Using the Human Microbiome to Treat Common Diseases

Using the Human Microbiome to Treat Common Diseases

Microbes living in us and on us outnumber our own cells. Microbiota in the human gut is one of the most densely populated bacterial ecosystems known in nature. It regulates metabolic function and immune responses and contributes to mood and behavior. Imbalances have been linked to different diseases including inflammatory bowel disease (IBD) and metabolic disorders. A healthy microbiome, on the other hand, can have a protective function as has been shown in the case of Helicobacter pylori, which was previously only known for its harmful effects.

Scientists now recognize that H.pylori—which incidentally, was also found in the stomach of 5,300-year-old Iceman Oetzi—might protect against acid reflux and asthma.

Microbiome or Microbiota?

Microbiome and microbiota have received a lot of press lately because of the scientific advances related to the treatment of gastrointestinal and immune diseases that involve microbial communities. There has been some ambiguity in the way the two terms are being used. Dr. Jonathan Eisen from the University of California, Davis noted that microbiome is now commonly used to refer to the collection of microorganisms that occupy a certain habitat in the body, for example, the human gut. The term was first used in the 1800s and appears in an old Italian book on obstetrics and gynecology. Some other trusted sources, such as the scientific journal Nature, also define the microbiome as the genetic material within a microbiota.

In their view, the microbiota refers to the entire collection of organisms.

Although there appears to be some inconsistency in the use of terminology, the science community univocally agrees that the contribution of microbes to human health is significant.

Nonetheless, it can sometimes be challenging to study their direct influence and causal relationship to different diseases.

Transferring the Microbiome between People

In 2016, a study was published in Nature Medicine that described the process of transferring the mother’s microbiome to her newborn child.

It has previously been established that babies born by cesarean section are more likely to develop autoimmune diseases. As their mode of delivery does not expose them to the vaginal microbiome, right after the birth, their gut microbiome resembles that of their mum’s skin. In contrast, vaginally born babies have a gut microbiome that resembles their mother’s vaginal microbiome, which appears to protect them against certain harmful conditions. An experiment designed by Associate Professor Maria Dominguez-Bello from the New York University looked at transferring the mother’s vaginal microbiome to babies born by C-section. The mothers were swabbed and the babies were colonized immediately after birth. When tested after a month, newborns who were inoculated with the vaginal microbiome still had a microbiome that closely resembled their mother’s vagina. These transfers of vaginal flora following a C-section, also known as “vaginal seeding”, might become an important procedure in the future and could help prevent some autoimmune conditions.

However, some experts warn that although the practice is becoming increasingly popular, its benefits have not been proven yet. Dr. Aubrey Cunnington, of Imperial College London, argues that vaginal fluid can also carry bacteria and viruses that could be harmful to a baby. For now, health professionals have been generally advised not to perform vaginal seeding.

Fecal microbiota transplantation (FMT) or bacteriotherapy has also been explored. It has, for example, been applied to patients who have bacterial imbalance in their gut as a result of a previous antibiotic treatment that destroyed helpful bacteria.

People who have been diagnosed with recurrent Clostridium difficile colitis (which can occur in people who take antibiotics) can now be treated with a transfer of stool from a healthy donor. C. difficile infections are considered the most common hospital-acquired infections. The infection often results in recurrent diarrhea. Two Danish doctors, Dr. Michael Tvede and Dr. Christian Rask-Madsen, developed a specific type of bacteriotherapy that shows a lot of potential in treating diarrhea associated with C.difficile bacterium. Like FMT their method, called rectal bacteriotherapy (RBT), aims to reintroduce normal intestinal microflora. A study of 55 patients who received RBT showed that treatment was successful in up to 80 percent of their patients (with better outcome in those with no gastrointestinal illness). Tvede and Rask-Madsen acknowledge that there are always risks involved when inoculating a patient with live bacteria, for example, a bloodstream infection can develop. Ten days post RBT, one of their patients was admitted to the hospital with an acute condition, possibly connected with RBT.

Human-gut-on-a-chip Technology

A team from Harvard University made significant progress in studying gut bacteria and inflammation by using human-gut-on-a-chip technology to micro-engineer a controlled model of human intestines. This model—the size of a computer memory stick—mimics the natural conditions in the human intestines, which enables researchers to study bacterial overgrowth and inflammation of the gut. For the first time, scientists are able to analyze different pathophysiological responses and the contribution of individual pathogens and cells in vitro.

Services like uBiome are also emerging, transforming the testing of human bacteria into citizen science. However, these popular institutions might have many limitations. The science is still in its infancy, and looking solely at the bacteria in our gut does not necessarily give us a comprehensive picture of the gut environment and overall intestinal health.

Sources

Blaser M, Chen Y, Reibman J. Does Helicobacter pylori protect against asthma and allergy?. BMJ Gut. 2008;(5):561-567

Cunnington A, Sim K, Deierl A, Kroll J, Brannigan E, Darby J. "Vaginal seeding" of infants born by caesarean section. BMJ.2016;352:1-2.

Dominguez-Bello M, De Jesus-Laboy K, Clemente J, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nature Medicine. 2016;(3):250-254

Kim H, Li H, Collins J, Ingber D. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proceedings of the National Academy of Sciences of The United States of America. 2016;113(1):E7-E15

Maixner F, Krause-Kyora B, Zink A, et al. The 5300-year-old Helicobacter pylori genome of the Iceman. Science. 2016;351(6269):162-165

Tvede M, Tinggaard M, Helms M. Original article: Rectal bacteriotherapy for recurrent Clostridium difficile-associated diarrhoea: results from a case series of 55 patients in Denmark 2000–2012. Clinical Microbiology And Infection. 2015;21:48-53

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