Genomic and Transcriptomic Analyses of Cryptosporidium infections

Sabir, Mumdooh J. (2026) Genomic and Transcriptomic Analyses of Cryptosporidium infections. Doctoral thesis, University of East Anglia.

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Abstract

The microbiome community play a key role in the body’s defence against pathogens. Not only do microbes in the gut help by outcompeting potential pathogens but they also play a key role in the development of the host immune system. Cryptosporidium is the parasite that causes cryptosporidiosis where the infected host can show symptoms such as diarrhoea and stomach pain but sometimes remains asymptomatic. Previous studies demonstrated an association between cryptosporidiosis and the microbiome, in particular changes in the abundance of Fusobacterium.

Advances in next generation sequencing have enabled the profiling of the microbiome in unprecedented detail. This research aims to use this technology to generate Metagenome Assembled Genomes (MAGS) and their annotations to improve bovine gut microbiome profiling, assess whether a particular Fusobacterium species changes in abundance during the infection, compare long and short-read sequencing methods for metagenomic analyses, and characterise gene expression patterns associated with Cryptosporidium host invasion.

This study investigated the microbial community patterns in calves focusing on their relationship to cryptosporidiosis through faecal samples. Short-read metagenomic datasets derived from cattle were reassembled to recover MAGs, a near complete Cryptosporidium genome was reconstructed. Subsequent subtyping analysis based on the GP60 Gene’s trinucleotide repeat and allele sequence, revealed the presence of C. parvum subtype IIaA15G2R1, known to be relevant to European cattle. Reconstructing Fusobacterium genomes revealed F. varium as the dominant species.

Oxford Nanopore long-read sequencing was employed to analyse longitudinal cattle samples and facilitated reconstruction of a high-quality Cryptosporidium genome, and allowing subtyping of IIaA19G2R1. Although bacterial MAGs recovery was achieved, no high-quality genomes of Fusobacterium were identified.

Transcriptomic analysis of COLO-N680 intestinal epithelial cells during cryptosporidiosis was conducted to characterise host cellular responses to Cryptosporidium. Gene expression analysis revealed coordinated activation of innate immune signalling and cytoskeletal remodelling in clear early and late gene clusters. These processes likely change the host environment and cause the observed shifts in the gut microbial communities.

This study has demonstrated the potential of long read sequencing technology to understand dynamics of microbiomes in response to infection and revealed coordinated transcriptomic responses to Cryptosporidium infection.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Chris White
Date Deposited:	20 Oct 2026 08:57
Last Modified:	20 Oct 2026 08:57
URI:	https://ueaeprints.uea.ac.uk/id/eprint/104822
DOI:

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