Introduction. The human gut microbiota is currently seen as an important factor that can promote autism spectrum disorder (ASD) development in children. Aim. This study aimed to detect differences in the taxonomic composition and content of bacterial genes encoding key enzymes involved in the metabolism of neuroactive biomarker compounds in the metagenomes of gut microbiota of children with ASD and neurotypical children. Methodology. A whole metagenome sequencing approach was used to obtain metagenomic data on faecal specimens of 36 children with ASD and 21 healthy neurotypical children of 3–5 years old. Taxonomic analysis was conducted using MetaPhlAn2. The developed bioinformatics algorithm and created catalogue of the orthologues were applied to identify bacterial genes of neuroactive compounds in the metagenomes. For the identification of metagenomic signatures of children with ASD, Wilcoxon's test and adjustment for multiple comparisons were used. Results. Statistically significant differences with decreases in average abundance in the microbiota of ASD children were found for the genera Barnesiella and Parabacteroides and species Alistipes putredinis , B. caccae , Bacteroides intestinihominis, Eubacterium rectale , Parabacteroides distasonis and Ruminococcus lactaris . Average relative abundances of the detected genes and neurometabolic signature approach did not reveal many significant differences in the metagenomes of the groups that were compared. We noted decreases in the abundance of genes linked to production of GABA, melatonine and butyric acid in the ASD metagenomes. Conclusion. For the first time, the neurometabolic signature of the gut microbiota of young children with ASD is presented. The data can help to provide a comparative assessment of the transcriptional and metabolomic activity of the identified genes.

Major depressive disorder (MDD) is among the most prevalent mental disorders worldwide. Factors causing the pathogenesis of MDD include gut microbiota (GM), which interacts with the host through the gut–brain axis. In previous studies of GM in MDD patients, 16S rRNA sequencing was used, which provided information about composition but not about function. In our study, we analyzed whole metagenome sequencing data to assess changes in both the composition and functional profile of GM. We looked at the GM of 36 MDD patients, compared with that of 38 healthy volunteers. Comparative taxonomic analysis showed decreased abundances of Faecalibacterium prausnitzii, Roseburia hominis, and Roseburia intestinalis, and elevated abundances of Escherichia coli and Ruthenibacterium lactatiformans in the GM of MDD patients. We observed decreased levels of bacterial genes encoding key enzymes involved in the production of arginine, asparagine, glutamate, glutamine, melatonin, acetic, butyric and conjugated linoleic acids, and spermidine in MDD patients. These genes produced signature pairs with Faecalibacterium prausntizii and correlated with decreased levels of this species in the GM of MDD patients. These results show the potential impact of the identified biomarker bacteria and their metabolites on the pathogenesis of MDD, and should be confirmed in future metabolomic studies.

Nowadays, depressive disorder is spreading rapidly all over the world. Therefore, attention to the studies of the pathogenesis of the disease in order to find novel ways of early diagnosis and treatment is increasing among the scientific and medical communities. Special attention is drawn to a biomarker and therapeutic strategy through the microbiota–gut–brain axis. It is known that the symbiotic interactions between the gut microbes and the host can affect mental health. The review analyzes the mechanisms and ways of action of the gut microbiota on the pathophysiology of depression. The possibility of using knowledge about the taxonomic composition and metabolic profile of the microbiota of patients with depression to select gene compositions (metagenomic signature) as biomarkers of the disease is evaluated. The use of in silico technologies (machine learning) for the diagnosis of depression based on the biomarkers of the gut microbiota is given. Alternative approaches to the treatment of depression are being considered by balancing the microbial composition through dietary modifications and the use of additives, namely probiotics, postbiotics (including vesicles) and prebiotics as psychobiotics, and fecal transplantation. The bacterium Faecalibacterium prausnitzii is under consideration as a promising new-generation probiotic and auxiliary diagnostic biomarker of depression. The analysis conducted in this review may be useful for clinical practice and pharmacology.

The gut microbiota (GM), which contains thousands of bacterial species, is a reservoir of antibiotic resistance genes (ARGs) called resistome. Early life exposure to antibiotics alters significantly the composition and function of the gut microbiota of children, which may trigger symptoms of autism spectrum disorder (ASD). This is because the GM plays an important role in the bidirectional communication between the gut and the brain and influences the brain normal functioning through multiple pathways. The goal of this article is to study the distribution of ARGs in the GM of 3- to 5-year-old healthy children and children with ASD living in Moscow, Russia. The metagenomic analysis of samples from both groups revealed differences in the signatures between them. The signatures consisted of the bacterial genera and aminoglycoside, β-lactam, macrolide, and tetracycline resistance genes that they harbored. Our results show an increase in ARGs in the resistome of the GM of children with ASD. These findings emphasize the negative influence of early-life antibiotic therapy. We found three ARGs, aac(6′)-aph(2′′), cepA-49, and tet(40), which could serve as markers of ASD. The additional functions carried out by the enzymes, encoded by these genes, are being discussed.

Antimicrobial peptides (AMPs) are the main components of the plant innate immune system. Defensins represent the most important AMP family involved in defense and non-defense functions. In this work, global RNA sequencing and de novo transcriptome assembly were performed to explore the diversity of defensin-like (DEFL) genes in the wheat Triticum kiharae and to study their role in induced resistance (IR) mediated by the elicitor metabolites of a non-pathogenic strain FS-94 of Fusarium sambucinum. Using a combination of two pipelines for DEFL mining in transcriptome data sets, as many as 143 DEFL genes were identified in T. kiharae, the vast majority of them represent novel genes. According to the number of cysteine residues and the cysteine motif, wheat DEFLs were classified into ten groups. Classical defensins with a characteristic 8-Cys motif assigned to group 1 DEFLs represent the most abundant group comprising 52 family members. DEFLs with a characteristic 4-Cys motif CX{3,5}CX{8,17}CX{4,6}C named group 4 DEFLs previously found only in legumes were discovered in wheat. Within DEFL groups, subgroups of similar sequences originated by duplication events were isolated. Variation among DEFLs within subgroups is due to amino acid substitutions and insertions/deletions of amino acid sequences. To identify IR-related DEFL genes, transcriptional changes in DEFL gene expression during elicitor-mediated IR were monitored. Transcriptional diversity of DEFL genes in wheat seedlings in response to the fungus Fusarium oxysporum, FS-94 elicitors, and the combination of both (elicitors + fungus) was demonstrated, with specific sets of up- and down-regulated DEFL genes. DEFL expression profiling allowed us to gain insight into the mode of action of the elicitors from F. sambucinum. We discovered that the elicitors up-regulated a set of 24 DEFL genes. After challenge inoculation with F. oxysporum, another set of 22 DEFLs showed enhanced expression in IR-displaying seedlings. These DEFLs, in concert with other defense molecules, are suggested to determine enhanced resistance of elicitor-pretreated wheat seedlings. In addition to providing a better understanding of the mode of action of the elicitors from FS-94 in controlling diseases, up-regulated IR-specific DEFL genes represent novel candidates for genetic transformation of plants and development of pathogen-resistant crops.