Gut microbiota contain communities of viruses, bacteria, fungi, and Eukarya, and live as biofilms. In health, these biofilms adhere to the intestinal mucus surface without contacting the epithelium. ...Disruptions to the equilibrium between these biofilms and the host may create invasive pathobionts from these commensal communities and contribute to disease pathogenesis. Environmental factors appear to dominate over genetics in determining the shifts in microbiota populations and function, including when comparing microbiota between low-income and industrialized countries. The observations discussed herein carry enormous potential for the development of novel therapies targeting phenotype in microbiota dysbiosis.
Gastrointestinal biofilms in health and disease Motta, Jean-Paul; Wallace, John L; Buret, André G ...
Nature reviews. Gastroenterology & hepatology,
05/2021, Letnik:
18, Številka:
5
Journal Article
Recenzirano
Microorganisms colonize various ecological niches in the human habitat, as they do in nature. Predominant forms of multicellular communities called biofilms colonize human tissue surfaces. The ...gastrointestinal tract is home to a profusion of microorganisms with intertwined, but not identical, lifestyles: as isolated planktonic cells, as biofilms and in biofilm-dispersed form. It is therefore of major importance in understanding homeostatic and altered host-microorganism interactions to consider not only the planktonic lifestyle, but also biofilms and biofilm-dispersed forms. In this Review, we discuss the natural organization of microorganisms at gastrointestinal surfaces, stratification of microbiota taxonomy, biogeographical localization and trans-kingdom interactions occurring within the biofilm habitat. We also discuss existing models used to study biofilms. We assess the contribution of the host-mucosa biofilm relationship to gut homeostasis and to diseases. In addition, we describe how host factors can shape the organization, structure and composition of mucosal biofilms, and how biofilms themselves are implicated in a variety of homeostatic and pathological processes in the gut. Future studies characterizing biofilm nature, physical properties, composition and intrinsic communication could shed new light on gut physiology and lead to potential novel therapeutic options for gastrointestinal diseases.
Mucin
-linked glycans are important mediators of host-microbiota-pathogen interactions in the gastrointestinal tract. The major component of intestinal mucus, the MUC2 mucin, is densely glycosylated, ...with up to 80% of its weight-to-volume ratio represented by
-linked glycans. Glycosylation of secretory gel-forming mucins has an enormous impact on intestinal barrier function, microbial metabolism, and mucus colonization by both pathogenic and commensal microbes. Mucin
-glycans and glycan-derived sugars may be degraded and used as a nutrient source and may regulate microbial gene expression and virulence. Short-chain fatty acids, produced as a by-product of glycan fermentation, can regulate host immunity and goblet cell activity and are important for host-microbe homeostasis. Mucin glycans may also act as microbial binding sites, influencing intestinal colonization and translocation through the mucus gel barrier. Recent findings indicate that alterations to mucin glycosylation impact the susceptibility of mucins to degradation, resulting in altered barrier function and intestinal permeability. Alterations to mucin glycosylation patterns are frequently observed during intestinal infection and inflammation and have been implicated in microbiota dysbiosis and expansion of pathobionts. Recent work has demonstrated that these alterations can play key roles in disease pathogenesis. The precise mechanisms remain obscure. This review highlights the important roles of
-linked glycans in host-microbe interactions and disease pathogenesis in the context of intestinal infections.
Giardia duodenalis is one of the most prevalent human enteropathogens and a major cause of diarrheal disease worldwide. Cysteine proteases (CPs) have been identified as major virulence factors in ...protozoan parasites, playing important roles in disease pathogenesis and in parasitic life cycles. G. duodenalis exhibits high proteolytic activity, and CPs play significant roles in giardiasis. Giardia CPs are directly involved in intestinal epithelial junctional complex disruption, intestinal epithelial cell apoptosis, and degradation of host immune factors, including chemokines and immunoglobulins. Giardia CPs have also been implicated in mucus depletion and microbiota dysbiosis induced by the parasite. This review discusses the most recent advances in characterization of Giardia Assemblage A and B CPs, including cathepsin B (catB)-like proteases.
