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The brain bidirectionally communicates with the gut to control food intake and energy balance, which becomes dysregulated in obesity. For example, endocannabinoid (eCB) signaling in the small-intestinal (SI) epithelium is upregulated in diet-induced obese (DIO) mice and promotes overeating by a mechanism that includes inhibiting gut-brain satiation signaling. Upstream neural and molecular mechanism(s) involved in overproduction of orexigenic gut eCBs in DIO, however, are unknown. We tested the hypothesis that overactive parasympathetic signaling at the muscarinic acetylcholine receptors (mAChRs) in the SI increases biosynthesis of the eCB, 2-arachidonoyl-sn-glycerol (2-AG), which drives hyperphagia via local CB1Rs in DIO. Male mice were maintained on a high-fat/high-sucrose Western-style diet for 60 d, then administered several mAChR antagonists 30 min prior to tissue harvest or a food intake test. Levels of 2-AG and the activity of its metabolic enzymes in the SI were quantitated. DIO mice, when compared to those fed a low-fat/no-sucrose diet, displayed increased expression of cFos protein in the dorsal motor nucleus of the vagus, which suggests an increased activity of efferent cholinergic neurotransmission. These mice exhibited elevated levels of 2-AG biosynthesis in the SI, that was reduced to control levels by mAChR antagonists. Moreover, the peripherally restricted mAChR antagonist, methylhomatropine bromide, and the peripherally restricted CB1R antagonist, AM6545, reduced food intake in DIO mice for up to 24 h but had no effect in mice conditionally deficient in SI CB1Rs. These results suggest that hyperactivity at mAChRs in the periphery increases formation of 2-AG in the SI and activates local CB1Rs, which drives hyperphagia in DIO.

Heat stress exposure in intermittent heat waves and subsequent exposure during war theaters pose a clinical challenge that can lead to multi-organ dysfunction and long-term complications in the elderly. Using an aged mouse model and high-throughput sequencing, this study investigated the molecular dynamics of the liver-brain connection during heat stress exposure. Distinctive gene expression patterns induced by periodic heat stress emerged in both brain and liver tissues. An altered transcriptome profile showed heat stress-induced altered acute phase response pathways, causing neural, hepatic, and systemic inflammation and impaired synaptic plasticity. Results also demonstrated that proinflammatory molecules such as S100B, IL-17, IL-33, and neurological disease signaling pathways were upregulated, while protective pathways like aryl hydrocarbon receptor signaling were downregulated. In parallel, Rantes, IRF7, NOD1/2, TREM1, and hepatic injury signaling pathways were upregulated. Furthermore, current research identified Orosomucoid 2 (ORM2) in the liver as one of the mediators of the liver-brain axis due to heat exposure. In conclusion, the transcriptome profiling in elderly heat-stressed mice revealed a coordinated network of liver-brain axis pathways with increased hepatic ORM2 secretion, possibly due to gut inflammation and dysbiosis. The above secretion of ORM2 may impact the brain through a leaky blood-brain barrier, thus emphasizing intricate multi-organ crosstalk.

Tau interacts with α-Synuclein (α-Syn) and co-localizes with it in the Lewy bodies, influencing α-Syn pathology in Parkinson's disease (PD). However, whether these biochemical events regulate α-Syn pathology spreading from the gut into the brain remains incompletely understood. Here, we show that α-Syn and Tau co-pathology is spread into the brain in gut-inducible SYN103+/− and/or TAU368+/− transgenic mouse models, eliciting behavioral defects. Gut pathology was initially observed, and α-Syn or Tau pathology was subsequently propagated into the DMV or NTS and then to other brain regions. Remarkably, more extensive spreading and widespread neuronal loss were found in double transgenic mice (Both) than in single transgenic mice. Truncal vagotomy and α-Syn deficiency significantly inhibited synucleinopathy or tauopathy spreading. The α-Syn PET tracer [18F]-F0502B detected α-Syn aggregates in the gut and brain. Thus, α-Syn and Tau co-pathology can propagate from the gut to the brain, triggering behavioral disorders. [Display omitted] • A gut-induced α-Syn and Tau co-pathology mouse model can spread into the brain • Gut-derived pathology is propagated into the DMV and NTS at early stage • Anxiety, cognitive, and motor behavioral impairments appear in a temporal manner • The α-Syn PET tracer [18F]-F0502B can detect α-Syn aggregates in the gut and brain Xiang et al. establish a gut-inducible transgenic mouse model and detect that the gut-derived α-Syn or Tau pathology can propagate into the DMV or NTS and then to other brain regions. The α-Syn PET tracer [18F]-F0502B can detect α-Syn aggregates in the gut and brain. [ABSTRACT FROM AUTHOR]

