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Оглавление3:Pregnancy: Eating for Two? Try Eating for Trillions
The Pregnant Microbiota: Another Reason to Eat Well
Seeing that positive result on a pregnancy test changes everything for most women. All of a sudden they’re going to the bathroom more times than they can count, forgetting where their keys are while they’re holding them in their hands, falling asleep at work (at 10 a.m.!), feeling full right after a meal, only to feel famished ten minutes later. From differences in her skin and hair to buying pants in three sizes within one year, pregnancy is a time of major changes in a woman’s body. In nine short months, a woman undergoes a series of drastic physiological transformations that nurture a single fertilized cell into a crying, hungry baby. Many of our organs alter their functions to facilitate these new biological needs of both the mother and her developing baby. For example, the liver produces 25–35 percent more fats in order to promote baby growth. Fats, also known as lipids, are formed as a way to store energy. By naturally adjusting liver metabolism to make more lipids, a pregnant mother’s body ensures that there will be enough energy for the baby to grow, and for the future production of milk following delivery.
Like the liver, a pregnant woman’s microbiota also responds to this new state. In fact, experts believe this change is a normal physiological adaptation to support the growth of the fetus. A recent study showed that the microbiota of a pregnant woman in her third trimester strikingly resembles the microbiota of an obese person (just what every pregnant women wants to hear . . .). Moreover, when the microbiota of a female mouse in late pregnancy was transferred into a germ-free mouse, the latter mouse gained a lot of weight, despite not increasing food intake or being pregnant. This study was carried out in the laboratory of Dr. Ruth Ley at Cornell University in New York, a scientist at the forefront of the microbiota field. She believes that late pregnancy is an energy-thirsty period, during which the body takes advantage of the energy-producing machinery of the microbiome to promote weight gain for the benefit of the mother and her baby. The timing for this large shift in microbiota couldn’t be better, occurring towards the end of the pregnancy when babies start packing on the pounds and when women need to start preparing for the energy demands of breastfeeding.
This same study, which sampled ninety-one pregnant women (the largest to date), also showed that some species of bacteria that were more predominant in the third trimester of pregnancy were also found in their babies at one month of age. This suggests that another consequence of the big change in microbiota during pregnancy is to pass many of these bacteria on to the newborn. It’s fascinating to think that a woman’s body and her microbiota work together during pregnancy, likely because both benefit from having a new baby. From a genetic perspective, having babies is the only way to propagate our genes; from a microbial perspective, a newborn is brand-new real estate where microbial genes can also multiply and propagate.
Another recent study showed that the shifts to microbiota during pregnancy reflect the amount of weight women gain. According to the American Institute of Medicine, a woman of normal weight should gain 25–35 pounds during pregnancy, underweight women should gain 28–40 pounds, and overweight women should gain only 15–25 pounds. Women who gain more weight than what is considered standard have distinct changes in their microbiota. Given that a baby inherits many of its mother’s microbes, and that some of these microbes actually promote weight gain, should we worry about passing obesity-associated microbes to our babies? Unfortunately, yes. Women need to watch their weight during pregnancy, especially during the last trimester. Obesity is a complex condition arising from both genetic and environmental (including microbial) factors (discussed in chapter 10), but it appears that even in cases in which obesity is considered genetic, microbes have a role in its development. This makes sense, as microbes are directly involved in the way we break down food and store fats. If you think no one is watching when you give in to that midnight snack craving, that’s sadly not the case—microbes are watching what we eat at all times, since it affects them directly!
The good news is that, just as we can foster weight-gain microbes through a poor diet, we can promote the growth of beneficial microbes through a healthy diet. Although scientists haven’t identified specific microbes associated with leanness yet, it has been shown that a varied diet that includes fruits, vegetables, and fiber promotes a diverse microbiota, a characteristic of lean (and healthy) individuals. Thus, you, and your microbiota, are what you eat—and there is probably no better time to watch your diet than when you’re pregnant. Bad dietary choices during this stage of life will not only make women gain more weight than what is considered healthy, they also have the potential to influence a child’s future ability to control weight. So, next time you walk by a candy machine, don’t listen to your sugar-loving microbes, and nourish the trillions of microbes that are begging you to grab a piece of fruit instead.
