BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.
- MeSH
- Biomarkers * blood MeSH
- Claudin-3 * metabolism MeSH
- Adult MeSH
- Intestinal Barrier Function MeSH
- Middle Aged MeSH
- Humans MeSH
- Permeability * MeSH
- Fatty Acid-Binding Proteins * blood MeSH
- Multiple Sclerosis * physiopathology metabolism blood MeSH
- Intestinal Mucosa metabolism MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
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
Střevní mikrobiom je právem označovaný jako neviditelný orgán, který významně ovlivňuje lidský organismus po celý jeho život. Procesů, na kterých se podílí, je mnoho. Kromě dobře známé role v oblasti trávení dále ovlivňuje maturaci imunitního systému, metabolické programování a propojuje i poměrně vzdálené orgány (např. osa střevo–mozek). Vývoj střevního mikrobiomu začíná záhy po narození a působící faktory můžeme rozdělit na modifikovatelné (výživa, antibiotická léčba, prostředí) a neovlivnitelné (gestační stáří, způsob porodu). Alterace střevního mikrobiomu těmito faktory je spojována jak s krátkodobou, tak dlouhodobou morbiditou. Cílem současného výzkumu je porozumět nejen vývoji samotnému, ale i všem činitelům, které mohou do tohoto přirozeného procesu zasahovat. Poznání a pochopení komplexity střevního mikrobiomu nám umožní činit taková medicínská rozhodnutí, která budou mít pro novorozence značné benefity. Tento přehledový článek přináší vhled do problematiky vzniku a vývoje střevního mikrobiomu a s tím spojené možné klinické aspekty u donošeného i nedonošeného novorozence. Součástí našeho sdělení jsou i doporučení, která vycházejí ze současného poznání, k ovlivnění negativních následků alterace střevního mikrobiomu v tomto křehkém období.
Gut microbiome is regarded as an invisible organ influencing the human organism throughout the entire lifespan. Microbiome determines various physiological processes including immune system maturation, metabolic programming and furthermore, facilitates connections even between relatively distant organs (e.g. gut-brain axis). Its development begins shortly after birth and is modified by various aspects. We can categorize them into modifiable (antibiotic treatment, diet) and non-modifiable factors (gestational age, delivery mode). Intestinal alteration caused by these influencing factors might contribute to short-term and long-term morbidity. Our objective is to comprehend the microbiome development itself and its modifying factors. Understanding the microbiome complexity could help us make such medical decisions to outweigh negative sequelae of an early gut alteration. This review presents topics concerning microbiome origin and its development along with potential clinical aspects in term and preterm newborn. We also include recommendations for parents and health care professionals regarding possible attitudes, based on current scientific knowledge, to diminish early gut microbiome alterations.
- MeSH
- Anti-Bacterial Agents adverse effects MeSH
- Immune System microbiology growth & development MeSH
- Breast Feeding MeSH
- Humans MeSH
- Infant, Premature immunology MeSH
- Infant, Newborn MeSH
- Brain-Gut Axis physiology immunology MeSH
- Risk Factors MeSH
- Gastrointestinal Microbiome * physiology drug effects MeSH
- Check Tag
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Review MeSH
PURPOSE OF REVIEW: The immunological processes that lead to multiple sclerosis (MS) and occur during the progressive phase of the disease are manifold and still not well understood. This review summarizes new insights on this topic that were gained through recent studies with diverse scientific approaches. RECENT FINDINGS: While genetic risk clearly contributes to MS, external factors play a key role in its pathogenesis as well. Epstein-Barr virus infection correlates significantly with MS risk and seems to be a major causal factor. Even though our knowledge on the human gut microbiome and its connection to the central nervous system is far from being complete, several studies have proven that the gut-brain axis influences neuroinflammation and disease progression in MS. It has become much clearer that MS is not solely a T cell-mediated disease but is also strongly driven by B cells and pathogenic antibodies. Beyond the peripheral immune cells, glial cells and their interactions with neurons are important players contributing to disease activity and progression in MS. SUMMARY: Taken together, recent publications on immunological processes in the context of MS implicate a multitude of noncanonical mechanisms that need to be further explored regarding their interplay and contribution to the degenerative course of the disease.
