Human intestine villi and microbiome. Photo/Credit: Marcin Klapczynski/iStock
Scientists long assumed that the human stomach was a sterile organ, completely inhospitable to bacteria and other microorganisms. After all, our stomach linings continuously produce and secrete gastric acid, creating a hostile environment that destroys any pathogens.
This belief held fast until the early 1980s, when Australian physicians Barry Marshall and J. Robin Warren noticed a new type of spiral bacteria in the stomach biopsies of several patients. Their discovery and isolation of H. pylori – which led to a Nobel Prize in Physiology and Medicine in 2005 – marked the beginning of a major paradigm shift in our understanding of the gut and its ecological potential.
Community of Microorganisms
Now we know the microorganisms that inhabit the gastrointestinal tract of humans, collectively called the gut microbiome, number in the hundreds. In total, less than half of the cells and only one percent of unique genes found in our bodies are actually human, with the rest being microbial. With such a skewed composition, researchers now understand that obtaining a complete picture of diseases and overall health must include a consideration of the microbiome.
Many studies initially focused on conditions with more obvious connections to the gut, such as obesity, diabetes and irritable bowel syndrome. More emerging work points to a much wider reach of the gut microbiome that even extends to the brain. The existence of a gut-brain axis, as it has been termed, means that the communities of microorganisms within the body could play a role in the development of disorders like depression and anxiety.
The gut-brain axis refers to bi-directional communication between the central nervous system and gut microbiota that regulate metabolism and energy balance. Signaling can occur by neural, hormonal or immunologic mechanisms. Tens of trillions of microorganisms – mostly bacteria, but also some viruses, phages, and fungi – populate the human gastrointestinal tract. Intestinal dysbiosis occurs when the gut’s equilibrium becomes disturbed due to underpopulation of beneficial microbes and overpopulation of harmful microbes.
Early research on animals revealed a surprising link between intestinal dysbiosis and behavioral impairment. For instance, a 2004 experiment on mice lacking intestinal and other microbiota displayed exaggerated response to stress compared to controls. When the germ-free mice had their guts recolonized with beneficial bacteria, the exaggerated response was successfully reversed. Similar studies on mice have demonstrated that the gut microbiome is essential for the development of neuronal circuits underlying motor control, anxiety behavior and social responses.
The last few years have seen a growing number of human studies set on further exploring the gut-brain axis. They provide some supportive evidence that the same kind of bi-directional communication observed in animals also exists in humans.
For example, a 2019 study investigated how microbiome features correlate with quality of life and depression in a large cohort of 1,054 adults. It found that certain types of bacteria were associated with higher quality of life indicators, while others were depleted in participants with depression. In 2020, a study of 171 patients with inflammatory bowel disorder in remission discovered an association between lower microbiota diversity and higher depressive, anxiety and stress symptoms.
Focus for the Future
However, the jury is still out on whether interventions that target the gut microbiome are truly effective for disorders like depression, anxiety and post-traumatic stress disorder. Randomized, controlled trials that administer probiotic treatment to boost mental health have had mixed results. A 2018 meta-analysis of ten clinical trials found that probiotic supplementation to alleviate depressive symptoms had an overall insignificant effect. However, other clinical trials have showed more promising results for probiotics in young adults with stress and anxiety.
All in all, much more research on the gut-brain axis is needed to determine whether the gut microbiome harnessed to treat debilitating mental illnesses. Cause-and-effect relationships must be elucidated, as the effects of disease on intestinal populations remains unclear. Instead of relying on simple associations, experts believe future work should focus on understanding when intestinal dysbiosis causes disease rather than just accompanying it.