Largest study to date benchmarks widespread, underrecognized microbiome-linked risk to infant immune system development, antibiotic resistance, acute conditions such as colic and diaper rash. [Evolve BioSystems, Inc.]

The results of a study by researchers at Stanford University, the University of Nebraska, and Evolve BioSystems suggest that the vast majority of infants in the United States may exhibit a substantial deficiency in an important gut bacterium that is key to breast milk utilization and immune system development, as well as protection against gut pathogens linked to common newborn conditions such as colic and diaper rash. The metagenomics study, published in Scientific Reports, found that the gut microbiomes of approximately nine out of ten infants were missing Bifidobacterium longum subsp. infantis (B. infantis), a type of bacteria that plays a critical role in infant health and development. This specific gut bacterium has been widely documented as providing the most beneficial impact on infant gut health, and possessing the ability to fully unlock the nutritional benefits of breast milk.

The study is claimed to be the largest to date to benchmark widespread deficiency in gut bacteria among U.S. infants, and the reduced function of their gut microbiomes that results. “The vast majority of infants are deficient in this key gut bacterium from the earliest weeks of life, and this is completely off the radar for most parents and pediatricians, alike,” said study co-author Karl Sylvester, MD, professor of surgery and pediatrics and associate dean of maternal child health research, Stanford University. “This study provides the clearest picture to date of just how widespread this issue is and highlights the need to address B. infantis deficiency in the infant gut right from the start.” Sylvester and colleagues reported on their findings in a paper titled, “Metagenomic insights of the infant microbiome community structure and function across multiple sites in the United States.”

The neonatal period represents a unique stage of life when “critical foundations of lifelong health”—including proper immune system development—are established, the authors wrote. Key to this foundation for health is the infant gut microbiome, which requires the presence of thousands of different bacteria to perform different functions, from biological processes to the development of biological structures and systems.

When present in the infant gut microbiome, B. infantis breaks down carbohydrates called human milk oligosaccharides (HMOs) that are present in human breast milk, and which would otherwise be inaccessible to the infant. B. infantis differs from other Bifidobacteria species in its unique adaptation to human breast milk and specifically in its ability to break down HMOs into usable nutrients. Perhaps more importantly, B. infantis is increasingly linked to development of the infant immune system, protecting the infant intestinal tract from potentially dangerous bacteria as well as lower incidence of common childhood conditions like colic and diaper rash.

It has also been shown that disruption to the neonatal gut microbiome—dysbiosis—may be relevant to continued problems, such as increased risk for immunological disorders later in life, and acute chronic inflammation, the researchers noted. Dysbiosis in newborns is marked by a substantial imbalance between beneficial and potentially pathogenic bacteria in the gastrointestinal tract.

There has been strong evidence characterizing a substantial loss of Bifidobacteria in the infant gut over the past 100 years, with research pointing to numerous factors including increased C section delivery, increased use of antibiotics, and increased use of infant formula. As a result of B. infantis loss, the infant gut is at greater risk for negative consequences, including suboptimal access to the full value of human breast milk, compromised immune system development, an increase in harmful gut pathogens due to increased gut pH, and negative impact on the infant’s intestinal wall. “In the past few years, reliable evidence has emerged on the status of the U.S. infant gut microbiome showing a general trend toward dysbiosis and associated negative acute- and long-term health consequences,” the researchers commented.

However, they explained, to date, researchers have based their conclusions largely from single-site microbiome studies, often limited to a geographical area where samples were collected. Small association studies also demonstrate inherent limits in terms of reproducibility of methods, from sample collection to analysis, they continued. “Currently, there are limited data to broadly assess the status of the U.S. healthy infant gut microbiome,” while most infant micoribiome studies have been carried out on preterm infants, which may exhibit microbiome instability and more severe dysbiosis than is seen in full term infants.

For their newly reported metagenomics study, the team collected fecal samples from 227 infants under six months of age, during pediatrician office visits, across five different U.S. states (CA, GA, OR, PA, SC). The samples were analyzed for bacterial type and amount present, which represents the bacterial composition in the infants’ guts. The fecal samples were assessed for bacterial ability to fully use human breast milk—a hallmark of the presence of health-promoting bacteria—as well as for the presence of antibiotic resistant genes in the bacteria.

“Specifically, we applied shotgun metagenomics to characterize: (1) gut bacterial communities of healthy U.S. infants in the first six months of life; (2) ecosystem functions by determining the metabolic potential of gut microbiomes in different enterotypes to metabolize human milk oligosaccharides (HMOs) from breast milk; and (3) the carriage of antibiotic resistant genes (ARGs) in infants across different U.S. states,” they explained. The researchers did not include samples from infants with jaundice, or those who were either actively undergoing antibiotic treatment, or who had been diagnosed with problems with absorbing carbohydrates in their intestine, due to the impact that such conditions may have had on the ability of the infant gut to carry out normal processes.

The findings showed that potentially dangerous bacteria comprised, on average, 93% of all bacteria in the infant gut microbiome, with the most prevalent bacteria being Escherichia coliKlebsiella pneumoniae, Salmonella, Streptococcus, Staphylococcus, and Clostridium difficile. Many of these bacteria are known to harbor genes related to antibiotic resistance. In fact, a total of 325 antibiotic resistant genes were found in the gut bacteria, with more than half (54%) of those genes being those that confer bacterial resistance to multiple antibiotics. The results also indicated that some 97% of infants were “likely missing B. infantis,” the scientists reported. Given that B. infantis has been so widely considered as one of the most prevalent bacteria in the GI tracts of infants, its absence from such a wide swath of outwardly healthy infants is surprising.

“This survey offers a new perspective when considering infants in the context of a healthy microbiome and the acute and long-term consequences it implies,” they wrote. “Given recent findings linking the microbiome in early life to key elements of infant health and the understanding of this community has improved, our findings reveal that infants in the United States have microbiomes that may fail to provide functions necessary in early life including shaping the immune system, protecting against pathogen colonization, and maximizing nutrition from breast milk (e.g., HMOs).”

As Sylvester further noted, “The infant gut is essentially a blank slate at birth, and rapidly acquires bacteria from mom and the environment. We were surprised not only by the extensive lack of good bacteria, but the incredibly high presence of potentially pathogenic bacteria and an environment of antibiotic resistance that appears to be so widespread. The infant gut microbiome in the United States is clearly dysfunctional, and we believe this is a critical factor underpinning many of the infant and childhood ailments we see today across the country.”

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