Genome Sequencing Detects Harmful Bacteria In Neonates

The Quadram Institute and University of East Anglia researchers have determined what makes some gut bacterial strains deadly in neonates. The research, which has just been published in the journal Nature Microbiology, will aid in the detection and tracking of harmful strains and the defense of neonates.

Necrotizing enterocolitis (NEC) poses a serious risk to neonates with exceptionally low birth weights. This microbial illness, which is rare in full-term newborns, preys on weaknesses to destroy gut tissue and cause serious consequences. Five cases out of ten result in death.

Clostridium perfringens is one bacterium species that is particularly prone to causing sudden and severe illness. These are widespread in the environment, and healthy human stomachs are home to non-disease-causing types.

Why are some strains particularly harmful to premature infants?

The first significant investigation on the C. perfringens genomes from preterm neonates, including some infants with necrotizing enterocolitis, was headed by Prof. Lindsay Hall and Dr. Raymond Kiu from the Quadram Institute and UEA.

The study team looked at the genomes of C. perfringens in the feces of 70 infants who were admitted to five NICUs in the UK. Based on chromosomal similarities, they discovered one group had a lower likelihood to cause disease. This made it possible to compare them to the more virulent ones. The less virulent strain is deficient in other elements required for colonization and survival as well as the genes required for the production of the PFO toxin.

This study has begun to identify genetic markers for C. perfringens in both healthy preterm infants and those who have necrotizing enterocolitis.

Prof Lindsay Hall, from UEA’s Norwich Medical School and the Quadram Institute, said, “Exploring genomic signatures from hundreds of Clostridium perfringens genomes has allowed us potentially to discriminate between ‘good’ bacterial strains that live harmlessly in the preterm gut, and ‘bad’ ones associated with the devastating and deadly disease necrotizing enterocolitis.

“We hope the findings will help with ‘tracking’ deadly C. perfringens strains in a very vulnerable group of patients—preterm babies.”

There may be a need for larger studies, in more locations, and with more samples, but this research could point to more effective strategies to manage necrotizing enterocolitis.

The group has previously collaborated with Prof. Paul Clarke and medical coworkers at the NICU of the Norfolk and Norwich University Hospital. They also showed the advantages of giving probiotic supplements to newborns.

Neonatal newborns with enterocolitis have dramatically altered gut microbiomes, which makes them more vulnerable to C. perfringens overgrowth.

Prof Hall said, “Our genomic study gives us more data that we can use in the fight against bacteria that cause disease in babies—where we are harnessing the benefits of another microbial resident, Bifidobacterium, to provide at-risk babies with the best possible start in life.”

Dr. Raymond Kiu, from the Quadram Institute, said, “Importantly, this study highlights Whole Genome Sequencing as a powerful tool for identifying new bacterial lineages and determining bacterial virulence factors at strain level which enables us to better understand disease.”

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