BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.
- MeSH
- Dysbiosis metabolism MeSH
- Blood-Brain Barrier metabolism MeSH
- Humans MeSH
- Brain * metabolism MeSH
- Neurodegenerative Diseases * microbiology metabolism MeSH
- Brain-Gut Axis * physiology MeSH
- Probiotics MeSH
- Aging * MeSH
- Gastrointestinal Microbiome * physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Breast milk, as the optimal food for infants and young children, contains all the components necessary for proper growth and development. It is a rich source of both essential nutrients and biologically active factors, making breast milk a unique food with scientifically proven health-promoting properties. Among the entire range of biologically active factors, breast milk microorganisms and prebiotic factors, in the form of breast milk oligosaccharides, occupy an important place. The aim of our research was to determine the occurrence of bacteria with probiotic potential, belonging to the Lactobacillaceae family, in the environment of breast milk and breast milk oligosaccharides. The study included 63 human milk samples from breastfeeding women at various stages of lactation. Microorganism identification based on culture tests and MALDI TOF/MS, macronutrient analysis using the MIRIS human milk analyser, as well as analysis of human milk oligosaccharides using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry were performed. The results have shown that breast milk from different breastfeeding women is characterized by great diversity in terms of the presence of Lacto-bacillaceae bacteria in its microbiological composition. These bacteria were present in 22.2 % of the tested breast milk samples. Analysis of the human milk oligosaccharide profile revealed a slightly higher content of prebiotic factors in breast milk samples containing Lactobacillaceae, including 2'-fucosyllactose, oligosaccharide occurring in the highest amount in breast milk.
An organism is considered "alive" if it can grow, reproduce, respond to external stimuli, metabolize nutrients, and maintain stability. By this definition, both mitochondria and viruses exhibit the key characteristics of independent life. In addition to their capacity for self-replication under specifically defined conditions, both mitochondria and viruses can communicate via shared biochemical elements, alter cellular energy metabolism, and adapt to their local environment. To explain this phenomenon, we hypothesize that early viral prototype species evolved from ubiquitous environmental DNA and gained the capacity for self-replication within coacervate-like liquid droplets. The high mutation rates experienced in this environment streamlined their acquisition of standard genetic codes and adaptation to a diverse set of host environments. Similarly, mitochondria, eukaryotic intracellular organelles that generate energy and resolve oxygen toxicity, originally evolved from an infectious bacterial species and maintain their capacity for active functionality within the extracellular space. Thus, while mitochondria contribute profoundly to eukaryotic cellular homeostasis, their capacity for freestanding existence may lead to functional disruptions over time, notably, the overproduction of reactive oxygen species, a phenomenon strongly linked to aging-related disorders. Overall, a more in-depth understanding of the full extent of the evolution of both viruses and mitochondria from primordial precursors may lead to novel insights and therapeutic strategies to address neurodegenerative processes and promote healthy aging.
- MeSH
- Energy Metabolism MeSH
- Humans MeSH
- Mitochondria * metabolism MeSH
- Origin of Life * MeSH
- Viruses * metabolism genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Juvenil, a nontoxic extract of bovine blood, is registered as a dietary supplement having no side effects. It contains a broad spectrum of free amino acids, as well as small proteins and oligopeptides (molecular weights up to 10 kDa), various nucleotides, and small amounts of phospholipids. The complex of these exclusively natural components has been shown to support physiological responses of supplemented organisms.Juvenil has been studied for several decades using a wide range of both experimental and clinical studies. Analyses have shown that it acts directly neither on individual functional systems of the body nor on individual metabolic processes. Current findings indicate that modulatory effects of Juvenil occur through modulation of gut microbiota composition, which is associated with the modulation of microbiota-gut-brain axis signaling. In murine model that modulatory effect is reflected in the expression of an early activation c-Fos marker in specific parts of the brain.In this review we present a set of findings about Juvenil, which has a wide range of positive effects on the functional systems of organisms. These effects can be used to strenghten the resistance, immunity, and regeneration of human beings. According to its effects Juvenil can be classified as a psychobiotics.
