German had his lightbulb moment in 1994, when he decided that food scientists were “overblowing the red wine thing.” He asked himself, what is the one food that’s clearly meant to help humans? German, a ruddy man in a white sweater vest that looks knit by a relative, answers his own question effusively: “Milk!”
German took a sabbatical in Switzerland to work at food giant Nestlé, one of the world’s leading sellers of infant formula. Where better to learn about human milk, he reasoned, than at a company so keen to mimic it? Nestlé researchers suspected that milk could “grab onto pathogens,” flushing them out of the baby, and even act as an anti-inflammatory, calming hypervigilant, immature immune cells. But like other researchers, they didn’t know the mechanism involved. If only the means of action could be decoded, and the healthy components isolated, identified, and produced in quantity, German thought, then they could be repurposed to treat everything from diarrheal diseases to cancer to hiv.
One class of substances in particular intrigued German: oligosaccharides. These sugar molecules, among the most common solid components of milk, are not digestible. Since we cannot metabolize them, he wondered, why are they there in such abundance? He had a hunch that the answer might be related to the human microbiome. If the molecules are not feeding us, he reasoned, maybe they are feeding the microbes that boost our health. On his return to Davis, German began collaborating with molecular biologists and chemists to isolate the oligosaccharides and test them against various bacteria.
To date, researchers have discovered more than 150 different human-milk oligosaccharides and believe there may be some 200 altogether. Built in combinations of 3 to 20 monosaccharides (simple sugars), these compounds are hard to fragment and analyze. German’s colleague Carlito Lebrilla decided to attempt the job with the university’s new nanoflow liquid chromatography time-of-flight machine, which identifies molecules by measuring the time it takes them to ping around a tube that looks like a stovepipe. In order to separate the 200-some compounds in breast milk so they could be analyzed individually, Lebrilla worked with a biotech company to develop a microchip that acts like a filter for the machine, allowing different compounds through at different speeds.
Another helpful technology was a superconducting magnet cyclotron—a million-dollar drum-shaped device that sends molecules racing around in circles. Researchers can blast the compounds apart with lasers and measure the mass of the molecular fragments that spew out, like smashing a geode to see what minerals are inside. Through painstaking work, German and his colleagues eventually identified dozens of new sugars that could be keys to human health and disease.
At another lab in Davis’s food-science complex, the effort is on to see just what these sugars actually do. At the heart of the effort is microbiologist David Mills, who spent years growing finicky bacteria in test tubes laced with oligosaccharides in oxygen-deprived chambers that mimic conditions in the human gut. It is not a project for the squeamish: To recreate the biology as exactly as he can, Mills works with fecal bacteria collected from infant stool samples. In this way he discovered that Bifidobacterium infantis, one of the dominant bacteria present in the poop of healthy breast-fed babies, is particularly good at eating large oligosaccharides capped at the end with a particular kind of sugar unit. These molecules, called large fucosylated oligosaccharides, are plentiful in breast milk despite the fact that humans cannot digest them at all. But B. infantis can. The microbe efficiently eats these sugars before other bacteria get to them, starving out bad bugs and aiding the infant that serves as its host.
At the Davis neonatal intensive care unit, concentrated breast milk rich with oligosaccharides is now being tested in babies unable to grow enough B. infantis on their own. The hope is that seeding their guts with regular doses of the bacterium and the sugar it eats will compensate for that lack. The B. infantis supplement is brewed in a food-grade facility and turned into a soluble powder. Underwood, German, and their colleagues believe it will have major potential, not just for preemies but for babies and small children in the developing world who suffer high rates of other gut infections leading to diarrheal disease.
Assuming this and several other related human trials currently under way are a success, the next step will be making enough of these crucial breast-milk sugars and doing it cheaply. One idea for ramping up production is through dairy cows, which naturally produce many of the same oligosaccharides as humans do, though in tiny quantities. Fortunately, California’s dairy industry produces more than 3,000 tons of cheese a day, and a corresponding amount of liquid whey that is extracted from it. Supported by funding from the Gates Foundation, U.C. Davis is working to find an efficient way to partition out and concentrate the human-active compounds.
Other breast-milk oligosaccharides are also showing promise. At the University of California, San Diego, a sugar called disialyllacto-N-tetraose reduced the mortality rate from necrotizing enterocolitis in rats from 25 percent to only 5 percent. Nutritional scientist Lars Bode believes the compound may act by encouraging the growth of beneficial bacteria or by reducing inflammation of the gut.