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The millions of bacteria, fungi, viruses (human microbiome) that live on and within us are extremely important for our health in all sorts of ways. The birth experience (as the baby travels down the birth canal) is one way that a mother's microbes get transmitted to the baby ("seeds" the baby's microbiome). But babies born by Cesarean delivery start out picking up different species of microbes - from dust in the operating room.

Thus there has been concern with the possibility that a baby born by C-section, as compared to a vaginal delivery, will have life long microbiome differences. Swedish researchers studied this issue in 471 children and determined that by 5 years of age that the microbiome differences at birth and first year of life have generally disappeared. The differences in microbial composition had decreased to less than 2% in the 2 groups. This is good news!

Over the 5 years everyone had a great increase in the number of microbial species that live in the gut. The gut microbiome became more "adult-like", but it wasn't yet like that of adults. A conclusion was that not only does it take years to develop adult microbial complexity, but there is also individual variation in how long this takes. A person's diet, especially the introduction of solid foods, and environment all have an effect on species diversity and composition.

By the way, another way mothers transmit hundreds of species of microbes to their babies is during nursing in the breast milk (this is great!), and these species change over time. This is a good reason to breast feed - it's not just the nutrition, but also the microbes.

From Science  Daily: Gut microbiota in Cesarean-born babies catches up

Infants born by cesarean section have a relatively meager array of bacteria in the gut. But by the age of three to five years they are broadly in line with their peers. This is shown by a study that also shows that it takes a remarkably long time for the mature intestinal microbiota to get established.  ...continue reading "Five Year Olds Have Similar Gut Microbes, No Matter the Type of Birth"

Well.., given the high rate of C-sections in the US (32%) and many other countries, this is disturbing news. A study found that if a woman delivers her first baby by C-section (Cesarean birth), than her rates of conceiving again and also carrying the second baby successfully to term (a live birth) are lower than women who deliver a first baby vaginally.

The Penn State College of Medicine researchers looked at "unprotected intercourse and resulting conceptions", so it really was a measure of conception rates, and not a matter of choice. The study followed more than 2000 women for 3 years after the first birth, but it is unknown if these findings continue in year 4 and more. By the way, other studies over the years have had similar findings.

What could be causing these results? The researchers point out that it has been reported that many women (61%) develop a defect at the site of the cesarean incision (a cesarean scar defect) that may increase the risk of infertility.

From Science Daily: Women who deliver by C-section are less likely to conceive subsequent children

Women who deliver their first child by cesarean section (C-section) are less likely to conceive a second child than those who deliver vaginally, despite being just as likely to plan a subsequent pregnancy, according to Penn State College of Medicine researchers. The team followed more than 2,000 women for three years after they delivered their first child.  ...continue reading "Conception Rates Are Different After C-Sections and Vaginal Births"

I posted about this amazing research while it was still ongoing (Jan. 16, 2015), but now a study has been published. The small well-done pilot study looked at the microbiome (microbial communities) and microbial differences between different groups of infants during the first 30 days of life. They found significant differences in the bacteria of C-section infants (not exposed to their mother's vaginal fluid in the birth canal) compared to C-section infants who were swabbed with a gauze pad right after birth with their mother's vaginal fluids. They found that the microbiota (community of microbes) is partially restored in the swabbed C-section infants and more similar to that of vaginally delivered infants (who were exposed to the maternal bacteria naturally in the birth canal). They found that the procedure restored some bacteria, such as Lactobacillus and Bacteroides, which were nearly absent in the skin and anal samples of non-swabbed C-section babies.

In the C-section group, four mothers who were free of infections that might harm the babies, incubated a sterile gauze in their vaginas for one hour before the operation (C-section). Then, within two minutes of birth, the babies were swabbed with the gauze first over their mouths, then their faces, and then the rest of their bodies. These results are important because it is thought that microbiome differences (depending on method of birth) are long-lasting (with higher incidence of some health problems later in life with C-sections), and because the baby's early microbiome helps educate the baby's developing immune system.

