Bacteria that break down breast milk colonize newborns better with Evivo probiotic

Pediatricians and microbiologists have shown that a short dose of a probiotic product given to breastfed newborns can have enduring impacts on their gut microbiomes. The probiotic Evivo boosts the presence of Bifidobacterium longum infantis, a beneficial bacteria that specializes in breaking down complex sugars found in human breast milk.

“The cool part of this story is here is one particular kind of bacteria that is really good at consuming human milk oligosaccharides — better than anybody else,” said Dr. Mark Underwood, who serves as chief of pediatric neonatology at UC Davis Medical Center. “And here’s the mom who is making these sugar molecules and putting them into her milk at great cost to herself. The bottom line is that the mom seems to be shaping the microbiota — or the composition of the bacteria in the gut — by putting these sugars into her milk to try to selectively feed healthy bacteria.”

Human breast milk is largely composed of lactose and fat, but substantial amounts of protein and human milk oligosaccharides are present. HMOs are complex chains of sugar that humans cannot digest. B. infantis is the only known bacteria that is equipped with the enzymes to break down all known HMOs found in human breast milk. These tools give it an advantage in colonizing space in the intestines of breastfed human infants and clearing out pathogenic bacteria, which can produce inflammatory enterotoxins.

Although young infants born in nations such as Gambia and Bangladesh have high levels of B. infantis in their guts, babies born in nations such as the United States have much lower levels of the beneficial bacteria, with the gulf widening over the last century. More pathogenic bacteria have taken the place of B. infantis in American babies’ guts.

“It’s most likely that a combination of interventions resulted in this effect,” said Steve Frese, the associate director of research and development at Evolve Biosystems. “Formula feeding reduces the abundance of human milk oligosaccharides that B. infantis depends on, caesarean sections reduce the ability of B. infantis to be transferred, and on top of that, this is an organism sensitive to penicillin antibiotics — which most kids get early in life at least a few times — and mothers are often given around birth to prevent Group B Streptococcus infection of infants or as antibiotics for C Section.”

After giving Evivo to breastfed babies between days seven and 28, B. infantis levels spiked from around 30 percent to 80 percent of all bacteria measured in stool. At day 60, after 32 days of not taking the supplement, the levels of B. infantis remained remarkably stable, a departure from typical probiotic responses.

“What we saw was dramatically different from any other probiotic study I’ve ever seen,” Underwood said. “Most of the time, when you give somebody a probiotic, you can measure small amounts of the probiotic in the stool. As soon as you stop giving it, it goes back to the way it was.”

Part of the unique response to B. infantis supplementation likely lies in its ancient adaptations to live in the human gut and break down milk sugars as a food source.

“Our hypothesis was that we didn’t need to keep them on a probiotic for weeks or months,” Underwood said. “We could just give a short course, and then as long as they were still getting human milk — as long as they were breastfed — those bacteria we gave as the probiotic should be able to outcompete the other bacteria and be the dominant strain. That’s what we saw.”

Besides consuming HMOs, which would normally be passed through the infant digestive tract, B. infantis creates short chain fatty acids as a byproduct. These acids help to lower the pH in the intestines, energizing intestinal cells to tighten junctions with neighboring cells and creating an uncomfortable environment for pathogenic bacteria.

Infant formula contains mostly lactose and other simple sugars that feed many types of bacteria, some of which are linked to poor gut health. Breastfeeding a baby helps B. infantis outcompete bacteria which can create inflammatory compounds in the belly.

“We see in the literature that when babies have higher levels of these pathogens early in life, they’re at higher risk for allergic diseases,” said Jennifer Smilowitz, the associate director of the Human Studies Research Program at the Foods for Health Institute. “We see higher rates of asthma, allergies, a type of eczema and type I diabetes. These are all immune-related diseases which are higher in people, adults and children, when they have higher levels of pathogens in their guts in infancy or early life.”

Infants are quickly colonized by bacteria during birth and being exposed to the world outside of the womb. Babies delivered vaginally are first colonized by microbes in the birth canal, while babies born via Caesarean section are first colonized by bacteria from medical equipment and mother’s skin. Since B. infantis is anaerobic, it’s unlikely to survive well on skin.

“We think mom has a constitutive amount in her colon, and during labor and normal delivery, it is passed into the baby,” Smilowitz said.

After analyzing commercial probiotics advertised as containing B. infantis, researchers found all but one product contained different types of Bifidobacterium than what the packaging suggested. Such products would not help a breastfeeding baby colonize their gut with beneficial B. infantis or improve gut health.

“They are so functionally different, but they look so similar when you do DNA sequencing,” Smilowitz said. “David Mills’ lab was one of the first to develop methods to differentiate the two. You’ve got all these products on the market claiming to have B. infantis, but they actually have B. longum.” B. infantis is being packaged into a product called Evivo by Davis startup company Evolve Biosystems, founded by UC Davis faculty members to translate academic research into tangible impacts for the community. Future experiments will look into how long the increases in Bifidobacterium concentration last, how older infants respond to Evivo treatments and how changes in the infant microbiome can affect health in adolescence and adulthood.

