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Irritable Bowel Syndrome
Published in Nicole M. Farmer, Andres Victor Ardisson Korat, Cooking for Health and Disease Prevention, 2022
Interestingly, around 10% or so of people with IBS recall a precipitating enteric infection. What is particularly interesting is that these people are developing IBS after the infection clears. The body’s reaction to the infection, not the infection itself, is causing lasting physiologic responses which cause symptoms that meet criteria for IBS (Beatty, Bhargava, and Buret 2014). One particularly interesting hypothesis, driven primarily by researchers at Cedar Sinai Hospital, argues that there are a handful of infective organisms that share a particular toxin (cytolethal distending toxin B), and an exposed person may develop antibodies to this toxin. As normally occurs when the body creates antibodies, the body retains a “memory” of the infection in the form of antibodies that circulate “looking” for this invader again, in order to have a faster response next time. Unfortunately, as the hypothesis argues, the body’s antibodies may attack elements of the motility system of the gut particularly the protein vinculin which is involved in gut motility (Pimentel et al. 2015).
Immune Response to Microbial Toxins in Inflammatory and Neurodegenerative Disorders
Published in David Perlmutter, The Microbiome and the Brain, 2019
The systemic presence of CDTs and the immune reaction that produces antibodies against them are the best indicators that CDT-producing bacterial strains are present in the gingival epithelium or the gut mucosal tissue [Ando et al. 2010]. Circulating antibodies to CdtB from E. coli, Salmonella, Shigella and Campylobacter jejuni have been shown both in animal models and in humans with irritable bowel syndrome and small intestinal bacterial overgrowth, due to the fact that CDTs are also produced by the gut bacteria that are handled by the immune system [Pimentel et al. 2015b; Morales et al. 2013]. In both cases—locally aggressive periodontitis and patients with irritable bowel syndrome and small intestinal bacterial overgrowth—circulating antibodies to cytolethal distending toxin B correlated with the development and severity of the disease [Pimentel et al. 2015b; Morales et al. 2013; Ando et al. 2010]. Therefore, CDT and CDT antibodies in the blood may play a role in the early development of periodontal, gastrointestinal, and neurological diseases. The proposed mechanisms outlined above through which oral pathogens and their toxins contribute to the pathogenesis of autoimmune, neuroimmune, and neurodegenerative disorders are illustrated in Figure 3.2.
Bacteria Causing Gastrointestinal Infections
Published in K. Balamurugan, U. Prithika, Pocket Guide to Bacterial Infections, 2019
B. Vinoth, M. Krishna Raja, B. Agieshkumar
Adhesion and invasion of the intestinal cells are the important features of Campylobacter infection. Because of their spiral shape and the polar flagella, they easily penetrate the mucus layer and reach the surface of epithelial cells. Large-molecular weight plasmids encoding certain virulence factors (pVir in C. jejuni) play a role in pathogenesis (Tracz et al. 2005). CadF adhesion factor is responsible for microtubule-mediated internalization of these organisms along the basolateral membrane of M cells resulting in mucosal damage. Though an enterotoxin called cytolethal distending toxin (CDT) is produced by C. jejuni, which causes cell cycle arrest and DNA damage, its exact role in the pathogenesis is not clearly known (Pickett et al. 1996; Whitehouse et al. 1998).
Critical roles of adherens junctions in diseases of the oral mucosa
Published in Tissue Barriers, 2023
Christina Kingsley, Antonis Kourtidis
Aggregatibacter actinomycetemcomitans, is another bacterial species that, in addition to P. gingivalis, has been shown to decrease E-cadherin levels and alter its cytosolic distribution78 (Figure 2). A. actinomycetemcomitans is a Gram-negative facultative anaerobe that is prevalent in 90% of localized aggressive periodontitis and in 40% of severe adult periodontal cases.79 One virulence factor that allows this pathogen to have significant effects on the cell cycle is the Cytolethal distending toxin (Cdt) (Figure 2). This toxin has been shown to cause extensive damage to the gingival tissue.80 Exposure of gingiva to the toxin results in increased cytosolic distribution of E-cadherin, accompanied by an increase in both β-catenin and β-actin levels,14 indicating AJ remodeling and eventually negatively affecting barrier integrity. It has been shown that these effects on E-cadherin, the gingival barrier, and the concomitant inflammation caused by A. actinomycetemcomitans, are alleviated by the use of Irsogladine maleate (IM), as well as by inhibiting p38 and ERK phosphorylation.81 These studies indicate that changes in the integrity of gingival cells in periodontal disease may be specifically due to AJ alternations. Indeed, it seems that the negative effects of Cdt to AJs contribute to compromised cell–cell adhesion and barrier function and could be a mechanism of interest in the progression of periodontal disease.