Increasing interest has recently been directed towards parasite CPs, and more specifically catBs and catLs, as virulence factors and targets for therapeutic intervention.Giardia CP activity is implicated in intestinal barrier dysfunction, mucus depletion and microbiota biofilm alteration during infection.Recent proteomic profile analysis of Giardia trophozoites in axenic cultures and upon attachment to intestinal epithelial cells has suggested a role for CPs in Giardia virulence and host–pathogen interactions.Biochemical and structural characterization of the most highly secreted Giardia CPs (i.e., CP2, CP3, CP16160) has prompted further interest in the role of these CPs during infection.Giardia CPs contribute to the protective role of Giardia during concurrent infections with attaching–effacing bacterial enteropathogens by inducing bacterial killing and reducing inflammation in the intestine.
Alteration of the intestinal microbiome by enteropathogens is commonly associated with gastrointestinal diseases and disorders and has far-reaching consequences for overall health. Significant ...advances have been made in understanding the role of microbial dysbiosis during intestinal infections, including infection with the protozoan parasite
, one of the most prevalent gut protozoa. Altered species composition and diversity, functional changes in the commensal microbiota, and changes to intestinal bacterial biofilm structure have all been demonstrated during the course of
infection and have been implicated in
pathogenesis. Conversely, the gut microbiota has been found to regulate parasite colonization and establishment and plays a critical role in immune modulation during mono and polymicrobial infections. These disruptions to the commensal microbiome may contribute to a number of acute, chronic, and post-infectious clinical manifestations of giardiasis and may account for variations in disease presentation within and between infected populations. This review discusses recent advances in characterizing
-induced bacterial dysbiosis in the gut and the roles of dysbiosis in
pathogenesis.
Background and Purpose
ATB‐346 is a hydrogen sulfide (H2S)‐releasing anti‐inflammatory and analgesic drug. Animal studies demonstrated negligible gastrointestinal (GI) damage despite marked ...inhibition of COX activity and significant analgesic and anti‐inflammatory effects. In humans, ATB‐346 (250 mg once daily) was found to inhibit COX to the same extent as naproxen (550 mg twice daily).
Experimental Approach
Two hundred forty‐four healthy volunteers completed a 2‐week, double‐blind study, taking either ATB‐346 (250 mg once daily) or naproxen (550 mg twice daily), with upper GI ulceration being examined endoscopically.
Key Results
Forty‐two per cent of the subjects taking naproxen developed at least one ulcer (≥3‐mm diameter), while only 3% of the subjects taking ATB‐346 developed at least one ulcer. The two drugs produced comparable and substantial (>94%) suppression of COX activity. Subjects in the naproxen group developed more ulcers per subject than ATB‐346‐treated subjects and a greater incidence of larger ulcers (≥5‐mm diameter). The incidence of dyspepsia, abdominal pain, gastro‐oesophageal reflux, and nausea was lower with ATB‐346 than with naproxen. Subjects treated with ATB‐346 had significantly higher plasma levels of H2S than those treated with naproxen.
Conclusions and Implications
This Phase 2B study provides unequivocal evidence for a marked reduction of GI toxicity of the H2S‐releasing analgesic/anti‐inflammatory drug, ATB‐346, as compared to the conventional dose of naproxen that produced equivalent suppression of COX.
