scholarly journals Inflammatory Immune Responses and Gut Microbiota Changes Following Campylobacter coli Infection of IL-10-/- Mice with Chronic Colitis

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 560
Author(s):  
Markus M. Heimesaat ◽  
Claudia Genger ◽  
Nina Biesemeier ◽  
Sigri Klove ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Underlying Disease ◽  
Campylobacter Coli ◽  
Chronic Colitis ◽  
Host Interactions ◽  
Human Infections ◽  
Gastrointestinal Colonization

Human infections with the food-borne enteropathogens Campylobacter are progressively rising. Recent evidence revealed that pre-existing intestinal inflammation facilitates enteropathogenic infection subsequently exacerbating the underlying disease. Given that only little is known about C. coli–host interactions and particularly during intestinal inflammation, the aim of the present study was to survey gastrointestinal colonization properties, gut microbiota changes and pro-inflammatory sequelae upon peroral C. coli-infection of IL-10-/- mice with chronic colitis. C. coli colonized the gastrointestinal tract of mice with varying efficiencies until day 28 post-infection and induced macroscopic and microscopic inflammatory changes as indicated by shorter colonic lengths, more distinct histopathological changes in the colonic mucosa and higher numbers of apoptotic colonic epithelial cells when compared to mock-infected controls. Furthermore, not only colonic innate and adaptive immune cell responses, but also enhanced systemic TNF-α secretion could be observed following C. coli as opposed to mock challenge. Notably, C. coli induced intestinal inflammatory sequelae were accompanied with gut microbiota shifts towards higher commensal enterobacterial loads in the infected gut lumen. Moreover, the pathogen translocated from the intestinal tract to extra-intestinal tissue sites in some cases, but never to systemic compartments. Hence, C. coli accelerates inflammatory immune responses in IL-10-/- mice with chronic colitis.

scholarly journals Toll-Like Receptor-4 Is Involved in Mediating Intestinal and Extra-Intestinal Inflammation in Campylobacter coli-Infected Secondary Abiotic IL-10−/− Mice

2020 ◽  
Vol 8 (12) ◽  
pp. 1882
Author(s):  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
Soraya Mousavi ◽  
Stefan Bereswill ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Clinical Signs ◽  
Campylobacter Coli ◽  
Toll Like Receptor ◽  
Host Interactions ◽  
Non Invasive ◽  
Health Burdens

Human Campylobacter infections are emerging worldwide and constitute significant health burdens. We recently showed that the immunopathological sequelae in Campylobacter jejuni-infected mice were due to Toll-like receptor (TLR)-4 dependent immune responses induced by bacterial lipooligosaccharide (LOS). Information regarding the molecular mechanisms underlying Campylobacter coli-host interactions are scarce, however. Therefore, we analyzed C. coli-induced campylobacteriosis in secondary abiotic IL-10−/− mice with and without TLR4. Mice were infected perorally with a human C. coli isolate or with a murine commensal Escherichia coli as apathogenic, non-invasive control. Independent from TLR4, C. coli and E. coli stably colonized the gastrointestinal tract, but only C. coli induced clinical signs of campylobacteriosis. TLR4−/− IL-10−/− mice, however, displayed less frequently fecal blood and less distinct histopathological and apoptotic sequelae in the colon versus IL-10−/− counterparts on day 28 following C. coli infection. Furthermore, C. coli-induced colonic immune cell responses were less pronounced in TLR4−/− IL-10−/− as compared to IL-10−/− mice and accompanied by lower pro-inflammatory mediator concentrations in the intestines and the liver of the former versus the latter. In conclusion, our study provides evidence that TLR4 is involved in mediating C. coli-LOS-induced immune responses in intestinal and extra-intestinal compartments during murine campylobacteriosis.

