**Abstract**

In conditions of severe gut dysbiosis, there is a risk of developing diseases of the host organism in general and of the brain in particular, as evidenced by a growing number of studies. This chapter focuses on several groups of low-molecular-weight compounds that originate primarily from the gut microbiota. It discusses the results of experimental and clinical studies on the effect of microbial metabolites (such as short-chain fatty acids, phenolic metabolites of tyrosine, indolic metabolites of tryptophan, trimethylamines) on the brain. Several studies have proven that the microbial metabolite profiles in the gut and serum are interlinked and reflect a disruption of the gut microbial community. Using 16S ribosomal RNA gene sequencing, it was found that the gut microbiota of patients with positive or negative dynamics of neurological status differ taxonomically. The chapter also presents data obtained from animal germ-free (GF) models. Many researchers would like to consider the gut microbiota as a new therapeutic target, including for the treatment of brain diseases, stroke prevention, reduction of neuroinflammation, and more successful neurorehabilitation of patients.

**Keywords:** human microbiome, microbial metabolites, brain damage, gut microbiota dysbiosis, mental health, Alzheimer's disease, autism, stroke, critical ill patients, neurorehabilitation

### **1. Introduction**

The human gut microbiome is a community of trillions of microorganisms that produce and use many molecules of microbial origin. Normally, the epithelial– immune–gut barrier supports homeostasis in the host body. The importance of the function of the gut microbiota for the host organism allows us to consider it as a large but "invisible organ" [1]. In conditions of severe gut dysbiosis, there is a risk of developing diseases of the host organism in general and of the brain in particular, as evidenced by a growing number of studies [2, 3]. The relevance of studying the relationship between the human microbiome and the brain is confirmed by a 20-fold increase in the number of publications on this topic in the PubMed database over the past 10 years (**Figure 1**).

Today, modern technologies allow us to identify hundreds of types of microorganisms in the human gut. Various microbial metabolites are also available for measurement in biological material samples, including feces, blood, urine, cerebrospinal fluid (CSF), and so on [1–3]. Thus, the possibilities of determining microbiota metabolites have expanded to studying their role both in healthy people and in patients with various diseases.

#### **Figure 1.**

*Graph showing a 20-fold increase from 2010 to 2019 in the number of publications on the relationship between the human microbiome and the brain, according to PubMed. Keyword search results: microbiome and brain, microbiome and behaviour.*

The results of numerous studies show that the gut microbiota affects the development of diseases of the central nervous system (CNS), including motor and behavioral disorders, neurodegenerative diseases, and cardiovascular and neuroimmune-mediated disorders [4–6]. The existence of the microbiome–gut–brain axis is now generally recognized. There are several different mechanisms of gut bacteria action on the nervous system, including changes in the activity of the stress-related hypothalamic–pituitary–adrenal axis, vagus nerve stimulation, and the secretion of short-chain fatty acids (SCFAs), which can activate microglial cells and affect the permeability of the blood–brain barrier. Evolutionarily conserved signals that are involved in the communication between microbiota and the host, which include different neuroactive substances, are known as neurochemicals [7].

This chapter focuses on several groups of low-molecular-weight compounds that originate primarily from the gut microbiota; their involvement in the interaction of the microbiota and the brain has been studied in various experimental and clinical studies.
