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

Pioneering research reveals certain human genes relate to gut bacteria

June 22, 2020

Science Daily/University of Bristol

The role genetics and gut bacteria play in human health has long been a fruitful source of scientific inquiry, but new research marks a significant step forward in unraveling this complex relationship. Its findings could transform our understanding and treatment of all manner of common diseases, including obesity, irritable bowel syndrome, and Alzheimer's disease.

The international study, led by the University of Bristol and published today in Nature Microbiology, found specific changes in DNA -- the chains of molecules comprising our genetic make-up -- affected both the existence and amount of particular bacteria in the gut.

Lead author Dr David Hughes, Senior Research Associate in Applied Genetic Epidemiology, said: "Our findings represent a significant breakthrough in understanding how genetic variation affects gut bacteria. Moreover, it marks major progress in our ability to know whether changes in our gut bacteria actually cause, or are a consequence of, human disease."

The human body comprises various unique ecosystems, each of which is populated by a vast and diverse array of microorganisms. They include millions of bacteria in the gut, known as the microbiome, that help digest food and produce molecules essential for life, which we cannot produce ourselves. This has prompted researchers to question if gut bacteria may also directly influence human health and disease.

Previous research has identified numerous genetic changes apparently related to bacterial composition in the gut, but only one such association has been observed consistently. This example involves a well-known single mutation that changes whether someone can digest the sugar (lactose) in fresh milk. The same genetic variation also predicts the prevalence of bacteria, Bifidobacterium, that uses or digests lactose as an energy source.

This study, the biggest of its kind, identified 13 DNA changes related to changes in the presence or quantity of gut bacteria. Researchers at Bristol worked with Katholieke Universiteit Leuven and Christian-Albrecht University of Kiel to analyse data from 3,890 individuals from three different population studies: one in Belgium (the Flemish Gut Flora Project) and two in Germany (Food Chain Plus and PopGen). In each individual, the researchers measured millions of known DNA changes and, by sampling their feces, also registered the presence and abundance of hundreds of gut bacteria.

Dr Hughes said: "It was exciting to identify new and robust signals across the three study populations, which makes the correlation of genetic variation and gut bacteria much more striking and compelling. Now comes the great challenge of confirming our observations with other studies and dissecting how exactly these DNA changes might impact bacterial composition."

Such investigations could hold the key to unlocking the intricate biological mechanisms behind some of the biggest health challenges of our time.

Study co-author Dr Kaitlin Wade, Lecturer in Epidemiology at the University of Bristol, said: "A strength here is that these findings provide a groundwork for causal analyses to determine, for instance, whether the presence of specific bacteria increases the risk of a disease or is a manifestation of it."

"The implications for our understanding of human health and our approach to medicine are far-reaching and potentially game changing."

https://www.sciencedaily.com/releases/2020/06/200622133018.htm