Have you ever considered that your body is its own ecosystem? Our bodies are host to countless microbial organisms, which live in and on every conceivable part of our body and outnumber our human cells ten to one. We depend on these microbes for a variety of reasons – their colonization of our skin keeps fungi and yeast from growing on us; in our gut they help digest some of the food we eat; and in our noses they even produce antibiotics to combat harmful microbes that we inhale. While we’ve known about the existence of bacteria since the 1670s, we know surprisingly little about most of them because of the difficulty in cultivating them in a laboratory. Recently, with the cost of DNA sequencing becoming ever more affordable, researchers have bypassed the old need to cultivate organisms in order to study them: they can now sequence the DNA from entire microbial communities (known as the “microbiome”) straight out of their natural habitats. This has led to an explosion in studies on microbial communities in the human body, including a project to map the entire human microbiome [1]. Our increasing understanding of the microbes that have coevolved with us and on which we depend is fascinating from a purely scientific perspective, but this research also offers myriad possibilities for improving our understanding and treatment of human diseases, from the obvious targets such as infections caused by harmful bacterial infections to subtler relationships between our microbiome and obesity, diabetes, and even cancer.

Growing up big and strong: healthy food, exercise… and bacteria

We live with bacteria from the moment we exit the womb, receiving our first coating of bacteria in the birth canal – or a different set of bacteria, usually found in adults, if the birth is done by cesarean-section. Early in the first trimester, the bacterial community in the vagina of a pregnant woman alters to include species that are important for the baby; for example, a species that produces enzymes for digesting milk, usually found in the gut, turns up in the vagina during pregnancy [2]. It has been speculated that this species in particular helps prepare infants to ingest breast milk, but there have not been any rigorous studies to support or refute this idea. The colonization of the baby doesn’t end there: mom’s breast milk also contains at least 700 types of bacteria that change as the baby grows [3].

Even after moving to solid foods, colonization by certain bacterial species can influence a range of health issues in infants and toddlers. For example, toddlers with eczema have been found to have gut bacteria more similar to the gut community of a healthy adult than a typical toddler, though it’s currently unclear how gut bacteria influence a skin condition [5]. Microbial communities in the gut can have even more dramatic effects in children: in a study of twins in Malawi, researchers were able to demonstrate that the gut microbiome is involved in propagating a form of acute malnutrition called kwashiorkor [5]. Eating a diet of therapeutic food (a paste composed of peanuts, sugar, oil, and milk, which is the standard defined by the World Health Organization for treating severe acute malnutrition) caused the gut microbes in kwashiorkor-suffering children to change toward a healthy state, but the microbiome reverted back to its original state when the child returned to eating a traditional Malawian diet [6].

While this study highlights the ability of single factors such as diet to influence the human microbiome, it also demonstrates that a single factor will not always be enough to induce permanent change – even though healthy changes were seen while the twins with kwashiorkor were on the therapeutic diet, those changes reverted back to disease-state upon cessation of the diet. These findings highlight a challenge that will have to be faced in order to integrate our findings about the microbiome into healthcare applications: the interplay between our body and its microbial symbionts depends on a wide array of influences beyond any single factor. Antibodies produced by cells, signals produced by certain bacteria, diet, and many other factors all influence the make-up of our bacterial communities, so it is unlikely that we will be able to restore balance to a bacterial community by changing a single factor. In the case of the Malawian twins suffering from kwashiorkor, however, there is hope of a different kind – treatment with antibiotics to target the community of microbes contributing to severe undernutrition combined with a therapeutic diet may help a healthier gut community gain a permanent foothold.

Fighting bacterial infections with bacteria

While antibiotic treatments are often beneficial for human health, as in the case of undernourished children with kwashiorkor, there is a darker side to antibiotic treatments as well. Patients who suffer from recurring infections of Clostridium difficile (C. difficile) bacteria in the gut usually get infected as a result of antibiotic treatments. This is because antibiotics indiscriminately kill both harmful and helpful bacteria; as a result, “good” bacterial communities can be wiped out along with the bad. The absence of healthy bacteria can allow harmful, often antibiotic-resistant bacterial strains to colonize places that would have been difficult for them to invade under normal circumstances (Figure 1, panels A-C).

