Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms

Abstract

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 between Molecular Approach and Clinical Expertise—Searching for Gap Fillers in the Oxidative Stress Way of Thinking

“…Furthermore, additional surveys indicate increased levels of families belonging to Bacteroidetes phylum [27,53], Giardia duodenalis constituting one of the commonly related post-infections parasites in IBS, microbiota's biofilm indicating a reduction from 100-210 to 10-105 µM [54]. Lyra et al [29] designed a study with the aim of distinguishing IBS subtypes by dividing volunteers into three categories: IBS-D, IBS-C, and IBS-M.…”

The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis

“…Exposure of lab strains of Escherichia coli or human intestinal microbiota to Giardia was able to convert the bacteria to a toxic state that is deadly to Caenorhabditis elegans [27]. Moreover, the same group demonstrated that Giardia caused not only microbial dysbiosis in co-cultures with human mucosal microbial biofilms, but also increased virulence of commensal microbiota towards human epithelial cells in vitro ; this report also described increased levels of inflammatory markers in humanized germ-free mice that were reconstituted with human intestinal microbes that had been exposed to Giardia products, but not the living parasite [28]. These Giardia -altered biofilms were capable of inducing immunopathology (intestinal permeability) that was dependent on microbial community disruption caused by Giardia secretory proteases.…”

Modeling Host-Microbiome Interactions in Caenorhabditis elegans

“…Infection with certain pathogens is known to lead to microbiome dysbiosis (Beatty et al, 2017), which has been implicated in a variety of post-infectious inflammatory disorders in humans. Parasitic (e.g., Giardia duodenalis) and bacterial (e.g., Campylobacter jejuni) infections have been found to cause post-infectious irritable bowel syndrome and flares in patients with inflammatory bowel (Buret, 2016).…”