Science Update

Loss of Bifidobacteria and HMO Utilization in Infants Linked to Immune Dysregulation Early in Life

Infant gut microbiome composition, especially during the first 3 months of life, is critical to immunological development. In a previous article, we discussed the beneficial effects that bifidobacteria have on shaping intestinal and immune health. Bifidobacteria may account for more than 90% of the total bacterial population in breastfed infants as they are believed to be among the first colonizing microbes in the intestines of newborns. Bifidobacteria are instrumental in the maturation of the immune system. Studies emphasize that loss of microbial ecosystem function and early gut microbiome dysbiosis are correlated with both acute and chronic immune system dysregulation that can lead to common conditions such as colic, atopic allergies, wheezing, and other immune-mediated disorders, such as Crohn’s disease.  

Bifidobacteria are specialized in metabolizing human milk oligosaccharides (HMOs), which are rich in human colostrum and breast milk, explaining their abundance in the gut of newborns and infants. Human enzymes are unable to break down HMOs. The HMOs aid in developing the infant immune system as they act as fuel for bacteria, producing short-chain fatty acids that induce regulatory T cells in the gut and stimulate the growth of a balanced microbiota with higher numbers of commensal bacteria. One such strain adapted to metabolizing HMOs includes Bifidobacterium longum subspecies infantis (B. infantis). 

According to a recent study published in the journal Cell, depletion of bifidobacteria and HMO utilization genes during the first months of life correlates with markers of intestinal and systemic inflammation and immune dysregulation. On the other hand, researchers found that breastfed babies fed additional B. infantis supplementation demonstrated a silencing of intestinal inflammation.  

To elucidate developmental immune system changes postnatally, researchers analyzed longitudinal blood samples from 208 breastfed babies. These infants were born between 2014 and 2019. The blood samples were analyzed by using mass cytometry and a panel of 44 antibodies targeting activation and differentiation markers across 64 immune cell populations. In a second cohort of exclusively fed breastfed infants, half of the infants were given B. infantis supplementation and were analyzed for enteric inflammation.

Feeding breastfed infants B. infantis upregulated intestinal interferon-beta (IFN-β) and silenced T-helper (Th)2 and Th17 cytokines. The babies who received additional bifidobacteria had higher levels of galectin-1 and indole-3-lactic acid (ILA) within the intestines compared to the controls. Galectin-1 is fundamental to immune activation in response to threats and attacks, and it is critical for preserving beneficial bacteria with anti-inflammatory properties. ILA is required to convert HMOs into fuel. These results demonstrate a functional connection between breast milk, beneficial gut microbiota, and immunoregulation during the first few months of life.

By helping the immune system establish its regulatory mechanisms, researchers believe that adding bifidobacteria supplementation to human breast milk may help to reduce the risk of developing allergies, autoimmune diseases, and asthma later in life. For mothers who are unable to breastfeed, it may be especially important to consider supplementing their baby’s formula with HMOs and bifidobacteria, including B. infantis, to support proper immune maturation and development, and to decrease intestinal inflammation.

By Caitlin Higgins, MSCN, CNS