The gut–brain axis

The human colon is home to a microbial ecosystem of more than 100 trillion microorganisms that functions as an endocrine organ in its own right. Anyone who wants to understand how body weight and insulin sensitivity are regulated cannot limit their view to the stomach and brain – they must decode the metabolic dialogue of the gut–brain axis.

Anyone who wants to understand the link between gut and brain has to decode the complex bidirectional communication pathway between the microbiome, gut and brain. This motorway, known as the vagus nerve, is not a one-way street. Around 90 per cent of signals travel afferently from the gut to the brain. Conversely, around 10 per cent reach their target efferently, travelling from the brain to the gut.¹

It therefore seems only logical that disturbances in this finely tuned ecosystem – made up of trillions of microorganisms, among other things – can be associated with mental disorders, neurological diseases and, of course, gastrointestinal complaints.²

All four routes can influence the activity of the mesolimbic reward system. The first is the neural route, the vagus nerve. The vagus nerve connects the gut and the brain like a fibre-optic cable. Signals can travel along it in both directions within milliseconds.

Together with the NTS and the nucleus accumbens, GLP-1 forms a central axis for controlling eating behaviour, reward and addiction dynamics. It originates in the NTS, which contains so-called preproglucagon-producing neurons. These are the main source of GLP-1 produced in the central nervous system. The nucleus accumbens, the target of many NTS axons, has a very high density of GLP-1 receptors. When GLP-1 – triggered by food intake or artificially by medication – reaches the receptors in the nucleus accumbens, “cravings” for high-calorie or highly palatable foods decrease. In fact, studies have shown that blocking these receptors can induce larger meal sizes and a greater appetite for sweet foods.

The axis between the NTS and the nucleus accumbens mainly controls hedonic hunger – eating purely for pleasure – rather than homeostatic hunger, which simply covers metabolic energy needs. And it is precisely this constant, pleasure-driven urge towards hedonic hunger that is considered one of the main causes of excess weight and obesity. GLP-1 therefore dampens reward via the mechanisms in the mesolimbic reward system described above. In doing so, it specifically modulates and dampens excessive addiction- or reward-driven dopamine release in the brain.⁵

Depending on molecular size, GLP-1 receptor agonists can cross the blood–brain barrier. This applies above all to the smaller, older molecules in this class of active ingredients. Larger molecules such as the more modern semaglutide are acylated – that is, linked to a fatty acid chain – so that they bind to albumin and thus have a longer half-life. Although this modification physically limits their ability to cross the blood–brain barrier, small amounts can still pass through. However, crossing it is not even strictly necessary: areas of the brain without a classic blood–brain barrier – the circumventricular organs such as the area postrema in the brainstem or the median eminence at the hypothalamus – are equipped with GLP-1 receptors. When GLP-1 binds to these receptors, the resulting neural signals are relayed deep into the brain.⁶

Pharmacology uses synthetic GLP-1 receptor agonists to stimulate the body's own satiety pathways. But the human body has a highly effective system of its own for endogenous incretin release:

At AVOLYA, precision medicine means not supporting the body solely through pharmacology, but restoring its physiological self-regulation. Gradually increasing soluble fibre to at least 30 to 40 grams a day is not a diet cliché but a targeted way of recultivating the body's own satiety biochemistry.