Rob Knight (a leading microbiologist and one of the researchers) pointed out that the study "provides the proof-of-concept that microbiome modification early in life is possible." Now we need to see if these microbial differences persist over time and if it makes a health difference. From Science Daily:

Vaginal microbes can be partially restored to c-section babies

In a small pilot study, researchers at University of California, San Diego School of Medicine and Icahn School of Medicine at Mount Sinai determined that a simple swab to transfer vaginal microbes from a mother to her C-section-delivered newborn can alter the baby's microbial makeup (microbiome) in a way that more closely resembles the microbiome of a vaginally delivered baby. 

Babies delivered by C-section differ from babies delivered vaginally in the makeup of the microbes that live in and on their bodies. These early microbiomes help educate the baby's developing immune system. Previous research suggests a link between C-section delivery and increased subsequent risk of obesity, asthma, allergies, atopic disease and other immune deficiencies. Many of these diseases have also been linked to the microbiome, though the role a newborn's microbiome plays in current or long-term health is not yet well-understood....Other research suggests that microbiome differences between vaginal and C-section babies can persist for years."

In the study, the researchers collected samples from 18 infants and their mothers, including seven born vaginally and 11 delivered by scheduled C-section. Of the C-section-delivered babies, four were exposed to their mothers' vaginal fluids at birth as part of this study. To do this, sterile gauze was incubated in the mothers' vaginas for one hour before the C-section. Within two minutes of their birth, the babies delivered by C-section were swabbed with the gauze starting with the mouth, then the face and the rest of the body.

Six times over the first month after birth, the researchers collected a total of 1,519 anal, oral and skin samples from the mothers and infants. Knight's team then used a gene sequencing technique to map the types and relative quantities of bacterial species present at each body site.

Here's what they found: the microbiomes of the four C-section-delivered infants exposed to vaginal fluids more closely resembled those of vaginally delivered infants than unexposed C-section-delivered infants, though the difference was more distinct in their oral and skin samples than in their anal samples. This partial microbial restoration could be due to the fact that the infants received only one surface application of maternal vaginal fluids, Knight said.

Yet the oral and skin microbiome differences between C-section-delivered infants who received the microbial transfer and those who did not was still noticeable one month after birth. The results were not due to diet differences, as all of the infants received breast milk either exclusively or supplemented with formula during the first month of life. In addition, consistent with previous studies, the babies' microbiome profiles did not correlate with the amount of breast milk they received.

"The present work is a pilot study -- we need substantially more children and a longer follow-up period to connect the procedure to health effects," said Knight...."This study points the way to how we would do that, and provides the proof-of-concept that microbiome modification early in life is possible. In fact, we already have more than 10,000 additional samples collected as part of this study that still await analysis."

An interesting Canadian study that followed young children for 3 years found that young infants may be more likely to develop allergic asthma if they lack four beneficial bacteria in their gut. Children with low levels of Lachnospira, VeillonellaFaecalibacterium, and Rothia bacteria in their gut in their first 3 months were at higher risk for asthma and tended to receive more antibiotics than healthier children before they turned 1 year old.

Other studies have shown that the risk of developing asthma and allergies has been linked with such things as taking antibiotics, cesarean birth, bottle fed with formula, not living on a farm, and not having furry pets in the first year of life.

The researchers wrote: "Our findings indicate that in humans, the first 100 days of life represent an early-life critical window in which gut microbial dysbiosis {the microbial community being out of whack} is linked to the risk of asthma and allergic disease." How do the infants get these microbes? It is thought that infants get exposed to the mother's microbiome (microbial community) via vaginal birth, breast-milk, and mouth contact with the mother's skin.  From NPR News:

Missing Microbes Provide Clues About Asthma Risk

The composition of the microbes living in babies' guts appears to play a role in whether the children develop asthma later on, researchers reported Wednesday. The researchers sampled the microbes living in the digestive tracts of 319 babies, and followed up on the children to see if there was a relationship between their microbes and their risk for the breathing disorder. In the journal Science Translational Medicine, the researchers report Wednesday that those who had low levels of four bacteria were more likely to develop asthma by the time they were 3-years-old.

