A gut feeling on depression treatment

Published 05 August 2020

It's an exciting breakthrough in the study of how microbes influence the effectiveness of medication taken by some 10% of people across the Western world.

In recent years, scientists have discovered that the microbe communities in our lower intestine (known as the gut microbiota or microbiome) play a significant role in the occurrence of major depressive disorder and other mood and anxiety disorders. Now, the UNE scientists believe the richness and diversity of the gut microbiome may also determine whether or not anti-depressant treatments are effective  and the results are as individual as we are.

"One of the issues for the treatment of depression is that anti-depressants are only effective in about 50% of people and we have been working to find out why," says Dr Gal Winter, from UNE's School of Science and Technology. "Our work has shown that anti-depressants may cause either increases or decreases in the diversity and abundance of gut microbes, which alters the composition and function of the overall gut microbiome. Such changes could make drug treatments more or less effective."

Our gut microbiome is a complex ecological community comprising trillions of microbes - mostly bacteria, but also fungi (particularly yeasts) and some viruses. The make-up of this community and the way it functions is unique to each of us, however one thing is consistent  the microbiota and its metabolic by-products have been found to have a direct affect on the human brain.

"Micro-organisms are very sensitive; they respond to any change in their environment, especially when you are taking medication for a long time," Dr Winter says. "Some microbes can metabolise a drug like Prozac, and the drug acts as a growth promoter that enhances their population. For other microbes, it's like an antibiotic that inhibits growth. Metabolism of the drug by even one microbial strain will have a rolling effect on the rest of the microbial community and lead to changes in its diversity."

In fact, those changes are as unique as our personal complement of microbes.

"In our experiments, taking faecal samples from individuals and culturing them in the lab with different concentrations of Prozac , we found that the response is very individualised," Dr Winter says. "We still don't know exactly what this means, but it could explain why treatment is only successful in half of all people for whom anti-depressants are prescribed. It points to the fact that the gut biome is important not only for the onset but also the treatment of depression and mood disorders."

Calculating the concentrations of the drug at different points along the digestive tract showing how much of the drug remains unabsorbed and where will hopefully provide an important reference point for future research.

"We are just scratching the surface here, but establishing this benchmark for recommended doses of Prozac could lead to better diagnosis and treatment success," Dr Winter says. "For instance, in future we might be able to look at the gut microbiota and predict the success of a particular drug treatment, depending on a person's composition of microbes. It suggests that the treatment of major depressive illnesses needs to be far more personalised."

Generally speaking, the more diverse the array of microbes in a person's gut, the healthier they are. Food, exercise and mood play a significant role, and it's looking like all three are linked via the common gut microbiome.

"When we eat, we absorb most of the nutrients in the small intestine, and what is left goes to the large intestine to feed our microbes," Dr Winter says. "The more diverse your nutrition is, the more food you can deliver to different types of microbes.

"We are making tremendous progress in terms of our understanding of the gut microbiome and I believe that it won't be too long before there is a routine test available, to assess where you are at and what you need to work on in terms of the diversity and health of your gut microbiome. If you have a specific condition that is gut related, understanding the sequences and identity of your gut microbiota will obviously have even greater impact."

The research team also included Dr Adam Hamlin, senior researcher and neuroscientist at UNE, and Bachelor of Science graduate Abigail McGovern, who worked on the research as part of her undergraduate studies.

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