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Modulation of the microbiota–gut–brain axis by antibiotics and probiotics. The communication between the gut microbiota and the brain includes neuronal, immune-mediated, and metabolite-mediated pathways. Gut dysbiosis leads to activation of the immune response and alters the production of neurotransmitters as well as bacterial metabolites. These may have a contribution to abnormal signaling through the vagus nerve. Reduction in the integrity of the gastrointestinal barrier causes bacterial migration and inflammation. Pro-inflammatory cytokines induce disruption of the blood–brain barrier permeability. Antibiotics can hinder the growth of certain bacteria, and probiotics have the potential to normalize the gut microbiota in microbiota–gut–brain processes.
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For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota–gut–brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is...
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This review describes current evidence supporting butyrate impact in the homeostatic regulation of the digestive ecosystem in health and inflammatory bowel diseases (IBDs). Butyrate is mainly produced by bacteria from the Firmicutes phylum. It stimulates mature colonocytes and inhibits undifferentiated malignant and stem cells. Butyrate oxidation i...
Citations
... This disease is incurable, rapidly progressive, and affects many cognitive functions and memory [34]. Various environmental and internal factors may have a role in initiating the disease [35,36]. By producing neuroactive chemicals, gut bacteria can alter neuronal function, plasticity, and behaviour. ...
... Various studies have demonstrated that perhaps the microbiota gut is vital for brain function, behavioural changes, and the generation of bacterial amyloids. The gut microbiota's bacterial amyloids and lipopolysaccharides can trigger immune cells in the brain, triggering an immunological response that leads to neuroinflammation [35]. ...
It is becoming widely understood that gut microbiota and human health are related. It is now well-accepted that healthy gut flora plays a significant role in the host's overall health. The gut flora is a diverse and dynamic collection of microorganisms in the human gastrointestinal (GI) tract, significantly impacting the host during homeostasis and disease. This microbial community's diversity is host-specific and changes throughout an individual's lifespan. The gut flora controls several metabolic pathways in the host, leading to interacting host-microbiota metabolic, signalling and immune-inflammatory axes that physiologically link the gut with the brain, heart, lung and skin. Numerous inflammatory illnesses and infections have been connected to altered gut bacterial composition or dysbiosis. Optimising therapeutic and probiotic approaches to control the gut microbiota to treat disease and promote health requires a deeper understanding of these axes. This review confers our current understanding of the connections between gut flora with the brain, heart, lungs, and skin and also portrays the diseases correlated with these axes.
... Shifting of the balanced and stable state of the GM composition directly affects the permeability of the blood-gut barrier, which leads to the passage of GM-released bioactive substances and, subsequently, activation of the enteric immune system [20]. In aged individuals, an activated systemic immune system significantly promotes neural injury and, finally, neuroinflammation, also known as "inflammaging" [21]. In germ-free mice (GFM), it has been found that the gut microbe composition significantly influences early CNS development and neurogenesis [22]. ...
... Top-down signaling proceeds directly via sympathetic and parasympathetic neurons or indirectly by stimulating the enteric nervous system located in the submucosa and myenteric plexi in the gut wall [29]. Alterations in gut microbiota leading to neuroinflammation in the brain are closely associated with the development of AD, which follows the progressive degenerative pathways leading to alteration/increase in permeability of the gut barrier and activation of active cellular components of the immune system that harm blood-brain functions, promote neuronal injury, neuroinflammation and, finally, development of AD [21]. The GM is well known as the origin of an abundant amyloid, LPS, and other toxic chemicals; therefore, microbiota predisposes animals to systemic inflammation and disruption of physiological barriers [21]. ...
... Alterations in gut microbiota leading to neuroinflammation in the brain are closely associated with the development of AD, which follows the progressive degenerative pathways leading to alteration/increase in permeability of the gut barrier and activation of active cellular components of the immune system that harm blood-brain functions, promote neuronal injury, neuroinflammation and, finally, development of AD [21]. The GM is well known as the origin of an abundant amyloid, LPS, and other toxic chemicals; therefore, microbiota predisposes animals to systemic inflammation and disruption of physiological barriers [21]. Microbiota inhabited in the human gut not only assist gut-specific activities like the fermentation of carbohydrates for byproduct formation, vitamin synthesis, and detoxification of xenobiotics [22,23] but also act as a protective tool against the pathogenic bacteria in the gut [30] and maintain the neuronal health of an individual. ...
The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut–brain axis, which significantly regulates the body’s physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasize the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut–brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut–brain axis and venture to clarify microbiota-based therapeutic strategies for AD.