Specifically, the researchers focused on 22 children who showed early signs of asthma, such as wheezing, when they were 1-year-old. They were much more likely than the other children to have had low levels of the four bacteria when they were 3-months-old. By the time they turned 3, most had developed full-blown asthma."The bottom line is that if you have these four microbes in high levels you have a very low risk of getting asthma," says Brett Finlay, a microbiologist at the University of British Columbia who helped conduct the research. "If you don't have these four microbes or low levels of these microbes you have a much greater chance of asthma."

Asthma is a common and growing problem among children. Evidence has been accumulating that one reason may be a disruption in the healthful microbes children get early in life, Finlay says."There's all these smoking guns like, for example, if you breast-feed versus bottle feed you have less asthma," he says. "If you're born by C-section instead of vaginal birth you have a 20 percent higher rate of asthma. If you get antibiotics in the first year of life you have more asthma." The microbiomes of kids who aren't breast-fed and are born by Caesarean section may miss out on getting helpful bugs. Antibiotics can kill off the good bacteria that seem important for the development of healthy immune systems.

"What's become clear recently is that microbes play a major role in shaping how the immune system develops. And asthma is really an immune allergic-type reaction in the lungs," Finlay says. "And so our best guess is the way these microbes are working is they are influencing how our immune system is shaped really early in life."

To further test their theory, the researchers gave laboratory mice bred to have a condition resembling asthma in humans the four missing microbes. The intervention reduced the signs of levels of inflammation in their lungs, which is a risk factor for developing asthma.

The bacteria are from four genuses: Lachnospira, Veillonella, Faecalibacterium and Rothia. The researchers aren't exactly sure how the microbes may protect against asthma. But babies with few or none of them had low levels of a substance known as acetate, which is believed to be involved with regulating the immune system.

Currently, during birth there are many potential disruptions to the healthy development of the infant's microbial ecosystem. Some practices to be concerned about: the use of antibiotics during pregnancy and during delivery, c-sections, newborns routinely given antibiotics, and then bottle feeding instead of breastfeeding. Sometimes one or more of these practices are medically necessary, but currently they are being done much too frequently and casually. In these ways we are conducting an experiment on every baby's microbial ecosystem with unknown long-term consequences. The following excerpts from Dr.Martin Blaser's popular 2014 book Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, even though written a year ago, are a nice summary of these issues. From Wired:

The Way You’re Born Can Mess With the Microbes You Need to Survive

THROUGHOUT THE ANIMAL kingdom, mothers transfer microbes to their young while giving birth....And for millennia, mammalian babies have acquired founding populations of microbes by passing through their mothers’ vagina. This microbial handoff is also a critical aspect of infant health in humans. Today it is in peril.

Microbes play a hidden role in the course of every pregnancy. During the first trimester, certain species of bacteria become overrepresented while others become less common. By the third trimester, just before the baby is born, even greater shifts occur. These changes, involving scores of species, are not random. The compositions change in the same direction across the dozens of women who have been studied.... Women of reproductive age carry bacteria, primarily lactobacilli, which make the vaginal canal more acidic. This environment provides a hardy defense against dangerous bacteria that are sensitive to acid. Lactobacilli also have evolved a potent arsenal of molecules that inhibit or kill other bacteria.

Whether the birth is fast or slow, the formerly germ-free baby soon comes into contact with the lactobacilli. The baby’s skin is a sponge, taking up the vaginal microbes rubbing against it. The first fluids the baby sucks in contain mom’s microbes, including some fecal matter.

Once born, the baby instinctively reaches his mouth, now full of lactobacilli, toward his mother’s nipple and begins to suck. The birth process introduces lactobacilli to the first milk that goes into the baby. This interaction could not be more perfect. Lactobacilli and other lactic acid–producing bacteria break down lactose, the major sugar in milk, to make energy. The baby’s first food is a form of milk called colostrum, which contains protective antibodies. The choreography of actions involving vagina, baby, mouth, nipple, and milk ensures that the founding bacteria in the baby’s intestinal tract include species that can digest milk for the baby.

