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Smart Sugar?

February 9, 2012

When future historians parse the life and language of early 21st century America, they will be struck by the word “smart.” It’s everywhere. This workhorse 20th-century adjective has morphed into a popular 21st-century prefix that designates new products as technologically cool, from the latest communications device to energy-saving motor vehicles and even our selection of foods.

A fascinating example of the latter is the emergence of the so-called smart sugars. You find them increasingly as sweeteners added to energy drinks, specialty waters, and candies. There are five, most prominently palatinose and leucrose. All have the same glucose-bound-to-fructose chemical composition as table sugar, or sucrose.

However, the five sucro-derivatives have slight structural tweaks in their glucose-to-fructose bonds. The tweaks, like crossing the two vertical lines in “H” slightly off center, seem to throw off the metabolic machinery of some bacteria, slowing their ability to recognize, break down, and metabolize the sugar.

These tweaks are significant for oral health because studies show the streptococcal species can’t metabolize smart sugars at all. Among these species is Streptococcus mutans, long presumed to be a leading cause of tooth decay.

But the presumed oral health benefits of these sugars assume tooth decay primarily is an S. mutans phenomenon. In recent years, the evidence has shifted progressively away from this single-species theory of tooth decay. It is not simply one or even two bacteria in isolation that spoils the tooth. The underlying problem involves a broad ecological shift in bacterial behavior. Think of it as the microbial equivalent of Gresham’s Law: Bad behavior, once unleashed, drives out good behavior. Like a big-city neighborhood fallen on hard times, the new and more unruly bacterial activity leads to trouble on a tooth surface.

How does this emerging theory of tooth decay square with the smart sugars? Not as impressively. One possibility is that although the streptococcal species cannot metabolize smart sugars, other bacteria in the oral biofilm may have the potential to do so. Assuming a person consumed a diet rich in smart sugars, a real possibility in the future, these other oral bacteria could gain a growth advantage. Conceivably, such a change in behavior could alter the community dynamic, and tip the mouth’s microbial balance in good, bad, or otherwise unpredictable ways. Nobody knows which way. Nature has yet to conduct this ecological experiment.

Andreas Pikis and Jack Thompson

Drs. Andreas Pikis and Jack Thompson

Now, in the February 2012 issue of the journal Molecular Oral Microbiology, NIDCR scientists Drs. Jack Thompson and Andreas Pikis show for the first time this potential is biologically real. They report that a common resident of the oral biofilm is genetically and enzymatically equipped to metabolize four of the five smart sugars.

First a little background. The paper builds on findings initially reported by Thompson’s group in the late 1990s. Namely, that several species of non-oral bacteria (eg; Bacillus, Klebsiella and Clostridia) unexpectedly used all five smart sugars as energy sources for growth. These organisms do so by producing specialized enzymes encoded within a functionally integrated cluster of genes, called the sucrose isomer metabolism (sim) operon. Think of an operon as Channels 671, 672, 673, and 674 on your cable menu. Not everybody gets them, but those who do have access to a numerical block of specialized food channels that expand their natural culinary skills.

While examining the DNA sequence of the oral species Leptotrichia buccalis in the Human Oral Microbiome Database, Thompson and Pikis discovered a cluster of genes that strikingly resembled those present in the sim operon. Assuming the two operons are functionally related, the two investigators wondered whether L. buccalis, might also metabolize smart sugars?

L. buccalis was a real interesting candidate. It is one of five species that comprise the Leptotrichia genus. Although typically found in low abundance in the oral biofilm, Leptotrichia species nevertheless are frequent colonizers, and readily ferment dietary sugars to lactic acid. Significantly, Finnish studies from the 1990s indicate that up to three of every four young children have members of the genus in their mouths.

To test their hypothesis, the two investigators grew cultures of L. buccalis on each of the five smart sugars. They found that not only did L. buccalis ferment four of the five – leucrose being the exception – the organism produced a protein similar in size to that encoded by one of the genes in the sim operon. The researchers cloned the gene (called Lebu_1525), and showed that its protein product readily attacked a structural analogue of the smart sugars, thus confirming its enzymatic role in the fermentation process.

Interestingly, Thompson and Pikis subsequently found that some of the Leptotrichia species were better at metabolizing the smart sugars than others. They wondered whether the metabolic variability might be written into the DNA sequence of the sim operon genes. Based on a genomic analysis from genus down to strain, they were able to show that the Lebu_1527 gene encodes a protein that transports the smart sugars into the bacterium. Once internalized, the sucro-derivatives are sliced by the Lebu_1525-encoded enzyme to yield glucose phosphate and fructose. The latter sugars are subsequently fermented to lactic acid.

While more research will be needed to expand upon their interesting findings, the NIDCR scientists conclude, “It remains to be seen whether continued commercial-scale use of [smart sugars] will impact upon the species composition or ecological distribution of the oral microflora.”

  • Thompson J, Pikis A. Metabolism of sugars by genetically diverse species of oral Leptotrichia. Mol Oral Microbial 2012 Feb;27(1):34-44. doi: 10.1111/j.2041-1014.2011.00627.x. Epub 2011 Oct 4.

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This page last updated: February 26, 2014