Tag Archives: Gut flora

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

Early antibiotics and obesity?

An English study of more than 11,000 children has turned up an association between early antibiotic use (that is, antibiotics given to babies less than 6 months of age) and later obesity.  Interestingly, the study did not find that antibiotics given to children between the ages of 6 and 14 months increased the risk of obesity, and the effect of antibiotics on children aged 15-23 months was inconsistent.

Why would the antibiotic-obesity association be found primarily in younger babies? The authors speculate that an altered gut microbiota may be the culprit.

The germs that make up the gut microbiota (GM) are acquired at birth and shortly afterwards. By a few months of age the “core” GM is more or less set for life. An altered GM has long been associated with obesity in older children and adults (see more extended discussions in my posts here and here)–it would make sense that antibiotics given in this sensitive period of GM development would have greater impact than later on, when the GM is more stable.

The added risk of obesity from early antibiotic administration is small for any individual baby,  the study’s authors stress, but even small increases spread over an entire population can have significant public health implications.

Still, sometimes babies need antibiotics. Studies like this one highlight the unintended (but real) consequences of the overuse of a sometimes life-saving tool.

***(Photo credit: Seattleye)

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Filed under Infectious diseases, Obesity

More on cesareans and obesity

Cesareans? Really?

Does cesarean birth put a baby at increased risk for obesity in the future? Seems a little far-fetched at first glance, but Dr. Susanna Huh and her Harvard colleagues just published a study that makes the link a bit more “near-fetched.” (The study itself is available here.)

Huh’s team found that children born by cesarean section were twice as likely to be obese at 3 years of age than were those born vaginally. This relationship held up even when factors like the mother’s weight, ethnicity, age and how many babies she’d already had  were taken into account. Interestingly, it didn’t make a difference whether the cesarean was performed before or after labor started.

The study wasn’t designed to look at the reasons for the increased risk in obesity, but the Harvard team suggested several possibilities:

The first is the alteration of the gut microbiota–the sum total of all the bacteria found in the human bowel–caused by a cesarean birth. (More detail on that here and here.) This alteration can lead to low-level inflammation in the bowel which is associated with obesity.

The second possibility is that cesarean birth is just a stand-in for something else that’s happening at the same time. In this case, Huh and colleagues wonder about all the antibiotics given to women who are having cesareans. Antibiotics are known to alter the gut microbiota, but research results are mixed as to whether this is a lasting effect.

Finally, it’s possible (though unlikely) that all of this has nothing to do with the gut microbiota. There are hormones and other factors related to inflammation that surge in a mother’s bloodstream (and her baby’s) during labor, and these, obviously, are missing if a mother undergoes a cesarean before she starts labor. The lack of maternal stress response during labor could adversely impact the development of the newborn immune system, leading to the inflammation associated with obesity.

My best guess: it’s a big moosh of all of the above, plus other factors no one has even dreamed of yet. In the meantime, the issue of increased obesity risk is one more thing physicians and pregnant women should consider before deciding on how a baby is to be born.

It’s a complicated matter, this business of hatching healthy humans…

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Cesareans and asthma: More evidence

No way to spend a childhood...

Yet another study links cesarean birth with asthma. This one involved 37,000 participants in the Norwegian Mother and Child Cohort Study, and compared cesarean- and vaginally-born children for evidence of asthma at age 3. Those born by cesarean section had an increased risk of asthma.

The authors speculate that the altered gut microbiota found in cesarean babies–the collection of bacteria that live in the bowel–may be the reason for the association. (See my posts here and here for an explanation of how and why an altered gut microbiota may be at the root of a number of later chronic illnesses.)

The study’s authors described the increased risk as “slight,” which contrasts with the “moderate” risk found by other researchers. This apparently lower risk may be due in part to the how the study was performed.

First, the researchers lumped all cesareans–both scheduled cesareans and those that followed a long labor, in which a baby may be exposed to the normal bacteria of the birth canal–rather than comparing scheduled cesareans to vaginal births. The latter comparison would give a clearer picture of childhood asthma risks from cesarean birth.

Second, the study only follows the children to 3 years of age. Many cases of asthma occur later in childhood, and a longer follow-up of these children (which is no doubt in the works) would give a clearer picture of the risks.

Studies like this one add more weight to the argument for reducing the number of cesareans currently being performed, particularly those done without any medical need. Women should be informed of the potential long-term health risks and benefits for their children when choosing how and where they want to have their babies.

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Filed under Asthma, Cesareans, Natural childbirth