The Human Microbiome—Our Body's Secret Weapon

Over the last few years—and during the last few months in particular—there has been a tremendous amount of media coverage on the role of microbes—specifically the gut microbes—in regulating human health and disease. Recent stories have covered a wide range of related topics, including research linking microbes to inflammatory bowel disease, autism, and type 1 diabetes. There have also been research reports about the use of microbial infusions to treat infection and restore a healthy gut microbiome. We are living in an exciting time, where a collective group of scientists and researchers are just beginning to unlock the full power of the human microbiome, the collective genomes of all microorganisms present in or on the human body.

The interest in the human microbiome was sparked in part by the Human Microbiome Project, a five-year effort sponsored by the US National Institutes of Health. The goal of the $115-million research effort was to characterize the microbial communities found at several different sites on the human body and to correlate the relationship between changes in a microbiome present at a particular body site to a specific illness.

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Why all the excitement about these developments? One of the reasons is that this research is dramatically changing the way medicine views bacteria. Another is the very real possibility of developing non-antibiotic treatments for disease.

Britain's Prime Minister David Cameron recently came out with a powerful statement when he said that "Antibiotic-resistant superbugs threaten to plunge the world back to the 'dark ages' of medicine," and also pledged that the UK will lead a global effort to develop new drugs.

Antibiotics and the rise of superbugs

First billed as the "miracle of modern medicine," antibiotics have been overused for so long that some types have become ineffective. In today's world, it's become quite common to turn on the evening news and find that the lead story is about a virulent antibiotic-resistant disease showing up in patients in a local hospital. What was once easily treatable now has no known cure. The frightening thing is that antibiotic resistance is even more problematic than most people realize.

Every year, an estimated two million people in the US are infected with antibiotic-resistant organisms, also known as superbugs, which result in about 23,000 deaths annually¹—and this number is growing. These developments can be directly attributed to the fact that antibiotics have been and continue to be a central component to the healthcare landscape. A multi-pronged effort that combines antibiotic stewardship with new non-antibiotic approaches to treating infectious disease is needed.

A superbug that's commonly overlooked

There exists a deadly superbug that goes mostly unnoticed among many, that is until an individual or someone they know contracts it. Clostridium difficile infection—commonly referred to as C. diff. infection—can cause life-threatening diarrhea and is the leading healthcare-acquired infection, with far more cases than Methicillin-resistant Staphylococcus aureus (MRSA) infection implicated in "flesh eating" necrotizing fasciitis.

In the US alone, there are about 250,000 cases of C. diff. infections each year, linked to 14,000 deaths annually.¹ The incidence and severity of infections began around the year 2000, placing a significant burden on the US healthcare system. At least $3 billion in excess medical costs per year have been attributed to C. diff. infection.²

C. diff. infection itself has been linked to the prior use of antibiotics. Indeed, C. diff. infection was one of the first diseases formally linked to perturbation of the microbiome³ and previous antibiotic use is a prerequisite for development.³ Yet, ironically, the first-line treatment for the disease is more antibiotics. While most people are cured using this treatment approach, about 20% to 30% of people will go on to have more than one episode, and each additional episode predisposes to additional episodes, leaving these individuals trapped in a vicious cycle of recurrent disease.

Those over 65 years old with concomitant medical conditions are at greatest risk of C. diff. infection, most cases of which are contracted while in a healthcare setting. However, an increasing number of cases are being seen in younger patients, and there is a higher incidence of community-acquired cases as well. People who develop chronic C. diff. infection can be very sick for months and are at risk of dying. More than 90% of deaths occur in people older than 65.

The secret weapon

Trillions of bacteria, viruses, and other organisms live in our bodies and work together to regulate processes critical to life, including metabolism and the immune system. Collectively, the genetic material of these microbes forms the human microbiome. In healthy individuals, commensal ("good") bacteria live in balance with pathogenic components of the microbiome, giving us an inherent resistance to disease.

Research dating to the 1950s and perhaps far earlier shows that transplanting microbes from a healthy person's gut into a sick patient is an effective treatment for some diseases, including C. diff. infection. It is thought that the transplanted microbes restore the intestinal microbiome to a healthy state and in the process overwhelm pathogenic bacteria such as C. diff. Thus, the patient is restored to health without using antibiotics.

Implications for the pharma industry

New therapeutics derived from the human microbiome have the potential to revolutionize the industry. As it becomes increasingly difficult and expensive to develop new antibiotics, it may be possible for non-antibiotic therapies based on human-derived microbes to fill the gap. It may even be possible for these new therapeutics to preserve the effectiveness of the remaining antibiotics by reducing their use and slowing the development of antibiotic resistance. It is crucial that we continue to expand our knowledge of the human microbiome and look to harness its power to treat C. diff and other diseases in the future.

References

1. CDC Threat Report 2013. http://www.cdc.gov/drugresistance/threat-report-2013/

2. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. CID. 2012;55(S2):S88-92.

3. Britton RA, Young RA. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology. 2014;146(6):1547-53.

Lee Jones is Founder, President, and CEO of Rebiotix. She can be reached at ljones@Rebiotix.com.