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Researchers Sequence Genome of Milk-Using Bacteria Found in Babies' Gut

NEW YORK (GenomeWeb News) – Researchers have sequenced the genome of a bacterial strain called Bifidobacterium longum subsp. infantis ATCC15697 that lives in the gut of breast-fed infants and uses sugars from human breast milk.
 
The work, which is scheduled to appear online this week in the Proceedings of the National Academy of Sciences, provides clues about the co-evolution of the bug, its infant host, and human milk itself.
 
“As an infant commensal, the evolutionary heritage of B. longum subsp. infantis is necessarily linked to milk and thus its genome dramatically recapitulates the pressures encountered in the mammalian [gastrointestinal tract],” the authors wrote. “Clearly, the refinement of milk through the millennia is reflected in benefits to the infant which offset the significant energetic costs exacted from the mother during lactation.”
 
Microbes colonize infants’ gastrointestinal tracts shortly after birth. The formation of a stable gut microbial consortium appears to be beneficial to the host, since it competes with pathogenic species that may otherwise colonize the region.
 
Breast-fed infants tend to have high levels of bifidobacteria — Gram positive, anaerobic bacteria that form symbiotic relationships with humans. Some of these bugs seem to specialize in using specific oligosaccharides in human breast milk that the infant host lacks enzymes to digest.
 
“[W]e have previously demonstrated that select bifidobacterial phylotypes use specific oligosaccharides ubiquitous in human milk and secreted early in the lactation cycle,” the authors wrote. “Of the 200 known compositions, five low molecular weight oligosaccharides abundant in breast milk are the preferred substrates of Bifidobacterium longum subsp. infantis ATCC15697, the archetypal [human milk oligosaccharide]-using bacterium.”
 
In an effort to dig up the genetic roots of this apparent co-evolution, researchers from the University of California at Davis, the US Department of Energy’s Joint Genome Institute, and the US Department of Agriculture’s Agricultural Research Service used whole-genome shotgun sequencing to sequence the 2,832,748 base pair genome of Bifidobacterium longum, subspecies infantis to about eight times coverage.
 
More than 20 other bifidobacterial genome projects are reportedly underway. Two other B. longum phylotypes — B. longum subsp. longum and B. longum subsp. adolescentis — have already been sequenced and are housed in public databases.
 
B. longum subsp. infantis has the largest bifidobacterial genome sequenced so far. The team’s analysis suggests the newly-sequenced genome contains 2,423 predicted protein-coding genes — including 702 unique genes not found in related organisms — and 91 non-coding RNA genes.
 
In general, the organism’s genes appear to group into similar functional clusters as those in the other bifidobacterial genomes, though B. longum subsp. infantis seems to have more genes involved in processes such as repair, replication, and recombination.
 
The researchers also found carbohydrate transport and metabolism genes that are consistent with B. longum subsp. infantis’ ability to use oligosaccharides, including clusters of genes involved in oligosaccharide import and processing.
 
And consistent with its role as a commensal organism, B. longum subsp. infantis appears to have genes involved in interactions with its human host as well as specialized machinery for sensing environmental cues. In addition, the team found that the genome contains genes that may benefit the host, including biosynthetic pathways for the vitamins riboflavin, thiamin, and folate.
 
Overall, the genome sequence supports the notion that B. longum subsp. infantis uses “a competitive nutrient-utilization strategy targeting milk-borne molecules which lack nutritive value to the neonate.”
 
“[T]he tripartite relationship of B. longum subsp. infantis, its infant host, and milk provides a fascinating example of co-evolution to be explored in subsequent studies of the human microbiome,” the authors concluded. “Moreover, it is through this evolutionary perspective that the present composition of milk must be considered, so as to fully appreciate the extent to which purifying selection has culled superfluous components from this fluid secretion and sustained beneficial properties including the enrichment of select commensals.”
 

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