Human fecal viral communities from Malawi family F112 ind T2 time point 26.9.08 - Ma_F112T2_26.9.08
The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 months of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth, and 12 twin pairs discordant for SAM (either marasmus or kwashiorkor). Both members of discordant pairs were sampled just prior to, during and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different assembly stages of the gut microbiota in the concordant healthy twin pairs. This normal developmental program was impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus viruses belonging to the Anelloviridae and Circoviridae families of single-stranded eukaryotic viruses discriminate discordant pairs from concordant healthy pairs. These results disclose that apparently healthy co-twins in discordant pairs have viromes indicative of familial risk for SAM and provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota’s viral component in populations at risk for malnutrition.