Microbiome Research Calls for Due Diligence in Pharmacy

July 21, 2020

Prepare to counsel patients on microbiome-related products.

Why are some individuals prone to developing certain health conditions? Why do some have a more robust immune system than do others? These are only 2 of the many questions that research into the microbiome—the complex community of bacteria, fungi, and viruses that live in and on the human body—may answer.

Microbiome studies, the latest wave of health research, explore the role of the microbiome in a host of chronic conditions and examine how it affects metabolism, regulates the immune system, and protects against pathogens. "Over 2000 years ago, Hippocrates, the father of medicine, said that all disease begins in the gut," said Suzanne Keyes, PharmD, IFMCP, FACA, of Keyes Com-pounding and 180 Wellness in Elk City, Oklahoma. “Now, with advances in med-ical technology, in testing and analysis, we can see that link clearly.”

Emerging Therapeutic Areas

Currently hundreds of pharmabiotics companies are engaged in more than 650 active research programs. At least 3 companies have microbiome-related treatments in the trial phase. The first microbiome-targeted products likely to win FDA approval are expected to be treatments for skin or gastrointes-tinal (GI) conditions.

“Emerging therapeutics are following the path of least resistance in terms of access to the therapeutic area and the regulatory path,” said Sandrine Miller-Montgomery, PharmD, PhD, executive director of the Center for Microbiome Innovation and professor of practice, bioengineering, at the Jacobs School of Engineering, University of California, San Diego. “In terms of therapeutic areas, skin diseases have quite a significant amount of product in development; the same is true for GI diseases. What will likely lag behind in reaching the market are therapeutics targeting organs. The notable exception will likely be in the cancer field, as it is starting to be well documented that microbes play a significant role in the effectiveness [of and] responsiveness to chemotherapy.” Research suggests that modulating the gut microbiome may help boost the immune system in patients with cancer and also reduce the adverse effects of some cancer treatments.

Antiobiotics: A Path to Resistance

The balance of the microbiome is vulnerable to a variety of factors, including medication and environmental exposure. One example is overexposure to antibiotics. “According to the latest statistics in 2017, the average 2-year-old has had 3 rounds of antibiotics,” said Keyes. “By the time a child is 17, they’ve had 21 rounds of antibiotics.”

Prolonged or frequent antibiotic use can lead to an increase in the number of antibiotic-resistant microbes. Individuals who frequently take antibiotics for an underlying condition are often prone to recurrent Clostridioides difficile infections, which damage the lining of the large intestine, causing diarrhea. Such infections affect half a million Americans every year.

A proposed donor stool therapeutic uses microbes to help restore a healthy microbiome balance, enabling the gut to fight the infection. Ferring Pharmaceuticals’ nonantibiotic therapeutic RBX2660 is currently in phase 3 clinical development for the prevention of recurrent C difficile infections. Fecal transplants may one day also play a role in correcting the microbiome imbalance, which has been suggested as a possible link to obesity and diabetes.

Probiotics vs Prebiotics

Although patients may ask pharmacists to recommend a probiotic supplement, it’s not a 1-size-fits-all remedy. Probiotic products sold as dietary supplements don’t require FDA approval, so quality may vary. Products also contain different strains, the most common being Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus.5

“Make sure to stock probiotics that you trust are stable and have data to show that they are still active once they get to the small intestine and the colon,” said Melody Hartzler, PharmD, PhD associate professor of pharmacy practice at Cedarville University School of Pharmacy in Ohio.

“There are some commercial products that have been shown in multiple clinical trials to have benefits. Find those products that you know are backed by good research and are strain specific to conditions you would recommend them for.

“The other thing you need to think about when you talk about probiotics is prebiotics. Prebiotics are the food that grows the good bacteria, so if we take probiotics and we don’t eat any fiber, it’s not going to be as helpful to our microbiome as [also] eating prebiotic fibers in our diet. People who don’t get enough in their diet...may need a prebiotic supplement. Some probiotics are mixed with prebiotics.” However, the effects of probiotics are usually not permanent. “When you take a probiotic, you take them every day,” said Suzanne Keyes, of Keyes Compounding and 180 Wellness. “The growth that is happening is very short lived.”

Studies investigating soil microbes suggest the effect of these microbes may last longer, said Hartzler. The effects of fecal microbe transplants may also be permanent. “Fecal transplants are definitely a big area of research, but there are 2...high-dose probiotics that are already available for doctors to prescribe: VSL#3 and Visbiome,” said Hartzler.

Although pharmacists may not yet encounter a slew of mi- crobiota-targeted medications, they can help patients achieve and maintain a healthier microbiome by exercising antibiotic stewardship, recommending probiotics, and encouraging a healthier lifestyle.

“Diversity of your microbiome is key, and commercially available probiotics usually [comprise] only a few strains,” said Sandrine Miller-Montgomery, of the Center for Microbiome Innovation. “So it will always remain crucial to eat a diverse diet and include a large variety of fermented food as well. Although pharmacists—and I am one by training—are always looking forward to providing a miracle pill to their patients, they need to keep in mind that having a healthy microbiome at the individual level starts with advising patients to have a good quality of life: a diverse and nutritious diet, quality sleep, appropriate amount of exercise, and a stress reduction practice.”

Gaps in Research, Development

In the past 2 decades, microbiome research has accelerated thanks to less invasive sampling techniques and more efficient means of analysis. But development of microbiome-based treatments remains complicated. Not only is an individual’s microbiome unique, but it also features trillions of organisms, making the determination of cause-and-effect relationships difficult. Sequencing an individual’s microbiome as a diagnostic tool has become increasingly popular, but it may not always provide useful information.

“Although there are some companies that have taken advantage of this market need, they are still not off ering true insights, as we are still in the observation phase when it comes to understanding the microbiome,” said Miller-Montgomery. “Sure, we have made humongous leaps in better understanding at the population scale the diversity of a microbiome profile, but translating this into something that works at the individual level despite the claims of some service providers—we are surely not there yet.”


1. Gosálbez L. The microbiome biotech landscape: an analysis of the pharmaceutical pipeline. Microbiome Times. March 26, 2020. Accessed May 17, 2020. https://www.microbiometimes.com/the-microbiome-biotech-landscape-an-analysis-of-the-pharmaceutical-pipeline/

2. Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell. 2018;33(4):570‐580. doi:10.1016/j.ccell.2018.03.015

3. Institute of Medicine (US) Food Forum. The Human Microbiome, Diet, and Health. National Academies Press; 2013.

4. Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus EP, Turnbaugh PJ. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science. 2013;341(6143):295‐298. doi:10.1126/science.1235872

5. National Institutes of Health. Probiotics: fact sheet for health professionals. Updated June 3, 2020. Accessed May 18, 2020. https://ods.od.nih.gov/factsheets/Probiotics-HealthProfessional/

download issueDownload Issue : Drug Topics July 2020