Alexander V. Oleskin

Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota

The symbiotic gut microbiota plays an important role in the development and homeostasis of the host organism. Its physiological, biochemical, behavioral, and communicative effects are mediated by multiple low molecular weight compounds. Recent data on small molecules produced by gut microbiota in mammalian organisms demonstrate the paramount importance of these biologically active molecules in terms of biology and medicine. Many of these molecules are pleiotropic mediators exerting effects on various tissues and organs. This review is focused on the functional roles of gaseous molecules that perform neuromediator and/or endocrine functions. The molecular mechanisms that underlie the effects of microbial fermentation-derived gaseous metabolites are not well understood. It is possible that these metabolites produce their effects via immunological, biochemical, and neuroendocrine mechanisms that involve endogenous and microbial modulators and transmitters; of considerable importance are also changes in epigenetic transcriptional factors, protein post-translational modification, lipid and mitochondrial metabolism, redox signaling, and ion channel/gap junction/transporter regulation. Recent findings have revealed that interactivity among such modulators/transmitters is a prerequisite for the ongoing dialog between microbial cells and host cells, including neurons. Using simple reliable methods for the detection and measurement of short-chain fatty acids (SCFAs) and small gaseous molecules in eukaryotic tissues and prokaryotic cells, selective inhibitors of enzymes that participate in their synthesis, as well as safe chemical and microbial donors of pleiotropic mediators and modulators of host intestinal microbial ecology, should enable us to apply these chemicals as novel therapeutics and medical research tools.

Inhibition of photosynthetic oxygen evolution by protonophoric uncouplers

The protonophoric uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP), 2,3,4,5,6-pentachlorophenol (PCP) and 4,5,6,7-tetrachloro-2-trifluoromethylbenzimidazole (TTFB) inhibited the Hill reaction with K3[Fe(CN)6] (but not with SiMo) in chloroplast and cyanobacterial membranes (the I50 values were approx. 1–2, 4–6 and 0.04–0.10 μM, respectively). The inhibition is due to oxidation of the uncouplers on the Photosystem II donor side (ADRY effect) and their subsequent reduction on the acceptor side, ie. to the formation of a cyclic electron transfer chain around Photosystem II involving the uncouplers as redox carriers. The relative amplitude of nanosecond chlorophyll fluorescence in chloroplasts was increased by DCMU or HQNO and did not change upon addition of uncouplers, DBMIB or DNP-INT; the HQNO effect was not removed by the uncouplers. The uncouplers did not inhibit the electron transfer from reduced TMPD or duroquinol to methylviologen which is driven by Photosystem I. These data show that CCCP, PCP and TTFB oxidized on the Photosystem II donor side are reduced by the membrane pool of plastoquinone (Qp) which is also the electron donor for K3 [Fe(CN)6] in the Hill reaction as deduced from the data obtained in the presence of inhibitors. Inhibition of the Hill reaction by the uncouplers was maximum at the pH values corresponding to the pK of these compounds. It is suggested that the tested uncouplers serve as proton donors, and not merely as electron donors on the oxidizing side of Photosystem II.

Lactic-Acid Bacteria Supplement Fermented Dairy Products with Human Behavior-Modifying Neuroactive Compounds

Using high performance liquid chromatography, we established that probiotic Lactobacillus strains ( Lactobacillus helveticus 100ash, L. helveticus NK-1, L. casei K 3 III 24 , and L. delbrueckii subsp. bulgaricus ) grown on two milk-containing nutrient media produce important neuromediators such as biogenic amines, their precursors and deamination products, as well as neuroactive amino acids. The concentrations of biogenic amines (such as catecholamines and, with L. helveticus 100ash, also serotonin) equal or exceed those contained in the bloodstream of healthy adult humans, whereas those of most amino acids are comparatively low, except for gamma-aminobutyric acid (GABA). Of paramount importance is the fact that the bacterial cultures can release micromolar amounts of GABA and L-3,4-dihydroxyphenylalanine (DOPA) into the milk-containing media. It is known that DOPA passes through the gut-blood and the blood-brain barrier and converts into major neurotransmitters (dopamine and norepinephrine) that influence important aspects of human behavior. The data obtained suggest that dairy products fermented by live lactobacilli-containing starters are potential sources of human behavior-modifying substances.