The Vaginal Microbiota
During pregnancy, microbiota adaptation also occurs in the vagina, an organ that hosts millions of microbes. The composition of this microbiota influences vaginal health tremendously. Many women develop yeast infections after being on antibiotics or oral contraceptives (birth control pills alter the pH of the vagina). Bacterial vaginal infections, also known as vaginoses, are very common. These infections occur when yeast (often Candida) or bacteria overrun a beneficial group of microbes known as Lactobacilli, a type of lactic acid bacteria that is very common in the vagina. Lactic acid bacteria are also used in the dairy industry for the production of yogurt, kefir, cheese, and buttermilk. Many of them have health benefits and are used as probiotics.
During pregnancy, the number of vaginal Lactobacillus increases dramatically, which is thought to occur for two important reasons. First, by keeping the vagina acidic, the presence of Lactobacillus helps discourage disease-causing microbes such as E. coli, which do not like to grow in acidic conditions. There’s probably no better time to arm the bacterial vaginal defenses than during pregnancy, when a pathogen could track up from the vagina, through the cervix, and into the uterus, where the baby is growing. In fact, it is known that certain vaginal infections during pregnancy are associated with preterm and low-weight births. Second, Lactobacilli are great at digesting milk, as their name suggests (lacto is Latin for “of milk,” and bacillus is the name given to rod-shaped bacteria). By ramping up the levels of Lactobacillus in vaginal secretions, more of these bacteria will reach the baby’s gut (when born vaginally), and facilitate the digestion of the only food the baby will eat for months: her mother’s milk. In this sense, Lactobacilli are probably a baby’s first and best microbial friend.
The vaginal microbiota plays a very important role during pregnancy and birth, as it is one of the sources (along with the gut microbiota) of the first microbes to set up camp in a newborn. As soon as a baby is born vaginally, she gets covered in vaginal secretions and, yes, with fecal matter, too. Consequently, the composition of vaginal secretions is of utmost importance during pregnancy, and vaginal health should be taken very seriously during this period of time. Just as women should take care of their diet to promote a healthy intestinal microbiota, they should look after their vaginal health, too.
To promote vaginal health, gynecologists recommend that pregnant women wear cotton underwear, avoid vaginal douching (never recommended), avoid vaginal cleaning products, and use gentle, unscented soaps to clean the outside of the vagina only. The vagina is an organ that cleans itself through the production of secretions and needs little extra hygiene. In fact, cleaning the interior of the vagina is strongly associated with infections, as it alters the balance of the resident microbiota. In addition, it has been shown that the consumption of probiotics containing Lactobacillus acidophilus decreases vaginal infections. Several clinical studies suggest that eating yogurt may help, too, although not to the same extent as probiotics alone. You can even get probiotic preparations in the form of vaginal suppositories, which are used to treat such infections. Safe sex is the best way to avoid sexually transmitted infections (STIs); it is a practice that should always be followed, and especially during pregnancy. An STI contracted during pregnancy can be more dangerous to the mother than an STI contracted at another time, as immune systems are weaker during pregnancy—a physiological adaptation meant to prevent a woman’s immune system from reacting to the fetus. Unfortunately, this makes a mother-to-be more vulnerable to infection.
Stress, Your Baby, and Your Microbes
Another important measure to maintain a balanced microbiota during pregnancy is to avoid stress, which is always easier said than done. We’ve all felt it—stress is a condition that affects most people at some point or another. It can be helpful sometimes, like when it compels you to finish an assignment for work that’s due the next day. The problems arise when stress becomes an everyday companion; this is when it affects our health. Stress can make you lose sleep, have headaches or stomachaches, overeat, or lose your appetite. While pregnancy is typically a very joyful time, it can also be difficult. Dealing with the physical discomforts such as nausea, exhaustion, and backaches may quickly add up. On top of that, hormonal changes affect mood and the ability to handle stress.
