Viruses in the gut may warn of a deadly disease in preterm infants


Date:
April 25, 2022
Source:
Arizona State University
Summary:
Medical researchers explore the galaxy of viruses present in the
gut, known as the gut virome. They find that some preterm infants
undergo marked alterations in their pattern of gut viruses shortly
before developing a serious and often fatal disease known as
necrotizing enterocolitis (NEC).



FULL STORY ========================================================================== Immediately after birth, human infants begin to develop a complex,
interwoven fabric of microbes in their gut. Known collectively as the
gut microbiome, this diverse ecosystem consists of bacteria, archaea,
viruses and fungi, numbering in the billions. All have important roles
to play in health and disease and researchers are racing to better
understand their enigmatic activities.


==========================================================================
In a new study published in the journal Nature Microbiology, Efrem Lim and
his colleagues explore the galaxy of viruses present in the gut, known
as the gut virome. They find that some preterm infants undergo marked alterations in their pattern of gut viruses shortly before developing a
serious and often fatal disease known as necrotizing enterocolitis (NEC).

Professor Lim is a researcher in the Biodesign Center for Fundamental
and Applied Microbiomics. He is also the principal investigator of the
Center for Viral Genomics at ASU and an assistant professor at ASU's
School of Life Sciences.

The study was conducted in collaboration with ASU colleagues and
researchers from the Washington University School of Medicine.

Although the bacterial component of the gut microbiome has received considerable research attention, viruses inhabiting the gut remain a
largely hidden realm. The viral signature highlighted in the study,
along with changes in gut bacterial communities, could provide an early
warning signal that an infant is at risk of developing NEC, allowing
clinicians to take emergency action.

"For many years now, there's been some inkling that the microbiome is implicated in this rapidly developing disease," Lim says. "Studies have
shown that changes in the microbiome of the gut in these preterm infants
seem to predict the progression to NEC disease." Yet teasing out the
specific microbial changes leading to the disease has been challenging
and the precise mechanism causing the affliction is still unknown.

The current study is the first to comprehensively investigate changes
in the viral microbiome that appear to set the stage for the development
of NEC in preterm infants.



==========================================================================
A microbial world is born Microbes begin colonizing the infant gut
during birth, when a baby encounters a variety of microorganisms from
its mother's vaginal tract. As the baby suckles, it picks up additional microbes from its mother's skin as well as those that have infiltrated
her breast milk.

The infant will acquire new microbes from other family and non-family
members and even from household pets. These all become incorporated into
the developing gut microbiome, composed of some 20-100 billion microbes.

This vast microbial community will go on to shape many aspects of an individual's health, throughout the person's life. Unsurprisingly,
abnormal alterations in the gut microbiome can spell serious trouble
and premature infants are particularly vulnerable to such disruptions.

Before their time Preterm birth usually refers to infants born after less
than 37 weeks of pregnancy. The condition appears to be on the rise,
though the causes of this are not fully understood. In many low-income countries, factors including HIV, infections, malaria, and high adolescent pregnancy rates have all been implicated.



==========================================================================
In 2020, preterm birth affected 1 of every 10 infants born in the United States. Babies born too early (particularly before 32 weeks), have higher
rates of death and disability. Those that survive may experience lasting
health issues, including feeding difficulties; breathing, vision and
hearing problems; and abnormalities including developmental delays and
cerebral palsy.

Babies born prematurely are also at risk of NEC. The disease often strikes suddenly. When babies are born after fewer than 32 weeks of gestation,
the incidence of NEC ranged from 2-7% in high-income countries. Mortality
among infants with necrotizing enterocolitis ranges from 22-38%.

A stealthy disease While rarely occurring in full-term infants, this
largely mysterious disease affects 1 in 1,000 premature babies. The
condition strikes without warning and can cause an infant to go from
appearing healthy to a dire state of illness within hours. The disease
usually occurs two to six weeks after birth.

The disease produces severe inflammation of intestinal tissue, causing
it to die. Such afflictions are known as necro-inflammatory diseases. A perforation may also form in the intestine, allowing bacteria to leak
into the abdomen or bloodstream. The sequence of steps leading to NEC
remain unclear, though risk factors are believed to include the prolonged
use of antibiotics early in life and formula feeding (in addition to
preterm birth).

Although studies have strongly implicated changes in the gut microbiome
as contributors to the development of NEC, no single bacterial genus
has been consistently associated with the disease.

Babies who survive the affliction often face lifelong health issues,
which can include neurodevelopmental disabilities and a condition known
as short bowel syndrome.

The role of viruses In the current study, 138 stool samples were collected
over the first 11 weeks of life. The samples were from 23 preterm infants
in a neonatal intensive care unit in St. Louis, Missouri. Nine of these
infants developed NEC, while 14, matched for weight and gestational age,
did not.

The study explored the samples using metagenomics, a sequencing
method that allows researchers to comprehensively sample genes from
all organisms present in a sample. This allows microbiologists like
Lim to evaluate bacterial diversity and detect microbial abundance in
various environments. The technique also enables the detailed study
of microorganisms that are difficult or impossible to culture 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.) The study demonstrates that the NEC infants showed a convergence of viral and bacterial signatures in the gut virome. Notably, babies with NEC showed a reduced diversity in viral composition between communities in the gut, a feature known as ?-diversity. The diminishing
viral ?-diversity occurred over a 10-day period preceding the onset
of NEC, providing a potential biomarker, alerting clinicians to the
looming danger. The findings suggest that the developing virome holds
vital clues reflecting on the health of preterm infants.

Microbial horizons The research could lead not only to faster diagnosis
and better therapies for NEC but also for a broad range of diseases
mediated by the microbiome. Further, existing therapies directed at
modifying the gut microbiome, for example, fecal transplant therapy,
could be further improved by taking stock of the viral component.

The study demonstrates that the underexplored viral constituents of the microbiome have much to teach us and almost certainly play 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 the virome for valuable diagnostic signposts
of disease and develop more effective therapies.

Efrem Lim is the 2022 recipient of the ASU Faculty Research Achievement
Award, delivered at the university's Founder's Day celebration on
March 17.


========================================================================== Story Source: Materials provided by Arizona_State_University. Original
written by Richard Harth. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Emily A. Kaelin, Cynthia Rodriguez, Carla Hall-Moore, Julie
A. Hoffmann,
Laura A. Linneman, I. Malick Ndao, Barbara B. Warner, Phillip
I. Tarr, Lori R. Holtz, Efrem S. Lim. Longitudinal gut virome
analysis identifies specific viral signatures that precede
necrotizing enterocolitis onset in preterm infants. Nature
Microbiology, 2022; DOI: 10.1038/s41564-022- 01096-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220425172138.htm

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