Figure 1. When healthy, our gut contains myriad different types of bacteria, which live in a symbiotic balance with our body (A). Antibiotic treatment for a different illness can kill off both good and bad bacteria, which in the case of C. difficile infection leaves the gut’s typical bacterial population decimated (B). In this state, the gut is susceptible to colonization by harmful bacterial strains such as C. difficile (C). Transplanting a bacterial community from a healthy donor repopulates “good” bacteria, which outcompete the C. difficile, restoring balance (D).

For many years, a last-line treatment for patients suffering from C. difficile infection was to use a fecal transplant, where the bacterial community from a healthy person’s feces is transplanted into the patient’s gut (Figure 1, panel D). The premise for this treatment is that the healthy bacterial community from the donor’s gut will out-compete the harmful C. difficile bacteria. A recent study in the Netherlands rigorously tested this treatment compared to traditional antibiotic therapies, and found that 15 of 16 people treated with the fecal transplant were cured, compared to 3 of 13 and 4 of 13 people in two comparison groups [7]. While that may seem like too few people to draw any sweeping conclusions about the efficacy of the two treatments, the difference in success rates was so stark that, although researchers had intended to include more people, it was considered unethical to continue treating two-thirds of the patients in the study with antibiotics when the fecal transplant was curing almost everyone who received it.

This success story is an inspiring example of the potential that microbiome research has for enabling us to devise smarter, more effective therapies for a variety of diseases. While the treatment of C. difficile infection with fecal matter is curing most patients, it is undeniable that a certain “ick” factor remains, even though researchers can remove the bacteria from the feces before the transplant. Ultimately, researchers hope to tease out exactly which bacteria in the gut are necessary to restore a healthy balance in patients. They could then figure out how to deliver a cocktail of those bacteria into the patient’s gut without needing to use fecal matter from a healthy donor, allowing them to achieve the same curative effect without the distasteful steps currently involved. In the meantime, doctors involved in the study hope that its publication will encourage this technique to become the standard of care for patients suffering from recurrent C. difficile infection. Additionally, this study proves what many microbiologists have long known – our bodies’ relationship to and dependence on the microbes who call us home is in a delicate symbiotic balance, and the more we can learn about how this relationship functions, the better equipped we will be to cultivate healthy microbial communities, in turn allowing us to care for the health of the human host.

Ilana Kelsey is a Ph.D. student in the Biological and Biomedical Sciences program.

References

[1] “Human Microbiome Project.”  Office of Strategic Health Coordination- The Common Fund.  National Institutes of Health, 23 January 2013.  <http://commonfund.nih.gov/hmp/>.  14 February 2013.

[2] Zimmer, Carl.  “Tending the Body’s Microbial Garden.”  New York Times, 18 June 2012.  <https://www.nytimes.com/2012/06/19/science/studies-of-human-microbiome-yield-new-insights.html?pagewanted=all>.  14 February 2013.

[3] Sohn, Emily.  “Breast Milk Contains Hundreds of Bacteria Types.”  Discovery News, 10 January 2013.  <http://news.discovery.com/human/health/breast-milk-contains-hundreds-of-bacteria-types-130110.htm>.  14 February 2013.

[4] “Eczema in Infants Linked to Gut Bacteria.”  Science Daily, 21 January 2013.  <http://www.sciencedaily.com/releases/2013/01/130122231351.htm>.  14 February 2013.

[5] “Kwashiorkor.”  PubMed Health.  National Institutes of Health, 1 February 2012.  <https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002571/>.  14 February 2013.

[6] Relman, David A.  “Undernutrition – Looking Within for Answers.”  Science, 30 January 2013.  <https://www.sciencemag.org/content/339/6119/530.full>.  14 February 2013.

[7] Grady, Denise.  “When Pills Fail, This, er, Option Provides a Cure.”  New York Times, 16 January 2013.  < https://www.nytimes.com/2013/01/17/health/disgusting-maybe-but-treatment-works-study-finds.html?pagewanted=1&_r=1>.  14 February 2013.