A moderate level of stress is unlikely to cause a major impact on the health of a mother or her baby. However, certain situations may lead to severe stress, which can have detrimental effects on the pregnancy and the health of the baby. Abrupt negative life events, such as divorce, serious illness, financial problems, partner abuse, depression, and the conflicting feelings surrounding an unplanned pregnancy—to name a handful—are all causes of long-lasting or severe forms of stress. Some women suffer severe stress and anxiety when faced with the idea of labor or parenting. Severe stress is associated with preterm and low-weight births, and with certain illnesses in children, including skin conditions, allergies, asthma, anxiety, and even attention-deficit hyperactivity disorder (ADHD; see chapter 14).
A recent study from the Behavioural Science Institute of Radboud University, in the Netherlands, suggests that the microbiota plays a leading role in the link between stress during pregnancy and the aforementioned disorders. This study, which recruited fifty-six pregnant mothers, found that women who experienced high and prolonged levels of stress had alterations in the vaginal microbiota that could also be detected in their babies’ gut microbiota. Infants born to highly stressed mothers showed lower levels of beneficial microbes, such as lactic acid bacteria. In the same study, these changes to the microbiota were associated with more gastrointestinal issues and allergic reactions in babies. They also found that the negative effects of severe maternal stress could not be corrected by breastfeeding, even though it has been repeatedly shown to promote a healthy microbiome in infants.
A similar study aimed at exploring the link between maternal stress and the microbiota was recently performed in mice. The study showed that a reduction in vaginal lactic acid bacteria, caused by stress, is accompanied by decreased immune functions in the offspring. Furthermore, the changes in the baby mice were not limited to the types of bacteria growing in their guts; there were also important metabolic differences detected in their blood and their developing brains. It may well be that the vaginal microbiota is at the center of this, responding to maternal stress and transferring its imbalanced state to the newborn, where it can lead to lasting health consequences. Although a casual relationship remains to be established, it appears that lactic acid bacteria from vaginal secretions are not only involved in facilitating milk digestion in newborns, but also carry out important metabolic functions in the developing newborn—yet another reason to reduce stress as much as possible and to take daily probiotics during pregnancy.
Infections and Antibiotics: Can We Avoid Them?
Controlling your diet and your stress levels during pregnancy is an enormously challenging goal for most women, but it can be done. However, the microbiota of pregnant women can suffer a big blow through a situation that’s out of their control: taking antibiotics to treat an infection. As mentioned before, pregnant women are more vulnerable to infections, and if they occur, they are likely to be more severe due to their compromised immune systems. This is why it’s recommended that pregnant women wash their hands often, avoid caring for people with infections (good luck with that when you have other kids!), avoid gardening without gloves, cook meats thoroughly, avoid changing the cat litter box, and avoid deli meats, sushi, and unpasteurized milk. Pregnancy is definitely not the time to get dirty and eat dirt, as we will later suggest our kids should do (although some pregnant women have an urge to do so—see Care for a Spoonful of Soil? on page 51).
