Zonulin — regulation of tight contacts in the brain and intestine — facts and hypotheses

Abstract

In recent years, the interrelationship between the brain and the gut has become an area of high scientific interest. The intestine is responsible not only for digestion, as it contains millions of neurons, its own immune system, and affects the emotional and cognitive processes. The relationship between the gut and the brain suggests that the processes carried out by the gut microbiota play a significant role in the regulation of brain function, and vice versa. A special role here is played by intercellular tight junctions (TJ), where the zonulin protein holds an important place. Zonulin, an unprocessed precursor of mature haptoglobin, is the only physiological modulator of intercellular TJ that can reversibly regulate the permeability of the intestinal (IB) and blood-brain (BBB) barriers in the human body. BBB disruption and altered microbiota composition are associated with many diseases, including neurological disorders and neuroinflammation. That is, there is a gut-brain axis (GBA) — a communication system through which the brain modulates the functions of the gastrointestinal tract (GIT) and vice versa. GBA is based on neuronal, endocrine, and immunological mechanisms that are interconnected at the organismal, organ, cellular, and molecular levels.