Breast milk, when it comes in a few days later, contains carbohydrates, called oligosaccharides, that babies cannot digest. But specific bacteria such as Bifidobacterium infantis, another foundational species in healthy babies, can eat the oligosaccharides. The breast milk is constituted to give favored bacteria a head start against competing bacteria.

Cesarian delivery is a largely unrecognized threat to the microbial handoff from mother to child. Instead of traveling down the birth canal picking up lactobacilli, the baby is surgically extracted from the womb through an incision in the abdominal wall....For all of these reasons, U.S. C-section rates increased from fewer than one in five births in 1996 to one in three births in 2011—a 50 percent increase.

The founding populations of microbes found on C-section infants are not those selected by hundreds of thousands of years of human evolution. A few years ago in Puerto Ayacucho, Venezuela, my wife, Gloria, conducted the first study of its kind to test whether the microbes found on newborn babies delivered vaginally or by C-section varied in any way....The mouths, skin, and first bowel movements of babies born vaginally were populated by their mother’s vaginal microbes: Lactobacillus, Prevotella, or Sneathia species. Those born by C-section harbored bacterial communities found on skin, dominated by Staphylococcus, Corynebacterium, and Propionibacterium.

In other words, their founding microbes bore no relationship to their mother’s vagina or any vagina. At all the sites—mouth, skin, gut—their microbes resembled the pattern on human skin and organisms floating in the air in the surgery room. They were not colonized by their mother’s lactobacilli. The fancy names of these bacteria don’t matter as much as the notion that the founding populations of microbes found on C-section infants are not those selected by hundreds of thousands of years of human evolution or even longer.

Another threat to a baby’s newly acquired resident microbes involves antibiotics given to the mother. Most doctors consider it safe to prescribe penicillins for all sorts of mild infections in pregnancy—coughs, sore throats, urinary tract infections. Sometimes when doctors think that the mother has a viral infection they also give antibiotics just in case it is actually a bacterial infection.

Then comes the birth itself. Women in labor routinely get antibiotics to ward off infection after a C-section....Antibiotics are broad in their effects, not targeted....The problem, of course, is that we know antibiotics are broad in their effects, not targeted. While the antibiotic kills Group B strep, it also kills other often-friendly bacteria, thus selecting for resistant ones. This practice is altering the composition of the mother’s microbes in all compartments of her body just before the intergenerational transfer is slated to begin.

The baby also is affected in similar unintended ways. Any antibiotic that gets into the bloodstream of the fetus or into the mother’s milk will inevitably influence the composition of the baby’s resident microbes, but we are only beginning to understand what this means.

Finally, the babies are directly exposed. Most parents are not aware that all American-born babies today are given an antibiotic immediately after birth. The reason is that many years ago, before antibiotics, women who unknowingly had gonorrhea would pass the infection to their babies, giving the newborns terrible eye infections that could cause blindness...The dose is low but is likely affecting the composition of the infant’s resident microbes just when the founding populations are developing. We should be able to develop a better way to screen, so we can target those babies at the highest risk, perhaps a few hundred among the millions of births a year.

Although babies are born into a world replete with diverse bacteria, the ones that colonize them are not accidental. These first microbes colonizing the newborn begin a dynamic process. We are born with innate immunity, a collection of proteins, cells, detergents, and junctions that guard our surfaces based on recognition of structures that are widely shared among classes of microbes. In contrast, we must develop adaptive immunity that will clearly distinguish self from non-self. Our early-life microbes are the first teachers in this process, instructing the developing immune system about what is dangerous and what is not.

A newborn infant, seconds after delivery. Amniotic fluid glistens on the child's skin.  Credit: Wikipedia, Ernest F

Research is accumulating that the microbial exposure from a vaginal birth, breastfeeding, and pets in the first year of life are all good for a baby's developing immune system and the gut microbiome.