Despite best efforts to avoid them, infections during pregnancy are quite common, with urinary tract infections (UTIs) and bacterial vaginoses both affecting about 1 in 6 pregnant women in the United States and about 1 in 10 pregnant women in Canada. Other commonly diagnosed infections during pregnancy are respiratory tract and skin infections. Fortunately, several antibiotic medications are safe to use during pregnancy, but they’re being prescribed to a lot of women—very likely more than necessary. The most recent National Birth Defects Prevention Study in the US, which has been collecting data since 1997, showed that almost 30 percent of women receive at least one course of antibiotics during pregnancy. A population-based study (a term given to studies involving a very large number of people) in the UK showed that the same is true for British women, while 42 percent of French and 27 percent of German women take antibiotics while pregnant. There’s no debate about the immense change that an antibiotic brings to the microbiota. After a course of antibiotics, the overall diversity of the microbiota is substantially reduced. Its effect can be compared to what happens when a lush rain forest gets chopped down, and only a few dominant species make a comeback. Fortunately, the adult microbiota is fairly stable, and after finishing a course of antibiotics, in a nonpregnant woman this microbial forest usually returns to normal. The concern during pregnancy is that the microbiota fluctuates considerably, which is a characteristic of unstable ecosystems that are more susceptible to abrupt changes and permanent damage. When expectant women take antibiotics, especially in the last two trimesters, their microbiota takes a major hit, and according to new research, so does the microbiota of their babies. What becomes even more concerning is that antibiotic use during pregnancy is now being associated with certain diseases seen later in children.
A study of more than seven hundred pregnant women from New York showed that children born to those who received antibiotics in their second and third trimesters had an 85 percent higher risk of childhood obesity by age seven. These results are very significant because they were obtained after correcting for other confounding variables of obesity, such as the weight of the mother, the birth weight of the child, and whether or not the infant was breastfed. All of these factors were previously shown to be associated with the risk of obesity, so it’s important (for this and any other similar study) to remove these variables from the analysis. These findings are quite new (published in 2014) and they still need to be replicated, but if more studies show a similar trend, it suggests that childhood obesity may have roots in the very early stages of human development, and that antibiotic use during pregnancy has significantly more risk than is currently assumed in medical practice.
Antibiotic use during pregnancy has also been associated with asthma, eczema, and hay fever in infants. Two large studies from Finland, a country that has experienced a twelve-fold increase in asthma rates since the 1960s, showed that using antibiotics during pregnancy is a significant risk factor for early asthma in babies. Other epidemiological studies have found similar associations between antibiotic use during pregnancy and inflammatory bowel disease (IBD) and/or diabetes, each of which is discussed in detail in forthcoming chapters. What’s very peculiar is that these diseases share common risk factors. They are all immune disorders that have become increasingly common in the past few decades, and they usually occur in individuals with certain known genetic predispositions. Recent research on humans and animals show that the risk factors associated with these diseases also involve the early microbiota. How early? According to the studies, these changes begin before we’re born, through mechanisms that are just beginning to be understood.
As frequently occurs in science, the insights on the mechanisms that explain a disease come from animal experiments. In this case, neonatology researchers from the Children’s Hospital of Philadelphia showed that baby mice born to mothers that received antibiotics during pregnancy had a reduced immunological response. Similarly, a separate study showed that mice predisposed to diabetes and born to females that were given antibiotics had persistent alterations in their immune cells. These same mice developed diabetes a lot sooner than mice born to females that did not receive antibiotics. While a lot more research is still needed to fully understand all of this, it’s becoming evident that complex interactions between microbes, the immune system, and other aspects of human metabolism, occurring as early as in utero (before birth), influence the risk of disease later in life.
Getting Smart About Antibiotics
In light of all these findings it is crucial to understand that using antibiotics should not be discouraged when they’re really needed, but the overuse or abuse of antibiotics should be prevented. So, when are antibiotics necessary during pregnancy? The answer is simple: antibiotics should be taken for serious bacterial infections, and only bacterial infections. However, this can be hard to put into practice, especially during pregnancy, when doctors want to prevent any possible complications that may arise from an infection. Because of this, many health providers are too quick to prescribe antibiotics, as a safety precaution, to expectant mothers for ailments that don’t require antibiotics, like the flu. The flu is a viral disease that causes symptoms that many people confuse for a bacterial respiratory infection. Its onset is very sudden and people feel awful for about a week, until they start getting better. It’s not hard to imagine a pregnant woman showing up at a doctor’s office almost begging to get a prescription that will make her feel a little bit better. However, antibiotics should not be used for the flu, regardless of how bad a patient feels.
