Gut Phageome Analysis Reveals Disease-Specific Hallmarks in Childhood Obesity

Abstract

Changes in the composition of the human gut microbiome are recognized to have a significant association with obesity and metabolic syndrome. Mexico leads worldwide childhood-obesity rankings representing an epidemic problem for public health. To this date, it is still unclear how the gut phageome, the bacteriophage component of the virome, influences childhood obesity and obesity with metabolic syndrome. We characterized the gut phageome of 28 school-age children with healthy normal-weight (NW), obese (O), and obese with metabolic syndrome (OMS) profiles, using metagenomic sequencing of virus-like particles (VLPs) from fecal samples. Viromes derived from VLPs were mainly dominated by Caudovirales, and only Inoviridae family was significantly increased in obesity. The three groups showed a similar number of VLPs, while a significant increase in phage richness and diversity was found in obesity groups compared NW. Few phage contigs dominated the phageome composition in NW, being increased in obesity groups. Interestingly, the majority of the phageome was shared among all individuals, establishing a core and common phageome, which abundances correlated with anthropometric and biochemical traits and bacteria previously associated with obesity and metabolic syndrome. We also established a healthy core phageome shared in >80% of NW samples, with a decreased prevalence in the O and OMS groups. Our data support that changes in the gut phageome may contribute to obesity and metabolic syndrome development via bacterial dysbiosis. We consider the phageome characterization provides the basis for novel diagnostic and therapeutic strategies for managing obesity and preventing metabolic syndrome development in obese children through potential phage manipulation. To the best of our knowledge, this study represents the most in-depth sequenced dataset of human bacteriophages, demonstrating for the first time that alterations of the gut phageome characterize obesity.

Phages modulate bacterial communities in the human gut following fecal microbiota transplantation

“…The time-consistent proportion of conserved and novel vOTUs in the GBT participants suggests that the gut phageomes could be divided into a stable and a uctuating component. The categorization of the phageome into a stable and a uctuating component is consistent with current literature [43,44], and could contribute to the identi cation of a core gut phageome [45][46][47][48][49][50].…”

Longitudinal Analysis of the Intestinal Microbiota in the Obese Mangalica Pig Reveals Alterations in Bacteria and Bacteriophage Populations Associated With Changes in Body Composition and Diet

“…Interestingly, the distinct differences between the gut microbial composition of the limit fed (lean) and ad libitum (obese) pigs observed in the first study are consistent with a role for the gut microbiota. Such changes mirror the evolution of the human gut microbiota during development of human obesity as obese humans experience enrichment of bacteriophage concomitant with abundance changes in numerous bacterial phyla ( Moreno-Gallego et al., 2019 ; Bikel et al., 2020 ; Gregory et al., 2020 ). This would be expected to both promote a more positive energy balance due to more efficient energy harvest from the diet as well as reflecting a more proinflammatory state ( Yang et al., 2021 ).…”

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

“…As the viral component of the human microbiome is presumed to be dominated by bacteriophages [310], temperate phages are believed to play a key role in shaping the bacterial community through horizontal gene transfer [311]. The sheer presence and diversity of available bacteriophages has allowed for disease-specific alterations to the phageome to be observed in relation to a number of gastrointestinal and systemic disorders, including inflammatory bowel disease [312], AIDS [313], malnutrition [314], and childhood obesity [315]. Nonetheless, the human gut phageome remains an area with plenty of "dark matter" yet to be recognized in comparison to the better understood phage marine ecosystems [309].…”