We have an organ in our body that is not your typical one. This one did not start and evolve at some stage of embryonic development. It started to exist at birth and is not derived from any human cell line. It is our microbiome and includes bacteria as well as fungi and viruses on our skin, crevices, and the mucosal surfaces throughout our body.
We just started to examine and understand this organ only recently; we were unaware of its size or importance, its functions, and how essential it is for our survival. Its diversity is huge, affording protection to us, and loss of this diversity signals a decline in health. The number of genes of our intestinal microbiota is 150 times greater than the number of genes in the human genome. Our body consists of approximately 30 trillion human cells; our microbiome outnumbers these 10 to 1. The total weight of our microbiome is estimated to be approximately 3 pounds, the same as our brain. It is sometimes called our “second brain,” and it consists of more neurons than the spinal cord, mainly in the myenteric and submucosal plexuses.
We start the digestive process of food in our mouth with chewing, saliva, enzymes, and bacteria. Our teeth, tongue, and periodontal tissues house approximately 1012 bacteria. We then pass this on through the esophagus, which, until 10 years ago, was thought to be bacteria free. A study published in 2014 showed that there are dozens of species residing there.1 After its passage through the esophagus, the stomach adds more digestive enzymes and acids, and even in this highly acidic environment, bacteria abound in this inhospitable environment, but in smaller amounts, 103 to 104. The next area is the ileum, adding enzymes and transporters to help break down and absorb foods for our body, with 108 bacteria. Last, we reach the large intestine where most of our bacteria reside, wall-to-wall, of which 70% cannot be cultivated by current laboratory microbiological methods. The numbers are astounding: in 1 mL of colonic content, there are more bacteria than there are people on the planet.2 The large intestine has the surface size of a tennis court, more than 200 m2, and it houses 70% of all lymphoid tissues in our body, helping it to prevent an outgrowth of pathogenic organisms.3 It provides up to 15% of our daily calories.
The most important function of our microbes is to provide immunity, and this begins at birth. Bacteria colonize the mucosal surfaces of the vagina and, until recently, we thought these were mostly 1 bacterium, namely lactobacilli. These bacteria produce lactic acid, helping maintain a lower pH to avoid the overgrowth of fungi, especially Candida. We now know that there are 5 types of vaginal microbiota, predominantly species of lactobacilli. The fetus grows in a sterile environment where nutrients, oxygen, and sometimes chemicals, such as medications or environmental chemicals, reach it through the placenta. Carbon dioxide and fetal waste are returned to the mother the same way, and the mother’s organs get rid of them. This sterile setting remains in place until the moment of birth, when the baby passes through the birth canal, the vagina, picking up its mother’s microbes. Shortly before, the mother’s water breaks, spreading the lactobacilli, which quickly colonize her skin. The first fluids entering the baby’s mouth contain the mother’s microbes. Mother’s milk contains lactobacilli as well, and these help break down lactose, the major sugar in milk. This first milk known as colostrum, and with it come protective antibodies. A few days later, breast milk provides the infant with carbohydrates. One of these carbohydrates is oligosaccharides, which the baby cannot digest: It is to provide nutrition for certain bacteria such as Bifidobacterium infantis. Another part of birth is the vernix, a veneer that coated the baby in the womb, which contains proteins that help suppress certain pathogenic bacteria. Today, we are in a hurry to clean it up for the baby’s first pictures. This first beginning of the microbiome is critical for the development of the immune system. We are born with an innate immune system; however, we must develop our adaptive immunity that will distinguish self from nonself. This early microbiome helps start and maintain that process. As the baby grows, it will acquire an increasingly more diverse microbiome. By the age of 3 years, this microbiome becomes the foundation for the adult microbiota. It is during these first 3 critical years that the baby develops immunologically, neurologically, and metabolically, and lays the foundation with its microbiome for childhood, adolescence, adulthood, and old age.
This has gone on for millennia. But there is a cloud looming on the horizon: the increasingly high number of Caesarian sections and the overuse of antibiotics in mothers and newborn. C-sections are safe, and when a mother’s or baby’s life is in danger, they are done quickly and efficiently. However, we are now reaching the rate of 20% for all births in the United States being C-sections, whereas in more holistic communities in Europe, the rate is around 4%. Why is this? There are a variety of reasons. For some mothers, it is knowing the date of birth so that work schedules can be planned ahead of time. Sometimes, especially if the birth is around certain holidays, the mother wants to be sure her obstetrician will be there or that the festivities are not interrupted. If one wants to take a more skeptical view, the time spent performing a C-section is much shorter than that of a vaginal birth and hospitals and doctors make more money than with a natural birth. The fact remains that the rates of C-section are increasing from 1 in 5 in 1996 to 1 in 3 in 2011, according to the Centers for Disease Control (CDC).