... The dysbiosis of intestinal flora can directly lead to the production of pathogenic proteins in the intestinal tract; the pathogenic proteins enter the brain through the vagus nerve and cause neurodegeneration such as ALS [59]. At the same time, the harmful substances produced by intestinal dysbiosis induce the production of a large number of inflammatory factors in the intestine, which enter the CNS and cause neuroinflammatory and immune reactions in brain and spinal cord leading to ALS through destroying the intestinal barrier and the blood-brain barrier [60,61]. ...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease mainly characterized by the accumulation of ubiquitinated proteins in the affected motor neurons. At present, the accurate pathogenesis of ALS remains unclear and there are still no effective treatment measures for ALS. The potential pathogenesis of ALS mainly includes the misfolding of some pathogenic proteins, the genetic variation, mitochondrial dysfunction, autophagy disorders, neuroinflammation, the misregulation of RNA, the altered axonal transport, and gut microbial dysbiosis. Exploring the pathogenesis of ALS is a critical step in searching for the effective therapeutic approaches. The current studies suggested that the genetic variation, gut microbial dysbiosis, the activation of glial cells, and the transportation disorder of extracellular vesicles may play some important roles in the pathogenesis of ALS. This review conducts a systematic review of these current potential promising topics closely related to the pathogenesis of ALS; it aims to provide some new evidences and clues for searching the novel treatment measures of ALS.
... Recently, however, a growing body of evidence has been giving rise to the hypothesis that gut dysbiosis (leading to/accompanied by compromised gut wall integrity underlined by bacterial migration and inflammation) leads to activation of the peripheral immune response, altered production of neurotransmitters and bacterial metabolites, and a possible contribution to abnormal signaling through the vagus nerve (it is known that microbiotarelated molecules can influence vagus nerve firing, and some can travel to the brain via the nerve [21]; also, neuropeptides, like cholecystokinin, for example, produced by endocrine cells in the gut can bind to specialized receptors on the vagus nerve [22]), leading to impaired blood-brain barrier function and an altered central immune response of microglia (but also of other brain cells), which promotes neuroinflammation and neuronal loss and contributes to the progression of AD or is implicated in its pathogenesis [23][24][25][26]. ...
Neurodegenerative diseases (NDs), characterized by progressive degeneration and death of neurons, are strongly related to aging, and the number of people with NDs will continue to rise. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs, and the current treatments offer no cure. A growing body of research shows that AD and especially PD are intricately related to intestinal health and the gut microbiome and that both diseases can spread retrogradely from the gut to the brain. Zeolites are a large family of minerals built by [SiO4]4− and [AlO4]5− tetrahedrons joined by shared oxygen atoms and forming a three-dimensional microporous structure holding water molecules and ions. The most widespread and used zeolite is clinoptilolite, and additionally, mechanically activated clinoptilolites offer further improved beneficial effects. The current review describes and discusses the numerous positive effects of clinoptilolite and its forms on gut health and the gut microbiome, as well as their detoxifying, antioxidative, immunostimulatory, and anti-inflammatory effects, relevant to the treatment of NDs and especially AD and PD. The direct effects of clinoptilolite and its activated forms on AD pathology in vitro and in vivo are also reviewed, as well as the use of zeolites as biosensors and delivery systems related to PD.
... Changes in microbiota can cause anxiety, memory impairment, cognitive and neurodegenerative disorders (Pluta et al., 2020). As indicated above the intestinal dysbiosis is the source of Ab, LPS and other toxins, which contribute to systemic inflammation and disruption of physiological barriers, e.g., intestinal wall (Megur et al., 2020). These products can transfer, through X cranial nerve, to CNS over years, triggering inflammation and microglia activation. ...
... Neuroinflammation is the reason of neuron loss in the brain. Combined with bacterial amyloid it promotes misfolding and aggregation of human amyloids (Megur et al., 2020;Pluta et al., 2020). There is hypothesis of antimicrobial protection in AD. ...
... In the AD rat model administration of Lactobacillus plantarum MTCC 1325, Lactobacillus spp. and Bifidobacterium, Bifidobacterium breve strain A1 have had positive impact on Ab formation or its effects on cognitive functions (Megur et al., 2020). The pathways to the development of Alzheimer's disease are shown in Figure 4. ...
Crohn’s disease (CD) is a chronic inflammatory disease that most frequently affects part of the distal ileum, but it may affect any part of the gastrointestinal tract. CD may also be related to systemic inflammation and extraintestinal manifestations. Alzheimer’s disease (AD) is the most common neurodegenerative disease, gradually worsening behavioral and cognitive functions. Despite the meaningful progress, both diseases are still incurable and have a not fully explained, heterogeneous pathomechanism that includes immunological, microbiological, genetic, and environmental factors. Recently, emerging evidence indicates that chronic inflammatory condition corresponds to an increased risk of neurodegenerative diseases, and intestinal inflammation, including CD, increases the risk of AD. Even though it is now known that CD increases the risk of AD, the exact pathways connecting these two seemingly unrelated diseases remain still unclear. One of the key postulates is the gut-brain axis. There is increasing evidence that the gut microbiota with its proteins, DNA, and metabolites influence several processes related to the etiology of AD, including β-amyloid abnormality, Tau phosphorylation, and neuroinflammation. Considering the role of microbiota in both CD and AD pathology, in this review, we want to shed light on bacterial amyloids and their potential to influence cerebral amyloid aggregation and neuroinflammation and provide an overview of the current literature on amyloids as a potential linker between AD and CD.
