Journal News

New clues on how lipid emulsions prevent liver disease in preterm babies

Ana María Rodríguez
By Ana María Rodríguez
June 16, 2020

Infants born prematurely may require parenteral or intravenous nutrition to provide the necessary nourishment, as their digestive system is immature and cannot digest nutrients. However, prolonged parenteral nutrition is associated with complications, including cholestasis, or lack of bile flow from the liver into the small intestine, which leads to accumulation of bile acids and injury in the liver. Emerging clinical studies have shown that cholestasis can be prevented in preterm infants with parenteral administration of oil emulsions ‒ mixtures made of multiple oil components ‒ but the mechanism mediating this effect remains unclear.

microbiome.jpg
Darryl Leja/National Human Genome Research Institute,NIH.
Gut bacteria, as shown in this artist’s representation, in preterm piglets are associated with the prevention of liver disease mediated by lipid emulsions.

Working with preterm piglets, an international group led by researchers at the USDA-ARS Children’s Nutrition Research Center (CNRC) at Baylor College of Medicine and Texas Children’s Hospital found evidence that the protective effect of parenteral oil infusions is accompanied by changes in the levels of gut bile acids (gut bile acid pools) and in the gut microbiome, making this study the first to connect parenteral oil infusions, the microbiome, metabolism and health. The study appears in the Journal of Lipid Research.

Studying parenteral oil emulsions

Burrin-Douglas-200x200.jpg
Douglas Burrin

“The piglet model enables us to study parenteral nutrition-associated liver diseases, such as cholestasis, in a way that is clinically relevant,” said senior author Dr. Douglas Burrin, research physiologist at the CNRC and professor of pediatrics at Baylor. “We treat preterm piglets similarly to how we treat preterm infants in the hospital and look at liver function and gene expression in the piglets to better understand the physiology.”

The original lipid emulsion developed for parenteral nutrition in infants was based on one component, soybean oil, and it has been the only parenteral lipid option used for preterm infants for about 45 years. Although this oil emulsion has helped support infants’ growth, physicians have been concerned that it could be involved in the development of several conditions, including liver disease. This prompted the development of new lipid emulsions with multiple oil components to prevent or treat parenteral nutrition-associated liver diseases.

They published their first findings in 2014. The Baylor researchers and others have shown that pure fish oil and multicomponent oil lipid formulations can reduce cholestasis associated with long-term parenteral nutrition, but how this happens still is not completely understood.

In the current study, the researchers expanded their original investigations by comparing two previously studied oil emulsions ‒ soybean oil only (Intralipid) and a combination of soy, olive, coconut and fish oils (SMOFlipid) ‒ and a new experimental formulation (EXP), that was similar to SMOFlipid, but with additional DHA, an omega-3 fatty acid, and arachidonic acid.

An additional experimental group (ENT) used for reference consisted of piglets fed infant formula through a feeding tube. The experiment lasted 22 days.

New insights into how parenteral oil emulsions work

The researchers evaluated the effects of the different oil emulsions in preterm piglets by measuring cholestasis, gut bile acids pools and the composition of microbial communities in the colon as well as the profiles of the microbes’ metabolic products or metabolites.

Call-Lee-200x200.jpg
Lee Call

The findings confirmed that multicomponent oil emulsions (SMOF and EXP), but not Intralipid, can prevent cholestasis and restore bile flow in preterm piglets as observed in the ENT group.

“One of the important findings showed that prevention of cholestasis was accompanied by maintaining normal gut bile acid pools. They were lowest in the piglets treated with Intralipid but increased in the SMOF and EXP groups and were comparable to ENT,” Burrin said.

A particularly interesting new finding was that cholestasis was associated with changes in the gut microbiome and their metabolite profile.

Premkumar-Muralidhar-200x200.jpg
Muralidhar Premkumar

“It’s exciting to see such a direct connection between gut bacteria and the lipid composition of parenteral nutrition,” said first author Dr. Lee Call, a former Translational Biology and Molecular Medicine graduate student in the Burrin lab during the development of this work. Call currently is a postdoctoral fellow at Department of Energy Joint Genome Institute at Lawrence Berkeley National Lab.

“We have been certain that the lipid emulsions contribute an important effect on growth and metabolism, but the mechanism and the direct causal effect was lacking. This work provides those missing links that offer newer insights that will go a long way in the development of better, safer lipid emulsions for use in preterm infants. It is exciting to be a part of this discovery,” said co-author Dr. Muralidhar Premkumar, assistant professor of pediatrics-newborn at Baylor and Texas Children’s.

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition weekly.

Learn more
Ana María Rodríguez
Ana María Rodríguez

Ana Rodríguez is the science writer for the Office of Communications at Baylor College of Medicine. She is the editor of the blog From the Labs and one of its main contributors. She was an immunoparasitologist working on basic research for about 20 years before she became a science writer and editor focused on basic and applied biomedical and natural sciences.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Gene-mutation pathway discovery paves way for targeted blood cancers therapies
News

Gene-mutation pathway discovery paves way for targeted blood cancers therapies

Nov. 3, 2024

A new study by researchers at the universities of Texas and Chicago explains the enzymatic activity that’s needed for tumor suppression in leukemias and other cancers.

Candy binges can overload your gut microbiome
News

Candy binges can overload your gut microbiome

Nov. 2, 2024

While most Halloween candies contain lots of sugar, some are better for your gut microbiome than others.

Water rescues the enzyme
Essay

Water rescues the enzyme

Oct. 31, 2024

“Sometimes you must bend the rules to get what you want.” In the case of using water in the purification of calpain-2, it was worth the risk.

Virtual issue celebrates water in ASBMB journals
Journal News

Virtual issue celebrates water in ASBMB journals

Oct. 30, 2024

Read a dozen gold open-access articles covering exciting research about the society’s 2024 Molecule of the year.

There are worse things in the water than E. coli
News

There are worse things in the water than E. coli

Oct. 29, 2024

E. coli levels determined whether Olympic swimmers could dive into the Seine this past summer. But are these bacteria the best proxy for water contamination?

Biobots arise from the cells of dead organisms
News

Biobots arise from the cells of dead organisms

Oct. 27, 2024

Given the right conditions, certain types of cells are able to self-assemble into new lifeforms after the organism they were once part of has died.