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Genome Analysis Hints at Co-Evolution by Infant Gut Bacteria

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – By sequencing the genome of a gut bacterial species called Bifidobacterium bifidum PRL2010 from baby stool, an international research team has found clues about how the bug acquires nutrients and interacts with its human host.

"The present study provides a firm basis from which we can define further factors that shape microbial ecology in health and disease and that influence interactions between microbiota and host," corresponding author Marco Ventura, a probiogenomics researcher at the University of Parma in Italy, and co-authors wrote.

The research, which appeared online yesterday in the early, online version of the Proceedings of the National Academy of Sciences, suggests B. bifidum can glean nutrients from glycan sugars found in sugar-protein compounds in the mucin that coats the inside of the human stomach and gastrointestinal tract.

In general, gut microbial communities are thought to contain metabolic enzymes that help break down glycans and other compounds found in food and in the gut itself, producing small molecules that are useful to both microbes and their hosts, the team explained.

"Apart from dietary components, host-derived glycans are believed to constitute a nutrient resource for (certain) members of microbiota," they noted, "and thus may influence the composition and activities of this complex microbial consortium."

For the current study, Ventura and his colleagues focused on B. bifidum, which can grow in the presence of mucin and belongs to a group of bacteria commonly found in the gut of breast-fed babies.

As such, the team reasoned that B. bifidum and related species "may serve as models for studying the interaction between members of the intestinal microbiota and the host mucosa to uncover host features that determine intestinal colonization."

Using a combination of Sanger and Roche 454 GS FLX sequencing, the researchers sequenced the roughly 2.2 million base genome of a B. bifidum PRL2010 strain to an average depth of about 25 times. The sequenced strain was initially isolated from the stool of a healthy three-month old, breast-fed baby.

When they analyzed the genome sequence and compared it to sequences from other bifidobacteria, the team found that the B. bifidum PRL2010 genome is about 96 percent similar to that of another partially sequenced B. bifidum strain called NCIMB 41171.

In both B. bifidum genomes, more than a third of the genes identified belong to a gene family implicated in carbohydrate metabolism and transport, they explained, consistent with a proposed role for the bug in mucin metabolism.

The genome also contains adhesion and other genes expected to contribute to the microbe's colonization of its human host, researchers explained, along with genes coding for glucose and fructose fermentation enzymes, carbohydrate transport genes, and genetic pathways involved in making purines, pyrimidines, riboflavin, thiamine, and folate.

And when they focused in on the genes expected to contribute to mucin metabolism, the team found evidence of gene clusters in B. bifidum that code for some of the enzymes used to degrade glycans found in mucin.

Together, such data — combined with information from comparative genome hybridization, mass spectrometry analyses of the bug's proteome, and transcriptomic analyses of the microbe done using Agilent microarrays — point to genetic specialization that helps B. bifidum use mucin as a carbon source when setting up shop in the human gut.

"[T]he relationship of B. bifidum and host-produced mucin constitutes an intriguing example of co-evolution which should be taken into consideration in future studies of the infant intestinal microbiome," the team concluded.

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