... Shifting of the balanced and stable state of GM composition directly affects the permeability of the blood-gut barrier, which leads to the passage of GM-released bioactive substances and, subsequently, activation of the enteric immune system (12). In aged individuals, an activated systemic immune system significantly promotes neural injury and, finally, neuroinflammation, also known as "inflammaging" (13). In germ-free mice (GFM), it has been found that the gut microbe composition significantly influences early CNS development and neurogenesis (14). ...
... The top-down signaling proceeds directly via sympathetic and parasympathetic neurons or indirectly by stimulating the enteric nervous system located in the sub-mucosa and myenteric plexi in the gut wall (22). Alteration in the interaction between gut dysbiosis and host microbiota leads to neuroinflammation in the brain closely associated with the development of AD, which follows the progressive degenerative pathways leading to alteration/increase in permeability of the gut barrier and activation of active cellular components of the immune system that harm blood-brain functions, promote neuronal injury, neuroinflammation and finally development of AD (13). The GM is well known as the origin of an abundant amyloid, LPS, and other toxic chemicals; therefore, microbiota predisposes animals to systemic inflammation and disruption of physiological barriers (13). ...
... Alteration in the interaction between gut dysbiosis and host microbiota leads to neuroinflammation in the brain closely associated with the development of AD, which follows the progressive degenerative pathways leading to alteration/increase in permeability of the gut barrier and activation of active cellular components of the immune system that harm blood-brain functions, promote neuronal injury, neuroinflammation and finally development of AD (13). The GM is well known as the origin of an abundant amyloid, LPS, and other toxic chemicals; therefore, microbiota predisposes animals to systemic inflammation and disruption of physiological barriers (13). Microbiota inhabited in the human gut not only assist gut-specific activities like the fermentation of carbohydrates for byproduct formation, vitamin synthesis, and detoxification of xenobiotics (14)(15) but also act as a protective tool against the pathogenic bacteria in the gut (23) and maintain the neuronal health of an individual. ...
The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.
... In this first part of the study, we found that the bacteria associated with SCFAproducing bacteria (especially butyric acid and propionic acid), such as Roseburia, Blautia, lostridium_sensu_stricto_1, and Lachnospira, were decreased at the genus level, while Acetatifactor, bacteria that produce acetic acid, were increased following MTX treatment. In addition, bacteria such as Mucispirillum and Alistipes, which were reported to be related to various human neurologic disorders such as Alzheimer's disease and major depressive disorder, increased markedly after MTX treatment [50,51]. To clarify the impact of gut microbiota changes on the nervous system following MTX treatment, we used the KEGG pathway enrichments analyzed by PICRUSt and found that butanoate and most of the lipid metabolism pathways were down-regulated in response to MTX, which was consistent with the reduced plasma levels of SCFAs found in our study. ...
Methotrexate (MTX) is an essential part of therapy in the treatment of acute lymphoblastic leukemia (ALL) in children, and inferior intellectual outcomes have been reported in children who are leukemia survivors. Although several studies have demonstrated that the interaction between gut microbiota changes and the brain plays a vital role in the pathogenesis of chemotherapy-induced brain injury, preexisting studies on the effect of MTX on gut microbiota changes focused on gastrointestinal toxicity only. Based on our previous studies, which revealed that MTX treatment resulted in inferior neurocognitive function in developing young rats, we built a young rat model mimicking MTX treatment in a child ALL protocol, trying to investigate the interactions between the gut and brain in response to MTX treatment. We found an association between gut microbiota changes and neurogenesis/repair processes in response to MTX treatment, which suggest that MTX treatment results in gut dysbiosis, which is considered to be related to MTX neurotoxicity through an alteration in gut–brain axis communication.
... Dementias that appear earlier and earlier in the population, such as Alzheimer's disease (AD) and Parkinson's disease (PD) may be directly related to intestinal dysbiosis [25][26][27]. Currently, the Mediterranean diet [28,29], as well as the consumption of foods with high antioxidant and anti-inflammatory properties, represent a significant portion of research investments, as they seek to understand the relationship of natural compounds such as polyunsaturated fatty acids ( balance in the intake of omegas 3 and 6, in particular) [30,31], polyphenols [32] and curcumin, which is the main component of Curcuma longa [33;34], for example, with modulation of the inflammatory response and how these molecules can act in the prevention and treatment of neurological diseases. ...
