Study tracks human milk nutrients in infant microbiome

September 1, 2020

Science Daily/Cornell University

A new study in mice helps explain why gut microbiomes of breastfed infants can differ greatly from those of formula-fed infants.

The study, "Dietary Sphinganine Is Selectively Assimilated by Members of the Mammalian Gut Microbiome," was published in July in the Journal of Lipid Research.

Sphinganine from milk Johnson Lab/Provided A new technique allows researchers to track specific nutrients as they are taken up by gut microbes in a mouse's digestive tract. The image shows certain microbes (red) taking in a nutrient common in human milk called sphinganine; blue microbes have not taken it in.

The paper describes an innovative technique developed at Cornell to track the fate of metabolites -- nutrients formed in or necessary for metabolism -- through a mouse's digestive tract and identify how they interact with specific gut microbes.

"We think the methods are expandable to many different microbiome systems," said senior author Elizabeth Johnson, assistant professor of nutritional sciences in the College of Agriculture and Life Sciences. She noted that researchers investigating effects of a high-fat vs. low-fat diet, or a keto diet, might use the technique to track metabolites.

The methodology could reveal how specific metabolites promote specific bacteria. This could allow nutritionists to prescribe that patients eat foods containing specific metabolites to intentionally change the composition of their microbiomes, Johnson said.

Human milk and many other foods contain a class of lipid metabolites called sphingolipids. Previous research suggested that these metabolites help shape an infant's microbiome, but it was not known if they actually interact with the microbiome.

The study identified two types of gut microbes, Bacteroides and Bifidobacterium, that use sphingolipids for their own metabolism.

While very little is known about the specific roles of gut microbes in human health, Bacteroides have been implicated in both beneficial and not-so-beneficial effects, depending on context. They are generally associated with microbiomes of healthy breastfed infants. Bifidobacterium, shown for the first time in this study to process dietary sphingolipids, are considered the quintessential beneficial bacteria, comprising up to 95% of breastfed infants microbiome.

They're also a highly popular over-the-counter probiotic.

"Our lab is very interested in how the diet interacts with the microbiome in order to really understand how you can best modulate it to have positive effects on health," Johnson said. "In this study, we were able to see that yes, these dietary lipids that are a big part of [breastfed] infants diets, are interacting quite robustly with the gut microbiome."

Sphingolipids originate from three main sources: diet; bacteria that can produce them; and most host tissues.

Johnson, along with first author Min-Ting Lee, a doctoral student, and Henry Le, a postdoctoral researcher, both in Johnson's lab, created a technique to specifically track dietary sphingolipids as they passed through the mouse gut.

"We custom synthesized the sphingolipid we added to the diet," Johnson said. "It is almost identical to ones derived from breast milk but with a small chemical tag so we could trace the location of the sphingolipid once it was ingested by the mice."

Lee then used a fluorescent label that attached to cells or microbes that absorbed the tagged lipid, such that any bacteria that had taken up sphingolipids lit up red. Microbes from the mice's microbiomes were then isolated and analyzed. Populations with red microbes were separated from the others, and these were then genetically sequenced to identify the species of bacteria.

With further investigation, Le was able to identify the metabolites that Bacteroides and Bifidobacterium produce when exposed to dietary sphingolipids. Further investigations are underway to determine whether these microbially-produced metabolites are beneficial for infant health.

Johnson recently received a five-year, $1.9 million Maximizing Investigators' Research Award from the National Institutes of Health (NIH) to expand on this work, to better understand how lipid-dependent host-microbe interactions affect human health..

The study was supported by seed funds from the Genomics Facility of the Biotechnology Resource Center at Cornell's Institute of Biotechnology.

https://www.sciencedaily.com/releases/2020/09/200901142725.htm

Breastfeeding boosts metabolites important for brain growth

April 27, 2019

Science Daily/Children's National Health System

Micro-preemies who primarily consume breast milk have significantly higher levels of metabolites important for brain growth and development, according to sophisticated imaging conducted by an interdisciplinary research team at Children's National.

"Our previous research established that vulnerable preterm infants who are fed breast milk early in life have improved brain growth and neurodevelopmental outcomes. It was unclear what makes breastfeeding so beneficial for newborns' developing brains," says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children's National. "Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites essential for growth and answer that lingering question."

According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. infants is born preterm. The Children's research team presented their findings during the Pediatric Academic Societies 2019 Annual Meeting.

The research-clinicians enrolled babies who were very low birthweight (less than 1,500 grams) and 32 weeks gestational age or younger at birth when they were admitted to Children's neonatal intensive care unit in the first week of life. The team gathered data from the right frontal white matter and the cerebellum -- a brain region that enables people to maintain balance and proper muscle coordination and that supports high-order cognitive functions.

Each chemical has its own a unique spectral fingerprint. The team generated light signatures for key metabolites and calculated the quantity of each metabolite. Of note:

·     Cerebral white matter spectra showed significantly greater levels of inositol (a molecule similar to glucose) for babies fed breast milk, compared with babies fed formula.

·     Cerebellar spectra had significantly greater creatine levels for breastfed babies compared with infants fed formula.

·     And the percentage of days infants were fed breast milk was associated with significantly greater levels of both creatine and choline, a water soluble nutrient.

"Key metabolite levels ramp up during the times babies' brains experience exponential growth," says Katherine M. Ottolini, the study's lead author. "Creatine facilitates recycling of ATP, the cell's energy currency. Seeing greater quantities of this metabolite denotes more rapid changes and higher cellular maturation. Choline is a marker of cell membrane turnover; when new cells are generated, we see choline levels rise."

Already, Children's National leverages an array of imaging options that describe normal brain growth, which makes it easier to spot when fetal or neonatal brain development goes awry, enabling earlier intervention and more effective treatment. "Proton magnetic resonance spectroscopy may serve as an important additional tool to advance our understanding of how breastfeeding boosts neurodevelopment for preterm infants," Limperopoulos adds.

https://www.sciencedaily.com/releases/2019/04/190427104808.htm