What’s Up With the Virgin Gut? Do Babies Really Have an “Open Gut” Until 6 Months of Age?

There is a persistent myth about infant gut development that comes up in nearly every online discussion of starting solid foods. It’s the myth that infants have a “virgin” or “open” gut until around 6 months of age. I’ve received so many emails, Facebook posts, and comments about the virgin gut over the last few years that I thought it was finally time to take a look at the science – and lack thereof – behind this myth.

I have written before, in my book and on my blog, about the controversy around when to begin introducing solid foods to a baby. Some health organizations recommend 6 months of exclusive breastfeeding, while others recommend starting to offer solids between 4 and 6 months, following baby’s cues of readiness as your ultimate guide. Based on my analysis of the most current science, I believe that the second approach is more evidence-based and helps parents to focus on their baby’s unique development rather than the calendar. I also think that it’s just fine to wait until 6 months if that is your preference.

However, whenever I discuss this science, someone lectures me about infant gut development, and they usually send me a link to KellyMom’s page on the topic, which urges parents not to offer solids before 6 months. Here’s what it says:

“In addition, from birth until somewhere between four and six months of age babies possess what is often referred to as an “open gut.” This means that the spaces between the cells of the small intestines will readily allow intact macromolecules, including whole proteins and pathogens, to pass directly into the bloodstream. This is great for your breastfed baby as it allows beneficial antibodies in breastmilk to pass more directly into baby’s bloodstream, but it also means that large proteins from other foods (which may predispose baby to allergies) and disease-causing pathogens can pass right through, too.”

Wow, that does sound scary! I can see how this “open gut” idea would worry parents approaching the transition to solid foods. But here’s the thing: There are no references given to support these statements, and in all my reading of the research literature on readiness for solids, I have not encountered science backing this concern. Yet somehow this idea of the open gut comes up over and over in online discussions, complete with judgment for parents who offer solids before 6 months and non-evidence-based suggestions about how to “heal” a baby’s gut. All of this only serves to increase anxiety in parents, which is the last thing any of us need.

It’s time to get to the bottom of this. Let’s look at some science…

What do we mean when we talk about an “open” or “closed” gut? How do we measure this?

The lining of the small intestine serves a critical role in absorption of nutrients and in immune protection. Food and bacteria from the environment enter the GI tract, and the lining of that tract is what separates it from the body’s bloodstream. It’s important that this lining is selective about letting in the good stuff and keeping out the less desirable elements, as this interface is one of an infant’s most important barriers to infection (1).

The intestinal lining is composed of a single layer of epithelial cells, called enterocytes, arranged in many deep folds that serve to increase the surface area for nutrient absorption. Nutrients are absorbed across the intestinal enterocytes and into the blood stream.

The spaces between the enterocytes are joined by protein complexes, the most important of which are called tight junctions. Despite their name, these junctions are never a complete seal and let some particles through while excluding others, mostly on the basis of size and charge (2).

Researchers use the term intestinal permeability to describe how easily particles can cross the lining of the intestine and into the blood stream. Intestinal permeability is tested in research settings by giving a person an oral dose of two sugars, usually mannitol and lactulose (not to be confused with lactose, which is the major sugar found naturally in milk). Mannitol is the smaller of the two (molecular weight 182) and is absorbed through pores in the intestinal enterocytes. Lactulose is too large to fit through those pores (molecular weight 342), but some of it will sneak through the tight junctions to get into the bloodstream. Once in the blood, neither lactulose nor mannitol are further metabolized; they’re just filtered by the kidneys and excreted in the urine. So, if you give a person (including a baby) a dose of these two sugars and collect their urine, you can measure how much of each was absorbed in the small intestine. Results are usually expressed as a lactulose to mannitol ratio (L/M), with higher values representing greater intestinal permeability and lower values representing less intestinal permeability or a more “closed gut” (3,4).

Does intestinal permeability change in infancy?

Yes, but the timeline is different from KellyMom’s description.

The sugar absorption test has been used to measure the process and timing of gut closure in infants. Contrary to the KellyMom’s claims that this critical process happens between 4 and 6 months, studies show that the most important gut closure actually happens in the newborn period. For example, one study measured intestinal permeability in 72 healthy newborns on days 1, 7, and 30 of life and found that the biggest drop occurred within that first week of life (5).

Image may be NSFW.
Clik here to view. Intestinal permeability is high at birth but quickly drops within the first week of life. (Data from Catassi et al. 1995)

Intestinal permeability is high at birth but quickly drops within the first week of life. (Data from Catassi et al. 1995)

Does whether an infant is breastfed or formula-fed affect intestinal permeability? Maybe a little, but the difference doesn’t last long. The study shown in the graph above found no difference in intestinal permeability in exclusively breastfed and formula-fed babies on day 1 or day 30. On day 7, intestinal permeability was slightly lower in breastfed compared with formula-fed infants, indicating that formula-feeding may slow the process of gut closure (5). It’s possible that this may contribute to the increased incidence of GI illness observed in formula-fed infants. But again, this difference is transient. By one month and beyond, there is no difference in intestinal permeability between breastfed or formula-fed infants (6).

Preterm infants have greater intestinal permeability at birth but have similar values as term infants by 3-6 days of life.⁷ The process of gut closure is delayed when preterm infants are fed only by IV rather than via the gastrointestinal tract (oral or tube-feeding), and at least partial human milk feeding rather than exclusive formula-feeding improves gut closure in these vulnerable babies (8,9).

What about later in infancy? Studies on this question show a very gradual decline (if at all) in intestinal permeability over the first several years of life. There is no gut closure door slamming shut on the 6-month birthday. In the graph below, I’ve plotted intestinal permeability by age from two studies (10,11).

