Physiologic and Pathologic Interactions of Bacteria with Gastrointestinal Epithelium
Section snippets
The composition of the gut's epithelial surface
An absorptive mucosa is the typical surface of the small intestine. To maximize absorptive surface area, the small intestine has evolved several adaptations, including the mucosa folded into finger-like projections called villi with intervening short glands called crypts of Lieberkühn. Thousands of microvilli per single enterocyte further increase surface area for absorption across the plasma membrane exposed to the intestinal lumen. The epithelial lining of the large intestine also contains
Bacterial sensing in the gut epithelium
The GI mucosa constantly encounters large quantities of microbes, which are, by and large, nonpathogenic. Indeed, it has been estimated that the number of the bacterial inhabitants of the GI tract exceeds that of total body eukaryotic cells by a factor of 10 [18]. To sense that myriad of microorganisms, the GI epithelium expresses various pattern recognition receptors (PRRs) including several forms of toll-like receptors (TLRs) [19] that recognize specific conserved pathogen-associated
Commensal microbial–enterocyte cross-talk: a key to intestinal homeostasis
The use of an in vivo gnotobiotic mouse model for the study of the intestinal microbial ecosystem has provided insight into the physiologic consequences of host–microbe interactions in the gut. In this model, germ-free mice were mono-colonized with a bacterial strain common to the mouse and human distal intestine, Bacteroides thetaiotaomicron [50], [51], [52]. Ileal transcriptional responses to colonization were measured by cDNA microarrays and confirmatory real-time quantitative RT-PCRs.
Enhancement of intestinal epithelial barrier function by commensals
Relative impermeability of the intestinal epithelial barrier to microorganisms represents one basis for the innate immune system in the gut. Consequently, translocation of potentially dangerous luminal antigens and detrimental effects of subsequent activation of systemic inflammatory responses can be diminished. Some probiotics, live microbial food ingredients that beneficially affect host health [56], have been shown to strengthen the intestinal epithelial barrier in vivo. Lactobacillus
Anti-inflammatory effects of commensals in intestinal epithelial cells
Several in vitro studies have demonstrated that certain strains of commensals and probiotics elicit anti-inflammatory responses in intestinal epithelial cells. Neish and colleagues [67] reported that a nonpathologic strain of Salmonella was able to attenuate IL-8 secretion elicited by pathogenic Salmonella in a polarized intestinal cell line T84 model. A similar inhibitory effect was noted if IL-8 activation occurred after other proinflammatory stimuli, including tumor necrosis factor α
Pathologic interactions with the gut epithelium
In the distal small intestine and colon, virtually every ecological niche is colonized by bacteria. Successful interaction of pathogens with the GI epithelium is dependent on their ability to perturb the homeostasis of the digestive tract. Not only do commensal bacteria and probiotics interact with the gut epithelium to help establish the mucosal barrier, but pathogens also communicate with the underlying epithelium to establish their niche. Therefore, enteropathogens have developed several
Pathogenicity and genomic islands
A pathogenicity island or locus is a region of the bacterial chromosome or within a plasmid that encodes one or more virulence factors necessary for expressing human disease [75]. The difference between a commensal and a pathogen may depend entirely on the presence of such virulence factors in pathogenicity loci. Transfer of such a pathogenicity package or virulence cassette to a commensal may transform it into a pathogen. For example, disparities between indigenous and pathogenic E coli
The type III secretion system
The type III secretion system (T3SS) is a virulence factor encoded by pathogenicity islands in multiple enteropathogens, including Salmonella species, Shigella species, Yersinia species, and E coli species. The gene product is a needle-like structure that bridges between bacterial and host cells, thus allowing delivery of bacterial proteins (eg, effector proteins and regulators of human enterocyte gene expression) from the bacterial cytoplasm into the host cell [78]. It in essence functions as
Bacterial enterotoxins
Noninvasive enteropathogens, such as Vibrio cholerae, enterotoxigenic E coli, enterotoxigenic Bacteroides fragilis, and Clostridium difficile, can cause diarrhea in people by delivering toxins that affect fluid homeostasis in the gut [3]. Overgrowth of C difficile and the release of toxin A and toxin B lead to inflammation and damage of colonic mucosa seen in antibiotic-associated diarrhea and pseudomembranous colitis [82]. These toxins inactivate the Rho guanosine triphosphatases (GTPases)
Summary
Knowledge of interactions of colonizing bacteria with GI epithelium has expanded significantly in recent years. This has helped gastroenterologists understand more precisely, not only the protective physiology of the GI tract, but also pathogenesis of infectious GI diseases. With efforts in clinical, experimental, and in vitro studies using new techniques of molecular biochemistry, more information likely will be provided about conventional and genetically engineered probiotics, their role in
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Impact of the gut microbiome on behavior and emotions
2019, Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic ApplicationsUse of probiotics in prevention and treatment of patients with Clostridium difficile infection
2016, Best Practice and Research: Clinical GastroenterologyCitation Excerpt :The gut epithelium is the initial site of interaction between commensal and pathogenic bacteria in the human host, and probiotics act on the intestinal mucosa by several mechanisms. Probiotics stabilize gut permeability by increasing expression of intestinal mucins [22], inhibit adherence of pathogenic organisms including C. difficile [23], decrease invasion of pathogens at the colonic epithelium preventing systemic bacterial translocation [22], and interfere with binding of C. difficile toxins A and B to intestinal epithelial cell receptors [15,24]. Probiotics are able to modulate both the innate and adaptive immune system through interactions with toll-like receptors [25].
Probiotics in dermatologic practice
2016, NutritionCitation Excerpt :The close association between gut barrier integrity and immune response has been demonstrated in a suckling rat model, where LGG reversed the increased intestinal permeability induced by cow's milk [38]. Probiotics may modulate epithelial barrier function through interactions with Toll-like receptor 2 (TLR2) [39]. They have been shown to modulate epithelial cell signal transduction pathways and cytokine production, thereby suppressing systemic inflammatory responses [40–42].
Intestinal microbiota diversity and expression of pattern recognition receptors in newly weaned piglets
2015, AnaerobeCitation Excerpt :Few studies have focused on the mRNA expression of NLRs in the intestinal epithelium of piglets. NOD1 recognizes diaminopimelic acid-containing peptides in peptidoglycans of Gram-negative bacteria and some Gram-positive bacteria [38], while NOD2 recognizes muramyl dipeptide that is ubiquitously presented in bacterial peptidoglycan [39]. In the present study, we observed a very different expression pattern for NOD1 and NOD2 in the d 4 post-weaning group, with a particularly notable downregulation of NOD1 expression.
Probiotics and the mechanism of necrotizing enterocolitis
2013, Seminars in Pediatric SurgeryCitation Excerpt :Probiotics also stimulate the expression of genes that encode immune protective factors, such as sIgA, largely through modulation of the Toll-like receptor (TLR) family of signaling molecules.25 Other processes that protect against NEC and that are stimulated by probiotics include induction of a balanced T-helper cell response, increased production of factors participating in repair,41 increased mucus production, and downregulation of proinflammatory genes42 (Figure 4). The Cochrane systematic review43 analyzed randomized or quasi-randomized controlled trials that enrolled preterm infants who were born at <37 weeks gestational age and/or had a birth weight of <2500 g. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one clinical outcome, such as NEC.
This article was supported by funding from the National Institutes of Health (R37 HD12437, RO1 DK70260, P30 DK40561 and PO1 DK33506, WAW). The Mucosal Immunology Laboratory has unrestricted funding from Wyeth Ayerst Nutritionals International.