Effects of Western Diet on Giardiasis: A Role for Fatty Acids and Gut Microbiota in the Persistence and Severity of Giardia Infections

Abstract

AIMSGiardia duodenalis is a protozoan parasite responsible for giardiasis, one of the most common cause of waterborne diseases. Giardia. sp causes epithelial disruptions as well as microbiota alterations. Giardia infections are common in countries with poor sanitation, where the diet is mostly agrarian and high in fiber content. Intriguingly, in such environments, giardiasis has commonly been reported to cause little or no illness. Giardiasis also occurs in developed countries with western/high fat diets, where infections are a common cause of diarrhea. This sutdy investigated the role of diet on the severity and the duration of giardiasis. We hypothesized that western diet may contribute to the persistence of Giardia in the gut. Experiments assessed the role of fatty acids and gut microbiota in pathophysiology.METHODSC57/BL6 mice were fed for two weeks with 5TJN Western diet or 5TJS Low‐Fat (LF) diet prior to infection with Giardia duodenalis GS/M strain (human isolate). The small intestines were collected at day 7 post infection (PI) for histological study and parasite burden. Gut microbiota composition was determined by Illumina Mi‐Seq 16S RNA sequencing. The effect of Oleic and Palmitic acid on Giardia metabolic activity was determined by resazurin assay. Finally, tight junction disruption of small intestinal epithelial cell line SCNB infected with G. duodenalis Assemblage A (NF strain) and Assemblage B (GS/M strain) in the presence of Oleic, Palmitic acid (0.3 mM) or both was determined by immunofluorescence.RESULTSWe observed that Giardia infected C57/BL6 mice that were fed with 5TJN Western diet exhibited a significantly higher trophozoite burden 7 days PI. Giardia infected mice also exhibited more severe mucosal damage (lower villus‐crypt ratio) when fed with Western diet. Fecal microbiota analysis showed that mice fed with Western Diet exhibit a higher abundance of Verrucomicrobia and a lower abundance of Firmicutes than mice fed LF diet. Upon Giardia infection, a decrease of Bacteroidetes and an increase of Firmicutes was observed. Overall, Giardia infection induced an increase of the alpha diversity in Western mice compared to mice given LF diet. Trophozoite metabolic activity was enhanced in the presence of Oleic acid (0.1 mM) and Palmitic acid (0.25mM). In addition, small intestine cell lines infected with G. duodenalis strain NF and GS/M showed a disruption and/or a rearrangement of tight junction proteins such as ZO‐1, Claudin‐1 and 4 when incubated with Oleic and Palmitic acids (0.3 mM).CONCLUSIONThis study gives insight into how diet may influence the outcome of parasitic diseases and intestinal pathophysiology. The findings suggest that a Western Diet may increase the severity of giardiasis by, at least in part, promoting the growth of Giardia through fatty acid supplementation and microbiota modulation. The potential of diet intervention in treatment against parasitic diseases warrants further research.Support or Funding InformationGrant support: NSERCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.