Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues (14 page)

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 newborn’s intestinal tract include species that can digest milk for the baby. These species are also armed with their own antibiotics that inhibit competing and possibly more dangerous bacteria from colonizing the newborn’s gut. The lactobacilli, which bloom in the mother’s vagina as pregnancy’s term nears, become the earliest organisms to dominate the infant’s formerly sterile gastrointestinal tract; they are the foundation of the microbial populations that succeed them. The baby now has everything it needs to begin independent life.

Breast milk, when it comes in a few days later, provides the infant with further extraordinary benefits. It contains carbohydrates, called oligosaccharides, that babies cannot digest. Why would the milk contain energy-rich compounds that babies cannot use directly? The reason is microbes. The oligosaccharides can be eaten and used as an energy source by specific bacteria such as
Bifidobacterium infantis
, another foundational species in healthy babies. The breast milk is constituted to select for favored bacteria to give them a head start against competing bacteria. Breast milk also contains urea, a major waste product in urine, which is toxic to babies. Again, it is there to feed select beneficial bacteria by providing them with a source of nitrogen to make their own proteins in a way that does not cause the bacteria to directly compete with the baby for nitrogen. How clever of Nature to devise a system in which a maternal waste product is used to enhance the growth of bacteria beneficial for her babies.

Although babies are born into a world replete with diverse bacteria, the ones that colonize them are not accidental. In a continuation of the script that has evolved over eons, Nature selects for the good guys, the ones that provide the vital metabolic functions for the developing baby that nurture the cells lining the infant’s intestines and crowd out bad guys.

Meanwhile, the mother’s skin bacteria are busy colonizing her baby, and each kiss introduces her oral bacteria. Long ago, mothers used to lick their babies clean, and many animals still do that, transferring their microbes to the next generation. But now when a baby is born vaginally, everyone is in a hurry to clean it up, to remove the coating that covered it in the womb. This material, the vernix produced by fetal skin, has hundreds of useful constituents, including proteins that suppress specific dangerous bacteria. Because the hospital staff is in a hurry to get that baby nice and clean to present to Mom and for all of those photographs, the vernix is usually washed off. Are they doing that baby a service by washing off a coating that for eons probably protected all human babies? While no one yet has studied this in detail, my hunch is that the vernix serves to attract particularly beneficial bacteria and repel potential pathogens.

These first microbes colonizing the newborn begin a dynamic process, setting the stage for the subsequent more adultlike microbiota. They activate genes in the baby and build niches for future populations of microbes. Their very presence stimulates the gut to help develop immunity. 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.

As months go by, babies acquire more microbes from eating a more complex diet as well as from the people who surround them: mom and dad, grandmother, siblings, and other relatives and then later from neighbors, classmates, friends, and other humans. Eventually the process gets more random. The exposures differ, and the ones that stick differ. As discussed before, by age three, each of us has acquired our own unique foundation of microbes. To me, this is remarkable. In just three years, a great diversity of microbes self-organizes into a life-support system with the complexity of the adult microbiota. This occurs for each and every person. Those three years, when the first resident microbes are most dynamic, are when the baby is developing metabolically, immunologically, and neurologically. This critical period lays the foundation for all the biological processes that unfold in our childhood, adolescence, adulthood, and old age—unless something comes along to disrupt it.

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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. The procedure was invented in Roman times to save the baby’s life. Mothers always died.

Today, C-sections are very safe, as they are almost always carried out in hospitals by experienced obstetricians. When the mother’s or baby’s life is in danger for any reason, emergency C-sections are performed, often with short notice. Prolonged labor or a failure for labor to progress, fetal distress, a ruptured amniotic sac or collapsed umbilical cord, high blood pressure in the mom, a breech position in the baby, or even a very large baby deemed too big to pass through the birth canal are common reasons for the surgery. In some populations, the rate for such emergency C-sections is pushing 20 percent, while in more holistic communities in Sweden the rate is about 4 percent.

C-sections are so safe that for a variety of reasons many women actually elect to have them. One is to diminish or avoid the pain of childbirth. This is not a trivial issue. For personal or cultural reasons, some women are frightened by giving birth. Given the availability of a safe alternative, it’s a choice millions of women make. Some professional women choose the surgery because their work schedules matter. Some women schedule the surgery so they can be sure to attend an important wedding or graduation. And others, whose OB is in a group practice, opt for an elective C-section so they can be sure of having the doctor they want deliver their baby.

Physicians also influence their patients’ choices of birth method. Some are very conservative when they see any signs of fetal stress or suspect that the mother will have problems. For example, when babies are in a breech position, natural childbirth can be dangerous. However, most breech babies turn head down not long before labor begins. On a more cynical note, it takes less time and fuss to do a C-section than to wait out a vaginal birth. And most doctors and hospitals make more money from performing operations like C-sections than from natural births.