The development of new drug therapies for Alzheimer's disease (AD) is an important research topic today, but the pathogenesis of AD has not been thoroughly studied, and there are still several shortcomings in existing drug therapies. Therefore, this study aimed to explore the molecular mechanism of lactoferrin (LF) in the treatments of AD and ulcerative colitis (UC) that is susceptible to AD, starting from the principle of one drug, two diseases, and the same treatment. This study used pathological staining and specific indicator staining to preliminarily evaluate the interventions of LF on UC injury and AD progression. We also used 16s RNA full-length sequencing to investigate the effect of LF on the abundance of intestinal microbiota in AD mice. Intestinal tissue and brain tissue metabolomics analysis were then used to screen specific metabolic pathways and preliminarily verify the metabolic mechanism of LF in alleviating the 2 diseases by regulating certain specific metabolites. Moreover, LF significantly changed the types and abundance of gut microbiota in AD mice complicated by UC. To conclude, this study proved the clinical phenomenon of AD susceptibility to UC, and verified the therapeutic effect of LF on 2 diseases. More importantly, we revealed the possible molecular mechanism of LF: Not only does it enrich the cognitive level of LF in alleviating AD by regulating the gut microbiota through the brain gut axis from the perspective of the theory of food nutrition promoting human health, but it also provides a practical basis for the subsequent research and development of LF and drug validation from the perspective of drug food homology. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether YTHDF1 and YTHDF3 play the same role in brain and gut damage after traumatic brain injury (TBI). Methods: We generated YTHDF1-/- and YTHDF3-/- mice using CRISPR/Cas9 technology, established a mouse brain injury model through severe controlled cortical impact (CCI), and finally observed the different types of damage between YTHDF1-/- and YTHDF3-/- mice by analysing the levels of oedema proteins in cortical tissue and inflammatory proteins and histopathological lesions in brain and gut tissues in mice at 3 days after CCI. Result: Compared with WT mice, YTHDF1-/- mice had decreased levels of oedema in cortical tissue and inflammation and histopathological lesions in brain and gut tissues at 3 days post-CCI, but YTHDF3-/- mice did not. Conclusion: Our results suggest that deletion of YTHDF1, but not YTHDF3, could reduce damage to the brain and gut following TBI. [ABSTRACT FROM AUTHOR]

