A Microbiome Researcher’s Advice: How to Support Formula-Fed Infants for Optimal Gut Health.

Learn how breastfeeding and formula feeding shape an infant's gut microbiome, plus tips for supporting healthy gut bacteria in formula-fed infants.

Medically Reviewed by Ari Brown, MD - Author of Baby 411, Chief Medical Advisor for Kabrita North America​​

Understanding the Infant Gut Microbiome 

An adult human gastrointestinal (GI) tract harbors tens to hundreds of trillions of microorganisms. The development of the adult microbiome begins during infancy where the initial colonization of microbes shapes the overall microbial structure that will dominate the GI tract throughout a lifetime. Interest in the microbiome has significantly increased in recent years due to the realization that it plays a central role in all aspects of human health, from regulating immunity, blood pressure, as well as glucose and cholesterol metabolism, to impacting brain function and behavior. While genetics play a role in the microbial species that inhabit the GI tract, mode of birth (Cesarean section vs vaginal birth) has been shown to impact early colonization. Importantly, the primary determinants of the gut microbial composition are modifiable behaviors that include environment, lifestyle and diet. Given that humans are born with few microbes, the first few months to years of life are critical in shaping the types and functional capacity of the microbes that inhabit the gut. 

How Breastfeeding Shapes the Microbiome

Human milk is considered the gold standard of infant nutrition as it provides all the macro- and micronutrients needed for optimal cognitive and metabolic development. It also provides all the necessary components, including proteins, peptides, lipid and glycan structures, and microbes, that aid in the optimal microbial colonization of the GI tract. In addition to providing potential probiotic species to seed the microbiome, it is the lipid and glycan structures present in human milk that are of particular interest when considering the development of the infant microbiome. Glycans are complex carbohydrates composed of monosaccharide units (such as glucose, galactose, fucose, sialic acid, or N-acetylglucosamine) linked through glycosidic bonds. They exist as either free entities (such as the human milk oligosaccharides, or HMOs), or conjugated to proteins or lipids. Conjugated glycans are important for helping cells recognize each other, so they can adhere to and signal one another. This makes them important for immune system recognition and immunological responses. Glycans are also recognized by viruses and bacteria who use them to either bind to cells to invade (such as with pathogens) or utilize them as a food source. It is therefore thought that in addition to providing food for the microbes in the developing neonatal GI tract, an important function of free HMOs and glycosylated milk proteins is to act as pathogen decoys through mimicking the glycan attachment sites on gut epithelial cells which help prevents colonization of pathogenic microorganisms.

Differences Between Breastfed and Formula-Fed Infant Microbiomes

While the HMOs in human milk constitute the third most abundant component (behind lactose and lipids), these molecules are conspicuously missing or very low in infant formula, because milk from ruminant animals contains low levels of these complex oligosaccharides (with cow milk having lower levels than goat milk). This means that unless a formula is enriched with HMOs, such as 2’-fucosyllactose and/or Sialyllactose, at levels comparable to human milk, the GI tracts of formula-fed infants will have low or absent levels of HMO-consuming Bifidobacterium species. HMO-consuming Bifidobacterium species are important because they produce a variety of metabolites that both support the growth of other beneficial microbes through cross-feeding and contribute to the infant’s immune and cognitive development.

Why Early Microbiome Development Matters for Long-Term Health

The specific composition of the infant gut microbiome plays a critical role in its overall function. Breastfed infants typically exhibit higher levels of fermentation byproducts from carbohydrate metabolism, leading to increased fecal water content and lower stool pH compared to formula fed infants. In contrast, formula fed infants have greater levels of byproducts from amino acid degradation. Babies lacking these fermentation products experience firmer stools and a higher stool pH. These differences highlight that there are distinct metabolic outputs between breastfed and formula-fed infants, and these outputs play key roles in signaling to the immune, endocrine, and nervous systems. The differences in the composition and functional capacity of the microbiome between breastfed and formula-fed infants may help to explain the elevated inflammatory markers often observed in formula-fed infants.
An important question, then, is whether a few species of bacteria early in life make a difference in the long run, since once infants transition to solid foods, differences in the microbiome generally disappear and composition is driven by diet. Given that gut microbiota can regulate metabolism, the answer to this question is likely yes. Studies have shown that formula-fed infants exhibit a higher caloric intake which may pre-program the brain early in life and contribute to a decreased ability to self-regulate food intake later in life due to a diminished response to internal cues of satiety. Moreover, formula-fed infants have higher levels of circulating insulin and branched chain amino acids, leading to accelerated growth which may pre-program systemic metabolism, as formula feeding has been associated with an increased odds of becoming overweight or obese in adolescence or adulthood. All of this points to the fact that composition of the gut microbiome in early life may be important for programming metabolism.

How to Support a Healthy Microbiome When Formula Feeding

Unfortunately, not everyone is able to breastfeed their infant. So, a question many will have is how to support formula-fed infants in having the best chance of developing a robust microbiome? See my guidance below: 

First, new research is showing that providing a formula that contains lactose as the main carbohydrate is important (parents should avoid using formulas containing maltodextrin or corn syrup solids). 
Lactose is both a source of energy and can exert prebiotic effects in the gastrointestinal tract, thus helping beneficial Bifidobacterium species to thrive.

Second, choose a formula that has a protein content closer to human milk.
New research is showing that too much protein early in life can lead to metabolic dysregulation and obesity. Additionally, too much protein in the diet means that more protein makes it into the colon, which can impact the microbiota by enhancing the selection of species of microbes that digest protein and produce unfavorable fermentation products. (It is important to note that a diet deficient in protein and essential amino acids is detrimental to health, so there is a balance. Protein levels should not be lower than human milk, and the type of protein should provide all necessary essential amino acids at appropriate levels.) 

Third, formulas containing triglycerides that contain primarily sn-2 palmitate are better choices than formulas containing primarily vegetable oils. 
Infant formulas containing sn-2 palmitate have been shown to increase bifidobacterial species in the infant gut, and studies have reported that infants consuming formulas with sn-2 palmitate have softer stools and less fussiness. 

Finally, an infant formula that contains prebiotic fibers such as 2’-fucosyllactose and/or Sialyllactose can help to establish and maintain beneficial bacteria in the infant; however, the amount is important. As mentioned above the formula should contain levels that approach the levels in observed human milk, or it will unlikely provide substantial benefit.

Additional Tips for Preserving the Infant Microbiome

Whether a family chooses to breastfeed or formula feed, it is important that you provide only breastmilk or formula for your infant for the first 6 months of life. Providing other beverages (even water) or food (cereal or any other food) is not recommended until the infant reaches approximately 6 months of age. When a baby reaches 6 months, parents can start to provide other foods, starting with taste portions and increasing gradually over time. Introducing solid foods around 6 months of age is important for exposing infants to a variety of tastes and textures, which can help reduce the likelihood of picky eating later in life. For breastfed infants, it is especially important to include iron-rich or iron-fortified foods at this stage, as their natural iron stores are typically depleted by 6 months. Without adequate iron intake, infants are at risk of iron deficiency, which can cause irreversible developmental harm. Because infant formulas are fortified with iron, formula-fed infants are generally at lower risk for iron deficiency during this period, and thus iron intake is less of a concern when starting solids. By providing a gradual introduction to complementary foods, the microbiome will gradually shift to a more adult-like microbiome, thus retaining the benefits of the microbiome that was established over the first 6 months.