er’s vagina. Infants born via Cesarean section carry a more skin-like flora that does not match the skin microbiomes of their mothers but might have derived from other people present in the delivery room. The microbiome differences between these infant groups last for many months, and C-section-delivered children appear to have a higher risk for asthma, atopic diseases, and obesity later in life.3
What They Do: Functions of the Human Microbiome
Not only have scientists investigated who our bacterial inhabitants are but we have also learned about what they can do. Together, the human gut microbiome contains 150 times more genes than our own genome, therefore supplementing our own functional capacity with an enormous additional potential.4 An important function of the gut microbiome is the digestion of complex carbohydrates in our food for which we lack the enzymes. The presence of a gut microbiome allows a mammalian host to break down these starches and fibers and to extract more energy out of the diet. Germ-free mice, born and raised in sterile incubators, need to eat 30 percent more food to remain at the same body weight as mice with a conventional microbiome. In addition, the gut microbiome is involved in an ever-increasing list of other functions, such as lipid metabolism, blood glucose levels, release and response to hormones, vitamin synthesis, and the correct development of anatomical structures and the immune system.1
Microbiome and Obesity
About 35 percent of American adults are obese, and sedentary lifestyle and poor food choices are obvious causes. But, given the important roles that our gut microbes play in food digestion and fat metabolism, could they be involved in obesity as well? Studies from the laboratory of Jeffrey Gordon have shown that obesity is indeed partly determined by the composition of our microbiome. Although the precise role of the microbiome in obesity is as yet unclear, obese humans have less bacterial species in their stool than lean people. Working with human pairs of twins discordant for obesity, Gordon’s group showed that stool from an obese human twin could transfer obesity to mice, while mice that received stool from the lean human twin stayed thin.5
Collateral Damage of Antibiotics
The human-associated microbiome is relatively stable over time in the absence of travel, diet changes, or diseases.6 However, a single course of antibiotics can have a dramatic impact on its composition. Most antibiotics are designed to kill broad groups of bacteria and cannot distinguish between the pathogenic bacteria causing a sore throat or skin infection and the beneficial microbes in our guts. Each time we take a course of antibiotics to treat an infection, we are also killing parts of our microbiome. The gut communities usually bounce back, but it can take weeks or even months to reach their starting point. In some cases, the intestinal microbiota never completely recovers from this perturbation, and particular groups might be permanently lost.7 Antibiotic use can also lead to antibiotic-associated diarrhea. This is often caused by a toxin-producing bacterium called Clostridium difficile, which is normally present at very low abundance in the human gut, where it’s competing with many other bacteria for space and food. It is less sensitive to antibiotics than most beneficial gut microbes and can take advantage of the open space left by antibiotics. The overgrowth of C. difficile can lead to persistent and WWW.SFMS.ORG
hard-to-treat diarrhea, and C. difficile infection is now the leading cause of hospital-acquired infections.8
Low Exposure to Germs
Despite an increasing awareness that some microbes might be good for us, many people try to avoid contact with germs. We eat nearly sterile food, put paper on the toilet seat, disinfect toothbrushes with UV light, and clean grocery carts and exercise equipment with germ-killing wipes. In addition, we wash our skin with antibacterial soaps and decimate our gut bacteria when we take antibiotics for a suspected infection. While many infectious diseases have rapidly declined in the past decades, many other diseases such as allergies, inflammatory bowel diseases, asthma, celiac disease, diabetes, and obesity are on the rise. In his recent book Missing Microbes, Martin Blaser links their increase to the overuse of antibiotics, which has not only contributed to an increasing number of antibiotic-resistant strains but is also detrimental to our microbiome.9 At the age of three years, the average U.S. child has already received three to six doses of antibiotics, exactly during the time that their microbiome is developing.10 Since our microbiome is involved in many processes in our bodies, including educating and balancing our immune system, the increased use of antibiotics and reduced exposure to bacteria early in life might be related to the increase in diseases of the immune system and obesity.
A Healthier View of Microbes
Obviously, we do not want to return to the Dark Ages, when infectious diseases could kill half of a continent’s population. We should support vaccination, treat life-threatening infections with antibiotics, and wash our hands with regular soap. But knowing how important a healthy and diverse microbiome is for our health, we should embrace the thought that low amounts of bacterial exposure might be good. Maybe we should not disinfect children’s school desks or buy antibacterial soap, and take antibiotics only when it’s absolutely necessary. Maybe we should be eating more live bacteria by consuming fermented food and yogurts with probiotics, and let the kids play in that dirty sandbox. Even grosser treatment options are emerging. Stool transplants, in which a patient’s own microbiota is killed and replaced with the gut microbes of a healthy donor, have been successfully used to treat patients with recurrent C. difficile diarrhea.8 People have even suggested that we should smear babies born via C-section with rectal and vaginal samples from their moms, immediately after birth. But realizing that we have to take care of our internal microbes is already a start. Microbiome research is a very hot topic and an exciting field to work in, and scientists expect to find many more roles that these little buddies play in our health.
Elisabeth Bik, PhD, is a research associate at the Department of Microbiology and Immunology at Stanford University School of Medicine. For the past twelve years she has worked in the laboratory of David Relman, MD, on the characterization of the human microbiome in hundreds of oral, gastric, and intestinal samples. She currently works on the microbiota analysis of marine mammals and children with inflammatory bowel diseases. Her blog, www.microbiomedigest.com, is an almost daily compilation of scientific papers in the rapidly growing microbiome field. Find her on Twitter at @MicrobiomDigest. A full list of references is available online at www.sfms.org. SEPTEMBER 2014 SAN FRANCISCO MEDICINE
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