For all of these reasons, the 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. If this trend continues, half of all U.S. babies (2 million a year) might be delivered surgically by 2020.

C-section rates around the world show astonishing variation. In Brazil, over 46 percent of all births are by C-section. In Italy, it is 38 percent, but in Rome, where the operation is thought to have been invented, the rate is 80 percent. In Scandinavian countries, which pride themselves on medical conservatism, fewer than 17 percent of births are Cesarian, and the rate is 13 percent in the Netherlands.

Why such differences? The act of giving birth is the same everywhere. The only explanation is variations between local practices and customs. Women from Rome, who these days tend to have but one child, often become pregnant in their thirties and often have busy careers. They are twice as likely to have a C-section than women in the rest of Italy, suggesting that the procedures are not driven by pelvic anatomy.

But so what? Do high C-section rates matter? Why not perform a Cesarian if it makes the mother more comfortable and is easier on the physician, if there is no cost other than the hospital bill?

Well, there is a cost—a biological one—and it affects the baby. A few years ago, my wife, Gloria, was stuck for a couple of weeks in Puerto Ayacucho, the capital of Amazonas State in Venezuela. She had been conducting nutritional and microbiological studies there for nearly twenty years and had permits to sample the microbiomes of Amerindians living there. She had been waiting to go into the jungle to collect microbes from a newly discovered Amerindian village, but the helicopter flight assigned to the health team was canceled. So, thinking she might make herself useful, she headed over to the local hospital. Would the microbes found on newborn babies delivered vaginally or by C-section vary in any way? No one had ever conducted this kind of study.

Nine women, aged twenty-one to thirty-three years, and their ten newborns participated. Four mothers delivered naturally and five had C-sections that had been planned. Gloria sampled each mom’s skin, mouth, and vaginal microbes one hour before delivery. By DNA sequencing, she showed that the women all had similar proportions of the major bacterial groups present at each site.

Each baby’s skin, mouth, and nose were sampled less than fifteen minutes after birth. She sampled their first stool, called meconium, twenty-four hours later.

While all of the mothers had many different types of bacteria on and in their bodies before giving birth, the moms who gave birth vaginally now had the signature splash of amniotic fluid on their skin with lots of lactobacilli. Most important, the babies showed a different pattern, depending on mode of delivery. 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, including those on the skin of nurses and doctors and bacteria on sheets from the laundry. 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.

Gloria studied newborns, but we know from other researchers that as babies are exposed to the wider world during the first months of life the microbiomes of C-section and vaginally delivered infants begin to converge. The earlier differences between them diminish. One reason may be that sooner or later everyone gets exposed to organisms that play similar roles in the body. But maybe those initial differences at birth are more important than we have realized. What if those first microbial residents provide signals that critically interact with cells in the rapidly developing baby’s body? We will consider this in later chapters.

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Another threat to a baby’s newly acquired resident microbes involves antibiotics given to the mother. After thalidomide, the medical community became much more cautious about giving drugs to pregnant women. Does that mean that the antibiotics recommended for pregnant women are safe? And who are they safe for, the mother or her fetus?

Most doctors consider it safe to prescribe penicillins, including ampicillin, amoxicillin, and Augmentin, 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 as well “just to be sure” (for the small chance that it is actually a bacterial infection). As we know, the antibiotics affect the mother’s resident microbes in all locations, inhibiting susceptible bacteria and selecting for resistance. The closer the dose is to birth, the greater the possibility that she will pass a skewed population of microbes to her baby.

Then comes the birth itself. Women in labor routinely get antibiotics to ward off infection after a C-section and to prevent an infection called Group B strep. About 40 percent of women in the United States today get antibiotics during delivery, which means some 40 percent of newborn infants are exposed to the drugs just as they are acquiring their microbes.

Thirty years ago, 2 percent of women developed infection after C-section. This was unacceptable, so now 100 percent get antibiotics as a preventive prior to the first incision.

Antibiotics are also used to prevent a serious infection in newborns caused by Group B strep. This bacterium lives in the gut, mouth, skin, and sometimes the vagina and rarely causes any problem in the mother. Recall that streptococci are among the most common groups of microbes found in the human body. Between a quarter and a third of pregnant women in the United States carry Group B strep.

But sometimes Group B strep can be lethal to newborn babies whose immune system is not up and running. While such infections are uncommon, professional groups recommend that all pregnant women be screened for the microbe near the time of delivery. If they are positive, they get a dose of penicillin or a similarly effective antibiotic shortly before the baby descends the birth canal.

But 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 affects other often-friendly bacteria, killing susceptible bacteria and 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.