Role of Neurochemicals in the Interaction between the Microbiota and the Immune and the Nervous System of the Host Organism

This work is concerned with the role of evolutionary conserved substances, neurotransmitters, and neurohormones, within the complex framework of the microbial consortium–immune system–nervous system axis in the human or animal organism. Although the operation of each of these systems per se is relatively well understood, their combined effects on the host organism still await further research. Drawing on recent research on host-produced and microbial low-molecular-weight neurochemicals such as biogenic amines, amino acids, and short-chain fatty acids (SCFAs), we suggest that these mediators form a part of a universal neurochemical “language.” It mediates the whole gamut of harmonious and disharmonious interactions between (a) the intestinal microbial consortium, (b) local and systemic immune cells, and (c) the central and peripheral nervous system. Importantly, the ongoing microbiota–host interactivity is bidirectional. We present evidence that a large number of microbially produced low-molecular-weight compounds are identical or homologous to mediators that are synthesized by immune or nervous cells and, therefore, can bind to the corresponding host receptors. In addition, microbial cells specifically respond to host-produced neuromediators/neurohormones because they have adapted to them during the course of many millions of years of microbiota–host coevolution. We emphasize that the terms “microbiota” and “microbial consortium” are to be used in the broadest sense, so as to include, apart from bacteria, also eukaryotic microorganisms. These are exemplified by the mycobiota whose role in the microbial consortium–immune system–nervous system axis researchers are only beginning to elucidate. In light of the above, it is imperative to reform the current strategies of using probiotic microorganisms and their metabolites for treating and preventing dysbiosis-related diseases. The review demonstrates, in the example of novel probiotics (psychobiotics), that many target-oriented probiotic preparations produce important side effects on a wide variety of processes in the host organism. In particular, we should take into account probiotics’ capacity to produce mediators that can considerably modify the operation of the microecological, immune, and nervous system of the human organism.

Mitochondria-targeted quinones suppress the generation of reactive oxygen species, programmed cell death and senescence in plants

This work focuses on the effect of mitochondria-targeted quinones (SkQs) on plants. SkQs with antioxidant properties are accumulated in the mitochondria of pea cells and suppress the generation of reactive oxygen species. At nanomolar concentrations, SkQs prevented the death of pea leaf epidermal or guard cells caused by chitosan, bacterial lipopolysaccharide or KCN. The protective effect of SkQs was removed by a protonophoric uncoupler. SkQs at micromolar concentrations inhibited the O2 evolution by illuminated chloroplasts and stimulated the respiration of mitochondria. SkQs slowed down the senescence and the death of Arabidopsis thaliana leaves and improved the wheat crop structure.

Testing Neurotransmitters for Toxicity with a Luminescent Biosensor: Implications for Microbial Endocrinology

Qualitative and quantitative analysis of individual carotenoids content and composition are complicated, time consuming and in fact very costly. The crucial and vital part is the availability and reliability of the pure standards. Most of the individual carotenoids are commercially available either in natural or synthetic form but they are quite expensive and some of it not available in the market anymore. These problems strongly associated with the accuracy and reliability of High Performance Liquid Chromatography (HPLC) analysis data. Therefore, this study aimed to set up an analytical scheme of obtaining b-carotene standard from the leaves of Morinda citrifolia as one of the carotenoid standards for HPLC analysis. M. citrifolia has been selected due to its abundance throughout the year with tropical climate. The scheme via open column chromatography (OCC) established that the purity of β-carotene standard was 97% and the coefficient of correlation was 0.9923. However after 30 day storage period of time, the purity decreased to 95.46%. Although these had an effect on the carotenoid standard stability but it can be a reliable source of β-carotene standard for HPLC analysis as well as active pharmaceutical ingredient for cosmeceutical, nutraceutical, food and beverage industries.

The Dibromothymoquinone Effect on Membrane Potential Generation in Rhodospirillum rubrum Chromatophores

2,5-Dibromo-3-methyl-6-isopropyl benzoquinone (DBMIB) inhibits the light-dependent membrane potential generation in Rhodospirillum rubrum chromatophores. The inhibition is relieved by electron donors and is obviously due to oxidation of the photosynthetic electron transfer chain components. In addition, high DBMIB concentrations elicit another effect probably caused by disruption of quinone functions in chromatophores. However, in quinone-depleted chromatophores and proteoliposomes containing the P-870 reaction center and light-harvesting antenna complexes, DBMIB stimulates membrane potential generation in the light, probably restoring some of the quinone-dependent processes in the membrane. DBMIB inhibits the inorganic pyrophosphate- and ATP-induced membrane potential generation in chromatophores.