There are ten times more bacterial cells in your body than human cells. They live in our noses, in our guts, and everywhere in between. These microbes, our microbiota, are not mere passengers here for a ride but also interact with us in significant ways that affect our health.
This blog will briefly review what we know about health and our microbiota and look at how medical researchers are introducing changes to the gut microbiota of their patients to make cancer treatments more effective.
A Brief History
Investigation of the link between microbes and human health goes back thousands of years. The Ebers Papyrus, an Egyptian medical papyrus dating back to 1550 BCE, describes a treatment consisting of incising tumors to cause an infection to shrink tumors. Work in the intervening millennia would implicate a large set of viruses that have the potential to cause tumors. However, it wasn’t until 1861 when the pioneer of microscopy, Antoine van Leeuwenhoek, looked at a stool sample using his microscope and saw “more than 1000 living” microbes that we had evidence that something else lived inside of us.
Tissier and Gasching published a paper in 1903 that is probably the first scientifically rigorous attempt to alter gut microbiota as a form of treatment. In this seminal work, the two researchers determined that a bacteria called Bacillus acidiparalactici could prevent milk from spoiling and was normally found in healthy infants. Tissier grew a pure culture of these “good bacteria” and gave a couple of teaspoons every day to infants who were having gut issues. He found that the gut microbiota of these infants was restored and their gut issues cleared up.
The Biome Inside Me
You may wonder how these microbes get into your gut in the first place. Where does your gut microbiota come from?
It all starts at the beginning: our gut microbiota are populated at birth. A newborn will get a different set of microbes depending on if they are born vaginally or by C-section. Different microbes thrive if the newborn is breastfed or bottle-fed. These effects continue as we grow. People tend to have a similar gut microbiota to the people they live with. Your environment and your diet have a large effect on which particular microorganisms can live inside of you.
Changing Your Gut Microbiome
Researchers have come up with multiple ways of affecting a patient’s gut microbiota. One way is by changing your diet. Fermented foods, probiotics, and prebiotics have been increasingly used with positive effects to treat diseases that are heavily diet-related, such as diabetes, obesity, or inflammatory bowel disease.
A more direct approach is a procedure called fecal microbiota transplant (FMT). With FMT, feces that contain beneficial “good” microbes are transferred into a patient. Multiple methods are available depending on where the bacteria should be placed and what the patient can tolerate. Endoscopy can be used to deliver microbes through the rectum (to reach the colon) or the nose (to reach the stomach). Enemas can be used but can take multiple applications as the transplanted feces may not reach the colon. In addition, capsules with fecal matter, so-called “poop pills,” can be swallowed.
The idea of transplanting human feces has been increasingly accepted over the past five years. Despite concerns about risks like causing an infection from unidentified microbes, FMTs have displayed short- and long-term safety and are generally considered well-tolerated even in high-risk patients.
Gut Microbiota in Cancer Research
Despite the long history and growing evidence in other fields, changing the gut microbiota for cancer research has faced recent pushback.
Starting around 2010, preclinical work in mice and rats began to establish that changes to the gut microbiota can lead to different anticancer drug responses. In 2018, Bertrand Routy published his research in Science looking at the effect of gut microbiota on anticancer therapy. Routy’s team worked with patients who were receiving a class of anticancer drugs called immune checkpoint inhibitors, or ICIs. Some of the patients responded well to ICIs, while other patients were unresponsive. The researchers analyzed stool samples from both types of patients and found that unresponsive patients had low levels of the bacterium Akkermansia muciniphila.
Despite promising research in humans, investigators debated in 2018 whether new clinical trials that alter the microbiome should proceed. Some people argued that more work was needed to establish exactly which microbes are beneficial and to standardize the methods used.
Clinical trials went through anyway and many of these were successful. One trial showed that dietary fiber and probiotics influenced the gut microbiome and positively affected the response to melanoma immunotherapy. Another trial found that restoring a patient’s gut microbiota after chemotherapy reduced life-threatening complications, such as inflammation. Phase II studies have shown the positive effects of transferring gut microbiota between patients. These ground-breaking trials have paved the way for a new standard of care to be explored.
Next Steps
Our knowledge of gut microbes and how to best make use of them has increased significantly over the past few millennia. We’re currently at a point where research has demonstrated that our gut microbiota influences cancer therapy. Today, there’s been an explosion of clinical trials being conducted to translate the potential benefits of the gut microbiota into real-world advances in human health.
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