- MeSH
- Amino Acids metabolism MeSH
- Biological Products pharmacology MeSH
- Immune System * drug effects MeSH
- Humans MeSH
- Nucleotides metabolism MeSH
- Oligopeptides metabolism MeSH
- Brain-Gut Axis physiology drug effects MeSH
- Dietary Supplements * MeSH
- Prebiotics MeSH
- Probiotics pharmacology MeSH
- Gastrointestinal Microbiome * drug effects MeSH
- Check Tag
- Humans MeSH
Chladná část roku je u dětí spojena se zvýšeným rizikem respiračních virových infekcí. Je to důsledkem přirozené cirkulace některých virů v zimním období. Podstatnou příčinou je rovněž snížená obranyschopnost dětí. Ta má komplexní důvody. Zdůraznit můžeme negativní vliv životního stylu převážné většiny dětí v kombinaci s nutričně nevyváženou stravou. Úpravou životního stylu, především dostatkem nočního spánku, v kombinaci s pohybovou aktivitou a otužováním, lze zvýšit obranný potenciál dětí. Další možností je optimalizace jídelníčku dětí, který by měl obsahovat v dostatečné míře potřebné živiny nutné pro rozvoj imunitní reakce. Obranyschopnost je významně zesílena dostatečným příjmem vitaminu C, vitaminu D a zinku. Slizniční i systémovou imunitu pozitivně ovlivňují látky charakteru prebiotik a zdraví prospěšné mikrobi, přijímané v potravě, probiotika.
Cold season is characterized by increased presence of respiratory viral infections. It is cost by seasonal increase in presence of viruses with substantial contribution of decreased protective immunity of children. This is the result of complex interplays between immunity and other body systems. One from the major contributors is unhealthy lifestyle of children characterized by low physical activity, disturbances in night sleep and inadequate nutrition. Changes foccusing on lifestyle in combination with physical activity can enhance protective potential of children. This could be also improved by intervention into the nutrition. Nutrition has to contain sufficient sources of basic nutrients to mount optimal immune response. Effectivnes of protective immunity could be also enhanced by supplementation with vitamin C and D, prebiotics and probiotics and zinc.
- MeSH
- Cholecalciferol immunology deficiency MeSH
- Child MeSH
- Ergocalciferols immunology deficiency MeSH
- Respiratory Tract Infections immunology prevention & control MeSH
- Ascorbic Acid therapeutic use MeSH
- Humans MeSH
- Disease Resistance * immunology MeSH
- Immunity, Innate immunology MeSH
- Diet, Food, and Nutrition MeSH
- Healthy Lifestyle MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Střevní mikrobiota může hrát klíčovou roli v rozvoji řady metabolických onemocnění včetně diabetu 2. typu (T2D). Dieta s vysokým obsahem tuků a jednoduchých cukrů vede ke snížení diverzity složení mikrobiomu a potencuje druhy se zvýšenou schopností extrahovat energii z potravy. Diety založené převážně na konzumaci rostlinných produktů jsou pro diabetiky přínosné, ale není dosud objasněno, zda tento přínos je pouze důsledkem složení diety, nebo se na něm podílí i jiné složení mikrobioty a její metabolická aktivita. Jedním z možných terapeutických přístupů je nahrazení „diabetogenní“ mikrobioty „zdravou“ variantou, ale dosud není známo, jaké je složení a podmínky stability a funkčnosti mikrobioty pozitivně působící na hostitele. Cílem této studie je: 1. identifikace klíčových charakteristik u T2D pacientů a veganů na úrovni mikrobiomu a metabolomu; 2. analýza stability veganské mikrobioty v diabetogenních podmínkách; 3. vypracování metody predikce individuální odpovědi na intervenci prebiotiky a vliv dlouhodobé prebiotické intervence na střevní mikrobiom a metabolom T2D pacientů.; Gut microbiota may play a key role in many metabolic diseases, including type 2 diabetes (T2D). Consumption of high-fat/high-sugar western diet seem to alter human resident microbiota towards reduced genetic diversity and to influence its metabolic activity towards enhanced energy extraction. Plant-based diets are effective in the treatment of T2D but it is not clear whether their effect results solely from diet composition or whether it is mediated, at least partly, by different microbiota and its metabolic activity. One possible therapeutic approach is replacement of “pro-diabetic” microbiota with its “healthy” variant but we do not know what the “healthy” microbiota is and under which conditions this microbiota could stay stable and functional. The aim of the proposed study is to identify possible metagenome/metabolome characteristics in different human cohorts (T2D vs vegans), to assess the stability of vegan microbiota in T2D-like environment and to evaluate the possibility to influence human T2D microbiota/metabolome towards more protective composition by dietary intervention.
