scholarly journals Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 386 ◽  
Author(s):  
Sigri Kløve ◽  
Claudia Genger ◽  
Soraya Mousavi ◽  
Dennis Weschka ◽  
Stefan Bereswill ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Immune Cell ◽  
Fecal Microbiota Transplantation ◽  
Clinical Signs ◽  
Toll Like Receptor ◽  
Human Gut ◽  
Toll Like Receptor 4 ◽  
Host Immune Responses ◽  
Human Gut Microbiota

Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10-/- mice and IL10-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10-/- counterparts. Furthermore, C. coli infected IL10-/-, as opposed to TLR4-deficient IL10-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail.

scholarly journals HUMAN GUT MICROBIOTA AND ITS EFFECTS ON HUMAN HEALTH IN NORMAL AND PATHOLOGICAL CONDITIONS

2017 ◽  
Vol 64 (3) ◽  
pp. 185-193
Author(s):  
Anca Magdalena Munteanu ◽  
◽  
Raluca Cursaru ◽  
Loreta Guja ◽  
Simona Carniciu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
New Technologies ◽  
Fecal Microbiota Transplantation ◽  
Current Knowledge ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Research Subjects ◽  
Human Gut ◽  
Human Host ◽  
Human Gut Microbiota

The medical research of the last 1-2 decades allows us to look at the human gut microbiota and microbiome as to a structure that can promote health and sometimes initiate disease. It works like an endocrine organ: releasing specific metabolites, using environmental inputs, e.g. diet, or acting through its structural compounds, that signal human host receptors, to finally contributing to the pathogenesis of several gastrointestinal and non-gastrointestinal diseases. The same commensal microbes were found as shapers of the human host response to drugs (cardiovascular, oncology etc.). New technologies played an important role in these achievements, facilitating analysis of the genetic and metabolic profile of this microbial community. Once the inputs, the pathways and a lot of human host receptors were highlighted, the scientists were encouraged to go further into research, in order to develop new pathogenic therapies, targeting the human gut flora. Dual therapies, evolving these “friend microbes”, are another actual research subjects. This review gives an update on the current knowledge in the area of microbiota disbalances under environmental factors, the contribution of gut microbiota and microbiome to the pathogenesis of obesity, obesity associated metabolic disorders and cardiovascular disease, as well as new perspectives in preventing and treating these diseases, with high prevalence in contemporary, economically developed societies. It brings the latest and most relevant evidences relating to: probiotics, prebiotics, polyphenols and fecal microbiota transplantation, dietary nutrient manipulation, microbial as well as human host enzyme manipulation, shaping human responses to currently used drugs, manipulating the gut microbiome by horizontal gene transfer.

scholarly journals Role of Microbiome in Rheumatic Diseases

2017 ◽  
Vol 17 (2) ◽  
pp. 58-63 ◽  
Author(s):  
Chi Kit Au ◽  
Tin Lok Lai ◽  
Cheuk Wan Yim
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Rheumatic Diseases ◽  
Pivotal Role ◽  
Human Gut ◽  
Future Role ◽  
Human Gut Microbiota ◽  
Rheumatic Manifestations

AbstractMajority of rheumatic diseases are complex and multifactorial in etiology. Emerging studies has suggested that the change of human microbiota, especially in the gut, play a pivotal role in its pathogenesis. Dysequilibrium of the gut microbiota triggers the imbalance between pro- and anti- inflammatory immune responses and results in different rheumatic manifestations, such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). In this article, current and future role of the human gut microbiota in rheumatic diseases are discussed.

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 Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection

2020 ◽  
Vol 8 (2) ◽  
pp. 200 ◽  
Author(s):  
Melina Kachrimanidou ◽  
Eleftherios Tsintarakis
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Colonization Resistance ◽  
Human Gut ◽  
Major Health Problem ◽  
Human Gut Microbiota ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
The Way

Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut’s metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut’s microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.

scholarly journals ARE THEY ALSO MIND COLONIZERS? EXPLORING THE ASSOCIATION BETWEEN GUT MICROBIOTA AND DEPRESSION

2020 ◽  
Vol 4 (2) ◽  
pp. 168-177
Author(s):  
Funmilola Ayeni ◽  
Tolulope Elizabeth Fadeyi
Keyword(s):  
Mental Health ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Strong Evidence ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Healthy State ◽  
The Relationship

The association of the gut microbiota with many diseased and healthy state is currently of global interest.  Gut microbiota is able to alter immune responses and behaviour and it is also involved in the pathophysiology of depression. Depression is a disorder that is etiologically heterogeneous. There is a strong evidence for microbiome links to mental health, which point to a possible future of manipulation of gut microbiota for better health. This review compiled existing literature on the relationship between depression and human gut microbiota.

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 Defining Innate Immune Responses to the Human Gut Microbiota from Phylum to Strain

2021 ◽  
Author(s):  
Matthew P. Spindler ◽  
Sophia S. Siu ◽  
Ilaria Mogno ◽  
Zihua Li ◽  
Chao Yang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Pathogenic Bacteria ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Bacterial Strains ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Screening Platform

The functional potential of the gut microbiota remains largely uncharacterized. Efforts to understand how the immune system responds to commensal organisms have been hindered by the large number of strains that comprise the human gut microbiota. We develop a screening platform to measure innate immune responses towards 277 bacterial strains isolated from the human gut microbiota. We find that innate immune responses to gut derived bacteria are as strong as responses towards pathogenic bacteria, and vary from phylum to strain. Myeloid cells differentially rely upon TLR2 or TLR4 to sense particular taxa, an observation that predicts in vivo function. These innate immune responses can be modeled using combinations of up to 8 TLR agonists. Furthermore, the immunogenicity of strains is stable over time and following transplantation into new humans. Collectively, we demonstrate a powerful high-throughput approach to determine how commensal microorganisms shape innate immune phenotypes.

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