Table 1.

Selection of studies on gut virome changes in humans in various disease states

Disease	Study population	Major finding	Authors
Malnutrition	Healthy twins (n = 8 pairs) versus twins discordant for severe malnutrition (n = 12 pairs)	Bacteriophage as well as members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs	Reyes et al. 2015 [50]
Clostridium difficile infection (CDI)	CDI patients (n = 24) versus healthy controls (n = 20)	Treatment response in FMT associated with a high colonization level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI	Zuo et al. 2018 [51]
Inflammatory bowel disease (IBD)	Crohn’s disease (n = 16) and ulcerative colitis (n = 36) and household controls (n = 21)	Enteric virome richness was increased in Crohn’s disease and ulcerative colitis, and both forms of IBD were associated with a significant expansion of Caudovirales bacteriophages	Norman et al. 2015 [52]
Colorectal cancer (CRC)	CRC cases (n = 74) and controls without CRC (n = 92) in Hong Kong. Validated in three independent European cohorts	Dysbiosis of the gut virome was associated with early- and late-stage CRC. A combination of four taxonomic markers was associated with reduced survival of patients with CRC	Nakatsu et al. 2018 [53]
Acquired immune deficiency syndrome (AIDS)	HIV-negative (n = 40), treatment naïve (n = 40), and treated HIV patients (n = 40) in Uganda	Alterations in the enteric virome and bacterial microbiome were associated with low peripheral CD4 T cell counts rather than HIV infection alone	Monaco et al. 2016 [54]
Type 1 diabetes (T1D)	11 infants from Finland and Estonia recruited at birth based on their HLA risk genotype and followed for 36 months	Significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Higher diversity and richness of bacteriophages in controls compared with cases	Zhao et al. 2017 [55]
Type 2 diabetes (T2D)	T2D patients (n = 71) and non-diabetic Chinese adults (n = 74), validated in independent cohort	Observed a significant increase in the number of gut phages in the T2D group and identified seven phage operational taxonomic units specific to T2D. Significant alterations of the gut phageome not explained by co-variation with the altered bacterial hosts	Ma et al. 2018 [56]
Hypertension	Healthy controls (n = 41), pre-hypertension (n = 56), and hypertension patients (n = 99) in China	Noted that certain viruses can be selected as biomarkers to distinguish healthy people, pre-hypertension people, and hypertension patients. Viruses had superior resolution and better discrimination power than bacteria for identifying hypertension samples	Han et al. 2018 [57]
Parkinson’s disease (PD)	PD patients (n = 31) and control individuals (n = 28)	Identified shifts of the phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, both major factors implicated in PD pathogenesis	Tetz et al. 2018 [58]