The gut microbiota has recently come to the forefront of scientific interest, particularly due to its broad spectrum of action not only on tissues that it comes into direct contact with, but also - through a variety of agents - on distant tissues and organs. There are a number of previously described mechanisms through which gut-colonizing microorganisms can affect the host's immune or endocrine systems as well as the central nervous system and behaviour of the host. A number of research teams are studying the microbiome in relation to neurological diseases, investigating the possible effect of specific microorganisms and microbial metabolites on the development and progression of these diseases. This publication deals with those diseases that have been most widely studied and described in this context.
- MeSH
- Alzheimer Disease diagnosis etiology MeSH
- Humans MeSH
- Brain-Gut Axis * physiology genetics MeSH
- Parkinsonian Disorders diagnosis etiology MeSH
- Autism Spectrum Disorder diagnosis etiology genetics MeSH
- Multiple Sclerosis diagnosis etiology MeSH
- Gastrointestinal Microbiome * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.
- MeSH
- Humans MeSH
- Monocytes metabolism immunology MeSH
- Cell Movement MeSH
- Serotonin * metabolism MeSH
- Signal Transduction MeSH
- Intestinal Mucosa * metabolism pathology MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Inflammation metabolism pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article 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
Psychiatric and mood disorders may play an important role in the development and persistence of irritable bowel syndrome (IBS). Previously, we hypothesized that stress-induced implicit memories may persist throughout life via epigenetic processes in the enteric nervous system (ENS), independent of the central nervous system (CNS). These epigenetic memories in the ENS may contribute to developing and perpetuating IBS. Here, we further elaborate on our earlier hypothesis. That is, during pregnancy, maternal prenatal stresses perturb the HPA axis and increase circulating cortisol levels, which can affect the maternal gut microbiota. Maternal cortisol can cross the placental barrier and increase cortisol-circulating levels in the fetus. This leads to dysregulation of the HPA axis, affecting the gut microbiota, microbial metabolites, and intestinal permeability in the fetus. Microbial metabolites, such as short-chain fatty acids (which also regulate the development of fetal ENS), can modulate a range of diseases by inducing epigenetic changes. These mentioned processes suggest that stress-related, implicit, long-term epigenetic memories may be programmed into the fetal ENS during pregnancy. Subsequently, this implicit epigenetic stress information from the fetal ENS could be conveyed to the CNS through the bidirectional microbiota-gut-brain axis (MGBA), leading to perturbed functional connectivity among various brain networks and the dysregulation of affective and pain processes.
