TRAJECTORY OF AGE-ASSOCIATED CHANGES IN THE MICROBIAL COMMUNITY OF THE SMALL INTESTINE OF HEALTHY PERSONS IN THE CONTEXT OF METAORGANISM

The study of the small intestine microbiota in humans is difficult due to the low availability of biomaterial. Non-invasive methods of metabolomics and bioinformatic data analysis can expand our understanding of the structure and role the small intestine microbiota in maintaining homeostasis of the body. The article presents the trajectory of age-related changes in the microbial community of the small intestine in healthy individuals in the context of interaction with the cytokine and neuroendocrine systems within the metaorganism, using the methods of gas chromatography - mass spectrometry of microbial markers (GCMS MM) and optimal scaling. 110 practically healthy individuals: children, adults and elderly, were included into the study. The number of the main types of small intestine microbiota (Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Fusobacteria) was determined in peripheral blood by the GCMS MM method. To construct the trajectories of changes in the small intestine microbiota and indicators of the cytokine and neuroendocrine systems with age, the optimal scaling technique based on the multivariate Gifi transformation (CATPCA method) was used. It was found, that the bacterial community of the small intestine of both children and the elderly and seniors has a significantly low total number of microorganisms, due to the low content of bacteria of the types Firmicutes and Actinobacteria against the background of a high number of representatives of the types Proteobacteria and Fusobacteria, in comparison with similar indicators in adults. Assessment of the trajectory of age-associated changes in the microbiota of the small intestine showed: 1) children have strong dynamic fluctuations in the number and connections within the community of microorganisms against the background of the formation of connections between the main regulatory systems of the metaorganism – immune and neuroendocrine; 2) adults present the plasticity and consistency of the functioning of the immune and nervous systems, what determine the state of dynamic balance of the small intestine microbiota; 3) healthy aging characterize by hight degree of cooperation between the main members of the bacterial community, which ensures the stability of the system at a new level, as one of the mechanisms of adaptation of the organism. Thus, the using the methods of GCMS MM and optimal scaling, allows us to expand our understanding of the age-associated trajectory of changes in the small intestine microbiota and its cooperation with the immune and neuroendocrine systems within the metaorganism, which can be used in the development of new methods of therapy of an infectious and non-infectious diseases.

Obesity as a Neuroendocrine Reprogramming

Obesity represents a health problem resulting from a broken balance between energy intake and energy expenditure leading to excess fat accumulation. Elucidating molecular and cellular pathways beyond the establishment of obesity remains the main challenge facing the progress in understanding obesity and developing its treatment. Within this context, this opinion presents obesity as a reprogrammer of selected neurological and endocrine patterns in order to adapt to the new metabolic imbalance represented by obesity status. Indeed, during obesity development, the energy balance is shifted towards increased energy storage, mainly but not only, in adipose tissues. These new metabolic patterns that obesity represents require changes at different cellular and metabolic levels under the control of the neuroendocrine systems through different regulatory signals. Therefore, there are neuroendocrine changes involving diverse mechanisms, such as neuroplasticity and hormonal sensitivity, and, thus, the modifications in the neuroendocrine systems in terms of metabolic functions fit with the changes accompanying the obesity-induced metabolic phenotype. Such endocrine reprogramming can explain why it is challenging to lose weight once obesity is established, because it would mean to go against new endogenous metabolic references resulting from a new “setting” of energy metabolism-related neuroendocrine regulation. Investigating the concepts surrounding the classification of obesity as a neuroendocrine reprogrammer could optimize our understanding of the underlying mechanisms and, importantly, reveal some of the mysteries surrounding the molecular pathogenesis of obesity, as well as focusing the pharmacological search for antiobesity therapies on both neurobiology synaptic plasticity and hormonal interaction sensitivity.

