RASBAK /WIK IM EDIA CO M M O N S (CHICO RY RO OT ) AN D SHU T T ERSTO CK
SCIENCE & TECHNOLOGY
sor at Belgium’s Catholic University of Louvain, who launched the prebiotics field with Gibson. The field of probiotics aims to boost gut bacteria through consumption of live, beneficial bacteria. These living organisms must survive a trip through the acidic stomach to the large intestine, where they then compete for real estate among the trillions of other microbes that already call the gut home. “You would have to consume really high concentrations of live bacteria to get benefits from probiotics,” Roberfroid argues.
FEEDING FRIENDS
Chicory root, artichokes, and onions are common sources of fructooligosaccharides.
FEEDING YOUR GUT MICROBIOME Digestive health benefits correlate with high levels of good bacteria promoted by UNUSUAL CARBOHYDRATES added to food SARAH EVERTS, C&EN BERLIN
HUMANS HARBOR an army of beneficial
bacteria in our guts that build essential vitamins, digest plant fibers, and fight the populations of pathogens that also exist in our intestines. Because all gut bacteria subsist on scraps from our diet, some researchers argue that we should throw the good bugs a bone on occasion, by eating specific foods that can boost their populations and thus their beneficial impact on us. This is the logic for prebiotics, a field of food science that studies how to cultivate healthy gut bacteria through nutrition. The term “prebiotic”—which refers to carbohydrates in food that boost good bacteria—was first coined in 1995 by a U.K.-based researcher named Glenn R. Gibson at the University of Reading, who was investigating ways to increase levels of beneficial bifidobacteria and lactobacilli in the large intestines. By the 2000s, food companies were adding prebiotic ingredients such as fructooligosaccharides and galactooligosaccharides to cereals, cottage cheese, breads, drinks, and infant formula, claiming the carbohydrates improved digestive health, such as ensuring regular bowel movement. To back up such claims, researchers have shown that consuming the oligosaccharides indeed increases populations of beneficial
bifidobacteria and lactobacilli in human guts. They’ve also found that an increase in these bacterial populations correlates to a range of digestive health benefits. However, researchers have had a harder time proving the causal relationship: that eating prebiotics causes these health benefits in humans. For example, a 2010 review in the British Journal of Nutrition (DOI: 10.1017/ S0007114510003363) noted evidence that prebiotics might assuage the incidence or severity of traveler’s diarrhea, colon cancer, irritable bowel syndrome, diabetes, and obesity, but pointed out that for many of these ailments, prebiotic treatments remain to be “definitively proven” in humans. Human trials to help confirm the proposed health benefits are under way. They’ve already met with some success, conclusively showing that prebiotics can improve calcium absorption in humans. Meanwhile technological advances coming from human microbiome projects are also helping to validate the prebiotics field. Some people confuse prebiotics with its food-science sibling, probiotics, which studies how to boost levels of good gut bacteria through inoculation. The two fields have some important differences, explains Marcel Roberfroid, an emeritus profes-
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WITH PREBIOTICS, the idea is to eat mol-
ecules that boost endogenous populations of beneficial bacteria in the gut. For the idea to work, the prebiotic carbohydrates can’t be digested by human enzymes. That way they are still available for bacteria in the large intestine. “Lots of food ingredients, such as starches and dietary fibers get into the large intestine,” Gibson notes. But prebiotic interventions are designed to be broken down only by the targeted beneficial bacteria. The best-studied prebiotic molecules are fructooligosaccharides. Also known collectively as inulin, these oligosaccharides are composed of multiple fructose units capped by a glucose unit at the end. When the number of fructose units exceeds four, Gibson explains, human digestive enzymes cannot break down the oligosaccharides, which can then reach the large intestine. Once there, beneficial bifidobacteria—which have the appropriate machinery to metabolize the oligosaccharides—convert the component sugars to energy molecules such as lactate and acetate, Gibson says. Boosting the number of bifidobacteria in the gut helps the beneficial bacteria defeat pathogens competing for colonization sites, Gibson says. They also produce acid and antimicrobial peptides that help control populations of several problematic species of bacteria, he adds. The fructooligosaccharides added to food usually come from companies that extract the sugar from chicory root, although artichokes and onions also contain the carbohydrate, says Bernd Stahl, a research and development director at Danone’s Centre for Specialized Nutrition in Friedrichsdorf, Germany. Fructooligosaccharides from
FOOD COMPANIES have been adding
fructooligosaccharides and galactooligosaccharides to adult foods since the early 2000s without contention, but the more recent application of prebiotics in infant formula has been controversial. Formula-fed newborns have higher