There are exceptions to this, though; the flu can lead to secondary bacterial infections that do require antibiotic treatment. This usually manifests a little bit differently: you feel truly awful, and after a week or so, you start to get better, but then you start feeling worse, with coughing and chest congestion, which can lead to pneumonia. This is the classic example of a secondary bacterial infection following the flu, which should be treated with antibiotics.
However, the key concept here is to prevent infections from occurring in the first place if possible. As such, it is currently recommended that pregnant women get a flu shot. Fortunately we have an effective vaccine that is completely safe to use during pregnancy, which significantly decreases the chances of getting the flu and a secondary respiratory bacterial infection during flu season.
Despite the precautions you can take, infections do happen during pregnancy and antibiotics are prescribed. So what then? Based on the current research, it seems that the period at which antibiotics are taken is important, with microbial changes in the later stages of pregnancy being the most influential. If antibiotics must be used in the second and especially the third trimester, one should start or continue microbial supplementation with probiotics and a diet rich in fiber and vegetables. It’s important to choose a probiotic that contains several species of Lactobacillus and Bifidobacterium, both known to be important early members of an infant’s microbiota. As with any supplement or medication taken during pregnancy, we recommend discussing this with your health care provider.
Heading Off Group B Strep
During the births of her first two children, Neve had been given antibiotics, an increasingly common occurrence nowadays, with 1 in 3 women receiving antibiotics during labor. Neve knew how frequent antibiotic use is during delivery because she had tested positive for a type of bacteria known as Group B streptococcus, or GBS for her first two births. (Other very common circumstances that require antibiotics during labor are scheduled C-sections, which will be discussed extensively in chapter 4.) In many countries, all women between 35–37 weeks of gestation get tested for GBS. These bacteria commonly reside in 15–40 percent of all pregnant women, yet they rarely cause any symptoms. However, between 40–70 percent of GBS-positive women will pass it on to their babies during natural birth, and a small but very significant number of babies (1–2 percent) will develop a GBS infection (for further discussion of GBS infections, see chapter 4). Fortunately, if a pregnant woman who tests positive for GBS is treated with antibiotics during labor, the risk of her baby developing a GBS infection is reduced by 80 percent, making GBS prevention a pertinent use of antibiotics.
However, recent studies have shown that receiving antibiotics during labor alters the microbiota of the newborn, even if they are administered only an hour before birth. Reading about these studies made Neve, pregnant with her third child, feel uneasy. She knew that GBS could potentially be very serious and she understood the need for antibiotics during labor, but she wondered if anything could be done to prevent testing positive for GBS. Her second child has asthma and although it’s impossible to know whether his exposure to antibiotics during birth is to blame, she’s left wondering if it contributed. More importantly, Neve wanted to do whatever she could to decrease the risk of her new baby developing asthma, too. She hoped to help by testing negative for GBS, but how could she do something about that?
It turned out that she might actually have some say in the matter. GBS are bacteria that will expand in numbers only if they’re given the chance. Normally other members of the microbiota keep them in check, usually our bacteria superstars, the Lactobacilli in the gut and the vagina. In fact, if you grow Lactobacilli and GBS together in the lab, the Lactobacilli make it very hard for GBS to multiply; they beat them easily. Furthermore, a small number of studies suggest that applying probiotics directly to the vagina increases Lactobacilli and decreases the number of GBS. This finding was shown in healthy nonpregnant women and remains to be supported in bigger studies, but given how safe it is to administer probiotics to pregnant women, Neve was open to trying this approach and her midwife supported this prophylactic treatment.
Neve ended up testing negative for GBS at her 36-week visit, and she is expecting to have an antibiotic-free birth very soon. However, it’s important to mention that it remains to be proven in a randomized clinical trial that the prophylactic use of vaginal probiotics prevents or reduces the chance of a GBS-positive test during pregnancy. The use of vaginal probiotic suppositories, as with any treatments during pregnancy, should always be discussed with a health practitioner.