Written by: George Ugartemendia — science@theaggie.org

Plant-based meat product may have better environmental, health impacts

In 2011, Patrick Brown founded Impossible Foods Inc., which is based in Silicon Valley. The company is dedicated to creating alternative forms of animal produce and released its first product four years ago. Composed of wheat protein, potato protein and soy, this alternative meat has been the subject of intense debate over the last few years.

In many developed countries, new food items must attain a government seal of approval before they go on sale. However, U.S. policy dictates that a company must simply self-certify as “generally recognized as safe,” and then they have permission to sell. Impossible Foods got its GRAS certification in 2014 and has been selling its flagship product ever since.

This food item is the Impossible Burger, a plant-based meat replacement.

“We’ve done all these tests and, as of 2014, we’re generally recognized as safe,” said Rebekah Moses, the sustainability and agriculture director of Impossible Foods. “We wanted to introduce more transparency to the process so we pursued a ‘letter of no questions asked’ that entails rigorous testing on animals which was a tough thing for us because we do not want to engage with animal testing, but we did so in order to meet this additional step. That is still under review right now.”

Despite the product still undergoing review, it is available for purchase.

Ermias Kebreab, a professor of animal science and the deputy director of the Agricultural Sustainability Institute, took issue with the product’s availability.

“In animal agriculture, you never would’ve been able to get away with that,” Kebreab said. “All the tests that the FDA asks from industry have to be done. There are a number of cases where the technology is good but because there wasn’t really a champion or an organization behind it, that idea died because of the requirements from the FDA. We only have [AquaAdvantage salmon] officially FDA-approved after 20 years, to be sold in the market, and it’s only found in Canada right now. If the FDA required that something be verified and have data on it that then that should be completed before it is available to consumers.”

A UC Davis club, Peace for the Elimination of Animal Cruelty through Education, still sees great potential for this burger.

“There [are] definitely environmental benefits for consuming a product that is similar tasting and with a similar nutritional profile as meat,” said McKenna Maxwell, the co-vice president of PEACE and an environmental studies and management major at UC Davis. “But the environmental impacts — the land use, the water use, the carbon dioxide equivalent — is much less when you’re consuming a plant-based burger versus a traditional animal-based burger. There are also health benefits. There’s no cholesterol, there’s no saturated fat, there is unsaturated fat found in plant foods that’s easier for the body to digest.”

Although the Impossible Burger might have the same number of grams of protein and have fewer calories than a beef burger, Kebreab argued that there is more to nutrition than these values.

“It’s not just having livestock products,” Kebreab said. “It’s looking at amino acid profiles. Animal proteins have the amino acids that we need as humans. Eggs for example have a nearly perfect profile of essential amino acids, which you will not get from plants. I am not saying you should eat animal sourced food all the time. You need to balance vegetables, fruits and animal proteins. For some groups this is more important than others, like children or pregnant women — you have to have some type of animal sourced food in order to have good development.”

Environmental factors are another issue at play when it comes to creating the Impossible Burger. Impossible Foods wanted to reduce the amount of land needed to create a meat-product, thereby improving the sustainability of their item.

“We do need to find alternative means of producing animal-based products,” Moses said. “The demand for those is going to increase by 60 to 70 percent. One-seventh of human based greenhouse gases are the results of animal farming. 30 percent of our water goes to it globally, 50 percent of the ice free surface of the planet is devoted to [livestock].”

Environmental concerns is also a hot debate in the livestock industry. But depending on where you are, those numbers change. In the US, where resources are carefully controlled and research is constantly ongoing to mitigate livestock’s impact on the environment, there is a different picture.

“It really depends where you are,” Kebreab said. “Here, in the United States, it’s going to 4 percent, but if you go to New Zealand, it’s going to be 50 percent because they have a lot of sheep. For greenhouse gases, it varies where you are. Globally, the number is about 14.5 percent from animals. That number comes from the FAO. In terms of water use, yes, 30 percent sounds correct, but this includes the water used for crops grown as feed for livestock animals. In terms of space, 50 percent of the ice free land doesn’t really make any sense. You have to think if this area good for agriculture or not. If it’s not, like a lot of the rangeland isn’t in California, most rangeland would be barren. The grass will not grow because you need to have the cycle where animals graze and deposit their manure. This adds value to the land.”

With the global population expected to reach over 10 billion people by 2050, precise and responsible stewardship of limited resources is becoming more essential than ever before. According to the Center for Food Integrity, the world will need twice the amount of food produced today by 2050.

“I see the Impossible Burger playing a key role as a transition into making better products with better technology that will decrease the environmental footprint of our individual consumption habits,” Maxwell said.

Technology will definitely be on the forefront of how food will be produced in the future. Humanity needs to learn produce more with less and, depending on who you ask, livestock can either be part of the solution or be part of the problem.

