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Changes in the Microbiome of Cryptosporidium-Infected Mice Correlate to Differences in Susceptibility and Infection
Raheela Charania1, Brandy E Wade1, Nina N McNair1
1Department of Pediatrics, Emory University, Atlanta, GA 30033, USA.
Abstract:
Cryptosporidium spp. are opportunistic protozoan parasites that infect epithelial cells of the small intestine, causing diarrheal illness in humans. Differences in severity may be due to the immunological status of the host, malnutrition or prior exposure but may also be due to differences in the host gut flora. We examined changes in bacterial flora following antibiotic treatment to determine how cryptosporidial infections and gut integrity were affected by alterations in the microbiome. DNA was extracted from fecal and intestinal samples during peak infection. V4 region amplicons were generated and sequenced using 16sRNA on an Illumina MiSeq. Species evenness and richness were estimated using the Shannon diversity index. There was a significant decrease in anaerobes and overgrowth of Enterobacteriaceae in mice treated with cloxacillin. We also examined levels of short-chain fatty acids in fecal samples. There was a significant decrease in acetate, propionate, and butyrate in these same mice. Concurrent with the shift in bacterial infection was a significant increase in severity of cryptosporidial infection and increase in gut permeability. Treatment with other antibiotics significantly altered the microbiome but did not change the infection, suggesting that specific alterations in the host microbiome allow for more favorable growth of the parasite.
Insights
Antibiotic treatment altered the gut microbiome, decreasing beneficial anaerobes and increasing harmful bacteria. This shift worsened cryptosporidiosis severity and gut permeability in mice.
Area of Science:
- Microbiology
- Immunology
- Parasitology
Background:
- * Cryptosporidium parasites cause diarrheal illness by infecting intestinal epithelial cells.
- * Infection severity can be influenced by host immunity, nutrition, and gut microbiome composition.
Purpose of the Study:
- * To investigate how antibiotic-induced alterations in the gut microbiome affect cryptosporidial infections and intestinal integrity.
- * To determine if specific microbiome changes favor parasite growth.
Main Methods:
- * Fecal and intestinal DNA extraction and 16S rRNA gene sequencing (Illumina MiSeq) to analyze bacterial flora.
- * Estimation of species evenness and richness using the Shannon diversity index.
- * Measurement of short-chain fatty acids (SCFAs) in fecal samples.
Main Results:
- * Cloxacillin treatment significantly reduced anaerobes and increased Enterobacteriaceae, alongside decreased SCFA levels (acetate, propionate, butyrate).
- * This specific microbiome shift correlated with increased cryptosporidial infection severity and gut permeability.
- * Other antibiotics altered the microbiome but did not impact infection severity.
Conclusions:
- * Specific alterations in the host gut microbiome, such as those induced by cloxacillin, can promote more favorable conditions for Cryptosporidium parasite growth.
- * The gut microbiome plays a critical role in modulating the host's susceptibility and response to cryptosporidiosis.
