Baby, It’s Dirty Outside

Nurturing the Infant Microbiome

It’s a scary world out there.

But from the moment we are born, an entire battalion is armed and at the ready to offer us protection against the perils of the world around us — and it’s not even human.

Babies born vaginally encounter an enormous population of microbes in their mothers’ birth tracts. These microbes will ultimately colonize the newborn’s intestines, seeding the first of many waves as the infant grows. Fed by nutrients from the mother’s milk, the burgeoning gut community eventually develops into a robust microbiome that supports digestion, immunity, metabolic health, and much, much more. But what happens when this process goes awry — if, for instance, a baby is born instead by C-section, or fed formula instead of human milk? It turns out that the microbiomes of these infants often look strikingly different than those of vaginally born and breastfed babies — and many of these children go on to suffer from conditions like obesity and asthma (1, 2, 3, 4). Are these phenomena linked?

Alarm bells have been raised in the scientific community and beyond in the last decade, fueling suspicion that we could be immediately and irreversibly imperiling infants who do not enter the world or acquire nutrition through “natural” means. How well-founded are these claims, and if there is any truth to the concern, are C-section and formula-fed babies being set on an irreversible course?

Hello, World

Let’s start at the beginning.

For better or for worse, we all have a little more of our mothers in us than our fathers. We grow inside our mothers, enter the world through our mothers, even inherit mitochondrial DNA exclusively from our mothers. But all those contributions are dwarfed, at least in number, by the trillions of microbes our mothers pass on to us.

It was once assumed that the uterine environment was sterile, and that newborns encountered their first microbes in the birth canal. However, recent evidence has shown that infants don’t enter the world as a tabula rasa — not completely. Fetuses may actually be colonized by microbes in utero, perhaps through the mother’s placenta. Regardless, it’s clear that the first colonization event that occurs en masse is at birth.

The microbiome starts off relatively simple, but, over the first few years of life, quickly matures into the robust, diverse microbiome characteristic of adults. From day one, the microbiome appears to influence everything from immunity to metabolism, and scientists are discovering new impacts of these communities on our health at an ever-increasing rate. So it’s unsurprising that perturbations to the microbiome during these early periods could pose particular risk to a growing child’s health.

The first cut is the riskiest

Even before we meet our fathers, we meet our gut microbes. During vaginal birth, newborns swallow fluid from their mother’s vaginas, which are full of friendly bacteria like Lactobacillus, a name you may recognize from the lid of your Greek yogurt. There also appears to be some contribution from the mother’s gut microbiota, as the microbiomes of infants born vaginally strongly resemble those of their mothers’ guts. But babies aren’t encountering the intestines — so how do these microbes gain access?

Birth is full of difficult truths. One of them is that the barriers separating the vagina and rectum become compromised during labor, and newborns end up swallowing some of mom’s feces on their way into the world.

On the other hand, babies born by C-section inherit a very different first microbiome — one that resembles the microbiome of the mother’s skin or mouth rather than her vagina, and contains fewer species than one of a vaginally-delivered infant. These differences persist through the first several months of life, and several studies have linked C-section births to higher rates of obesity and asthma.

Scientists believe that this may be due to the critical role the early microbiome plays in training the immune system to recognize foreign invaders and raise its defenses at the right time and place. Certain bacterial species acquired from the mother’s vagina may play essential roles in this immune training.

However, no research so far has been able to directly link mode of delivery to the development of metabolic disease and autoimmunity, and many of the differences between the microbiomes of infants delivered vaginally and by C-section disappear as early as six weeks of age, and sometimes entirely by 12 months of age. But many scientists currently believe that even though the microbiome normalizes over time, the temporary perturbations during infancy may be to blame for some of these syndromes that rear their heads only later in life. Even if the course is eventually set straight, small bumps in the road can have lasting and insidious effects.

In light of this possibility, doctors and scientists have begun to investigate restoring the vaginally-derived microbiome in babies delivered by C-section. In one study, researchers swabbed a small group of C-section infants with their mothers’ vaginal fluid. All things considered, the swabbing was a success: just weeks later, the infants’ gut microbiomes more closely resembled those of vaginally born babies than babies delivered by C-section who had not received the treatment. But the researchers only kept up with the infants through the first month of life, and the long-term effects of the restoration are still unclear.

Are C-sections entirely responsible for declines in infant health or increasing rates of autoimmune disease? Probably not. But they are becoming an increasingly relevant phenomenon in developed countries for reasons that aren’t always medical — such as timing and convenience for both doctors and mothers. In the past several decades, C-sections have come to account for over 30% of total births in the U.S., and over 50% of total births in several other regions of the world — despite the fact that doctors estimate as few as 19% of births necessitate surgical intervention. Taking into account the C-section risks above and beyond microbiome disruptions, including increased risk of complications for both mother and child, we might want to think twice about opting for surgery that isn’t medically necessary.

