Saturday, February 16, 2019

Missing Microbes

FLASHBACK SERIES: Blog posts written during my residency training at Central Washington Family Medicine

by Kim Ha Wadsworth, DO | PGY-1
Ambulatory pediatrics rotation with Dr. Stephen Pearson, MD

My reflection on reading:

Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues
by Martin J. Blaser

In his book, Dr. Blaser presents evidence from his own research and personal experiences to support his central thesis that early life exposure to antibiotics reduces microbial diversity in our GI tract, which in turn leads to long term effects and metabolic consequences associated with chronic conditions later in life, including obesity, diabetes, allergies, celiac disease, and even autism—what he calls “modern plagues” (see figure below from his book). He believes that the widespread, and often imprudent, use of antibiotics is causing the extinction of some important species of microbes that are uniquely tailored to coevolve and coexist with us. He cautions that this problem is getting worse, with reduced microbiota in each generation.

Figure from Missing Microbes by Dr. Blaser (2014)

Dr. Blaser points out the overuse—and often reflexive use—of antibiotics in modern society. While we often think that this problem stems from inappropriately taking penicillin for a URI, we almost ignore our everyday exposure to antimicrobial soaps and hand sanitizers as well as antibiotics that are present in many animal products that we eat. This liberal use of antibiotics has resulted in widespread resistance among microbes, and common infections are now requiring increasingly powerful drugs to control.

As an aside, in 2001-2002, I identified this problem of antibiotic resistance and the lack of novel antibiotics in the market. I tried to start my own biotechnology company in Monterey, CA to discover bioactive molecules from marine microbes for the development of anti-infectives. At the time, I recognized that research on terrestrial microbes were not yielding any novel candidates for antibiotics. Similarly, chemical shuffling methods did not generate new drug leads since they were based on the same molecular scaffolds. I wanted to look at marine microbes for drug discovery, specifically focusing on bacteria living in sponges that produce potent toxins to protect their immobile hosts. Marine microbes were largely untapped due to the inability to study them in the laboratory when taken out of their complex marine environment; however, I had hoped to apply new (at the time) molecular biology techniques of cloning and PCR to study the microbial diversity in the ocean.

Unfortunately, I did not get funded to start my biotech company and instead started my own IT consulting company supporting small businesses in the Monterey Bay region. A decade later, an investor who was a former scientist at Genentech (and who was the Chief Scientific Officer of the first biotech start-up that I worked at after college) told me that I was ahead of my time in recognizing the shortage of novel antibiotics and the increasing problem with drug-resistant bacteria. But I digress…

Back to the topic at hand, I found several noteworthy points that Dr. Blaser makes as I read through all 16 chapters (yes, it took a long time to finish this book while on rotation!):

  • In the last few decades, people appear to be getting sicker from “modern plagues” that result in chronic conditions that impact quality of life for decades compared to the lethal plagues of the past (eg., cholera, scarlet fever, small pox, diptheria in the 1800’s) that struck relatively fast and hard.
  • Our microbiome is acquired early in life by the age of three, and the microbial populations within children resemble those of adults. Bacterial specialization makes each of us distinct (health, metabolism, immunity, and cognition).
  • If a child was born by C-section, the process does not enable him/her to inherit the mother’s full library of microbes (aka: microbiota).
  • H. plyori (previously dubbed “gastric campylobacter-like organism”), the comma-shaped bacteria found in the human stomach, is both a good and bad germ. As we know, it is associated with ulcers and stomach cancer in adults. However, eradication of H. pylori with antibiotics has now caused an increase in GERD and even esophageal cancer. It turns out that this germ is instrumental in protecting the human esophagus and has a protective effect in children based on Dr. Blaser’s own research.
  • The meat industry has exploited the fact that antibiotics cause weight gain, adding subtherapeutic doses of antibiotics to animal’s feed to fatten them for slaughter. This is the same mechanism that contributes to obesity when eating these animal products.
  • The loss of diversity within our microbiome—a process Dr. Blaser calls the “disappearing microbiota”—changes our metabolism, immunity, cognition, and overall health. As we lose our ancient microbes, we are headed toward a worse future that Dr. Blaser calls the “antibiotic winter.”
  • Dr. Blaser recommends several sensible actions:
    • Use antibiotics cautiously, not “just in case”
    • Ban their use to fatten animals for human consumption
    • Improve birth practices to ensure C-sections are a last resort

While the long-term effects of these “missing microbes” remain scientifically hypothetical, Dr. Blaser makes a convincing argument that antibiotics are NOT without harm and increase our susceptibility to chronic disease. Certainly, I will adhere to the principles of antibiotic stewardship (especially having been aware of this issue myself almost two decades ago) not only to prevent further development of antibiotic resistance and overgrowth of pathogenic species but also to prevent the loss of diversity in the human microbiota as laid forth by Dr. Blaser in his book.

Thank you for the opportunity to read a compelling book on a very important topic.