scholarly journals The Inflammatory Processes Driven by Gut Microbiota

Acta Medica ◽  
2021 ◽  
pp. 1-9
Author(s):  
Ayşe Buruş ◽  
Başak Çeltikçi ◽  
Yasemin Aksoy

Microbiome studies have shown alterations in bacterial communities in the state of many diseases, including inflammatory bowel disease, metabolic disorders, autoimmune diseases, neurodegenerative diseases, and cancer. Chronic inflammation is a common promoter of many of these pathological processes. Shifting in the microbial diversity is also known as dysbiosis. Dysbiosis, increased detrimental bacterial products, decreased favorable microbial metabolites, interrupted tissue barriers, and bacterial translocation cause excessive immune response and inflammation. Several mechanisms play a role to maintain intestinal homeostasis by limiting bacterial translocation from the intestinal lumen into the lamina propria. Among these mechanisms, most importantly, the mucosal barrier that consists of the antimicrobial peptides, mucus, and immunoglobulin A is fundamental to protect epithelial barrier integrity to reduce the excessive immune response. Moreover, recognizing bacteria and metabolites through receptors results in T cell regulation and immune modulation, which is the keystone of the controlled immune response. This review summarizes the anti-inflammatory and pro-inflammatory mechanisms driven by gastrointestinal microbiota, and it also highlights the recent approaches, including epigenetics and precision medicine.

2017 ◽  
Vol 8 (4) ◽  
pp. 605-614 ◽  
Author(s):  
J.R. Bailey ◽  
V. Vince ◽  
N.A. Williams ◽  
T.A. Cogan

Treatment of inflammatory bowel disease (IBD) is mainly based on suppression of symptoms, often with numerous side effects. Trials of probiotics in IBD have frequently produced disappointing results. The majority of probiotics are unusual, since they do not require iron for growth, unlike many bacteria resident in the intestine. The IBD intestine is iron-rich due to bleeding and use of oral iron supplements; conventional probiotics would be rapidly outcompeted. We have evaluated an iron-responsive Streptococcus thermophilus strain for its potential to reduce signs of colitis. Efficacy of S. thermophilus was evaluated in the dextran sodium sulphate mouse model of colitis. Treated animals were given 1×108 cfu S. thermophilus per day and clinical observations were taken daily. At termination, gross and histopathological signs of disease, cellular infiltration, location of bacteria, and cytokine expression in the intestine were determined. S. thermophilus delayed onset of colitis and reduced clinical signs of disease, including bodyweight loss and gastrointestinal bleeding. It reduced bacterial translocation into the colonic tissue. Increased numbers of CD8+ intraepithelial lymphocytes were seen in control animals treated with S. thermophilus. S. thermophilus had no effect on gross pathology, histopathology or cytokine production in either colitic or control animals. We propose that S. thermophilus promotes maintenance of mucosal barrier function which reduces bacterial translocation, thereby reducing immune stimulation and associated inflammation. This allows mucosal healing, reducing gastrointestinal bleeding and weight loss. This could be studied as a locally-acting adjunct or alternative to current IBD treatments.


2021 ◽  
Vol 42 ◽  
Author(s):  
P. Tavakoli ◽  
U. Vollmer-Conna ◽  
D. Hadzi-Pavlovic ◽  
M. C. Grimm

Objective: Inflammatory bowel diseases (IBDs) are complex chronic inflammatory disorders of the gastro-intestinal (GI) tract with uncertain etiology. IBDs comprise two idiopathic disorders: Crohn’s disease (CD) and ulcerative colitis (UC). The aetiology, severity and progression of such disorders are still poorly understood but thought to be influenced by multiple factors (including genetic, environmental, immunological, physiological, psychological factors and gut microbiome) and their interactions. The overarching aim of this review is to evaluate the extent and nature of the interrelationship between these factors with the disease course. A broader conceptual and longitudinal framework of possible neuro-visceral integration, core microbiome analysis and immune modulation assessment may be useful in accurately documenting and characterizing the nature and temporal continuity of crosstalk between these factors and the role of their interaction (s) in IBD disease activity. Characterization of these interactions holds the promise of identifying novel diagnostic, interventions, and therapeutic strategies.Material and Methods: A search of published literature was conducted by exploring PubMed, EMBASE, MEDLINE, Medline Plus, CDSR library databases. Following search terms relating to key question were set for the search included: “Inflammatory bowel diseases,” “gut microbiota,” “psychological distress and IBD,” “autonomic reactivity and IBD,” “immune modulation,” “chronic inflammation,” “gut inflammation,” “enteric nervous system,” “gut nervous system,” “Crohn’s disease,” “Ulcerative colitis”, “depression and IBD”, “anxiety and IBD”, “quality of life in IBD patients,” “relapse in IBDs,” “remission in IBDs,” “IBD disease activity,” “brain-gut-axis,” “microbial signature in IBD,” “validated questionnaires in IBD,” “IBD activity indices,” “IBD aetiology,” “IBDs and stress,” “epidemiology of IBDs”, “autonomic nervous system and gut inflammation”, “IBD and environment,” “genetics of IBDs,” “pathways of immune response in IBDs,” “sleep disturbances in IBD,” “hypothalamic-pituitary-adrenal axis (HPA),” “sympatho-adrenal axis,” “CNS and its control of gut function” “mucosal immune response,” “commensal and pathogenic bacteria in the gut,” “innate and adaptive immunity.” Studies evaluating any possible associations between gut microbiome, psychological state, immune modulation, and autonomic function with IBDs were identified. Commonly cited published literatures with high quality research methodology/results and additional articles from bibliographies of recovered papers were examined and included where relevant.Results: Although there is a substantial literature identifying major contributing factors with IBD, there has been little attempt to integrate some factors over time and assess their interplay and relationship with IBD disease activity. Such contributing factors include genetic and environmental factors, gut microbiota composition and function, physiological factors, psychological state and gut immune response. Interdependences are evident across psychological and biological factors and IBD disease activity. Although from the available evidence, it is implausible that a single explanatory model could elucidate the interplay between such factors and the disease course as well as the sequence of the effect during the pathophysiology of IBD.Conclusion: Longitudinal monitoring of IBD patients and integrating data related to the contributing/risk factors including psychological state, physiological conditions, inflammatory/immune modulations, and microbiome composition/function, could help to explain how major factors associate and interrelate leading to exacerbation of symptoms and disease activity. Identifying the temporal trajectory of biological and psychosocial disturbances may also help to assess their effects and interdependence on individuals’ disease status. Moreover, this allows greater insight into understanding the temporal progressions of subclinical events as potential ground for disease severity in IBD. Furthermore, understanding the interaction between these risk factors may help better interventions in controlling the disease, reducing the costs related to disease management, further implications for clinical practice and research approaches in addition to improving patients’ mental health and quality of life.