scholarly journals Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases

2020 ◽  
Author(s):  
Carolina Battistini ◽  
Rafael Ballan ◽  
Marcos Herkenhoff ◽  
Susana Saad ◽  
Jun Sun
Keyword(s):  
Vitamin D ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Chronic Inflammation ◽  
Immune Cell ◽  
Future Directions ◽  
Dihydroxyvitamin D3 ◽  
Host Interactions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

scholarly journals The Crossroads of Glycoscience, Infection, and Immunology

2021 ◽  
Vol 12 ◽  
Author(s):  
Tanya R. McKitrick ◽  
Margaret E. Ackerman ◽  
Robert M. Anthony ◽  
Clay S. Bennett ◽  
Michael Demetriou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Response ◽  
Immune Cell ◽  
Microbial Infection ◽  
Surface Receptors ◽  
Host Interactions ◽  
Host Immune Responses ◽  
Immune Mediators ◽  
Immune Mediated ◽  
And Function

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell–cell interactions that initiate and regulate the host response and modulates the effects of antibodies and soluble immune mediators. This perspective reports on a workshop organized jointly by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research in May 2020. The conference addressed the use of emerging glycoscience tools and resources to advance investigation of glycans and their roles in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. Future discoveries in these areas will increase fundamental scientific understanding and have the potential to improve diagnosis and treatment of infections and immune dysregulation.

Fucose Ameliorate Intestinal Inflammation Through Modulating the Crosstalk Between Bile Acids and Gut Microbiota in a Chronic Colitis Murine Model

2020 ◽  
Vol 26 (6) ◽  
pp. 863-873 ◽  
Author(s):  
Jun Ke ◽  
Ying Li ◽  
Chaoqun Han ◽  
Ruohang He ◽  
Rong Lin ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Murine Model ◽  
Intestinal Inflammation ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Chronic Colitis ◽  
16S Rna ◽  
Bile Acid Profiles

Abstract Background Recurrent intestinal inflammation is frequently associated with aberrant bile acid profiles and microbial community. Fucose exerts a protective effect on commensal bacteria in the case of intestinal pathogen infection. We speculated that fucose might also have certain impact on the microbial ecosystem under the chronic colitis setting. Methods To validate our hypothesis, multi-omics examination was performed in combination with microbiomics and metabonomics in a chronic dextran sulfate sodium (DSS) murine model in the presence or absence of fucose. The 16S RNA sequencing was carried out to determine the ileum and colon microbiota. Primary and secondary bile acids, together with the respective taurine and glycine conjugates, were quantified through ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS). Moreover, enzymes involved in regulating bile acid synthesis were also detected. Finally, an experiment was carried out on the antibiotic-treated mice to examine the role of gut microbiota. Results Administration of exogenous-free fucose markedly alleviated the inflammatory response in colitis mice. In addition, excessive intestinal bile acid accumulated in DSS mice was decreased in the presence of fucose, along with the restoration of the compromised regulation on hepatic bile acid synthesis. Moreover, the shifts in bile acid profiles were linked with the improved gut microbiome dysbiosis. However, the protective effects of fucose were abolished in mice treated with antibiotic cocktail, indicating that microbiota played a pivotal role. Conclusions Findings in this study suggest that fucose ameliorates colitis through restoring the crosstalk between bile acid and gut microbiota.

scholarly journals Immune Modulation in PrimaryVaccinia virusZoonotic Human Infections

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Juliana Assis Silva Gomes ◽  
Fernanda Fortes de Araújo ◽  
Giliane de Souza Trindade ◽  
Bárbara Resende Quinan ◽  
Betânia Paiva Drumond ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Modulation ◽  
Immune Cell ◽  
Acute Infection ◽  
Immunological Responses ◽  
Cellular Immune Responses ◽  
Cell Compartments ◽  
Acute Infections ◽  
Human Infections ◽  
Cellular Immune

In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, includingMonkeypox,Cowpox,andVaccinia virus(VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans.

