The problem

Modern populations are increasingly overfed, malnourished, sedentary, sunlight-deficient, sleep-deprived, and socially-isolated.This seems to come with an impact for both their physical and mental health. Available research data tend to accuse modern environments of causing an epidemic of depression. With 1 in 20 adults experiencing serious mental illness in 2021 in the U.S., it is now, more than ever, the right time to drastically change the lives of people suffering from mental health disorders.Apart from this, according to the World Health Organization (WHO), anxiety and depression prevalence increased by 25% globally during the COVID-19 outbreak.

Depressive disorder (also known as depression) is a common mental disorder. It involves a depressed mood or loss of pleasure or interest in activities for long periods of time. Depression is different from regular mood changes and feelings about everyday life. It can have an impact on all aspects of life, including interactions with family, friends and community. It can result from or lead to problems at school and at work.

Some Statistics

Depression affects a significant portion of the population, with approximately 3.8% of people experiencing this condition. Among adults, the prevalence is around 5%, with men accounting for 4% and women for 6%. The occurrence of depression is even higher among adults over the age of 60, affecting about 5.7% of this age group. 10% of pregnant women and women who have just given birth worldwide experience depression. Globally, an estimated 280 million individuals are affected by depression. Depression can lead to suicide. Tragically, suicide claims the lives of over 700,000 individuals annually, making it the fourth leading cause of death among 15 to 29-year-olds.

Current Treatment

There are effective treatments for depression. These include psychological treatment and medications.

SSRIs are currently the first choice medicine for depression. However, antidepressants have many side effects with:

• sexual dysfunctioning
• sleepiness (Drowsiness) and
• weight gain

being the most common, leading many to stop their treatment.

Despite the importance of maintenance treatment for depression, many patients discontinue antidepressant medication earlier in the course of treatment, with this being a major obstacle for effective treatment of MDD.

Our Idea

Our project is based on the gut-brain axis. As explained in the Background section, the gut-brain axis offers bidirectional communication between the central and the enteric nervous system. In this interaction, specific groups of gut microbiota play an important role.

More specifically, the decrease of taxa that produce SCFAs result in the reduction of SCFAs. This gut dysbiosis is a major characteristic of various psychiatric disorders, including depression.

We are proposing that by interfering with the concentration of SCFAs in the gut, we could possibly offer a personalized, targeted therapy for depression.

DEPREGUT is about designing a probiotic that aims to increase the concentration of SCFAs' in the gut and, in this way, treat depression.

DEPREGUT

DEPREGUT is a genetically modified probiotic (Lacticaseibacillus rhamnosus GG) that produces two short chain fatty acids (SCFAs), acetate and butyrate. SCFAs trigger enterochromaffin cells (ECs) in the gut to produce serotonin by enhancing TPH1 gene expression. L. rhamnosus GG is a broadly used probiotic and is known for its therapeutic anti-depressant potential. Basically, Depregut uses SCFAs to produce serotonin in the gut.

How does Depregut alleviate depressive symptoms?

Under certain circumstances, such as stress, proinflammatory stimuli etc., tryptophan metabolism leans towards kynurenine rather than serotonin, leading to a higher concentration of kynurenine and its metabolites: kynurenic acid, anthranilic acid and quinolinic acid. Quinolinic acid is a neurotoxic agent and is alleged to cause depression. So, DEPREGUT redirects the tryptophan metabolic pathway towards serotonin instead of kynurenine. The importance of this is twofold: first, this cascade of the kynurenine metabolism is restricted and so do the negative effects from its metabolites, and second, 5-hydroxytryptophan can cross the blood-brain barrier and produce serotonin in the brain, following the tryptophan-serotonin pathway as described above. This way the serotonin produced there serves as the neurotransmitter related to mood and offers a more direct way to deal with depression.

DEPRETECT

At the same time, taking treatment of depression to another level, our team is also developing DEPRETECT. This machine learning application offers an AI-enabled chatbot that can supervise the patient during the time between their appointments with their mental health specialists. This machine learning application can prove to be immensely valuable for the detection and monitoring of depression and its associated therapy. It offers users a chatbot that engages them in conversations about their daily life. The user's responses are then assessed using artificial intelligence techniques for natural language processing to determine if they may be experiencing symptoms of depression. You can read more about this in the Software section.

So, combining the probiotic that we are designing with the use of the DEPRETECT digital solution, DEPREGUT offers a comprehensive set of tools for the treatment of depression.

References

Food and Drug Administration (FDA), November 2019.

Hidaka, B. H. (2012). Depression as a disease of modernity: explanations for increasing prevalence. Journal of affective disorders, 140(3), 205-214.

Jung, W. Y., Jang, S. H., Kim, S. G., Jae, Y. M., Kong, B. G., Kim, H. C., ... & Kim, C. R. (2016). Times to discontinue antidepressants over 6 months in patients with major depressive disorder. Psychiatry Investigation, 13(4), 440.

Kupcova, I., Danisovic, L., Klein, M., & Harsanyi, S. (2023). Effects of the COVID-19 pandemic on mental health, anxiety, and depression. BMC psychology, 11(1), 1-7.

National Health Service (NHS), November 2021.

Ramachandraih, C. T., Subramanyam, N., Bar, K. J., Baker, G., & Yeragani, V. K. (2011). Antidepressants: from MAOIs to SSRIs and more. Indian journal of psychiatry, 53(2), 180.

World Health Organization (WHO), March 2023.