There is another price to pay for C-sections, and this involves the microbiome. Babies born from C-sections do not get colonized by the lactobacilli previously mentioned from the mother’s birth canal. The first bacteria they are exposed to are those found on skin, hospital personnel, etc, notably Staphylococcus, Corynebacterium, and Propionibacterium. The effects of this have been studied. Babies born from C-section are 80% more likely to develop asthma than those born via natural childbirth.4 Babies born via C-section are more likely than other babies to have diarrhea during their first year of life. Their chances of being allergic to cow’s milk are twice as high as babies born normally. Another study showed there is an increased risk of diarrhea and food allergies in the first year of life in babies delivered via C-section than those delivered vaginally. Both studies concluded this was due to the difference in bacteria in the microbiome in the gut.5
Then there are antibiotics. Women in labor usually get antibiotics, mostly to prevent infection after a C-section and to prevent group B streptococcal infection. This amounts to 40% of all women in the United States receiving an antibiotic during delivery, which means their baby is getting exposed to an antibiotic at the same time that they are getting their first microbes to build their microbiome. Group B Streptococcus resides in the gut, mouth, skin, and occasionally in the vagina of women, rarely causing any medical problem: 25% to 30% of women carry this bacteria that can be damaging to the newborn whose immune system is just starting to develop. Therefore, in the United States, more than 1 million pregnant women are group B strep-positive. This means that all will get an intravenous antibiotic during labor. However, only 1 baby in 200 gets sick from group B strep from the mother, so the other 199 will still get antibiotics. Could we discover a better screening method with all the technology we have available?
There is a second part to this: All babies born in the United States are given an antibiotic after birth. A while ago, women who had gonorrhea may not have had symptoms of the disease and passed it onto their baby during childbirth, causing gonnococcal ophthalmia, potentially leading to blindness. The prophylaxis for this is silver nitrate or tetracycline eye drops given to the 4 million babies born in the United States every year. In Sweden, babies do not get any antibiotics and there are no subsequent infections. With this precedent, again, could we possibly find a better screening method?
Going into childhood, I would be remiss not to mention the overuse in our current medical system in this country of antibiotics for the common upper respiratory infection. A child develops a sore throat, a runny nose, an earache, and sometimes a fever. This is common in children, especially those up to age 3 years while their immune system is developing. According to the CDC, by age 3 years, 80% of children in the United States will have had a least 1 acute middle ear infection. Most of these upper respiratory infections are caused by viruses, such as rhinovirus, parainfluenza, and others. Fewer than 20% are caused by bacteria, including Streptococcus, Pneumococcus, Staphylococcus aureus, and Haemophilus influenza. Most of the time they do not cause infection or any harm; instead, they have colonized the upper respiratory tract and arrived previous to the current episode of malaise and feeling ill. As an example, many people harbor S Aureus in the nasal passages and never know it. It is part of the microbiome. Take the child to the doctor who does a throat culture, which turns out positive for group A strep and the prescription pad gets whipped out with antibiotics prescribed. However, the real culprit is a virus, which will eventually go away anyway; the child gets better, the parent thinking it was thanks to the antibiotic. This demonstrates that correlation is not necessarily causation: It does not prove that the drug improved the health of the child. It did, however, have a negative effect on the microbiome, as an antibiotic kills all bacteria, good and bad. Doctors do this as a precaution; they err on the side of the safer course. They are pressed for time; they see 5 or 6 children an hour with similar symptoms; they have to complete paperwork for each. There is a lack of quick, reliable, inexpensive testing. And there is always the lawyer looking over the shoulder. This led to 258 million courses of antibiotics being prescribed in the United States in 2010.6,7 The highest rate of antibiotic prescribing was in children under the age of 2 years: 1,365 courses per 1000 babies. According to the CDC, by age 20 years, the average child will have received 17 courses of antibiotics. The cost to our health care system is huge, but the cost to our microbiome is even greater. As a result of all this, we now have drug resistant bacteria.
In an upcoming editorial, we will further examine our microbiome and the effects of all the antibiotics prescribed, and the greatest use of antibiotics in the United States: those in cattle, hogs, chickens, turkeys, and other foods we consume regularly.
Finally, I would like to recommend to our reader the book by Martin J. Blaser, MD, Missing Microbes,8 an eminently readable book full of information for patients, doctors, and the public in general.
Andrew W. Campbell, MD
Editor in Chief
- Pei Z, Bini EJ, Yang L, Zhou M, Francois F, Blaser MJ. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci U S A. 2004;101(12):4250-4255.
- Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915-1920.
- Forchielli ML, Walker WA. The role of gut-associated lymphoid tissues and mucosal defense. Br J Nutr. 2005;9(suppl 1):S41-S48.
- Roduit C, Scholtens S, de Jongste JC, et al. Asthma at 8 years of age in children born by caesarean section. Thorax. 2009;64(2):107-113.
- Laubereau, B, Filipiak-Pittroff B, von Berg A, et al. Caesarean section and gastrointestinal symptoms, atopic dermatitis, and sensitization during the first year of life. Arch Dis Child 2004;89(11):993-997.
- Sharland M. The use of antibacterials in children: a report of the Specialist Advisory Committee on Antimicrobial Resistance (SACAR) Paediatric Subgroup. J Antimicrob Chemother. 2007;60(Suppl 1):i15-i26.
- Hicks LA, Taylor TH Jr, Hunkler RJ. US outpatient antibiotic prescribing 2010. N Engl J Med. 2013;368(15):1461-1462.
- Blaser MJ. Missing Microbes. New York, NY: Henry Holt and Company; 2014.