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Viruses are the most abundant form of life on earth and play important roles in a broad range of ecosystems. Currently, two methods, whole genome shotgun metagenome (WGSM) and viral-like particle enriched metagenome (VLPM) sequencing, are widely applied to compare viruses in various environments. However, there is no critical assessment of their performance in recovering viruses and biological interpretation in comparative viral metagenomic studies. To fill this gap, we applied the two methods to investigate the stool virome in hepatocellular carcinoma (HCC) patients and healthy controls. Both WGSM and VLPM methods can capture the major diversity patterns of alpha and beta diversities and identify the altered viral profiles in the HCC stool samples compared with healthy controls. Viral signatures identified by both methods showed reductions of Faecalibacterium virus Taranis in HCC patients’ stool. Ultra-deep sequencing recovered more viruses in both methods, however, generally, 3 or 5 Gb were sufficient to capture the non-fragmented long viral contigs. More lytic viruses were detected than lysogenetic viruses in both methods, and the VLPM can detect the RNA viruses. Using both methods would identify shared and specific viral signatures and would capture different parts of the total virome.

The microbiome has been implicated in the development of metabolic conditions which occur at high rates in people with schizophrenia and related psychoses. This exploratory proof-of-concept study aimed to: (i) characterize the gut microbiota in antipsychotic naïve or quasi-naïve people with first-episode psychosis, and people with established schizophrenia receiving clozapine therapy; (ii) test for microbiome changes following a lifestyle intervention which included diet and exercise education and physical activity. Participants were recruited from the Eastern Suburbs Mental Health Service, Sydney, Australia. Anthropometric, lifestyle and gut microbiota data were collected at baseline and following a 12-week lifestyle intervention. Stool samples underwent 16S rRNA sequencing to analyse microbiota diversity and composition. Seventeen people with established schizophrenia and five people with first-episode psychosis were recruited and matched with 22 age-sex, BMI and ethnicity matched controls from a concurrent study for baseline comparisons. There was no difference in α-diversity between groups at baseline, but microbial composition differed by 21 taxa between the established schizophrenia group and controls. In people with established illness pre-post comparison of α-diversity showed significant increases after the 12-week lifestyle intervention. This pilot study adds to the current literature that detail compositional differences in the gut microbiota of people with schizophrenia compared to those without mental illness and suggests that lifestyle interventions may increase gut microbial diversity in patients with established illness. These results show that microbiome studies are feasible in patients with established schizophrenia and larger studies are warranted to validate microbial signatures and understand the relevance of lifestyle change in the development of metabolic conditions in this population.

Alteration of the gut virome has been associated with colorectal cancer (CRC); however, when and how the alteration takes place has not been studied. Here, we employ a longitudinal study in mice to characterize the gut virome alteration in azoxymethane (AOM)-induced colorectal neoplasia and identify important viruses associated with tumor growth. The number and size of the tumors increased as the mice aged in the AOM treated group, as compared to the control group. Tumors were first observed in the AOM group at week 12. We observed a significantly lower alpha diversity and shift in viral profile when tumors first appeared. In addition, we identified novel viruses from the genera Brunovirus, Hpunavirus that are positively associated with tumor growth and enriched at a late time point in AOM group, whereas members from Lubbockvirus show a negative correlation with tumor growth. Moreover, network analysis revealed two clusters of viruses in the AOM virome, a group that is positively correlated with tumor growth and another that is negatively correlated with tumor growth, all of which are bacteriophages. Our findings suggest that the gut virome changes along with tumor formation and provides strong evidence of a potential role for bacteriophage in the development of colorectal neoplasia.