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 Giardia duodenalis, 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 Giardia infection and have been implicated in Giardia 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 Giardia-induced bacterial dysbiosis in the gut and the roles of dysbiosis in Giardia pathogenesis.

Enteric tuft cells are chemosensory epithelial cells gaining attention in the field of host-parasite interactions. Expressing a repertoire of chemosensing receptors and mediators, these cells have the potential to detect lumen-dwelling helminth and protozoan parasites and coordinate epithelial, immune, and neuronal cell defenses against them. This review highlights the versatility of enteric tuft cells and sub-types thereof, showcasing nuances of tuft cell responses to different parasites, with a focus on helminths reflecting the current state of the field. The role of enteric tuft cells in irritable bowel syndrome, inflammatory bowel disease and intestinal viral infection is assessed in the context of concomitant infection with parasites. Finally, the review presents pertinent questions germane to understanding the enteric tuft cell and its role in enteric parasitic infections. There is much to be done to fully elucidate the response of this intriguing cell type to parasitic-infection and there is negligible data on the biology of the human enteric tuft cell—a glaring gap in knowledge that must be filled.

Exogenous factors that may influence the pathophysiology of Giardia infection remain incompletely understood. We have investigated the role of dietary fat in the pathogenesis of Giardia infection. Male 3 to 4-week-old C57BL/6 mice were fed either a low fat (LF) or a high fat (HF) diet for 12 days and challenged with G. duodenalis. In infected animals, the trophozoite burden was higher in HF + Giardia mice compared to the LF + Giardia group at day 7 post infection. Fatty acids exerted direct pro-growth effects on Giardia trophozoites. Analysis of disease parameters showed that HF + Giardia mice exhibited more mucosal infiltration by inflammatory cells, decreased villus/crypt ratios, goblet cell hyperplasia, mucus disruption, increased gut motility, and elevated fecal water content compared with LF + Giardia. HF diet-dependent exacerbation of Giardia-induced goblet cell hyperplasia was associated with elevated Atoh1 and Muc2 gene expression. Gut microbiota analysis revealed that the HF diet alone induces a taxonomic shift. HF + Giardia mice exhibited microbiota dysbiosis characterized by an increase of Firmicutes and a decrease of Bacteroidetes and significant changes in α- and β-diversity metrics. Taken together, the findings suggest that a HF diet exacerbates the outcome of Giardia infection. The data demonstrate that elevated dietary fat represents an important exogenous factor promoting the pathophysiology of giardiasis.

Body tissues are subjected to various oxygenic gradients and fluctuations and hence can become transiently hypoxic. Hypoxia-inducible factor (HIF) is the master transcriptional regulator of the cellular hypoxic response and is capable of modulating cellular metabolism, immune responses, epithelial barrier integrity, and local microbiota. Recent reports have characterized the hypoxic response to various infections. However, little is known about the role of HIF activation in the context of protozoan parasitic infections. Growing evidence suggests that tissue and blood protozoa can activate HIF and subsequent HIF target genes in the host, helping or hindering their pathogenicity. In the gut, enteric protozoa are adapted to steep longitudinal and radial oxygen gradients to complete their life cycle, yet the role of HIF during these protozoan infections remains unclear. This review focuses on the hypoxic response to protozoa and its role in the pathophysiology of parasitic infections. We also discuss how hypoxia modulates host immune responses in the context of protozoan infections.

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