Duodenal inflammation: an emerging target for functional dyspepsia?
Published in Expert Opinion on Therapeutic Targets, 2020
Lucas Wauters, Grace Burns, Matthias Ceulemans, Marjorie M Walker, Tim Vanuytsel, Simon Keely, Nicholas J Talley
Eosinophils and mast cells are normally present in the GI-tract except for the esophagus, but increased numbers and activation (e.g. clustering and degranulation) have been described in FGID, including FD [20]. Duodenal eosinophil infiltration in FD was first described in pediatric patients from the US although controls were not assessed [21] and in the first nested case–control study of adults from Sweden [11]. Interestingly, this early adult study showed increased duodenal eosinophil counts in ‘non-ulcer’ dyspepsia patients from a population-based cohort of 1001 subjects undergoing upper GI endoscopy [11]. Replication of these findings confirmed a predominance of duodenal eosinophilia in PDS patients from the UK [22] and Australia [23], but similar prevalence between PDS and EPS in other cohorts [24–29]. The inflammatory phenotype with predominantly mucosal eosinophils in FD is different from IBS patients with lymphocytes and mast cells in the colon [30] or duodenum [24], although duodenal mast cells can be elevated in FD patients [25–27]. In addition, infiltration of both eosinophils and CCR2-positive macrophages with increased counts surrounding the crypts and focal CD8+ T-cell aggregates were found in post-infectious (pi)-FD patients, indicating a persisting cellular immune response and delayed recovery of the initial infectious episode [31,32]. The higher levels of antibodies to Cytolethal distending toxin B (CdtB, produced by Gram-negative bacteria causing acute gastroenteritis) in an FD sample from the general Australian population also suggest that pi-FD with only subtle histological changes may be more common than previously thought [33].
Outer membrane vesicle-mediated serum protection in Aggregatibacter actinomycetemcomitans
Published in Journal of Oral Microbiology, 2020
Mark Lindholm, Marjut Metsäniitty, Elisabeth Granström, Jan Oscarsson
It has been clearly demonstrated that most Gram-negative bacteria release outer membrane vesicles (OMVs) during normal growth [23,24]. A. actinomycetemcomitans OMVs have been shown to deliver virulence factors, such as leukotoxin, and cytolethal distending toxin (CDT) to human cells [25,26], and to internalize into the host cells to act as a trigger of innate immunity [27]. Proteomics, and Western blot analysis of A. actinomycetemcomitans OMVs have identified several additional vesicle-associated proteins that can contribute to evasion of the immune defense, including the IL1β-binding lipoprotein, BilRI, Omp100, OmpA1, and OmpA2, and a Factor H-binding protein homologue [21,28,29]. A role of OMVs in contributing to bacterial serum resistance has been demonstrated in a number of bacterial species, including Moraxella catarrhalis, Neisseria gonorrhoeae, Porphyromonas gingivalis, and Vibrio cholerae [30–33]. Whether A. actinomycetemcomitans OMVs may also be involved in serum resistance is not known. A functional role of A. actinomycetemcomitans OMVs in complement interaction would be consistent with in vitro observations that the vesicles, in an OmpA1- and OmpA2-dependent manner, respectively, could bind to C4-binding protein [21], a major inhibitor of classical and MBL complement activation [34]. Lipopolysaccharide (LPS) is one of the most abundant components of OMVs, including those released by A. actinomycetemcomitans, and is displayed on the outer surface of the vesicles [23–25]. It was recently shown that LPS is involved in the binding of IL-8 by A. actinomycetemcomitans OMVs [35], and it cannot be excluded that the LPS in OMVs also may interact with complement. The serotype-specific polysaccharide (S-PA) determinant of A. actinomycetemcomitans resides in the LPS O antigen, which is immunodominant [36–39]. A. actinomycetemcomitans strains are occasionally isolated, which lack the ability to produce the serotype-specific antigen [40]. As speculated previously [40], this may represent a mechanism to evade from antibody-based host responses, which could be advantageous in blood circulation. However, a contradiction with this idea is that the absence of S-PA expression in A. actinomycetemcomitans appears to be scarce.