B. infantis: Our Partner in Newborn Growth and Development

Gut microbiome development during the first 100 days of life is emerging as a unique and critical window for conditioning the naïve immune system. Scientists have found that modern medical practices are disrupting the natural formation of the infant gut microbiome in a manner that might impact health later in life. Yet they have also found that it might be possible to restore native gut bacteria and put the infant microbiome back on track before it’s too late.

Vaginal birth kickstarts the microbiome, delivering bacteria from a mother’s gut and birth canal to the largely sterile infant gut, seeding a microbiome that can flourish throughout infancy and that may form the foundation for heath or disease later in life. Yet the growing prevalence of cesarean sections, as well as antibiotic use and other hygienic practices in the industrialized world, can disrupt development of the expected infant gut microbiome. Infants are not being seeded with the appropriate bacteria during the first 100 days of life that contribute to immune health. Meanwhile, opportunistic pathogenic bacteria colonize, setting the infant gut microbiome on the wrong trajectory.

Scientists are using multiomic approaches to untangle key relationships between gut bacteria, hygiene practices, and human milk – infants’ primary food source – to unlock how to guide and optimize long-term health. New research has demonstrated the extent of gut microbiome dysregulation among infants during their first 100 days of life and has explored methods to restore a healthy microbial balance.

How human milk supports immune development

One key ingredient to the formation of a healthy infant gut microbiome is human milk. Human milk meets an infant’s nutrition requirements; it contains human milk oligosaccharides (HMOs), which are involved in establishing the gut microbiome and putting it on the correct trajectory. However, HMOs cannot be digested by the infant directly. In fact, these fiber-rich compounds can reach the infants’ colons untouched.

Fortunately, a healthy human gut contains specific bacterial species that can digest HMOs and provide important nutrients to the infant. Microbes from the genus Bifidobacterium, for example, can break down the hundreds of complex HMO structures found in human milk after it has been consumed by the infant.

While scientists have known for some time that microbe-immune interactions contribute to the development of immune-associated diseases later in life, it wasn’t until recently that scientists discovered what connected the two: HMOs. Recently, researchers combined multiple analyses to investigate the relationship between HMO digestion by the gut microbiome and infant immune health. In one study, a group of 208 infants born in Sweden lacking bifidobacteria – the bacteria responsible for HMO digestion – showed elevated markers of systemic and intestinal inflammation. In contrast, when infants were colonized early in life by HMO-metabolizing  bifidobacteria, intestinal inflammation was reduced.   

Scientists are finding more and more evidence that the abundance of bacterial genes in one’s gut responsible for HMOs metabolism predicts the onset of atopic disease in infants. Key bacterial HMO metabolites regulate immune cell activation, potentially reducing the risk of immune-mediated disease later in life. This mechanism requires further investigation but scientists have already begun to establish a connection between gut microbiome and immune system development during the first 100 days of life. 

B. infantis colonization of the infant gut

Seeding the infant with the appropriate HMO-metabolizing bacteria during their first 100 days appears to help ensure that infants begin life on the correct immune and microbiome trajectory. One Bifidobacterium species that excels at breaking down HMO structures is B. infantis. The prevalence of this bacteria varies among different populations across the world, enabling scientists to correlate B. infantis levels with atopic disease risk. For instance, a recent survey in the United States found that 90% of infants were missing B. infantis. Meanwhile, among traditional, farming Old Order Mennonite populations, recent work found that B. infantis was more prevalent while atopic disease was less common. Such associations warrant investigation to understand how colonization with specialized microbes can influence atopic disease risk.

The microbe B. infantis breaks down HMOs, but not all B. infantis strains possess the same capabilities. For example, some B. infantis strains contain gene clusters H1 – H5, which are dedicated to transporting and metabolizing HMOs. Of particular interest to researchers is the H5 gene cluster, which binds core HMO elements during the metabolism process. B. infantis populations that possess the H5 gene cluster, referred to as H5+, grow more rapidly when fed specific HMOs when competing against H5- strains.

Early evidence suggests that that this gene cluster may support gut health. For instance, at least one commercially available strain of B. infantis that expresses the H5 gene cluster, EVC001, has been shown to successfully colonize the gut and reduce fecal cytokines and calprotectin, markers of enteric inflammation. This indicates that supplementing the infant diet with this strain may reduce the incidence of immune complications in early life. EVC001 has successfully been provided to all infant populations, including infants who are predisposed to disease and gut inflammation.

Bridging the gap between the microbiome and gut health

The infant gut microbiome, and B. infantis specifically, appears to play a critical role in the development and regulation of the infant immune system. Such interactions within the first 100 days of life may determine one’s risk for immune-associated disease later in life. Early evidence suggests that gut colonization by HMO-metabolizing H5+ strains of B. infantis immediately after birth will ensure infants attain important gut development, potentially placing them on a low-inflammation trajectory. The combination of a microbiome rich in Bifidobacterium and a background of a human milk diet provides a standard for understanding the interactions linking microbiome function, immune system development and health.

The next frontier for microbiome research pushes past profiling bacterial taxonomy and investigates the functional capacity of the microbial community with metagenomics and metatranscriptomics. The relationship between the microbiome and immune system can now be explored through measuring microbial metabolites, fecal inflammatory markers, single-cell RNA sequencing and immune cell profiling. A combination of these approaches permit researchers to further understand this critical window of infant development and help put infants on a course for better health later in life.