Sophisticated analyses can predict which gut microbiome profile may lead to better outcomes to immunotherapy for patients with advanced melanoma.
The past decade has brought about a tremendous amount of professional and societal interest in the microbiome — the bacteria and other microorganisms that colonize different parts of our body, ranging from the skin to the intestines/colon, mouth and even the ducts of the breast.
Intriguingly, each person’s microbiome possesses the uniqueness of a fingerprint. But the concept is not “new age” at all; it is mentioned in the writings of one of the founders of the field of microscopy himself, Antonie van Leeuwenhoek. In the 1670s, van Leeuwenhoek reported distinctions of the microbiota from the mouth or feces among individuals and even differences based on illnesses.
As it became clear that certain pathogenic bacteria — and later viruses — could cause distinct diseases, it also was recognized that normal colon bacteria such as E. coli (noting that some strains of E. coli can cause serious sickness) could be probiotic — that is, something that maintains the normal harmony. During some battles in World War I, more soldiers were lost to dysentery, an infection of the intestines, than to enemy fire. A specific strain of E. coli was discovered in an infantryman who survived a trench epidemic, and the strain was shown to antagonize harmful bacteria that were likely causing the scourge.
Fast forward to the third millennium, when modern genomic analysis has revolutionized how we identify and classify microbes by sequencing their DNA. We can more easily determine what is causing an infection (although it’s not always possible) and what populations of bacteria reside in body compartments. Using gene sequencing and bioinformatic tools, we can assess bacterial diversity in a specific habitat (alpha diversity), and variations in different regions (beta diversity). As you will read in this issue of CURE®, our gut microbiome often mirrors our health. Our microbiome interacts with and even sculpts our immune system. Each of us has a unique immune system with an inventory of activated T cells that can directly kill invaders (pathogens and cancer cells among them) and B cells that make antibodies that fit like a lock and key to inactivate bacteria and viruses and bring on additional waves of attack by other arms of the immune system.
As we teach immune systems to attack cancer and develop drugs to reverse the dampening effects that cancer cells have to evade immunity, we are recognizing that some people have a more “trained” or “fit” immune system. This may be due to the experiences and exposure gained over one’s lifetime, including interactions with the microbiome, which is an ever-present companion in many areas of our body. Not surprisingly, sophisticated analyses can predict which gut microbiome profile may lead to better outcomes to immunotherapy for patients with advanced melanoma. Trials are underway to transplant “good profile” colonic flora in patients receiving cancer immunotherapy. We invite you to read this and other fascinating breakthroughs that we are witnessing at accelerated paces — in this case, discoveries coming from within.
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