From Science Daily: Breastfeeding, other factors help shape immune system early in life

Researchers say that breastfeeding and other factors influence a baby's immune system development and susceptibility to allergies and asthma by what's in their gut. The striking findings from a series of studies further advance the so-called hygiene hypothesis theory that early childhood exposure to microorganisms affects the immune system's development and onset of allergies, says Christine Cole Johnson, Ph.D., MPH, chair of Henry Ford's Department of Public Health Sciences and principal research investigator.

The gut microbiome is the collection of microorganisms in the gastrointestional, or GI, tract, and the human body has billions of these microbes... The gut microbiome is known to play an important role in immune system development, and is thought to contribute to a host of diseases like obesity, autoimmune diseases, circulating disorders and pediatric allergies and infection.

"For years now, we've always thought that a sterile environment was not good for babies. Our research shows why. Exposure to these microorganisms, or bacteria, in the first few months after birth actually help stimulate the immune system," Dr. Johnson says."The immune system is designed to be exposed to bacteria on a grand scale. If you minimize those exposures, the immune system won't develop optimally."

In six separate studies, researchers sought to evaluate whether breastfeeding and maternal and birth factors had any effect on a baby's gut microbiome and allergic and asthma outcomes. Using data collected from the WHEALS birth cohort, researchers analyzed stool samples from infants taken at one month and six months after birth. They also looked at whether the gut microbiome impacted the development of regulatory T-cells, or Treg, which are known to regulate the immune system. Highlights:

Breastfed babies at one month and six months had distinct microbiome compositions compared to non-breastfed babies. These distinct compositions may influence immune system development.Breastfed babies at one month were at decreased risk of developing allergies to pets. • Asthmatic children who had nighttime coughing or flare-ups had a distinct microbiome composition during the first year of life. • For the first time, gut microbiome composition was shown to be associated with increasing Treg cells.

Researchers found that a baby's gut microbiome patterns vary by: • A mother's race/ethnicity. • A baby's gestational age at birth. • Prenatal and postnatal exposure to tobacco smoke. • Caesarean section versus vaginal delivery.• Presence of pets in the home.

Henry Ford's landmark 2002 study found exposure to dogs or cats in the first year of a baby's life reduced their risk for allergies.

After my January 9, 2015 post I was asked more about the microbial differences in babies who had been born by cesarean vs vaginal deliveries. What could be done about this? Should this be of concern when C-section rates in some places are approaching 50% of all births?

Well, some researchers are concerned, including Dr. Dominguez-Bello, who is doing ground-breaking research in this area. She is doing a long-term study in which babies born by cesarean section are immediately swabbed with a gauze cloth laced with the mother's vaginal fluids and resident microbes. Several (but not all) articles that I looked at said that the gauze is a "saline-soaked gauze".

Summary of the method:1) Incubate gauze in mother's vagina for 1 hour 2) Extract gauze before C-section  3) Expose newborn to the vaginal gauze (Mouth first, then face, then rest of body). If for some medical reason they don’t (and there is a C-section), then this is a restoring intervention.

Note that Dr. Dominguez-Bello always first checks to make sure the mother is HIV-negative and strep-B negative, and showing no signs of a STD. The basic premise is that babies should have crossed the mother's birth canal to be "seeded" with the mother's microbes, but if for some medical reason they don’t (and there is a C-section), then this is a (somewhat) restoring intervention.

From Feb. 2014 New York Academy of Sciences: Hats Off to Bacteria!

Why are bacteria in the body? What do we, and the bacteria, gain from this arrangement? And who's in charge? "There is a dialogue," Dominguez-Bello said, "sometimes a fight, sometimes a good dialogue. We have evolved with them. The first form of life on Earth was bacteria. Whatever came after had to deal with bacteria, cope with bacteria, associate with bacteria ...  ...continue reading "Can Missing Birth Canal Bacteria Be Restored to Cesarean Birth Babies?"