Changes in the Microbiome of Cryptosporidium-Infected Mice Correlate to Differences in Susceptibility and Infection Levels

Charania, Raheela; Wade, Brandy E.; McNair, Nina; Mead, Jan R.

doi:10.3390/microorganisms8060879

Cited by 38 publications

(32 citation statements)

References 45 publications

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“…Individuals infected with Entamoeba histolytica , the causative agent of amebiasis, were found to have a decreased abundance of protective bacteria generally associated with gut health ( Verma et al, 2012 ). Cryptosporidium was found to alter microbiota composition in mouse models as well as in primates (Coquerel’s sifakas – Propithecus coquerel ), and dysbiosis was associated with enhanced parasite growth ( Ras et al, 2015 ; McKenney et al, 2017 ; Charania et al, 2020 ). Individuals infected with the protist Blastocystis show increased diversity of the gut microbiota in their fecal contents ( Audebert et al, 2016 ; Nieves-Ramirez et al, 2018 ).…”

Section: The Intestinal Microbiomementioning

confidence: 99%

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

et al. 2021

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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.

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Section: The Intestinal Microbiomementioning

confidence: 99%

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

et al. 2021

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“…Furthermore, loss of the microbiota in gnotobiotic and antibiotic-treated adult mice results in an increased susceptibility to Cryptosporidium infection ( 17 ), indicating that a diverse, mature microbiota provides a protective effect against Cryptosporidium sp. A recent study comparing different antibiotics revealed that cloxacillin treatment of mice induced changes in the microbiota and altered metabolites with increased susceptibility ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Neonatal Mouse Gut Metabolites Influence Cryptosporidium parvum Infection in Intestinal Epithelial Cells

VanDussen

Funkhouser-Jones

Akey

et al. 2020

mBio

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The protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals.IMPORTANCECryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvumin vitro. Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo. The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite’s interactions with exogenous fatty acids during the initial stages of infection.

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“…For example, previous work found that antibiotics alone did not sensitize immunocompetent mice to infection [25], although certain probiotics [71], antibiotics [72], and deprivation of prebiotics [73] could exacerbate disease severity.…”

Section: Discussionmentioning

confidence: 99%

Megasphaerain the stool microbiota is negatively associated with diarrheal cryptosporidiosis

Carey

Medlock

Alam

et al. 2020

Preprint

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Background: The protozoan parasites in the Cryptosporidium genus cause both acute diarrheal disease and subclinical (i.e. non-diarrheal) disease. It is unclear if the microbiota can influence the manifestation of diarrhea during a Cryptosporidium infection. Methods: To characterize the role of the gut microbiota in diarrheal cryptosporidiosis, the microbiome composition of both diarrheal and surveillance Cryptosporidium-positive fecal samples was evaluated using 16S rRNA gene sequencing. Additionally, the microbiome composition prior to infection was examined to test whether a preexisting microbiome profile could influence the Cryptosporidium infection phenotype. Results: Fecal microbiome composition was associated with diarrheal symptoms at two timepoints. Megasphaera was significantly less abundant in diarrheal samples when compared to subclinical samples at the time of Cryptosporidium detection (log2(fold change) = -4.3, p=10-10) and prior to infection (log2(fold change) = -2.0, p=10-4). Random forest classification also identified Megasphaera abundance in the pre- and post-exposure microbiota.as predictive of a subclinical infection. Conclusions: Microbiome composition broadly, and specifically low Megasphaera abundance, was associated with diarrheal symptoms prior to and at the time of Cryptosporidium detection. This observation suggests that the gut microenvironment may play a role in determining the severity of a Cryptosporidium infection.

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Changes in the Microbiome of Cryptosporidium-Infected Mice Correlate to Differences in Susceptibility and Infection Levels

Cited by 38 publications

References 45 publications

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

Giardia spp. and the Gut Microbiota: Dangerous Liaisons

Neonatal Mouse Gut Metabolites Influence Cryptosporidium parvum Infection in Intestinal Epithelial Cells

Megasphaerain the stool microbiota is negatively associated with diarrheal cryptosporidiosis

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