Exagerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the ...food animal industry by reducing growth, feed intake, reproduction, milk production,
and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent,
and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate
that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical
benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical
benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects.
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.
Understanding how intestinal enteropathogens cause acute and chronic alterations has direct animal and human health perspectives. Significant advances have been made on this field by studies focusing ...on the dynamic crosstalk between the intestinal protozoan parasite model Giardia duodenalis and the host intestinal mucosa. The concept of intestinal barrier function is of the highest importance in the context of many gastrointestinal diseases such as infectious enteritis, inflammatory bowel disease, and post-infectious gastrointestinal disorders. This crucial function relies on 3 biotic and abiotic components, first the commensal microbiota organized as a biofilm, then an overlaying mucus layer, and finally the tightly structured intestinal epithelium. Herein we review multiple strategies used by Giardia parasite to circumvent these 3 components. We will summarize what is known and discuss preliminary observations suggesting how such enteropathogen directly and/ or indirectly impairs commensal microbiota biofilm architecture, disrupts mucus layer and damages host epithelium physiology and survival.
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.
Current limitations in the understanding and control of antimicrobial resistance (AMR) in Canada are described through a comprehensive review focusing on: (1) treatment optimization; (2) surveillance ...of antimicrobial use and AMR; and (3) prevention of transmission of AMR. Without addressing gaps in identified areas, sustained progress in AMR mitigation is unlikely. Expert opinions and perspectives contributed to prioritizing identified gaps. Using Canada as an example, this review emphasizes the importance and necessity of a One Health approach for understanding and mitigating AMR. Specifically, antimicrobial use in human, animal, crop, and environmental sectors cannot be regarded as independent; therefore, a One Health approach is needed in AMR research and understanding, current surveillance efforts, and policy. Discussions regarding addressing described knowledge gaps are separated into four categories: (1) further research; (2) increased capacity/resources; (3) increased prescriber/end-user knowledge; and (4) policy development/enforcement. This review highlights the research and increased capacity and resources to generate new knowledge and implement recommendations needed to address all identified gaps, including economic, social, and environmental considerations. More prescriber/end-user knowledge and policy development/enforcement are needed, but must be informed by realistic recommendations, with input from all relevant stakeholders. For most knowledge gaps, important next steps are uncertain. In conclusion, identified knowledge gaps underlined the need for AMR policy decisions to be considered in a One Health framework, while highlighting critical needs to achieve realistic and meaningful progress.
Giardia is an important cause of diarrhoea, and results in post-infectious and extra-intestinal complications. This chapter presents a state-of-the art of our understanding of how this parasite may ...cause such abnormalities, which appear to develop at least in part in Assemblage-dependent manner. Findings from prospective longitudinal cohort studies indicate that Giardia is one of the four most prevalent enteropathogens in early life, and represents a risk factor for stunting at 2 years of age. This may occur independently of diarrheal disease, in strong support of the pathophysiological significance of the intestinal abnormalities induced by this parasite. These include epithelial malabsorption and maldigestion, increased transit, mucus depletion, and disruptions of the commensal microbiota. Giardia increases epithelial permeability and facilitates the invasion of gut bacteria. Loss of intestinal barrier function is at the core of the acute and post-infectious complications associated with this infection. Recent findings demonstrate that the majority of the pathophysiological responses triggered by this parasite can be recapitulated by the effects of its membrane-bound and secreted cysteine proteases.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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.
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