scholarly journals The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 37
Author(s):  
Ashwinipriyadarshini Megur ◽  
Daiva Baltriukienė ◽  
Virginija Bukelskienė ◽  
Aurelijus Burokas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Cell Activation ◽  
Immune Cell ◽  
Neuronal Loss ◽  
Internal Factors ◽  
Host Interactions ◽  
Immune Cell Activation ◽  
New Treatment

For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota–gut–brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is determined by increase in the permeability of the gut barrier and immune cell activation, leading to impairment in the blood–brain barrier function that promotes neuroinflammation, neuronal loss, neural injury, and ultimately AD. Numerous studies have shown that the gut microbiota plays a crucial role in brain function and changes in the behavior of individuals and the formation of bacterial amyloids. Lipopolysaccharides and bacterial amyloids synthesized by the gut microbiota can trigger the immune cells residing in the brain and can activate the immune response leading to neuroinflammation. Growing experimental and clinical data indicate the prominent role of gut dysbiosis and microbiota–host interactions in AD. Modulation of the gut microbiota with antibiotics or probiotic supplementation may create new preventive and therapeutic options in AD. Accumulating evidences affirm that research on MGB involvement in AD is necessary for new treatment targets and therapies for AD.

scholarly journals Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases

2020 ◽  
Vol 22 (1) ◽  
pp. 362
Author(s):  
Carolina Battistini ◽  
Rafael Ballan ◽  
Marcos Edgar Herkenhoff ◽  
Susana Marta Isay Saad ◽  
Jun Sun
Keyword(s):  
Vitamin D ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Chronic Inflammation ◽  
Immune Cell ◽  
Future Directions ◽  
Dihydroxyvitamin D3 ◽  
Host Interactions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e.g., vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α,25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g., butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD/VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

scholarly journals The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?

2021 ◽  
Vol 12 ◽  
Author(s):  
Benedetta Parodi ◽  
Nicole Kerlero de Rosbo
Keyword(s):  
Multiple Sclerosis ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Intestinal Permeability ◽  
Crucial Role ◽  
Intestinal Inflammation ◽  
Neurological Diseases ◽  
Gastrointestinal Symptoms ◽  
Leaky Gut ◽  
Disease Pathogenesis

A large and expending body of evidence indicates that the gut-brain axis likely plays a crucial role in neurological diseases, including multiple sclerosis (MS). As a whole, the gut-brain axis can be considered as a bi-directional multi-crosstalk pathway that governs the interaction between the gut microbiota and the organism. Perturbation in the commensal microbial population, referred to as dysbiosis, is frequently associated with an increased intestinal permeability, or “leaky gut”, which allows the entrance of exogeneous molecules, in particular bacterial products and metabolites, that can disrupt tissue homeostasis and induce inflammation, promoting both local and systemic immune responses. An altered gut microbiota could therefore have significant repercussions not only on immune responses in the gut but also in distal effector immune sites such as the CNS. Indeed, the dysregulation of this bi-directional communication as a consequence of dysbiosis has been implicated as playing a possible role in the pathogenesis of neurological diseases. In multiple sclerosis (MS), the gut-brain axis is increasingly being considered as playing a crucial role in its pathogenesis, with a major focus on specific gut microbiota alterations associated with the disease. In both MS and its purported murine model, experimental autoimmune encephalomyelitis (EAE), gastrointestinal symptoms and/or an altered gut microbiota have been reported together with increased intestinal permeability. In both EAE and MS, specific components of the microbiota have been shown to modulate both effector and regulatory T-cell responses and therefore disease progression, and EAE experiments with germ-free and specific pathogen-free mice transferred with microbiota associated or not with disease have clearly demonstrated the possible role of the microbiota in disease pathogenesis and/or progression. Here, we review the evidence that can point to two possible consequences of the gut-brain axis dysfunction in MS and EAE: 1. A pro-inflammatory intestinal environment and “leaky” gut induced by dysbiosis could lead to an altered communication with the CNS through the cholinergic afferent fibers, thereby contributing to CNS inflammation and disease pathogenesis; and 2. Neuroinflammation affecting efferent cholinergic transmission could result in intestinal inflammation as disease progresses.