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rates of asthma, allergies, and dermatitis others have been working on ways to procompared with those fed with breast milk. duce a human milk oligosaccharide called These babies also have hard stools, sug2′-fucosyllactose in large batches using gesting they have poorly established or bacterial fermentation, so that the carbounhealthy gut microbiomes. hydrate can be put through human trials to Researchers who study breast milk examine whether it is prebiotic. are finding that the amazing diversity of complex oligosaccharides found in breast FOR MORE THAN 15 years, prebiotics research has been focused primarily on milk helps establish the gut microbiome bifidobacteria and lactobacilli. The past five of a newborn—among myriad other roles years, however, have seen a revolution in in a developing infant—says Lars Bode, a technology to study the human microbiome. researcher at the University of California, Scientists have begun tabulating the wider San Diego, who studies breast milk olidiversity of bacteria living in and on our gosaccharides. The fact that breast milk bodies, showing that different people can oligosaccharides are in part responsible for have radically different gut bacteria and that creating healthy stool in breast-fed babies these differences can dramatically affect has galvanized prebiotics researchers. health. In the late 1990s, Stahl began evaluating the possibility of including prebiotic For example, human microbiome researchers have found that obese people oligosaccharides in infant formula to see have a consistently higher proportion whether the carbohydrates could proof several bacterial phyla compared mote healthy gut flora in formula-fed HO with leaner folks (Nature, DOI: infants. Stahl’s research team showed O HO 10.1038/4441022a). The microthat adding fructooligosaccharides and galactooligosaccharides to infant formuOH bial phyla in obese people’s OH guts are more efficient at exla increased bifidobacteria levels in fortracting energy from food bemula-fed infants and made their stool O cause they have more genes look more similar to that of a breast-fed O HO coding for carbohydratebaby. His team also showed that adding these carbohydrates to infant OH metabolizing enzymes OH OH than do the microbes in formula helps reduce n O HO O thin people. atopic dermatitis. O Researchers haven’t These and other reHO HO O OH precisely figured out sults motivated many food OH why some people have companies to add these preOH an obese-promoting biotic carbohydrates to their infant Inulin microbiome or one that formula. Stahl says he accepts the consensus view that “breast milk is best,” causes digestion problems such as irritabut wants to improve formula for the bable bowel syndrome. It probably has a lot bies who consume it. to do with infant diets, geographical locaAn important distinction to make, Bode tion, and other environmental factors—as says, is that the fructooligosaccharides well as a person’s own gut biochemistry, and galactooligosaccharides added to inGibson says. fant formula are not found in breast milk Then last month researchers reported itself. That fact has Bode concerned about that long-term diets also help establish the possible long-term health effects a person’s gut microbiome: They found of feeding infants these carbohydrates. that bacteria growing in the intestines “While there may be some reports on of vegetarians are consistently different beneficial effects of these nonhuman milk from those of meat eaters (Science, DOI: oligosaccharides,” scientists haven’t yet 10.1126/science.1208344). This finding investigated their long-term effects in inadds evidence to the prebiotics argument fants, he cautions. that people might be able to curate their Infant formula would ideally have actual gut bacteria through diet choices. human milk oligosaccharides in it, says DaAs human microbiome researchers imvid S. Newburg, a glycobiologist at Boston prove their ability to tabulate the entirety College. The problem is that many breast of our gut microbiome and what beneficial milk oligosaccharides are so complex that activities are related to which species or scientists can’t yet prepare them in a lab, phyla, they may expand the list of benefilet alone produce them on an industrial cial bacteria that prebiotics researchers scale for addition to formula. Newburg and want to target. ◾
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chicory come in a variety of lengths, he explains. Research has shown that those with 10–60 fructose units are better food additives, he adds. That’s because food scientists don’t want the bifidobacteria to metabolize the oligosaccharides too quickly: Slower bacterial metabolism of fructooligosaccharides reduces the risk for gas, which “seems to be the only possible side effect” of eating the carbohydrates, Gibson says. Gas doesn’t usually occur unless a person consumes more than 5–10 g of fructooligosaccharides, and it may also be the result of other gut bacteria dining on the carbohydrates, Gibson adds. The second well-studied prebiotic ingredient is galactooligosaccharides, which consist of five or more units of galactose, capped at the end by a glucose unit. Bifidobacteria and lactobacilli can use these carbohydrates for energy. In the 1990s and early 2000s, Roberfroid, Gibson, and others found that when people ate various lengths of these two well-characterized prebiotic carbohydrates, their stool contained increased concentrations of the beneficial bacteria, which generally corresponds to regular bowel movements. More recently, Gibson also found that when levels of bifidobacteria increased in the human gut, incidences of traveler’s diarrhea decreased and people with irritable bowel syndrome had reduced symptoms. He suggests that’s likely because the multiplying bifidobacteria better compete with pathogens for real estate in the gut. But in both cases, a causal relationship between eating prebiotics and the improved health seen in human trials has yet to be established. Many researchers point to the work of Steven A. Abrams, a professor of pediatrics at Baylor College of Medicine in Houston, as being the most conclusive evidence that prebiotics can be causally related to a health benefit. His team showed that when young adults consumed fructooligosaccharides, their absorption of both calcium and magnesium in the gut improved by 5–8%. Abrams explains that production of lactate and acetate by bifidobacteria lowers the pH in the gut, which improves ion absorption.
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