- MeSH
- Epigenesis, Genetic * MeSH
- Humans MeSH
- Brain-Gut Axis physiology MeSH
- Stress, Psychological * metabolism MeSH
- Gastrointestinal Microbiome physiology MeSH
- Enteric Nervous System * MeSH
- Irritable Bowel Syndrome * metabolism MeSH
- Pregnancy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- MeSH
- Alcoholism * immunology complications physiopathology MeSH
- Enterocytes pathology MeSH
- Humans MeSH
- Microglia pathology MeSH
- Neurotransmitter Agents MeSH
- Brain-Gut Axis * physiology immunology MeSH
- Alcohol-Induced Disorders, Nervous System MeSH
- Gastrointestinal Microbiome immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Úvod: Poruchy interakcie čreva a mozgu predstavujú skupinu širokého spektra chronických gastrointestinálnych ochorení s množstvom symptómov súvisiacich s poruchou špecifického orgánu. Neexistuje žiadny špecifický liek na DGBI a terapia je väčšinou zameraná na zmiernenie symptómov. Jednou z potenciálnych nových terapií na zmiernenie symptómov by mohol byť tréning hlbokého dýchania. Dostupné údaje naznačujú, že stimulácia hlbokého dýchania pomocou biofeedbacku môže viesť k zníženiu vnímania bolesti, dokonca aj viscerálnej bolesti pochádzajúcej z gastrointestinálneho traktu. Metódy: Ide o retrospektívnu analýzu klinických údajov získaných od pacientov, ktorí boli liečení nácvikom hlbokého dýchania pre refraktérny prípad ochorenia interakcie čreva a mozgu. DGBI bol diagnostikovaný na základe kritérií ROME IV. Pred tréningom bol pacientom dôkladne vysvetlený správny mechanizmus hlbokého brušného dýchania. Pacienti tiež vyplnili dotazníky STAI-X1, STAI-X2 na posúdenie úrovne ich úzkosti. Po úvodnom tréningu v ordinácii boli pacienti inštruovaní, aby pokračovali v domácom hlbokom brušnom dýchaní 3- až 5-krát týždenne. Účinok terapie bol hodnotený po jednom mesiaci. Výsledky: Pätnástim vhodným pacientom bol ponúknutý tréning hlbokého dýchania s pomocou biofeedbacku. Deväť pacientov sa dostavilo na kontrolu po 4 týždňoch, a preto sú zohľadnení v analýze. U piatich pacientov došlo k miernemu zmierneniu symptómov. U dvoch pacientov došlo k vymiznutiu symptómov a naopak dvaja pacienti neuviedli žiadnu zmenu symptómov. V úrovniach úzkosti neboli žiadne štatisticky významné zmeny. Záver: Tréning hlbokého dýchania na zmiernenie symptómov pri poruchách interakcie čreva a mozgu sa zdá byť sľubnou reklamou na terapiu. Vyplýva to z publikovaných štúdií a našich vlastných skúseností. Pred jednoznačnejším záverom sú však potrebné prísnejšie údaje.
Introduction: Disorders of gut-brain interaction represents a group of a wide variety of chronic gastrointestinal diseases with plethora of symptoms related to disorder of specific organ. There is no specific cure for DGBI and the therapy is mostly focused on alleviating the symptoms. One of the potential new therapies to alleviate the symptoms could be deep breathing training. Available data suggest that biofeedback assisted deep breathing pacing may lead to reduction of pain perception even visceral pain originating from gastrointestinal tract. Methods: This is a retrospective analysis of clinical data obtained from patients who were treated with deep breathing training for refractory case of disease of gut-brain interaction. The DGBI was diagnosed based on the ROME IV criteria. Before the training, the proper mechanism of deep abdominal breathing was thoroughly explained to the patients. Patients have also filled the STAI-X1, STAI-X2 questionaries to assess their anxiety levels. After initial office-based training, the patients were instructed to continue in home-based deep abdominal breathing for 3 to 5 times a week. The effect of the therapy was evaluated after one month. Results: Fifteen eligible patients were offered biofeedback assisted deep breathing training. Nine patients attended the check-up appointment after 4 weeks and are therefore considered in the analysis. Five patients experienced mild alleviation of the symptoms. Two patients experienced resolution of the symptoms and contrary, two patients didn’t report any change in symptoms. There were no statistically significant changes in the anxiety levels. Conclusion: The deep breathing training for symptom alleviation in disorders of gut-brain interaction seems to be a promising ad on therapy. This is based on published studies and our own experience. However more rigorous data are needed before more definite conclusion.
- Keywords
- poruchy integrace střeva a mozku, disorders of gut-brain interaction, DGBI,
- MeSH
- Biofeedback, Psychology MeSH
- Breathing Exercises MeSH
- Gastrointestinal Diseases * physiopathology MeSH
- Humans MeSH
- Brain-Gut Axis * physiology MeSH
- Retrospective Studies MeSH
- Enteric Nervous System physiopathology MeSH
- Check Tag
- Humans MeSH
