Lee Poul O’Brien Andersen:
Blastocystis in a gut microbiota context and aspects of Blastocystis genomics

Date: 29-01-2016    Supervisor: Anders Krogh

Blastocystis is a single-celled intestinal parasite of undetermined clinical and public health importance comprising 17 subtypes (species), of which 9 have been found in humans. In the first study of this thesis, general trends in Blastocystis research are accounted for, and the general assumption that Blastocystis is pathogenic is challenged. For instance, several studies have explored the prevalence and molecular epidemiology of Blastocystis in various groups of patients suffering gastrointestinal symptoms, apparently ignoring the necessity of inclusion of suitable control groups of healthy individuals in order to infer conclusions on pathogenicity.

The second study of this thesis attempts to determine if the vast amount of existing metagenomics data could be used as a resource for Blastocystis prevalence and molecular epidemiology studies. A co-abundance binning method was applied, and Blastocystis information extracted. The results illustrate that the prevalence of Blastocystis in healthy individuals is similar to that observed in patients with gastrointestinal symptoms, including inflammatory bowel disease, or even higher, and that the parasite is negatively associated to gut microbiota predominated by Bacteroidetes.

The latter result was followed up and confirmed by the third study, which utilized a quantitative detection technique. Lastly, several different approaches exist with regard to determining the potential pathogenicity of Blastocystis, one of which includes identification and characterization of genome repertoires, and some studies have suggested that pathogenicity depends on Blastocystis subtype. However, until now, genomes have been available for only two Blastocystis subtypes (ST7 and ST4WR1), with ST1 in the process of being published, and so additional Blastocystis genomes are required to elucidate potential subtype-associated genomic differences.

In the fourth study, the genomes of six different subtypes (ST2, ST3, ST4BT1, ST6, ST8, and ST9) were sequenced, with further exploration into the genetic diversity of the four most prevalent human subtypes (ST1–ST4). All six genomes were assembled and genes called, which increased the combined genetic knowledge, making comparisons on sequence level somewhat possible. The study illustrated the high level of genetic diversity existing between different subtypes, and proposed that subtypes differ in terms of motifs for intron-exon splice sites.