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 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."

 Image result for toddlers  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.

Image result for faecalibacterium prausnitzii  Faecalibacterium prausnitzii - a beneficial gut bacteria. Credit:News Press Agency

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

Labrador Retriever image 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. 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 ... 

Human microbiota perform many essential functions, such as producing vitamin B12, digesting plant fibers, helping to train our immune system to distinguish self-molecules from nonself-molecules, and helping to fight off pathogens. It is increasingly clear that we cannot accomplish these functions alone, and in exchange the bacteria receive food and a warm, safe home. [Martin]Blaser noted that some species are "obligate symbionts," meaning that our bodies are the only environment in which they can survive. If these strains are killed with antibiotics before they are transmitted to other people, especially to the next generation, the bacteria could disappear forever.

One of the hallmarks of mammals is birth through a birth canal. The birth canal is rife with bacteria; as babies travel down it, they are inoculated with lactic acid bacteria that accumulate during the last trimester of pregnancy. These bacteria are the initial educators of the baby's naïve immune system, which must learn to "tolerate our microbiota and attack microbes." Babies born by cesarean section—approximately 50% of babies in New York City—miss out on this natural initial exposure and instead are first inoculated with bacteria floating around the operating room. These bacteria are comprised predominantly of human skin bacteria not from the mother but from the doctors, nurses, and previous patients in the room. We do not yet know the health consequences of this alternate initial exposure. "[Cesarean sections] are breaking a natural law," Dominguez-Bello said, "and there are consequences."... Importantly, only babies born via elective C-section miss out on the inoculum; those born by emergency C-section, after their mother's water has broken, are exposed to the bacteria in the birth canal.

"What antibiotics have in common with C-sections is ... abuse," Dominguez-Bello said. Both are medically necessary in some cases, but overused..." While both C-sections and antibiotics are valuable tools, we can no longer pretend that they do not have some detrimental outcomes. Research has found the colon microbiome of Americans is half as diverse as that of hunter-gatherer populations, such as Amerindians in the Amazon jungle and African populations living a traditional lifestyle. There is also less diversity in Americans' skin and mouth microbiomes. Thus antibiotics, while necessary in emergencies, should not be used in every infection. Some species of bacteria never recover after an antibiotic exposure, and others can only colonize us during a specific time in our lives; if we miss this chance, we can never recover it. Current antibiotics are "like atomic bombs," Dominguez-Bello said, obliterating every bug they encounter. 

Dominguez-Bello is conducting a study in Puerto Rico in which babies born via C-section are immediately swabbed with their mother's vaginal secretions; these babies will be followed for years, and compared to those born vaginally and those born via C-section without swabbing. If significant differences between the babies are detected, she hopes that swabbing will one day become mainstream practice, or that more women will learn about the importance of the human microbiome and opt for vaginal birth when possible.

Excerpts from an interview with Dr. Domingues-Bello.Her study is now going on in Puerto Rico, Chile, Bolivia, and soon in Ecuador, Stockholm, and USA. From the June 2014 Common Health:

Research: Could Birth-Canal Bacteria Help C-Section Babies?

The usual drill is to wipe the effluvia of birth off of newborn babies, cleaning them up and readying them for snuggling. But in a fascinating departure, researchers have begun to experiment with the opposite: collecting birth-canal bacteria and wiping them onto babies after birth. Why in the world? For good reason: to explore whether it might help babies delivered by C-section to restore some of the vaginal bacteria that they would have been exposed to if they’d gone through the birth canal.Why do that? On the theory that altered bacterial populations could help explain why C-section babies tend to have higher odds of asthma, allergies, obesity and other health risks.

Dr. Maria Gloria Dominguez-Bello, an associate professor in the Human Microbiome Program at the NYU School of Medicine, presented some preliminary results on that research at a recent conference of the American Society for Microbiology here in Boston. Those initial findings suggest that indeed, using gauze to gather a mother’s birth-canal bacteria and then impart them to babies born by C-section does make those babies’ bacterial populations more closely resemble vaginally born babies — though only partially.

Many questions remain. But the research sounded so intriguing — and the intervention so simple, if it gains medical approval — that I asked Dr. Dominguez-Bello to discuss it. Our conversation, edited: Your poster reports that there were six vaginal births, seven C-sections and four C-sections in which the babies also received the ‘inoculum’ of vaginal bacteria. But it wasn’t clear to me: To what extent did the mothers’ bacteria restore a more normal balance of bacteria in the C-section babies? A little or a lot?

When we analyzed the sharing — how many microbes any site of the baby’s body share with their mom’s vagina — we doubled the number of bacteria that the C-section babies were exposed to. But the vaginal process was six times as much. So the vaginal delivery still exposes the baby to a lot more... So those C-section babies still don’t have the full exposure of the vaginal babies.

That’s logical because during labor, the baby is rubbing against the mucosa of the birth canal for a long time and bacteria start growing even before the baby is out — growing and colonizing the baby during birth. In half an hour, you get multiplication of bacteria. If the baby gets one cell, an hour later the baby has probably four of those cells and five hours later, it’s exponential. Also, C-sections involve antibiotics. There is no C-section without antibiotics, and we don’t know what the effect is of that gram of penicillin. If it’s good enough to kill strep B, I’m sure it’s killing a lot more than that community of bacteria.

[Interviewer] If your research pans out, using this gauze technique for C-section babies would seem to be such an easy intervention. I imagine there might already be women saying, ‘I want to do that.’ Possibly even, ‘I want to schedule a C-section and do that.’ What would you say to them?

I would say labor is a very complex process and labor is far more than inoculating the baby. And it’s a process that we don’t fully understandwhat’s its adaptive value, why is it important? There is a lot of stress in labor and some people think that stress is healthy for both the mother and the baby. It’s a long process, so during all those hours, physiological changes occur in the mom and the baby. So I think we have not studied labor enough and tried to understand what it is about labor that is healthy.

Plus, with the restoration we did, we do restore the bacteria partially but not completely. And also, the mother’s body prepares to breastfeed, for example — and who knows how many other things — much better after a natural birth than a C-section. A C-section is a sudden interruption of a process before the process finishes. So the body of the mother doesn’t even know that the baby’s out. It takes a while for the body to realize, ‘Oh, there is no baby.’ 

The basic premise is that babies that should have crossed the birth canal, and for no medical reason they don’t, then this is a restoring intervention. But we still, as with any vaginal delivery, we check for strep B; I would make sure the mother is HIV-negative, strep-B negative, and has an acid, lactobacillus-dominated vagina.So far it’s not a medical practice. It hasn’t been accepted as a standard practice. ..So I don’t know how much it will be regulated, if at all. Some people are doing it more or less individually, independently, because they believe it will be good for the baby.