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Our results suggest that H(2)S donors could be used therapeutically during colitis, facilitating correction of microbiota biofilm dysbiosis and mucus layer reconstitution.

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 microbiota 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.

Irritable bowel syndrome (IBS) is a commonly encountered chronic functional gastrointestinal (GI) disorder. Approximately 10% of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery. The appearance of new IBS symptoms following an infectious event is defined as post-infectious-IBS. Indeed, with the World Health Organization estimating between 2 and 4 billion cases annually, infectious diarrheal disease represents an incredible international healthcare burden. Additionally, compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features. A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota, epithelial barrier integrity, effector cell functions, and innate and adaptive immune features, all proposed physiological manifestations that can underlie GI abnormalities in IBS. Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms, and illicit successful infections. Consequently, the impact of infectious events on host physiology can be multidimensional in terms of anatomical location, functional scope, and duration. This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease, but may also lead to the establishment of chronic GI dysfunction compatible with IBS.

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