cited by 28 | Viewed by 5971
Abstract
COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, [...] Read more.
COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut–lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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17 pages, 972 KiB  
Review
Dysbiosis in the Development of Type I Diabetes and Associated Complications: From Mechanisms to Targeted Gut Microbes Manipulation Therapies
by Gratiela Gradisteanu Pircalabioru, Nicolae Corcionivoschi, Ozan Gundogdu, Mariana-Carmen Chifiriuc, Luminita Gabriela Marutescu, Bogdan Ispas and Octavian Savu
Int. J. Mol. Sci. 2021, 22(5), 2763; https://doi.org/10.3390/ijms22052763 - 9 Mar 2021
Cited by 16 | Viewed by 4687
Abstract
Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation [...] Read more.
Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host–microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approaches. Full article
(This article belongs to the Special Issue Gut Microbiota and Immunity)
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