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Twins Study Explores Gut Virome Role in Severe Acute Malnutrition Risk

NEW YORK (GenomeWeb) – By tracking the gut viromes of twins with or without severe acute malnutrition, a team from the US, Colombia, and Malawi has uncovered viral patterns linked to both normal microbiome development and malnutrition risk.

As they reported in the Proceedings of the National Academy of Sciences, the researchers used metagenomic sequencing to identify virus-like particles in fecal samples collected over more than two years from 20 identical or non-identical twin pairs from Malawi. In eight of the twin pairs, both individuals were healthy. But another 12 pairs were discordant for severe acute malnutrition, with one twin appearing healthy and the other suffering from malnutrition-related conditions such as kwashiorkor or marasmus.

Despite appearances, though, the team's results uncovered gut virome similarities between malnourished and seemingly healthy members of discordant twin pairs, even after treatment with therapeutic foods meant to curb malnutrition. In each case, gut virome features diverged from those found in healthy twin pairs.

"[W]e identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs," senior author Jeffrey Gordon, director of Washington University's Center for Genome Sciences and Systems Biology, and his co-authors noted. "This developmental program is impaired in both members of the [severe acute malnutrition] discordant pairs and not repaired with [ready-to-use therapeutic food]."

While some children affected with severe acute malnutrition experience a form of progressive wasting known as marasmus, the researchers explained, others develop a set of symptoms known as kwashiorkor, which include liver problems, anorexia, skin irritations, and so on.

Past studies suggest gut bacterial community progression tends to lag behind in children experiencing both types of severe acute malnutrition, hinting that gut microbiome immaturity contributes to the risk of such conditions. But less is known about the role that viral components of the gut microbiome play in severe acute malnutrition risk, particularly in cases where one twin is affected by the condition and the other is not.

To explore this in more detail, Gordon and his colleagues focused on a subset of Malawian twin pairs tested for a prior malnutrition study, including a dozen sets of twins who were discordant for severe acute malnutrition and eight pairs of healthy twins.

Using multiple displacement amplification and shotgun pyrosequencing, the team searched for DNA viruses in 231 fecal samples collected from members of the twin pairs, their mothers, and siblings over the span of 30 months.

From the nearly 17,700 viral-like particle contigs in the samples, together with viral contig abundance measurements, the researchers were able to characterize the diversity and relative representation of DNA viruses in the gut microbiomes of healthy and malnourished twins over time.

In particular, their results pointed to distinct age-related gut virome patterns in concordantly healthy twin pairs, which shared more gut virome similarities with one another than did healthy American adults, who had more variable viral compositions in their gut microbiomes.

The team saw altered and delayed gut microbiome development in both healthy and malnutrition-affected children from discordant twin pairs, both before and after these children received ready-to-use therapeutic food to treat severe acute malnutrition. Gut virome diversity also tended to be lower in the twin pairs where one child suffered from marasmus or kwashiorkor.

Based on these and other findings, the study's authors concluded that "specification of normal [gut virome] community 'fate' is perturbed in both members of a discordant twin pair."

"[T]he shared virome features of their 'healthy' sibling provide an operational definition of a sensitized, at risk host/microbial community," they noted.