According to the World Health Organisation (WHO), 5% of the global population suffered from depression and/or anxiety in 2019 [1], and the rate of these has risen up by up to 25% since the beginning of the COVID-19 pandemic [2]. In fact, globally 20% of children and adolescents are said to be diagnosed with any mental health condition [3]. Moreover, there is a yearly estimated cost of US$ 1 trillion due to depression and anxiety [3].
Depression (the subthreshold mood state in the context of mood fluctuations) in young people has experienced an increase regarding its concern due to its occurrence during a period of fast social, emotional and cognitive development, along with key life transitions [4,5], affecting females after adolescence as much as two times to males [6,7]. Although there are multiple meta-analyses of risk factors, the reasons why the prevalence of depression has risen and what needs to be done to reduce depression at a population level are unknown and are a priority for the next generation of research [8].
Anxiety disorders (the disproportionate feeling evoked from the anticipation of a real or imaginary future threat or danger) form the most common type of mental diseases, and are high in prevalence, chronicity and comorbidity [9,10]. Anxiety disorders usually comprise separation anxiety, selective autism, specific phobias, social anxiety disorder, generalised anxiety disorder, panic disorder and agoraphobia [9]. Globally underdiagnosed and undertreated [11], ironically, the consumption of benzodiazepines remains excessive, and the prescriptions of this kind of drug are maintained for periods greater than recommended in different parts of the world, especially in developed Western countries [12], leading to the landscape we now face.
However, most of the currently available drugs lack therapeutic requirements, resulting in an inadequate response that occurs in approximately 30% patients [13]. Thus, deeply exploring the pathogenesis of mental illnesses and the development of potential solutions are both imperative and necessary [14].
Biologically, serotonin is the key neurotransmitter in the Central Nervous System (CNS), and it is the main responsible for mood regulation, among other functions [15]. In fact, a link between lowered serotonin and depression was first suggested in the 1960s [16]. Increased synaptic serotonin availability in the CNS is associated with elevated mood and reduced anxiety [17]. Gut microbiota likely regulates intestinal motility by acting directly on specialised gut cells, rather than on serotonin-producing enteric neurons [18]. Nevertheless, intestinal microbiota also plays a crucial role in the development and maintenance of the serotonergic network within the Enteric Nervous System, which in turn, is essential for the development and survival for other enteric neuron populations [19].
Aside from the canonical regulation of the gastrointestinal function [20], the gut microbiota has demonstrated to play roles in mood and cognition regulation [21]. Indeed, accumulating evidence has revealed that the brain may impact the gut microbiota, which may, in turn, shape the brain via the microbiota-gut-brain axis [22]. Dysfunction of the microbiota-gut-brain axis may play an important role in the pathogenesis of a subset of mental illnesses [23]. In fact, psychobiotics, a novel class of probiotics bearing the ability to deliver mental health benefits in a number of situations, have risen up as a potential solution to deal with these diseases [24].
In humans, serotonin is synthesised in serotonergic terminals from tryptophan [25, 26]. Where via enzymes Tryptophan 5-Hydroxylase 1 (TPH, performing the rate-determining step of serotonin biosynthesis) and Human Aromatic-L-amino-acid decarboxylase (TDC) tryptophan transforms into 5-Hydroxytryptamine, also known as serotonin.
Circular economy strategies comprise a regenerative system in which resource input and waste, emission, and energy leakage are minimised by slowing, closing and narrowing material and energy loops. Achievable via long-lasting design, maintenance, repair, reuse, remanufacturing, refurbishing and recycling [27]. That way, it is the responsibility of each proposal to determine the approach that will bi given to their initiative to the environment-society-economy nexus [28].
Commoner [29] explored circularity in terms of closing the circle between economics, technology, environment and government. Here we set out the idea of the circularity of a functional, sustainable economy relating to the resonance between landscape, society and economics, wherein sustainability can only be delivered within the framework of the Earth system. And thus, for the circular economy to truly aspire to contributing to a sustainable role, it must be integrated within the Earth system, in terms of both the social and environmental contexts. Here, technology has an important part to play, not in mimicking nature, but as a portal of feedback, allowing our activities to dynamically respond to the emergent, nonlinear properties of the Earth system [28, 30].
A circular economy constantly reuses and recycles materials through a variety of applications, minimising material inputs to the economy and maximising utility from each of these inputs [31]. Circular bioeconomy generally incorporates the following features [32, 33, 34, 35, 36]:
The use of inputs that can be reused and/or over multiple applications, and ultimately returned to nature.
A focus on long-lasting or durable products.
Selection of renewable forms of energy to power systems, including waste-to-energy options.
Organisation across multiple sectors to meet the needs of human populations at local or regional scales, rather than around individual sectors.
Our project consists of the synthesis of serotonin from tryptophan using modified E. coli strains. As mentioned above, two enzymes are necessary for the transformation of tryptophan into serotonin; TPH, which catalyses the reaction of tryptophan to 5-hydroxytryptophan; and TDC, which transforms this intermediate product into serotonin. Here in the first steps of this multi-year-long project, we aim to first produce the enzymes individually in two separate bacterial strains, to then track serotonin synthesis starting from by-product-coming tryptophan.
As a way to optimise the serotonin synthesis process, we propose a kinetic study of the two reactions, the steps of which are detailed below. This study would allow us to know the reaction times and enzyme concentrations necessary to obtain a given reaction yield.
As a source of tryptophan we propose food industry by-products, such as milk whey and broccoli waste, because they are very rich in this amino acid and because they are a by-product of agricultural and livestock enterprises in our region.
The strength of our project lies in the opportunity to solve two problems at once and giving them a solution simultaneously.
On the one hand, we are, by means of this project, facing a prominent issue such as mental health diseases, a global problem particularly impactful in our region. When defining the work topic, we wanted to do something related to the consequences of the pandemic, and the worsening of mental health as a result of covid-19 seemed to us to be a problem that needed to be adressed (https://www.unicef.org/es/comunicados-prensa/efectos-nocivos-covid19-salud-mental-ninos-ninas-jovenes-punta-iceberg).
On the other hand, and for what we have perceived during our formation along the project, there is a lack of initiatives and knowledge regarding by-product leverage. Circular economy is a powerful tool that is useful for us to increase the value of many of these for farmers and ranchers in our region, thus allowing us to give a great boost to the local economy. In addition, circular economy strategies allow us to reduce the consumption of scarce raw materials, with the economic and environmental benefits this entails.
Our project, therefore, tries to find an innovative solution to a global problem, but with a local impact, such as mental health, while helping to promote the growth of primary producers in our region. Moreover, in a context like the current one in which we have gone from seeking globalization to moving towards decentralization, our project allows us to provide a local solution.Therefore not making us dependent on third parties against a problem that is global but also has a major local impact.
In addition, we believe that our project has been a great opportunity to disseminate the importance of both mental health and the circular economy, in so far that technical advances are not useful if their relevance is not transmitted to society. Especially as far as mental health is concerned, we believe that this is still a taboo subject that needs to be disclosed with the appropriate rigour (https://www.unicef.es/noticia/la-salud-mental-no-debe-ser-un-tabu). So that our contribution to these areas has not only been technical but we have also helped to make them visible by talking about them in all our human practices.
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