scholarly journals Modelling the effect of birth and feeding modes on the development of human gut microbiota

2021 ◽  
Vol 288 (1942) ◽  
pp. 20201810
Author(s):  
Xiyan Xiong ◽  
Sara L. Loo ◽  
Li Zhang ◽  
Mark M. Tanaka
Keyword(s):  
Breast Milk ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Feeding Practices ◽  
Human Gut ◽  
Host Interactions ◽  
Human Gut Microbiota ◽  
Feeding Modes ◽  
Birth Environment

The human gut microbiota is transmitted from mother to infant through vaginal birth and breastfeeding. Bifidobacterium , a genus that dominates the infants’ gut, is adapted to breast milk in its ability to metabolize human milk oligosaccharides; it is regarded as a mutualist owing to its involvement in the development of the immune system. The composition of microbiota, including the abundance of Bifidobacteria, is highly variable between individuals and some microbial profiles are associated with diseases. However, whether and how birth and feeding practices contribute to such variation remains unclear. To understand how early events affect the establishment of microbiota, we develop a mathematical model of two types of Bifidobacteria and a generic compartment of commensal competitors. We show how early events affect competition between mutualists and commensals and microbe-host-immune interactions to cause long-term alterations in gut microbial profiles. Bifidobacteria associated with breast milk can trigger immune responses with lasting effects on the microbial community structure. Our model shows that, in response to a change in birth environment, competition alone can produce two distinct microbial profiles post-weaning. Adding immune regulation to our competition model allows for variations in microbial profiles in response to different feeding practices. This analysis highlights the importance of microbe–microbe and microbe–host interactions in shaping the gut populations following different birth and feeding modes.

scholarly journals Balance between protective and pathogenic immune responses to pneumonia in the neonatal lung enforced by gut microbiota.

2021 ◽  
Author(s):  
Joseph Stevens ◽  
Shelby Steinmeyer ◽  
Madeline Bonfield ◽  
Timothy Wang ◽  
Jerilyn Gray ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Intestinal Microbiota ◽  
Early Life ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Developmental Trajectory ◽  
Antibiotic Exposure ◽  
Clinical Practices ◽  
Pulmonary Immunity

While modern clinical practices like cesarean sections and perinatal antibiotics have improved infant survival, treatment with broad-spectrum antibiotics alters intestinal microbiota and causes dysbiosis. Infants exposed to perinatal antibiotics have an increased likelihood of life-threatening infections, including pneumonia. Here, we investigated how gut microbiota sculpt pulmonary immune responses, promoting recovery and resolution of infection in newborn rhesus macaques. Early-life antibiotic exposure, mirroring current clinical practices, interrupted the maturation of intestinal commensal bacteria and disrupted the developmental trajectory of the pulmonary immune system as assessed by single-cell proteomic and transcriptomic analyses of the pulmonary immune response. Early-life antibiotic exposure rendered newborn macaques susceptible to bacterial pneumonia, mediated by profound changes in neutrophil senescence, inflammatory signaling, and macrophage dysfunction. Pathogenic reprogramming of pulmonary immunity was reflected by a hyperinflammatory signature in all pulmonary immune cell subsets. Distinct patterns of immunoparalysis, including dysregulated antigen presentation in alveolar macrophages, impaired costimulatory function in T helper cells, and dysfunctional cytotoxic responses in natural killer (NK) cells, were coupled with a global loss of tissue-protective, homeostatic pathways in lungs of dysbiotic newborns. Fecal microbiota transfer corrected the broad immune maladaptations and protected against severe pneumonia. These data demonstrate the importance of intestinal microbiota in programming pulmonary immunity. Gut microbiota promote balance between pathways driving tissue repair and inflammatory responses, thereby leading to clinical recovery from infection in infants.

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