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Characterizing Enterotypes in Human Metagenomics: A Viral Perspective

ABSTRACT: The diversity and high genomic mutation rates of viral species hinder our understanding of viruses and their contributions to human health. Viral enterotypes as a description of the gut virome, its characteristics have not been thoroughly studied. Here we investigated the human gut virome composition using previously published sequencing data of 2,690 metagenomes from seven countries with various phenotypes. We found that the virome was dominated by double-stranded DNA viruses in our data, and young children and adults showed different stages in their fecal enterovirus composition. Beta diversity showed there were significantly less homogeneous in individuals with severe disorders of bile acid secretion, such as cirrhosis. In contrast, there were no significant differences in distances to centroids or viral components between patients with phenotypes unrelated to bile acid, such as hypertension. Enterotypes determined independently from various projects showed similar specific viruses and enrichment direction. Confounding factors, such as different sequencing platforms and library construction, did not confuse enterotyping. The gut virome composition pattern could be described by two viral enterotypes, which supported a discrete, rather than a gradient, distribution. Three main components, enterotype 1 and 2 specific viruses and the other, comprise the total viral variation in these sets. Compared with enterotype 2, enterotype 1 had a higher viral count, Shannon index, and similarity between samples. The relative abundance of enterotype-specific viruses is a crucial determinant of enterotype assignment. Samples not matching any of the defined enterotypes in the database did not necessarily correlate to sickness. Therefore, the background context must be carefully considered when using a viral enterotype as a feature for disease prediction. Our results highlight important insights into the human gut virome composition by exploring two-main viral enterotypes in population and providing an alternate covariate for early disease screening.

SUBMITTER: Song L

PROVIDER: S-EPMC8511818 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Two molecular phenotypes of sepsis and acute respiratory distress syndrome, termed hyperinflammatory and hypoinflammatory, have been consistently identified by latent class analysis in numerous cohorts, with widely divergent clinical outcomes and differential responses to some treatments; however, the key biological differences between these phenotypes remain poorly understood. We used host and microbe metagenomic sequencing data from blood to deepen our understanding of biological differences between latent class analysis-derived phenotypes and to assess concordance between the latent class analysis-derived phenotypes and phenotypes reported by other investigative groups (e.g., SRS1-2, MARS1-4, reactive/uninflamed). We analyzed data from 113 hypoinflammatory and 76 hyperinflammatory sepsis patients enrolled in a two-hospital prospective cohort study. Molecular phenotypes had been previously assigned using latent class analysis. The hyperinflammatory and hypoinflammatory phenotypes of sepsis had distinct gene expression signatures, with 5,755 genes (31%) differentially expressed. The hyperinflammatory phenotype was associated with elevated expression of innate immune response genes, while the hypoinflammatory phenotype was associated with elevated expression of adaptive immune response genes, and notably, T-cell response genes. Plasma metagenomic analysis identified differences in prevalence of bacteremia, bacterial DNA abundance and composition between the phenotypes, with an increased presence and abundance of Enterobacteriaceae in the hyperinflammatory phenotype. Significant overlap was observed between these phenotypes and previously identified transcriptional subtypes of acute respiratory distress syndrome (reactive/uninflamed) and sepsis (SRS1-2). Analysis of data from the VANISH trial indicated that corticosteroids might have a detrimental effect in hypoinflammatory patients. The hyperinflammatory and hypoinflammatory phenotypes have distinct transcriptional and metagenomic features that could be leveraged for precision treatment strategies.

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Characterizing Enterotypes in Human Metagenomics: A Viral Perspective

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