• Viruses in the gut may warn of a deadly

    From ScienceDaily@1:317/3 to All on Monday, April 25, 2022 22:30:42
    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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