Evolutionary explanation? Research reveals how gut bacteria adapted to human breast milk

Researchers say they have uncovered a possible evolutionary route for the mutually beneficial relationship between gut microbes and humans. Academics from Japan and Australia believe that Bifidobacterium longum has successfully adapted to the unique niche of the infant gut by producing an enzyme called LnbX, which enables this microbe to grow on a sugar that is abundant only in human milk.

"Given the health-promoting effects of bifidobacteria, our findings reveal a possible evolutionary route for the breast milk-driven symbiosis between gut microbes and humans," said co-senior study author Takane Katayama of Kyoto University.

Writing in the journal Cell Chemical Biology, the research team stated they had previously characterised the enzymes LnbB and LnbX, which degrade the human milk oligosaccharide lacto-N-tetraose in Bifidobacterium bifidum and Bifidobacterium longum, respectively.

In the new study, they found LnbX has a distinct structure and catalytic mechanism from LnbB.

"Even though B. longum and B. bifidum belong to the same genus and inhabit the same environment, they use different enzymes to break down lacto-N-tetraose, taking advantage of the varied structures of this unique human milk sugar," said co-author Shinya Fushinobu, from the University of Tokyo.

"The findings suggest that different strains and species of beneficial bifidobacteria have independently evolved distinct molecular tools to digest the same human milk sugar, explaining their ability to co-exist and thrive in the gastrointestinal tract of breast milk-fed infants."

Selective pressure

Additional experiments showed that the LnbX gene is critical for the ability of B. longum to grow specifically on lacto-N-tetraose.

Moreover, an analysis of faecal DNA revealed that B. longum and the lnbX gene were more abundant in the gastrointestinal tract of ten infants that exclusively consumed breast milk compared with six infants fed a mixture of formula and breast milk.

"Taken together, these findings suggest that LnbX is important for B. longum to persist in the gut ecosystem of breast milk-fed infants, and human milk sugars have been the main selective pressure for the evolution of LnbX," Katayama said.

In future studies, the researchers will investigate whether other bifidobacterial species produce different enzymes to digest breast milk sugars. They will also look for bifidobacterial metabolites that promote infant health.

This research could improve formula milk through fortification either with beneficial bacterial compounds, or with microbial enzymes that have been manipulated to carry out the reverse reaction and synthesize human milk sugars at a low cost and large scale.

"Although breast feeding during the first year of life is recommended in most cases, some mothers have to rely on formula milk because they have viral infections or do not produce milk with key nutrients such as zinc," Katayama said

"Therefore, the development of new strategies to fortify formula milk with health-promoting ingredients will be especially critical in these rare cases where breast milk feeding is not possible."

Source: Cell Chemical Biology “Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum”

Authors: Takane Katayama, et al.