Linked Articles
This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc
A diverse range of effects of the intestinal microbiota on mucosal defense and injury has become increasingly clear over the past decade. Hydrogen sulfide (H
S) has emerged as an important mediator ...of many physiological functions, including gastrointestinal mucosal defense and repair. Hydrogen sulfide is produced by gastrointestinal tract tissues and by bacteria residing within the gut and can influence the function of a wide range of cells. The microbiota also appears to be an important target of hydrogen sulfide. H
S donors can modify the gut microbiota, and the gastrointestinal epithelium is a major site of oxidation of microbial-derived H
S. When administered together with nonsteroidal anti-inflammatory drugs, H
S can prevent some of the dysbiosis those drugs induce, possibly contributing to the observed prevention of gastrointestinal damage. Exogenous H
S can also markedly reduce the severity of experimental colitis and plays important roles in modulating epithelial cell-mucus-bacterial interactions in the intestine, contributing to its ability to promote resolution of inflammation and repair of tissue injury. In this paper we review recent studies examining the roles of H
S in mucosal defense, the possibility that H
S can damage the gastrointestinal epithelium, and effects of H
S on the gut microbiota and on mucus and biofilm interactions in the context of intestinal inflammation.
Our understanding of polymicrobial gastrointestinal infections and their effects on host biology remains incompletely understood. Giardia duodenalis is an ubiquitous intestinal protozoan parasite ...infecting animals and humans. Concomitant infections with Giardia and other gastrointestinal pathogens commonly occur. In countries with poor sanitation, Giardia infection has been associated with decreased incidence of diarrheal disease and fever, and reduced serum inflammatory markers release, via mechanisms that remain obscure. This study analyzed Giardia spp. co-infections with attaching and effacing (A/E) pathogens, and assessed whether and how the presence of Giardia modulates host responses to A/E enteropathogens, and alters intestinal disease outcome. In mice infected with the A/E pathogen Citrobacter rodentium, co-infection with Giardia muris significantly attenuated weight loss, macro- and microscopic signs of colitis, bacterial colonization and translocation, while concurrently enhancing the production and secretion of antimicrobial peptides (AMPs) mouse β-defensin 3 and trefoil factor 3 (TFF3). Co-infection of human intestinal epithelial cells (Caco-2) monolayers with G. duodenalis trophozoites and enteropathogenic Escherichia coli (EPEC) enhanced the production of the AMPs human β-defensin 2 (HBD-2) and TFF3; this effect was inhibited with treatment of G. duodenalis with cysteine protease inhibitors. Collectively, these results suggest that Giardia infections are capable of reducing enteropathogen-induced colitis while increasing production of host AMPs. Additional studies also demonstrated that Giardia was able to directly inhibit the growth of pathogenic bacteria. These results reveal novel mechanisms whereby Giardia may protect against gastrointestinal disease induced by a co-infecting A/E enteropathogen. Our findings shed new light on how microbial-microbial interactions in the gut may protect a host during concomitant infections.
(syn.
) is the protozoan parasite responsible for giardiasis, the most common and widely spread intestinal parasitic disease worldwide, affecting both humans and animals. After cysts ingestion ...(through either contaminated food or water),
excysts in the upper intestinal tract to release replicating trophozoites that are responsible for the production of symptoms. In the gut,
cohabits with the host's microbiota, and several studies have revealed the importance of this gut ecosystem and/or some probiotic bacteria in providing protection against
infection through mechanisms that remain incompletely understood. Recent findings suggest that Bile-Salt-Hydrolase (BSH)-like activities from the probiotic strain of
La1 may contribute to the anti-giardial activity displayed by this strain. Here, we cloned and expressed each of the three
genes present in the
La1 genome to study their enzymatic and biological properties. While BSH47 and BSH56 were expressed as recombinant active enzymes, no significant enzymatic activity was detected with BSH12.
assays allowed determining the substrate specificities of both BSH47 and BSH56, which were different. Modeling of these BSHs indicated a strong conservation of their 3-D structures despite low conservation of their primary structures. Both recombinant enzymes were able to mediate anti-giardial biological activity against
trophozoites
. Moreover, BSH47 exerted significant anti-giardial effects when tested in a murine model of giardiasis. These results shed new light on the mechanism, whereby active BSH derived from the probiotic strain
La1 may yield anti-giardial effects
and
. These findings pave the way toward novel approaches for the treatment of this widely spread but neglected infectious disease, both in human and in veterinary medicine.
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