Natural Infection with Giardia Is Associated with Altered Community Structure of the Human and Canine Gut Microbiome

Abstract

Enteric parasitic infections are among the most prevalent infections in lower- and middle-income countries (LMICs) and have a profound impact on global public health. While the microbiome is increasingly recognized as a key determinant of gut health and human development, the impact of naturally acquired parasite infections on microbial community structure in the gut, and the extent to which parasite-induced changes in the microbiome may contribute to gastrointestinal symptoms, is poorly understood. Enteric parasites are routinely identified in companion animals in the United States, presenting a unique opportunity to leverage this animal model to investigate the impact of naturally acquired parasite infections on the microbiome. Clinical, parasitological, and microbiome profiling of a cohort of 258 dogs revealed a significant correlation between parasite infection and composition of the bacterial community in the gut. Relative to other enteric parasites, Giardia was associated with a more pronounced perturbation of the microbiome. To compare our findings to large-scale epidemiological studies of enteric diseases in humans, a database mining approach was employed to integrate clinical and microbiome data. Substantial and consistent alterations to microbiome structure were observed in Giardia-infected children. Importantly, infection was associated with a reduction in the relative abundance of potential pathobionts, including Gammaproteobacteria, and an increase in Prevotella—a profile often associated with gut health. Taken together, these data show that widespread Giardia infection in young animals and humans is associated with significant remodeling of the gut microbiome and provide a possible explanation for the high prevalence of asymptomatic Giardia infections observed across host species. IMPORTANCE While enteric parasitic infections are among the most important infections in lower- and middle-income countries, their impact on gut microbiota is poorly understood. We reasoned that clinical symptoms associated with these infections may be influenced by alterations of the microbiome that occur during infection. To explore this notion, we took a two-pronged approach. First, we studied a cohort of dogs naturally infected with various enteric parasites and found a strong association between parasite infection and altered gut microbiota composition. Giardia, one of the most prevalent parasite infections globally, had a particularly large impact on the microbiome. Second, we took a database-driven strategy to integrate microbiome data with clinical data from large human field studies and found that Giardia infection is also associated with marked alteration of the gut microbiome of children, suggesting a possible explanation for why Giardia has been reported to be associated with protection from moderate to severe diarrhea.

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

“…Conversely, Giardia infection was correlated with a decrease of Natronobacillus , Lactobacillus , and Leuconostoc . Similar results were observed in MAL-ED participants (Peru), where Giardia Infection was associated with an enrichment of Prevotella and a reduction in Escherichia (Gammaproteobacteria; Berry et al, 2020 ). LEfSe also revealed an association between Giardia infection and an increase of Faecalibacterium , Blautia , Roseburia , Ruminococcus , and Ruminoccaceae , and an increase of Lachnospiraceae and Lactobacillus contrary to the GEMS study.…”

“…Among the GEMS participants, 215 individuals tested positive for Giardia and were subclassified as having either moderate to severe diarrhea (MSD) or no MSD. Metagenomic biomarker discovery analysis (LEfSe score) revealed that Giardia infection was associated with an enrichment of Prevotella and a reduction in Gammaproteobacteria, regardless of the presence of mild to severe diarrhea ( Berry et al, 2020 ). To a lesser extent, Giardia infection was also associated with an increase of Lachnospiraceae , Ruminococcus , and Clostridiales .…”

“…Giardia positive groups showed an increase in Catenibacterium , Pseudomonas , and Howardella , while Giardia negative groups had higher levels of Bacteroides and Pseudobutyrivibrio ( Slapeta et al, 2015 ). Domesticated dogs infected with Giardia in the United States similarly showed significant changes to fecal microbiome beta-diversity compared to uninfected animals ( Berry et al, 2020 ). Of all the parasites studied ( Giardia , Cystoisospora, hookworm, whipworm, ascaris, and tapeworm), Giardia alone, and Giardia with polymicrobial infections, caused the most significant difference in the beta diversity as compared to non-infected control animals.…”

“…Specifically, Giardia was associated with an enrichment of Clostridium and Lactobacillus and a reduction in Bacteroides as determined by both Bray-Curtis and weighted UniFrac metrics, even when the confounding variables such as age and sex were controlled for. The distinct microbiome profile associated with Giardia positive samples was evident even in the context of co-infections and was observed with and without a history of antibiotic treatment or diarrheal symptoms ( Berry et al, 2020 ). In fact, the Giardia co-infected animals were indistinguishable in terms of beta diversity from the animals that were infected with Giardia alone.…”

Impact of Eukaryotic Enteric Pathogens on Malian Children’s Gut Mycobiota

“…In another study, Saccharomyces boulardii showed a potential benefit for the treatment of acute gastroenteritis in paediatric patients [29]. More interestingly, Blastocystis is usually associated with a "healthy" gut microbiota whereas Giardia is usually associated with gut dysbiosis [29,30]. Thus, whether the wood decaying Coriticiaceae Stereum hirsutum, or the common human opportunistic pathogenic yeast Candida tropicalis are associated with a dysbiotic or a healthy gut microbiota warrant further studies.…”