Nature sub-journal: Enteroviromics can predict disease

At birth, human babies begin to develop a complex, intertwined microbial structure in their guts

In a new study published in the journal Nature Microbiology , Efrem Lim and his colleagues explored a galaxy of viruses, known as enterovirus groups, that reside in the gut

Professor Lim is a research fellow at the Centre for Fundamental and Applied Microbiology of Biodesign

The study was conducted in collaboration with colleagues at Arizona State University and researchers at the University of Washington School of Medicine

Although the bacterial composition of the gut microbiome has received considerable research attention, viruses that inhabit the gut remain a largely unknown area

"Over the years, there have been some indications that the microbiome is involved in this rapidly evolving disease," Lim said

However, teasing out the specific microbial changes that lead to the disease has been a challenge, and the exact mechanisms that cause it remain unknown

A microbial world is born

Microbes begin to colonize the baby's gut at birth, when the baby encounters a variety of microbes from the mother's vagina

Babies acquire new microbes from other family members and non-family members, and even household pets

This vast microbial community will affect many aspects of an individual's health throughout a person's lifetime

before their time

Preterm birth usually refers to a baby less than 37 weeks gestational

In 2020, 1 in 10 babies born in the United States will be affected by preterm birth

Premature babies are also at risk for NEC

an invisible disease

While the disease rarely occurs in full-term infants, the mysterious disease affects one in 1,000 premature babies

The disease causes severe inflammation of intestinal tissue, leading to death

While research strongly suggests that changes in the gut microbiome are responsible for NEC pathogenesis, no single bacterial genus has been consistently associated with the disease

Infants who survive often face lifelong health problems, including neurodevelopmental disorders and short bowel syndrome
.

The role of the virus

In the current study, stool samples were collected from 138 infants 11 weeks after birth
.
The samples came from 23 premature babies in a neonatal intensive care unit in St.
Louis, Missouri
.
Nine of the infants had NEC, while 14 weight- and gestational-age-matched infants did not
.

The study explored the samples using metagenomics, a sequencing method that allows researchers to comprehensively sample genes from all organisms present in the sample
.
This enables microbiologists like Lim to assess bacterial diversity and detect microbial abundance in various environments
.
The technology also enables detailed studies of microorganisms that are difficult or impossible to grow in the laboratory
.
(In early 2020, Lim used metagenomic sequencing to rapidly probe the 30,000-letter code of the SARS CoV-2 virus, identifying a unique mutation
.
)

Studies have shown that NEC infants exhibit viral and bacterial aggregation characteristics in the enterovirus population
.
Notably, children with NEC had reduced viral composition diversity between different populations in the gut, a feature known as beta-diversity
.
Viral beta-diversity decreased in the 10 days prior to NEC onset, providing a potential biomarker that alerts clinicians to potential dangers
.
The findings suggest that the development of viral populations holds important clues to the health of preterm infants
.

Microbial vision

This research could lead not only to faster diagnosis and better treatment of NEC, but also to a broad spectrum of diseases mediated by the microbiome
.
Furthermore, existing treatments targeting the gut microbiota, such as fecal transplant therapy, could be further improved by assessing viral components
.

This study shows that there is much to learn from as-yet-unexplored viral components of the microbiome, which almost certainly plays an important role not only in the transition to NEC in preterm infants, but also in other diseases
.
With new and rapidly evolving sequencing technologies, researchers can begin to mine virus populations for valuable diagnostic markers of disease and develop more effective treatments
.

Efrem Lim is the recipient of the 2022 ASU Faculty Research Achievement Award presented at ASU Founders Day celebrations on March 17
.

Author: Richard Harth