Crying over spilled formula

After birth, the floodgates are open. Colonization occurs rapidly and repeatedly, and during the first year of life, the infant microbiome is incredibly dynamic.

Infants who are breastfed are primarily colonized by the microbes present in their mothers’ milk — namely, Bifidobacterium, a type of bacterium that thrives on human milk oligosaccharides, a type of sugar exclusively found in breastmilk. These oligosaccharides aren’t digested by humans, instead making it down to the babies’ colons, where they nourish the thriving community of Bifidobacterium species.

The Bifidobacterium return the favor. They turn the milk oligosaccharides into short-chain fatty acids that the human body cannot produce itself. These short-chain fatty acids nourish the cells of the newborn’s intestines and the nearby immune cells, which play essential roles in development and metabolism.

Babies who are formula fed, on the other hand, have an unexpectedly more diverse microbiome that resembles the microbiomes of older children who have already transitioned to solid foods. At first glance, this may seem like a good thing — after all, diversity is protective in almost all other cases. But this seems to be one of the few exceptions. Formula-fed infants’ microbiomes appear to be skipping that crucial, short-chain fatty acid-rich developmental step.

Concerns about formula aren’t new, though, and researchers have long been tinkering with recipes to more closely resemble human milk. New research on the importance of the breast milk microbiome has only reinvigorated this work. Recently, there has been some success supplementing formula with doses of Bifidobacterium, leapfrogging the middleman. In the end, the microbiomes of infants fed these probiotic formulas look significantly more like those of breastfed babies. That being said, acquiring living, metabolically active Bifidobacterium straight from mom may have other benefits we haven’t yet identified.

In this same vein, there are known differences we can’t account for by tweaking recipes alone. For instance, infants get about 30% of their gut microbiome from their mother’s milk, and another 10% from the skin surrounding their mother’s nipples. That 10% isn’t accounted for in even the best formulas. And it’s likely there are more factors at play that we haven’t yet identified.

In this same vein, there are known differences we can’t account for by tweaking recipes alone. For instance, infants get about 30% of their gut microbiome from their mother’s milk, and another 10% from the skin surrounding their mother’s nipples. That 10% can’t be accounted for by even the best ingredients. And it’s likely there are factors at play that we haven’t yet identified, and are thus lost to infants who drink only from the bottle.

Nothing to sneeze at

It’s literally too early to tell how big an effect variations in infant delivery and feeding have. What’s more, the list of early perturbations with potentially long-lasting consequences continues to grow beyond birth mode and diet; for instance, antibiotic use can be particularly damaging to the burgeoning microbiota during this sensitive period. And the further out from birth we look, the muddier the waters get.

But what’s clear is this: babies born and nursed by any means go on to live rich, diverse lives that expose them to a vast array of microbes that also undoubtedly influence their development. There are infinite ways to exist in this world — and certainly more than one to enter it. A lifetime of healthy behavior can still have a lasting impact on a perturbed microbiome. And with each passing day, we are coming closer and closer to recapitulating what our mothers provide us naturally — and our understanding of the infant microbiome will continue to grow alongside our children.

It’s literally too early to tell how big an effect variations in infant delivery and feeding have — and babies born and nursed by any means go on to live rich, diverse lives that expose them to a vast array of microbes that also undoubtedly influence their development. There are infinite ways to exist in this world — and certainly more than one to enter it. The further out from birth we look, the muddier the waters get.

Katherine Wu is a PhD candidate at Harvard University, where she studies bacterial stress responses. She is Co-Director of Science in the News, a graduate student organization that trains scientists to better communicate with the general public.

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Citations:

1. “The Risks of Not Breastfeeding for Mothers ….” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812877/. Accessed 23 Feb. 2018.
2. “Breast-feeding’s role in ‘seeding’ infant microbiome … — ScienceDaily.” 8 May. 2017, https://www.sciencedaily.com/releases/2017/05/170508112411.htm. Accessed 23 Feb. 2018.
3. “The Influence of Early Infant-Feeding Practices on the … — NCBI — NIH.” 16 Dec. 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686345/. Accessed 23 Feb. 2018.
4. “Role of breast feeding in primary prevention of asthma and … — NCBI.” https://www.ncbi.nlm.nih.gov/pubmed/18386435. Accessed 23 Feb. 2018.

I Contain Multitudes is a multi-part video series dedicated to exploring the wonderful, hidden world of the microbiome.