Author(s):  
Silvia Pastoriza ◽  
José Ángel Rufián-Henares

Molecular damage signals attract neutrophils to sites of infection or inflammation. The G-protein coupled receptor (GPR43) and the receptor for advanced glicosilation compounds (RAGE) recognize short-chain fatty acids (propionate and butyrate) and AGEs (advanced glycosylation compounds) respectively, both receptors being abundantly expressed in neutrophils and intestinal epithelial cells. The functional role that activation of these receptors plays in the in vivo orchestration of the immune response is unclear. Our work examines the effect of the ingestion of AGEs on the immune response, both in healthy mice and in mice that were induced to colitis, using transgenic mice deficient in GPR43 or RAGE receptors. One of the main findings is that both the GPR43 receptor and RAGE are necessary for the recruitment of neutrophils in a model of intestinal inflammation due to mucosal barrier injury. We have also verified that the AGEs ingested with the diet promote the appearance of an imbalance in the inflammatory balance at the intestinal level, giving rise to a pro-inflammatory status. We have also show that carboxymethylisine (CML), a specific type of AGE, is capable of stimulating the GPR43 receptor and acting as a neutrophil chemoattraction factor. Finally, we have tested the treatment with sRAGE, a protein capable of capturing free AGEs. This procedure could be a promising therapy for the treatment of inflammatory bowel disease.


2021 ◽  
Vol 1 (6) ◽  
pp. 88-95
Author(s):  
A. A. Khryanin ◽  
M. F. Osipenko ◽  
O. B. Nemchaninova ◽  
O. N. Pozdnyakova ◽  
T. B. Reshetnikova ◽  
...  

The surface of the intestinal tract in healthy people is free of bacteria in all segments of the intestine. Thus, the attachment of bacteria to epithelial cells is a sign of infection. Unlike the mucous membrane, the intestinal lumen is never sterile. The reason for this is the polymicrobial nature of the gut microbiota. In the intestine, segments such as the stomach or small intestine, where bacteria are actively suppressed, the microbiota is random in appearance, composition, and concentration. However, the situation is completely different in the colon, where the growth of bacteria increases and their suppression is suspended. The concentration and diversity of bacteria in the colon reaches astronomical numbers. Some of these bacteria are required for the colon to function. Many of the local bacteria in the colon are potential pathogens: Bacteroides, Enterobacteriaceae, Enterococci, and Clostridium histolyticum. Control of pathogens in the colon is achieved through an impenetrable mucus layer. Inflammatory bowel disease is a polymicrobial infection characterized by persistent disruption of the mucosal barrier, subsequent migration of bacteria to the mucous membrane, and overgrowth of a complex bacterial biofilm on the surface of the epithelium, resulting in invasive and cytopathological effects. As long as the mucosal barrier function is impaired, the inflammatory process cannot successfully remove bacteria from the mucosal surface, and inflammation itself is detrimental. Due to the inflammatory reaction, the composition and structure of the fecal microbiota changes. Based on the biostructure of the fecal casts, active Crohn’s disease and ulcerative colitis can be distinguished from each other and from other gastrointestinal diseases. The relationship between the gut microbiome and various dermatological diseases (psoriasis, acne, rosacea, atopic dermatitis) is discussed.