The immune system's inflammatory response is a crucial defense mechanism against infectious agents. At the onset of the pandemic, researchers primarily focused on the respiratory consequences of coronavirus, while overlooking the virus's impact on other organs, such as the brain. However, it is now apparent that post-covid sequelae can persist, especially in those who suffered severe forms of the disease. These symptoms include memory impairment, excessive fatigue, and mood swings. This study examines the possible link between the brain's inflammatory response and these prevalent sequelae, as well as strategies to improve the quality of life for those affected.
... 18 Previous studies on the communication between gut bacteria and human brain, which is called the microbiota-gutbrain axis, have been focused on the pathogenesis of diverse neurological diseases. [19][20][21] Brain function in long-lived people is also of great scientific interest, as some preserve cognitive function or delay the onset of dementia until advanced age. 22 However, few studies have evaluated brain functional connectivity in long-lived individuals, and whether it is associated with the gut microbiota and metabolites is also unclear. ...
... To our knowledge, this is the first study to integrate gut metagenome, metabolomics, and brain function to create a clear link between gut microbes and longevity. Interestingly, we found that interactions existed among the alternate gut microbiota, metabolites, and brain functional connectivity in nonagenarians, suggesting that the microbiota-gutbrain axis is not only involved in neurological diseases [19][20][21] but also in longevity. Our results Figure 6. ...
The role of microbiota-gut-brain axis in modulating longevity remains undetermined. Here, we performed a multiomics analysis of gut metagenomics, gut metabolomics, and brain functional near-infrared spectroscopy (fNIRS) in a cohort of 164 participants, including 83 nonagenarians (NAs) and 81 non-nonagenarians (NNAs) matched with their spouses and offspring. We found that 438 metabolites were significantly different between the two groups; among them, neuroactive compounds and anti-inflammatory substances were enriched in NAs. In addition, increased levels of neuroactive metabolites in NAs were significantly associated with NA-enriched species that had three corresponding biosynthetic potentials: Enterocloster asparagiformis, Hungatella hathewayi and Oxalobacter formigenes. Further analysis showed that the altered gut microbes and metabolites were linked to the enhanced brain connectivity in NAs, including the left dorsolateral prefrontal cortex (DLPFC)-left premotor cortex (PMC), left DLPFC-right primary motor area (M1), and right inferior frontal gyrus (IFG)-right M1. Finally, we found that neuroactive metabolites, altered microbe and enhanced brain connectivity contributed to the cognitive preservation in NAs. Our findings provide a comprehensive understanding of the microbiota-gut-brain axis in a long-lived population and insights into the establishment of a microbiome and metabolite homeostasis that can benefit human longevity and cognition by enhancing functional brain connectivity.
... Several factors including age-related deterioration, degeneration of anatomical pathways, environmental in uences, mitochondrial malfunction, immune system dysfunction, and genetic susceptibility have been identi ed as potential contributors to AD [7] . Apart from in uencing the physiology and metabolism of the host [8] , the gut microbiota has been demonstrated to exert an effect on cognitive development and function [9] . ...
Background:
Alzheimer's Disease (AD) is a neuropathological condition marked by cognitive deterioration and chronic neuroinflammation. Previous investigations have unveiled a strong correlation between the gut microbiota and the progression of AD. In this study, our objective is to probe the effects of Parabacteroides distasonis (P.distasonis), previously found to be conspicuously diminished in AD patients, on the APP/PS1 mice model.
Methods:
To assess the impact of orally administered P.distasonis on gut microbiota and metabolites, we utilized 16s rDNA sequencing and GC-MS to analyze gut composition and short-chain fatty acids in APP/PS1 mice after one month of P.distasonis gavage. To investigate the effects of P.distasonis administration over a six-month period on APP/PS1 mice, we evaluated cognitive function using novel object recognition and Y-maze tests, assessed intestinal barrier integrity and AD-related pathological features with immunofluorescence, and analyzed immune cell subpopulations in intestine, blood, spleen, and brain tissues via flow cytometry. The Luminex assay was employed to detect inflammatory cytokine secretion in the same regions.
Results:
One-month oral administration of P.distasonis modulated the gut microbiota, elevated butyrate levels. Six-month oral administration of P.distasonis improved cognitive function in APP/PS1 mice, reducing Aβ deposition and inhibiting glial cell proliferation. It also amplified Treg cells within the gut, concomitant with the decreased Th1 proliferation and intestinal inflammation. Additionally, we observed the migration of peripheral CD4⁺ T cells to the brain through chemotaxis, accompanied by an increase in Treg cells and higher levels of anti-inflammatory factors such as IL-10 and TGF-β in the brain. Collectively, these multifaceted effects contributed to the alleviation of neuroinflammation.
Conclusion:
These findings underscore the potential of transplanting P.distasonis in alleviating AD-related pathology, suggesting a role for gut microbiota in neuroinflammation attenuation.
