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.

Highlights

  • Cryptosporidiosis can be severe and life threatening in immunocompromised individuals [1]

  • We found that in contrast to decreasing parasite load, oral antibiotic treatment with cloxacillin significantly increased cryptosporidial infection in treated mice compared to vehicle control (Figure 1a)

  • We examined differences in the microbiome that occurred in antibiotic treated mice that might be responsible for altered growth patterns

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Summary

Introduction

Cryptosporidiosis can be severe and life threatening in immunocompromised individuals [1]. It is the second major cause of diarrheal illness in children globally [2] and repeated infections can lead to long-term growth deficits and cognitive impairment [3]. Differences in susceptibility to and severity of Cryptosporidium parvum infections have been observed but are not fully understood. These differences are likely multifactorial, including immunological status of the host, previous exposure, nutrition, and genetics. A disrupted gut microbiome increases susceptibility to several parasitic diseases including amoebic dysentery in children [5], Giardia infections [6], and malaria [7]

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