“I don’t think it’s feasible to feed 10 billion people on the system we have now,” Moses said. “There are improvements in yield across plant-based foods and increases in efficiency for livestock. Those are good things but we need, in order to feed that many people, a transformative technology in addition to yield improvements if we do not want to hugely compromise natural resources. There are many ways we can initiate food system sustainability, for the 2050 population I just don’t see how we do that with the existing system.”

Many individuals within the UC Davis Animal Science department argue that livestock is an essential part of that future transformative system Moses is referring to.

“A lot of beef cattle are grazing on grassland where you can’t do anything else. A lot of the crops being grown for human food are being fertilized by manure,” Kebreab said. “If you’re going to get rid of animal agriculture, this would increase the amount of inorganic fertilizers you would have to produce, which takes quite a lot of energy and would result in a lot of associated emissions and the whole system would collapse.”

Moses said this product will help bring optionality to our food production system in order to meet growing demands.

But does the Impossible Burger stand up to the challenge? Moses said that blind taste tests have found the Impossible Burger comparable to a beef burger. Other consumers are not convinced.

“To actually call the Impossible Burger a burger doesn’t seem right because nutritionally it is not comparable,” Kebreab said. “It’s not just calories and proteins. You need to look at the trace elements that we get, like iron, which are essential for human beings. This comparison will give you a better picture as to why we need animal sourced protein.”

Written by: Alice Rocha — science@aggie.org

New research improves noninvasive brain imaging

What might a stroke patient, a drowning person, and someone with severe traumatic brain injury have in common? If the stroke results from a blood clot in the brain, then all three might experience changes in their cerebral circulation. Blood flow in the brain is an important indicator of its health; proper blood pressure and circulation means enough oxygen and glucose are reaching the cells, and they require a lot of circulation to stay healthy.

Traditional methods for measuring cerebral blood flow and pressure include MRI and probes. However, they come with their own caveats. Metal and electronic items should not be taken inside MRI machines, including implants, prostheses, and pacemakers. This procedure is thus limited to people who don’t have those items, and is also relatively expensive, making conditions where multiple scans are necessary costly. Probes are invasive, as they must be inserted into the head to sense pressure.

One alternative is diffuse correlation spectroscopy, where certain wavelengths of light are able to penetrate into the brain and create an image. This procedure is noninvasive and can be used at the bedside, allowing for continuous monitoring. However, the spatial resolution isn’t very good compared to an MRI, and the materials needed to make it so are very expensive. Currently, DCS is not commonly used in medical practice.

New research from a biomedical engineering lab at UC Davis may help change that. Wenjun Zhou, a postdoctoral fellow working in Vivek Srinivasan’s biophotonics lab, and his colleagues have developed an improved light-based method for measuring cerebral blood flow they call interferometric diffusing wave spectroscopy, or iDWS.

“The previous methods required very expensive detectors,” said Srinivasan, an associate professor of biomedical engineering and ophthalmology at UC Davis. “We looked at that method, and while it worked, the problem was that you couldn’t have many detectors detect the light, because it would be too expensive; the technology is somewhat difficult to use; and it’s sensitive to ambient light, or environmental light, which makes it difficult to use if you want to monitor blood flow in a hospital environment where the lights are very bright. So we tried to improve the detector, and we came up with this idea, which is really an combination of two ideas. The first idea is that if you think of what the cheapest, most widely used light detection device out there, it’s got to be the CMOS camera.”
The CMOS camera is the type of camera found in smartphones, which uses a sensor chip to record images. It is easily integrated into other technology, but its resolution isn’t as fine, so it wouldn’t be able to pick up the weak light used for DCS. To resolve this problem, the researchers changed the strength of the light field without strengthening the source.  

“Measuring blood flow centimeters below the surface has required expensive approaches to count the small numbers of light particles, or photons, that make it back,” Zhou said in an email interview. ”Boosting the light power on the scalp is not possible due to concerns about heating. Instead we use an interferometric approach to boost the weak sample light field with a strong reference field, creating intensity fluctuations that are strong enough to be measured by a inexpensive CMOS camera.”

The combination of multimode fiber interferometry and CMOS cameras is a promising one; not only does it cut much of the cost, but it also has highly sensitive and parallel detection capabilities for faster and deeper imaging. It also has the potential to become better as CMOS camera quality continues to improve at a fast rate. The lab is currently collaborating with doctors at the UC Davis Medical Center to further develop this technology, including Lara Zimmerman, an assistant professor in the department of neurological surgery and neurology at UC Davis and co-director of the Neurocritical Care Service.

“When the brain is injured, it undergoes a period of swelling and the pressure inside the skull (intracranial pressure) increases,” Zimmerman said in an email interview. “This is a very dangerous problem which can lead to additional brain injury due to lack of blood flow and oxygen delivery to the brain. Currently we are able to monitor intracranial pressure with invasive probes, but ideally want to develop a technique to monitor cerebral blood flow non-invasively, which is the goal of this collaboration.”

Written by: Kira Burnett — science@theaggie.org