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In the past, people used to believe that all bacteria were harmful “germs,” and the idea of having vast numbers of bacteria living inside them would have been shocking.
However, nowadays, there has been a significant shift in popular perception of the human body. The bacteria and other microorganisms that reside within us, collectively known as our microbiome or microbiota, are now seen as friendly guests that contribute to our overall health.
Over the last two decades, extensive research by medical experts from universities and industry has focused on exploring deficiencies in the human microbiome. These deficiencies have been linked to a wide range of diseases, including autoimmune conditions, mental illnesses, and cancer. It has been discovered that microbiome deficiencies weaken the immune system, making individuals more susceptible to harmful infections.
Simultaneously, this increased understanding of the microbiome has created new business opportunities in the development of therapies to improve the composition of unhealthy microbiomes. These include treatments using pills derived from human feces, as well as prebiotic and probiotic foods and supplements.
However, amidst the excitement surrounding the microbiome, certain misconceptions and hype have emerged. In a recent article published in Nature Microbiology, microbiome experts Alan Walker and Lesley Hoyles debunk 12 myths associated with the microbiome. These myths range from exaggerations about its size and weight to misconceptions about the connection between certain microbial patterns and disease.
The widely quoted claim that the number of microbial cells in our bodies is ten times higher than human cells actually originated from a rough estimate made in the 1970s, and the actual ratio is closer to 1:1, according to Walker and Hoyles. Another misconception is the weight of the human microbiome, which is often estimated at 1kg to 2kg but is typically below 500g in most individuals.
The gut is the primary location of the microbiome, although there are smaller populations of bacteria residing in other areas of the body and on the skin. While the terms microbiome and microbiota are used interchangeably, there is a technical distinction between the two.
Hoyles explains that much of the research linking disease to changes in the microbiome’s bacterial balance is based on studies with rodents, which are poor models for human physiology, as well as “underpowered human studies.” This leads to misleading or irreproducible conclusions. So far, it has been challenging to establish a definite causal link between an unhealthy microbiome and disease in human studies. The opposite scenario, where disease causes specific bacteria to proliferate in the gut, also needs to be considered.
In the early days of microbiome research, the focus was on developing pre- and probiotic foods and supplements, such as yogurt, which promote the growth of healthy bacteria in the gut. However, this field has declined recently due to stricter regulations imposed by European authorities, who now require robust scientific evidence to support health claims made by food producers, Hoyles notes.
So far, the only proven success of microbiome therapy, specifically through fecal transplants from healthy donors, has been in the treatment of excessive growth of the superbug Clostridioides difficile in the gut. This condition is a direct result of an unhealthy microbiome. The greater challenge lies in dealing with diseases caused by the secondary effects of the microbiome elsewhere in the body.
One undisputed effect of the microbiome is its influence on the host’s immune system. This impact extends to a wide range of common inflammatory conditions, not only in the gut but also throughout the body. The microbes produce metabolic molecules that can either strengthen or weaken the immune system.
Hoyles predicts that cancer treatment will be the key focus of microbiome research in the coming years. A recent study published in Nature by Harvard scientists demonstrated how differences in gut bacteria affect the body’s response to PD-1 checkpoint blockade, an immunotherapy that has revolutionized cancer treatment. In experiments with mice, the researchers found that specific bacteria influenced the activity of two immune molecules that play a crucial role in determining the effectiveness of checkpoint inhibitors in unleashing the immune system’s power to fight cancer. The next step is to replicate these findings in human subjects.
However, Francesca Gazzaniga, a member of the Harvard research team, emphasizes that the development process will not be easy: “Cancer, the immune system, and the microbiome are astoundingly complex individually, but when you put these systems together, the resulting interplay is exponentially more intricate.”
A different study conducted at the Fred Hutchinson Cancer Centre in Seattle and published in Immunity demonstrated how the microbiome affects immune responses. The researchers found that the type of bacteria present in the gut before a bone marrow transplant for blood cancer influenced the risk of developing graft-vs-host disease, where immune cells from the donor attack healthy recipient cells.
Further research is necessary to fully understand how to manipulate the complex microbial ecosystem in the gut and improve transplant outcomes. According to study leader Motoko Koyama, “There is still a lot to understand about how to manipulate the microbiome, but our work shows that the pre-transplant microbiome is an important place to focus future research.”
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