Category Archives: Gut microbiota

Is it the cesarean, or the absence of labor?

Stem cells, pondering the future

Stem cells, pondering the future

I’ve written a fair amount about the association between cesarean birth and the increased risk of immune-related diseases like asthma, diabetes, celiac disease, and even obesity. Most of the research out there has focused on the newborn gut microbiota—the collection of bacteria that colonize a baby’s intestines at birth and play a key role in the development of the immune system. These bacteria are primarily acquired from the mother’s birth canal and rectum during a vaginal birth, but for cesarean-born babies those “pioneer” bacteria are often derived from the hospital environment. Such “wrong” bacteria in the bowel early on can lead to inflammation and, the theories go, to immune-related diseases later in life.

But is the cesarean per se at the root of all this? Or might the absence of labor (or an incomplete labor) have something to do with it? Childbirth is, after all, a fabulously complicated dance of maternal and fetal hormones, anti-oxidants, and other chemicals that are known to influence the immune system. What happens to the newborn’s immune system development when that dance is cut short, or never starts in the first place?

A study from Sweden’s Karolinska Institutet published in the current issue of the American Journal of Obstetrics and Gynecology has me wondering about the “absent-labor” scenario again. The study’s authors compared cord blood samples from babies born by elective cesarean section (ECS) with those who were vaginally born (VB). They looked specifically at hematopoietic stem cells—the precursor cells that go on to become, among other things, the white blood cells that play a critical role in the human immune system.

Here’s what they found: the DNA in stem cells from ECS babies was significantly different from that of the VB babies, particularly in an area devoted to production of antibodies. The study’s genetic analysis is way above my pay grade, but boiled down to the essentials, the differences are all about epigenetics, which is defined as:

 “…the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence.”

Ouch!

Plain English version (mine): Epigenetics is the study of how genes are turned on and off, typically by the addition of methyl groups (ouch, again!) to genes. The timing of all this light-switch-like activity, and the potential for permanent change, has big-time implications for health throughout life.

The Swedish researchers found that stem cell DNA methylation (the addition of methyl groups to genes) increased steadily with the duration of labor. So one could conclude, couldn’t one, that normal labor plays an important role in preparing future white blood cells for their task, and, ergo, the absence of labor is why everyone’s so chubby these days? Sure, one could conclude that…but one would be jumping the gun, big time.

Hold that smokin' gun, pardner!

Hold that smokin’ gun, pardner!

Why? Because this was a small, observational study—the kind of study designed to make readers sit up and take notice (Hmm…that’s interesting!”) but that requires much more research before any guns start smoking. The small numbers of subjects in this study makes it easier for error to creep in, for example, and there were significant differences between the mothers as well—the ECS group was significantly older than the VB group, and their babies were born an average of a week and a half earlier, factors which might cause their own epigenetic effects.

It’s going to take much larger studies to see if these findings are in fact true, and if so to tease out how significant such cesarean-related epigenetic changes may be in the grand scheme of childhood immune system diseases. A lot of vaginally born kids end up asthma, after all. Including me.

But still, how fascinating! I’m looking forward to reading more about this.

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Photos courtesy Joseph Elsbernd, Jim Sher

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Filed under Asthma, Cesareans, Gut microbiota, Natural childbirth, Obesity

Starvation and the infant gut

Even worse for babies...

Even worse for babies…

The gut microbiota—the collection of trillions of bacteria that populate the bowel in humans—goes through somewhat predictable developmental stages in infancy and early childhood. Some types of bacteria dominate right after birth, while others increase in number as the diet changes from milk to solid foods over the course of the first two years of life. The final profile is largely set by about age 3—what you’ve got in your gut at that point is basically what you’ll have into adulthood.

Many factors can affect the final profile—I’ve written about cesarean birth, antibiotic use, and the typical high-calorie, high-fat western diet as likely culprits. As you might suspect, these are problems of affluence. We can debate the effects of too many cesareans, too much antibiotics, and too many calories, but in developing countries there’s another potent shaper of the developing gut microbiota in childhood: starvation.

A recent study performed by Washington University in St. Louis and the International Center for Diarrheal Disease Research in Dhaka, Bangladesh, showed that children with severe acute malnutrition (SAM) have immature gut microbiota profiles—the types of bacteria in the bowel didn’t change over time as would be expected in well-nourished infants and children.

The study followed Bangladeshi infants and toddlers with SAM over the course of acute treatment and for several months afterwards. The malnourished children did gain weight rapidly with very high-calorie diets, but they were unable to achieve or maintain a normal weight once the treatment ended and they switched to a more typical diet. Signficantly, their gut microbiota remained immature—the bacteria present in the gut both before and after treatment were woefully inefficient at extracting calories from food.

So now we have evidence that the gut microbiota plays an important role in two very different nutritional diseases: obesity and malnutrition. Future SAM research will be aimed at supplementing probiotic bacteria as well as calories in hopes of promoting healthy, long-lasting changes to the microbiota.

The sooner the better, given the terrible toll malnutrition takes on children in many parts of the world.

Photo courtesy of Chris Turner

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Filed under Gut microbiota, Nutrition, Obesity