STATE OF NEUROENDOCRINE SYSTEMS DURING ACTIVATION AND INHIBITION OF CENTRAL CHOLINERGIC SYSTEMS IN BRAIN INJURY

The aim of the study was to determine the state of the neuroendocrine systems during the activation and inhibition of the central cholinergic systems (CChS) in traumatic brain injury (TBI) and their effect on mortality and neurological deficit. TBI was applied by the standard method with the free fall of metal weight on the fixed animal head. 161 white male Wistar rats were divided into three groups: in the 1st group, 0.5 ml of Ringer’s solution was injected intraperitoneally before injury (control), in the 2nd – solution of choline alfoscerate at a dose 6 mg/kg (CChS activation), in the 3rd – solution of biperidene hydrochloride at a dose 0.6 mg/kg (CChS blockade). Neurological deficits were assessed using the 100-point Todd scale. In the blood was determined the content of Adrenocorticotropic (ACTH) and Thyroid-Stimulating Hormones, Corticosterone (Cs), free Thyroxine and Triiodothyronine (fT3) by the enzyme immunoassay. It was established that in the acute period of TBI, post-traumatic stress central hypercortisolism is formed with an increase in blood levels of ACTH and Cs, and central hypothyroidism with a predominant decrease in blood fT3. The CChS activation significantly reduced mortality and neurological deficit, which was accompanied by moderate activation of ACTH and Cs and no effect on the thyroid system. The CChS blockade led to the suppression of the post-traumatic reaction of ACTH and Cs activation and the development of deep central hypothyroidism against the significant neurological deficit. Thus, the important role of CChS in the implementation of the post-traumatic stress reaction of the neuroendocrine system has been established, and the possibility of using pharmacological stimulation of the CNS with central cholinomimetics has been substantiated.

Congruency and phenotypic plasticity of immune and nervous systems in children with autism spectrum disorders compared to schizophrenia spectrum disorders”, Medical Immunology (Russia)

According to new views on communication ways and principles in the main regulatory systems of the body, i.e., immune and neuroendocrine, there is a risk for disintegration of pathways and structures in these systems which may underlie disorders such as autism-spectrum disorders (ASD) and schizophreniaspectrum disorders (SSD). Both disorders are classified as neurodevelopmental disorders, with unclear etiology and partially overlapping pathophysiological developmental mechanisms. Diagnosis of ASD and SSD is based on patterns of clinical symptoms/syndromes that demonstrate high heterogeneity and similarity. Therefore, it is very important to find the ways of discerning children with ASD from those with SSD. Our aim was to identify peripheral activity indexes for immune and neuroendocrine systems, and their integration for usage as information hubs of congruency and phenotypic plasticity of these systems in children with ASD, as compared to SSD patients. The levels of 14 indexes of the immune and neuroendocrine systems in blood plasma were determined in 82 children with ASD, 9 children with SSD and 45 children with typical neurodevelopment (TD). To assess peripheral activity of the immune and neuroendocrine systems and their relationships, we applied a multivariate exploratory analysis using a method of nonlinear principal components. The following results were obtained: (1) absence of differences in proinflammatory cytokines between ASD and TD children; (2) patients with SSD have significantly higher values of IL-6 and IFNγ, and lower values of IL-1β, TNFα and IL-10 in blood plasma compared to children with ASD and TRD; (3) the level of neurohormones in children with ASD is in accordance with physiological reference values. The children with SSD have lower levels of epynephrine and dopamine compared to ASD and TD, respectively; (4) integration degree of regulatory systems assessed by principal component analysis has shown the following: (4.1) TD children have strong correlations within each of the systems and between them, thus showing their communicative abilities and plasticity, characteristic of normal values; (4.2) In SSD children, minimal numbers of strong relations were demonstrated within the cytokine system; (4.3) The children with ASD exhibited two clusters: one of them had a complete similarity with TDC, in terms of tension and assortment of immune and neuroendocrine indices; the other one presented low coupling between the parameters of regulatory systems, similar to the children with SSD; (4.4) Analysis of peripheral indices of cytokine and neuroendocrine systems for clusters 1 and 2 in children with ASD compared to children with SSD and TD demonstrated that, in children with ASD of cluster 1, the indices did not differ from TDC, except of epinephrine, ACTH, kynurenine, and tryptophan. In the children with ASD of cluster 2, the values of the indices are equal to children with SSD, except of dopamine and tryptophan. Thus, we have shown phenomenon of transdiagnostic clustering, i.e., allocation of two clusters among ASD children. One of them is similar to levels of indices and connections between the immune and neuroendocrine systems with TD, and another cluster is similar to SSD children. Therefore, they could be potentially useful as diagnostic criteria when discriminating the two disorders.