Image may be NSFW.
Clik here to view.

Over the first few years of life, a very gradual process of gut closure occurs. Some fine print about this figure: The Noone study actually used a different sugar absorption test, so these values may not be directly comparable, but you can see the same trend in both studies. The data from Noone are individual children, and those from Kalach are averages given in a group of children in each age group.

Another study (3) established a reference value for normal intestinal permeability measured by the sugar absorption test (lactulose/mannitol) among healthy children as 0.033 (average of 30 children with mean age of 5 years), and you can see that most of the babies in the above graph actually reached that degree of gut closure by 3 months. The reference value for intestinal permeability in adults established in the same study was just a tad lower at 0.027.

In other words, when it comes to readiness for solid foods, gut closure is probably irrelevant. It happens long before today’s parents are offering bites of banana or oatmeal.

KellyMom also claims that an infant’s “open gut” allows breast milk antibodies to pass directly into the bloodstream. That actually doesn’t happen in human infants – except for maybe in the first few days of life when intestinal permeability is truly high (and the evidence isn’t clear on that point). Instead, human babies get maternal antibodies (IgG) into their bloodstream when they cross the placenta during pregnancy. These include IgG developed by the mother in response to infection or immunization, and this is why maternal immunization for pertussis and flu during pregnancy is so effective at protecting babies from infection after birth. This is different from many other species of animals, in which IgG can’t cross the placenta and are instead transferred to baby via milk (especially colostrum) after birth (12,13).

The most important antibody type in human milk is secretory IgA, which coats mucosal surfaces such as the lining of the GI tract and can protect against infection in that way. However, IgA can’t be absorbed into the blood in human babies. This post on The Scientific Parent explains how this works in humans in more detail: Passive Immunity 101: Will Breast Milk Protect My Baby From Getting Sick?

What IS important for gut readiness for solid foods?

When infants start eating solid foods, they are shifting from the relatively simple diet of easy-to-digest breast milk and/or formula to a more complex diet with a variety of foods (with milk still being an important one). These foods require more work to digest, which means greater activity of a suite of digestive enzymes. In addition, the kidneys have to work a bit harder to excrete metabolites from these foods. How do we know that infants have the capacity to adapt to a more complex diet by 4 months of age?

Here’s the opinion of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHN; PDF):

“The available data suggest that both renal function and gastrointestinal function are sufficiently mature to metabolise nutrients from complementary foods by the age of 4 months. With respect to gastrointestinal function, it is known that exposure to solids and the transition from a high-fat to a high-carbohydrate diet is associated with hormonal responses (eg, insulin, adrenal hormones) that result in adaptation of digestive functions to the nature of the ingested foods, by increasing the maturation rate of some enzymatic functions and/or activities. Thus, to a large degree gastrointestinal maturation is driven by the foods ingested.”⁽¹⁴⁾

This is a recurring theme in nutritional biology – that it is only by exposure to a type of food that the GI tract can actually become efficient at digesting it. This is one reason why the transition to solids may give you some interesting diapers, from very messy to very solid, as the GI tract adapts to digesting these new foods. That’s good reason to introduce new foods gradually and in small quantities at the beginning, but it isn’t a good reason to avoid feeding them at all.

Image may be NSFW.
Clik here to view. m and marble rye

OK, maybe not the best choice for a baby new to solid foods, but this guy really thinks he’s ready to try some marble rye.

If a baby’s GI tract was really too immature to handle solids by 4 months, we would also expect to see more GI illness and food allergies developing in babies starting solid foods at that age. However, this is not what we observe. Most studies find no difference in risk of GI infection whether babies start solids between 4 and 6 months or after 6 months (15-17).

When it comes to risk for food allergies, recent research suggests that introducing solids, including common allergens, between about 4 and 6 months may actually reduce the risk of food allergies. (I give more details on this, with lots of references, in this post.) A study just published found that babies who start solid foods at 4 or 5 months have significantly lower risk of eczema compared with babies exclusively breastfed for 6 months (18). (Eczema in infancy is often associated with later development of allergies (19).) The development of a baby’s digestive and immune systems are interwoven processes, and exposure to food proteins during the 4-6 month period seems to help steer the immune system towards tolerance of foods rather than reactivity to them.

All of this doesn’t mean that you need to rush your baby to start solid foods. It just means that you can cross the open gut off your list of things to worry about. Anytime in the 4-6 months range is a great time to try offering your baby solid foods, following your baby’s signs of developmental readiness and interest in eating solids as your guide.

I ran across this video when I was looking for images to accompany this post. It’s a little off-topic, but it made me laugh a little, because I don’t think I could ever call M’s gut “virgin,” whatever that means. And I don’t think that’s a bad thing. (Please rest assured that M and our dog have a mutual appreciation for this licking ritual.)

Corrections (5/6/16): The information about IgG passed from mother to fetus during pregnancy was updated to emphasize that those IgG can develop in response to infection and immunization of the mother. The previous version just focused on immunization. In addition, I deleted a paragraph about “leaky gut syndrome” as a cause and potential target for cures for autoimmune diseases. Response from readers indicated that paragraph was distracting from the rest of the post, and I felt it wasn’t relevant to this post on infants. In general, there is a lot of pseudoscience in information about the leaky gut, especially if it is coming from folks trying to sell cures. (See here, here, and here for more info.) However, it is an active area of research and may be one of the things mediating the development of autoimmune diseases. Whether or not that information will eventually lead to any progress in prevention or treatment of these disease is debatable.

References:

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van Elburg, R. M. et al. Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring intestinal permeability for sugars. J. Pediatr. Gastroenterol. Nutr. 20, 184–188 (1995).
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