2001 ◽  
Vol 69 (6) ◽  
pp. 3542-3549 ◽  
Author(s):  
Muniraj Manohar ◽  
Donald O. Baumann ◽  
Nicolaas A. Bos ◽  
John J. Cebra

ABSTRACT We used Listeria monocytogenes, a gram-positive, facultative intracellular bacterium, to study the gut mucosal immune responses following oral infection. We employed a germfree (GF) mouse model to try to accentuate the development of a humoral mucosal immune response in the gut, and we used oral colonization with one of the mutants, actA-negative (ΔactA) L. monocytogenes, to restrict infection largely to the gut. The ΔactA mutant was able to colonize the intestinal mucosa of formerly GF mice for long periods of time without causing disease while eliciting secretory immunoglobulin A (IgA) responses, as evidenced by gut tissue fragment culture assays. Flow cytometric analyses and immunohistochemical methods showed the development of only minimal germinal center reactions (GCR) in Peyer's patches and more robust GCR in mesenteric lymph nodes. Pronounced increases in total (natural) IgA production occurred in gut tissues by day 7 and were maintained for up to 90 days. Levels of specific IgA were modest in gut tissues on day 14, increased until day 76, and stabilized at day 90. We also observed a significant rise in serum IgA and IgG1 levels following oral infection by listeriae. Upon colonization, the organisms mainly infected the intestines and intestinal lumen, and we only sporadically observed few colony-forming bacteria in the liver and spleen. We observed a marked rise in IgA-secreting cells, including listeria-specific IgA antibody-secreting cells, in the lamina propria of the small intestine by enzyme-linked immunospot assays. To ascertain whether some of the IgA was specific for listeriae, we performed Western blot analysis to test the reactivity of IgA from fragment cultures to antigens in sonicates of L. monocytogenes. We detected IgA binding to antigenic proteins with molecular masses of 96, 60, 40, and 14 kDa in theListeria sonicates.


2019 ◽  
Vol 20 (20) ◽  
pp. 5232 ◽  
Author(s):  
Simone Perna ◽  
Tariq A. Alalwan ◽  
Zahraa Alaali ◽  
Tahera Alnashaba ◽  
Clara Gasparri ◽  
...  

The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy of glutamine and its effect on gut microbiota. As a result of this review, we have summarized that glutamine could affect gut microbiota via different mechanisms including the reduction in the ratio of Firmicutes to Bacteroidetes, with the activation of NF-κB and PI3K-Akt pathways, reducing the intestinal colonization (Eimeria lesions) and bacterial overgrowth or bacterial translocation, increasing the production of secretory immunoglobulin A (SIgA) and immunoglobulin A+ (IgA+) cells in the intestinal lumen, and decreasing asparagine levels. The potential applications of glutamine on gut microbiota include, but are not limited to, the management of obesity, bacterial translocation and community, cytokines profiles, and the management of side effects during post-chemotherapy and constipation periods. Further studies and reviews are needed regarding the effects of glutamine supplementation on other conditions in humans.


2002 ◽  
Vol 282 (4) ◽  
pp. G581-G585 ◽  
Author(s):  
Johan Auwerx

The peroxisome proliferator-activated receptor gamma (PPARγ) has recently been implicated in the pathogenesis of inflammatory bowel disease (IBD) and colon cancer. The observation that PPARγ agonists, through immune modulation, protect against inflammatory processes in the intestine justified their expedient evaluation in the clinical management of IBD. PPARγ agonists are reported to have both tumor-promoting and -inhibiting effects in models of colon cancer. These differences can, in part, be explained by PPARγ-independent effects of PPARγ agonists and by differences in the models used. Because it is still unclear how PPARγ impacts on colon cancer, careful monitoring of patients receiving PPARγ agonists and additional basic research is indicated before recommendations on the use of PPARγ ligands in colon cancer can be made.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fabian Bohländer ◽  
Dennis Riehl ◽  
Sabrina Weißmüller ◽  
Marcus Gutscher ◽  
Jörg Schüttrumpf ◽  
...  

The rapid spread of SARS-CoV-2 has induced a global pandemic. Severe forms of COVID-19 are characterized by dysregulated immune response and “cytokine storm”. The role of IgG and IgM antibodies in COVID-19 pathology is reasonably well studied, whereas IgA is neglected. To improve clinical outcome of patients, immune modulatory drugs appear to be beneficial. Such drugs include intravenous immunoglobulin preparations, which were successfully tested in severe COVID-19 patients. Here we established a versatile in vitro model to study inflammatory as well as anti-inflammatory processes by therapeutic human immunoglobulins. We dissect the inflammatory activation on neutrophil-like HL60 cells, using an immune complex consisting of latex beads coated with spike protein of SARS-CoV-2 and opsonized with specific immunoglobulins from convalescent plasma. Our data clarifies the role of Fc-receptor-dependent phagocytosis via IgA-FcαRI and IgG-FcγR for COVID-19 disease followed by cytokine release. We show that COVID-19 associated inflammation could be reduced by addition of human immunoglobulin preparations (IVIG and trimodulin), while trimodulin elicits stronger immune modulation by more powerful ITAMi signaling. Besides IgG, the IgA component of trimodulin in particular, is of functional relevance for immune modulation in this assay setup, highlighting the need to study IgA mediated immune response.


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