How Beneficial Gut Bacteria in Newborns Overcome the ‘Oxygen Barrier’ and Regulate Immunity

The mechanism that allows beneficial gut bacteria in newborns to overcome the initial “oxygen barrier” and establish themselves has been identified. Researchers found that Bacteroides fragilis, a representative commensal bacterium in the human gut, uses a specific membrane lipid to withstand oxygen and regulate the immune system.

An international research team involving U.S. and South Korean researchers announced the findings on the 7th (local time) in the international journal Cell. The paper’s first author is Dr. Gyu Heo.

Unlike the gut of an adult, a newborn’s gut retains trace amounts of oxygen for several days immediately after birth. This is because the infant is exposed to air during delivery, and an anaerobic microbiome has not yet become established. This “aerobic window” is a lethal environment for B. fragilis, which lives without oxygen.

The research team was the first to show that B. fragilis survives this period by producing a membrane glycolipid called alpha-galactosylceramide (BfaGC). Whole-genome fitness analysis showed that BfaGC biosynthesis was selectively essential early in life.

Within the bacterium, BfaGC lowered the membrane’s proton permeability, helping maintain the proton motive force needed for aerobic respiration. In effect, it acts as a “barrier” that prevents energy loss caused by oxygen metabolism.

At the same time, the molecule sent signals to the host immune system, regulating the development of natural killer T (NKT) cells and inducing immune tolerance. The researchers said a single metabolite links bacterial adaptation with immune maturation.

This strategy was not shared by all gut bacteria. Other major bacteria followed different evolutionary strategies, including adapting by synthesizing different glycolipids. The findings also showed that enterotoxin-producing B. fragilis can expand its habitat through the same mechanism.

The research team said the discovery could be applied to newborn care and treatment of chronic diseases in adults. Selecting strains that produce high levels of BfaGC or adding similar molecules could help establish the gut microbiome in infants who do not inherit maternal bacteria because they were born by cesarean section or prematurely.

The team also proposed using BfaGC derivatives to guide immune system development in newborns and reduce the risk of allergies or autoimmune diseases, as well as supplementing related metabolites during antibiotic treatment to reduce immune-related adverse effects.