Influence of bacteria from the duodenal microbiota of patients with symptomatic giardiasis on the pathogenicity of Giardia duodenalis in gnotoxenic mice (original) (raw)
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Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms
Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post-infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut micro-biota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic – even after the clearance of Giardia. These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia-induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll-like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection.
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ABSTRACTGiardia lambliais the most frequently identified protozoan cause of intestinal infection. Over one billion people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in endemic areas. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear as the parasite neither produces a known toxin nor induces a robust inflammatory response.Giardiacolonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact ofGiardiainfection on the host microbiota, we use culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the entire gastrointestinal tract in mice infected withGiardia. We discovered thatGiardia’scolonization of the small intestine causes a systemic dysbiosis of aerobic an...
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Giardia duodenalis (G. duodenalis) is a worldwide cause of acute diarrheal disease both in humans and in animals. Domestic dogs may either harbor the parasite subclinically or showing the infection typical clinical signs. However, because giardiosis is a recognized veterinary threat, testing for this agent is often performed when canine patients are presented to veterinarians. Usually, animals are treated with antiparasitic agents in case of positive test, regardless of the severity of enteric clinical signs. Here we report for the first time a study comparing two groups of clinically healthy German shepherd dogs differing for G. duodenalis colonization. Gut microbiota, the haematological, biochemical and faecal parameters related to the intestinal function were investigated. The results display a scenario in which G. duodenalis exerts an effect upon the gut microbiota affecting the proportion of few bacterial taxa known to be associated with improved lipids metabolism and protectio...