Boosting the Maternal Microbiome Sharply Reduces Biliary Atresia in Early-Stage Study

When pregnant mice were fed butyrate, most of their pups survived after exposure to infection that induces a fatal intestinal blockage, the results of a new analysis show.

New study results show that when pregnant mice were fed butyrate, a food supplement derived from intestinal bacteria, most of their pups survived after exposure to infection that induces fatal biliary atresia.

Investigators of the study, published in Nature Communications, said this occurred because the mothers receiving the enhanced diet transferred a healthier mic of gut bacteria to their newborns, which helped them resist the disease.

Biliary atresia is a rare disease that occurs when a delicate tree-like set of ducts that carry bile from the liver to the intestine becomes scarred and blocked. Although some treatments can slow the damage most children who develop the disease will die without a liver transplant.

"Other studies have shown that the maternal transfer of the microbiome to the baby may change susceptibility of later-onset conditions, such as allergies, obesity, even heart disease. Our study shows that this transfer also has implications for diseases that begin during the neonatal period, like biliary atresia," Jorge Bezerra, MD, director of the division of gastroenterology, hepatology, and nutrition at Cincinnati Children's Hospital Medical Center, said in a statement.

When the newborn mice were exposed to a virus that is known to cause biliary atresia, about 60% of those born to a mother given butyrate survived compared with approximately 20% of the mice born to mothers receiving typical food and water.

The key compound turned out to be glutamine, which is widely available as a food supplement.

However, investigators injected pups with glutamine after they were born, rather than feeding it to their mothers.

After further testing showed which compound produced by the healthier mix of gut bacteria offered the strongest protection, investigators improved the survival rate to as high as 83%.

These different results indicate that more research is necessary before making any recommendations to human mothers about what they might do to reduce the risk of their children developing biliary atresia, investigators said.

Butyrate is a short chain fatty acid that is metabolized by humans but depends upon gut bacteria to produce. Butyrate occurs when the gut bacteria break down otherwise non-digestible plant fibers.

Like mice in the study, human babies with biliary atresia often have very low amounts of butyrate in their systems, which makes the beneficial effects observed from the butyrate heavy diet worth investigating, investigators said.

There have been no human trials of the butyrate diet attempted for preventing biliary atresia.

"We think that the intestinal production of butyrate in neonates also enriched the population of bacteria that makes glutamine inside the intestinal lumen," Bezerra said.

"Both molecules are important, with glutamine serving as a survival factor for bile duct cells while butyrate may suppress an unwanted harmful immune response. It appears that both work together to decrease the risk of biliary injury,” Bezerra said.

Investigators also used DNA sequencing to analyze the population of gut bacteria, which demonstrated a common molecular signature between maternal and newborn microbiomes after the mothers were fed with butyrate.

A safe dose of butyrate that also would be strong enough to prevent biliary atresia is not known at this time.

Reference

Boosting the maternal microbiome sharply reduces biliary atresia risk in early-stage study. Science Daily. News release. January 10, 2022. Accessed January 17, 2022. https://www.sciencedaily.com/releases/2022/01/220110145306.htm

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