- Keywords
- mikrobiom, microbiome, personalizovaná medicína, personalized medicine, metabolom, diabetes 2. typu, veganská dieta, prebiotika, rozpustná vláknina, metabolome, type 2 diabetes, prebiotic, vegan diet, dietary fiber,
- NML Publication type
- závěrečné zprávy o řešení grantu AZV MZ ČR
The earliest proteins had to rely on amino acids available on early Earth before the biosynthetic pathways for more complex amino acids evolved. In extant proteins, a significant fraction of the 'late' amino acids (such as Arg, Lys, His, Cys, Trp and Tyr) belong to essential catalytic and structure-stabilizing residues. How (or if) early proteins could sustain an early biosphere has been a major puzzle. Here, we analysed two combinatorial protein libraries representing proxies of the available sequence space at two different evolutionary stages. The first is composed of the entire alphabet of 20 amino acids while the second one consists of only 10 residues (ASDGLIPTEV) representing a consensus view of plausibly available amino acids through prebiotic chemistry. We show that compact conformations resistant to proteolysis are surprisingly similarly abundant in both libraries. In addition, the early alphabet proteins are inherently more soluble and refoldable, independent of the general Hsp70 chaperone activity. By contrast, chaperones significantly increase the otherwise poor solubility of the modern alphabet proteins suggesting their coevolution with the amino acid repertoire. Our work indicates that while both early and modern amino acids are predisposed to supporting protein structure, they do so with different biophysical properties and via different mechanisms.
- MeSH
- Amino Acids * chemistry MeSH
- Prebiotics * MeSH
- Proteins chemistry MeSH
- Protein Folding MeSH
- Publication type
- Journal Article MeSH
Fructooligosaccharides (FOS) are fructose-based oligosaccharides employed as additives to improve the food's nutritional and technological properties. The rhizosphere of plants that accumulate fructopolysaccharides as inulin has been revealed as a source of filamentous fungi. These fungi can produce FOS either by inulin hydrolysis or by biosynthesis from sucrose, including unusual FOS with enhanced prebiotic properties. Here, we investigated the ability of Fusarium solani and Neocosmospora vasinfecta to produce FOS from different carbon sources. Fusarium solani and N. vasinfecta grew preferentially in inulin instead of sucrose, resulting in the FOS production as the result of endo-inulinase activities. N. vasinfecta was also able to produce the FOS 1-kestose and 6-kestose from sucrose, indicating transfructosylating activity, absent in F. solani. Moreover, the results showed how these carbon sources affected fungal cell wall composition and the expression of genes encoding for β-1,3-glucan synthase and chitin synthase. Inulin and fructose promoted changes in fungal macroscopic characteristics partially explained by alterations in cell wall composition. However, these alterations were not directly correlated with the expression of genes related to cell wall synthesis. Altogether, the results pointed to the potential of both F. solani and N. vasinfecta to produce FOS at specific profiles.