Can Bacteria Influence Us Before Birth?
So far we have discussed different ways to take care of the maternal microbiota during pregnancy in order to prepare the best kind of microbes that a mother can give to her baby at birth. This is when babies get soaked in microbes, during their trip down the vaginal canal. But very recent research shows that microbes may pay a visit to babies even before birth. For many years it has been widely accepted that humans are germ-free immediately before birth and that the presence of bacteria in utero is considered infectious and dangerous. Often this is true—bacteria growing in the placenta or the amniotic fluid can be a sign of infection and a cause of premature birth or even stillbirth. But what we’re just now beginning to learn is that there may be very low numbers of bacteria that commonly reach the baby in the uterus without causing any harm. We still don’t know how they get there and, more importantly, what they do, but in two separate studies bacteria were detected in the amniotic fluid and placentas of healthy babies. Although some scientists (including us) remain skeptical about these findings, the authors of these studies speculate that these bacteria are involved in immune stimulation of the fetus. Additional studies are needed before we can explain why this occurs, or if it even does.
Another more likely exposure to microbes before birth may occur in the form of bacterial metabolites, which are very small substances produced by the enormous amount of bacteria in our guts. Bacterial metabolites are known to travel in the bloodstream at all times, and are involved in biochemical reactions in just about every human organ, influencing many aspects of our metabolism. Thus, even if very few bacteria actually reach the fetus during pregnancy, the metabolites may reach the growing baby through the bloodstream and potentially affect fetal growth and development. Much-awaited studies are under way to explore the impact these microbes might have in human development before birth.
Dos and Don’ts
♦Do— eat for your microbes, not just your cravings. Make vegetables, fruits, and fiber staples of your diet, along with the other food groups, and reduce sugary foods. A varied diet is a healthy diet for you, your baby, and your microbiota.
♦Do— add daily probiotics, yogurt, or kefir (a fermented milk drink) to your diet. Increasing the growth of beneficial bacteria in your vagina will promote their passage to the newborn, where they carry out very important functions.
♦Do— prevent infections if possible. Not only will you avoid feeling awful while pregnant, but it also reduces the chances of having to take antibiotics. Wash your hands often, avoid being in close contact with sick people, and follow the current recommendations of foods that pregnant women should avoid. If antibiotics are necessary, start or continue taking probiotics.
♦Don’t– sweat the small stuff, and do try to control stress as much as possible. Severe stress is associated with a number of disorders in children and also with alterations to the microbiome. If stress is becoming a big part of your life, reach out for help through your health practitioner. Even if your stress is moderate, incorporating exercise, yoga, or meditation into your routine can help keep the edge off.
♦Do— consider vaginal probiotic suppositories in your third trimester in order to reduce the chances of testing positive for GBS. A negative GBS test will make an antibiotic-free birth more likely.
CARE FOR A SPOONFUL OF SOIL?
Perhaps the most bizarre of pregnancy cravings is the urge to eat dirt—a form of pica, a term used to describe an intense craving for nonfoods. Some suggest that dirt pica is the body’s attempt to consume minerals and that it may be linked to iron deficiency, which occurs in many expectant women. Still, it is not known for certain what drives some mothers-to-be to eat dirt.
The rates of dirt pica vary depending on culture and socioeconomic status. In Kenya, it is so common that people see it as a sign of pregnancy, with 56 percent of pregnant women following this practice. Even in the US, 38 percent of low-income women from southern Mississippi claim to crave dirt or clay. Dirt pica is common enough that you can order dirt online to satisfy your craving! However, pregnant women are also more vulnerable to infectious diseases, and eating dirt may prove dangerous. Dirt is a known source of pathogens, toxins, and even lead, making it a bad option for those hard-to-curb cravings.