- MeSH
- Fructose metabolism MeSH
- Fusarium * genetics metabolism MeSH
- Inulin * metabolism MeSH
- Oligosaccharides MeSH
- Sucrose metabolism MeSH
- Carbon MeSH
- Publication type
- Journal Article MeSH
ETHNOPHARMACOLOGICAL RELEVANCE: Geranium sanguineum L. is used for treatment of inflammations, anemia, malignant diseases of the blood-forming organs, diarrhea, respiratory infections, etc. Only flavonoids in root extracts have been elucidated as immunostimulating and anti-inflammatory compounds, and polysaccharides in the herb have not been examined. AIM OF THE STUDY: to compare the chemical features of polysaccharide complexes (PSCs) from leaves (GSL-PSC) and roots (GSR-PSC) of G. sanguineum, as well as their immunomodulatory activities on leukocytes after inflammation, and effects on the growth of different bacteria. MATERIALS AND METHODS: The samples were isolated by water extraction and their structural features were studied by 2D NMR spectroscopy. The stimulatory effects of both PSCs on human leukocytes were analyzed with flow cytometry. Their suppressive activities on the oxidative burst in blood and derived neutrophils against opsonized zymosan and phorbol myristate acetate were investigated. The effects of the samples on viability, NO and interleukin 6 (IL-6) syntheses in RAW264.7 cells after inflammation with lipopolysaccharides (LPS) were tested. The prebiotic and anti-biofilm activities of the PSCs were evaluated. RESULTS: The total carbohydrate content in the samples was significant (73.6-76.8%). GSL-PSC contained pectins, which were rich in homogalacturonan (HG), and smaller amounts of rhamnogalacturonan (RG) type I, decorated by 1,5-α-L-Araf, 1,4- and 1,6-β-D-Galp chains. GSR-PSC contained starch, followed by pectins with lower HG content and more RG-I regions, substituted by 1 → 3,5-α-L-arabinans and 1 → 3,6-β-D-galactans. GSL-PSC and GSR-PSC (200 μg/mL) increased monocyte and granulocyte cell counts, but GSR-PSC also elevated T helper and B cell levels in a normal and activated state. GSR-PSC triggered a dose-dependent (50-200 μg/mL) oxidative burst in blood, but alleviated it after inflammation even in blood-derived neutrophils. It was free of LPS, and activated NO and IL-6 productions in RAW264.7 cells better than GSL-PSC, without affecting their viability. Both PSCs (2.0%, w/v) stimulated probiotic co-cultures between Clostridium beijerinckii strains and Lactobacillus sp. ZK9, and inhibited the growth and biofilm formation of Escherichia coli, Streptococcus mutans and Salmonella enterica. CONCLUSIONS: The PSs in G. sanguineum could be involved in the stimulatory effects on blood-forming organs and anti-inflammatory action of aqueous root extracts in case of infections. These PSs should be included in synbiotic foods to support the treatment of inflammations and infections in the gut.
- MeSH
- Anti-Inflammatory Agents MeSH
- Geranium * chemistry MeSH
- Interleukin-6 MeSH
- Humans MeSH
- Lipopolysaccharides MeSH
- Mice MeSH
- Pectins pharmacology MeSH
- Polysaccharides * pharmacology MeSH
- RAW 264.7 Cells MeSH
- Inflammation drug therapy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Fructooligosaccharides (FOS) are compounds possessing various health properties and are added to functional foods as prebiotics. The commercial production of FOS is done through the enzymatic transfructolysation of sucrose by β-fructofuranosidases which is found in various organisms of which Aureobasidium pullulans and Aspergillus niger are the most well known. This study overexpressed two differently codon-optimized variations of the Aspergillus fijiensis β-fructofuranosidase-encoding gene (fopA) under the transcriptional control of either the alcohol oxidase (AOX1) or glyceraldehyde-3-phosphate dehydrogenase (GAP) promoters. When cultivated in shake flasks, the two codon-optimized variants displayed similar volumetric enzyme activities when expressed under control of the same promoter with the GAP strains producing 11.7 U/ml and 12.7 U/ml, respectively, and the AOX1 strains 95.8 U/ml and 98.6 U/ml, respectively. However, the highest production levels were achieved for both codon-optimized genes when expressed under control of the AOX1 promoter. The AOX1 promoter was superior to the GAP promoter in bioreactor cultivations for both codon-optimized genes with 13,702 U/ml and 2718 U/ml for the AOX1 promoter for ATUM and GeneArt®, respectively, and 6057 U/ml and 1790 U/ml for the GAP promoter for ATUM and GeneArt®, respectively. The ATUM-optimized gene produced higher enzyme activities when compared to the one from GeneArt®, under the control of both promoters.