Introduction: The global obesity crisis results from inactive lifestyles and poor diets, increasing the risk of metabolic disorders. Emerging research links obesity with gut microbiome changes influenced by factors like age, genetics, and diet. Gut-brain communication via neural, endocrine, and inflammatory pathways, influenced by microbial compounds, affects nervous system function. Materials and Methods of Research: A thorough literature review was performed using PubMed and Google Scholar, employing keywords related to the gut-brain axis and obesity. Results: Obesity shifts gut microbiota composition due to factors like childbirth method, diet, antibiotics, and environment. This imbalance impacts metabolism, appetite, and insulin sensitivity. Gut microbes influence the brain, regulating energy balance and inflammation. Dysregulated tryptophan metabolism leads to insulin resistance. Gut-brain communication via the vagal nerve affects nutrient metabolism. Hormones like insulin and leptin, along with microbial metabolites, affect lipid metabolism and appetite. Gut microbiota abundance correlates with leptin signaling, and changes in ghrelin levels relate to microbiota composition. Microbial presence affects food cravings. Inflammation in obesity is linked to gut microbiota changes, mediated by bile acids and microbial metabolites. Interventions like probiotics and fecal microbiota transplantation offer potential for managing obesity. Emerging therapies like peptide D3 hold promise but require further study. Conclusion: The microbiome-gut-brain axis is vital in obesity, affecting metabolism, inflammation, and appetite. Utilizing interventions such as dietary adjustments and probiotics targeting gut-brain signaling shows promise in managing obesity. Personalized approaches are crucial due to microbiome complexity. Further research is needed to develop effective therapies for the obesity epidemic. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder and is strongly associated with an increased risk of depression and anxiety. The brain–gut axis plays an important role in the pathophysiologic changes in IBS, yet effective treatments for IBS are still lacking. Sinisan, originating from the Treatise on Typhoid Fever by the medical sage Zhang Zhongjing, is a classic formula in the Eight Methods of Traditional Chinese Medicine (TCM) that focuses on dispersing the liver and regulating the spleen, relieving depression and transmitting evils, and has been widely used in the treatment of liver-depression and spleen-deficiency, diarrhea, and related liver and stomach disorders. However, the therapeutic effect of sinisan in IBS has not been clarified. The aim of this study was to investigate the effects of sinisan on stress-induced intestinal dysfunction and depressive behavior in IBS mice. We established a diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model using a 4% acetic acid enema combined with restraint stress, and analyzed the results using behavioral tests, relevant test kits, hematoxylin-eosin (HE) staining, immunofluorescence (IF), Western blot (WB), and quantitative fluorescence polymerase chain reaction (qRT-PCR). The results showed that sinisan administration significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice, improved mild colonic inflammation and intestinal mucosal permeability, up-regulated the expression of tight junction proteins ZO-1 and occludin. Sinisan significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice by decreasing the expression of TNF-α, promoting the expression of tight junction proteins (occludin, ZO-1) expression, and inhibiting the Tlr4/Myd88 signaling pathway, thereby attenuating the inflammatory response, protecting the intestinal barrier, and alleviating symptoms in the IBS-D mouse model. Taken together, sinisan may ameliorate intestinal inflammation and the intestinal barrier by regulating 5-HT expression and the Tlr4/Myd88 pathway, thereby alleviating stress-induced intestinal dysfunction and depressive behaviors in IBS-D mice. [ABSTRACT FROM AUTHOR]

• Eggerthella is enriched in bipolar and schizophrenia spectrum disorders. • Lachnoclostridium is enriched in bipolar and schizophrenia spectrum disorders. • Balances are reproducible gut microbial signatures in psychiatric disorders. • Antipsychotic use is positively associated with the levels of Klebsiella in the gut. • Lithium use is positively associated with the gut levels of Anaeromassilibacillus. Numerous studies report gut microbiome variations in bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) compared to healthy individuals, though, there is limited consensus on which specific bacteria are associated with these disorders. In this study, we performed a comprehensive metagenomic shotgun sequencing analysis in 103 Dutch patients with BD/SSD and 128 healthy controls matched for age, sex, body mass index and income, while accounting for diet quality, transit time and technical confounders. To assess the replicability of the findings, we used two validation cohorts (total n = 203), including participants from a distinct population with a different metagenomic isolation protocol. The gut microbiome of the patients had a significantly different β-diversity, but not α-diversity nor neuroactive potential compared to healthy controls. Initially, twenty-six bacterial taxa were identified as differentially abundant in patients. Among these, the previously reported genera Lachnoclostridium and Eggerthella were replicated in the validation cohorts. Employing the CoDaCoRe learning algorithm, we identified two bacterial balances specific to BD/SSD, which demonstrated an area under the receiver operating characteristic curve (AUC) of 0.77 in the test dataset. These balances were replicated in the validation cohorts and showed a positive association with the severity of psychiatric symptoms and antipsychotic use. Last, we showed a positive association between the relative abundance of Klebsiella and Klebsiella pneumoniae with antipsychotic use and between the Anaeromassilibacillus and lithium use. Our findings suggest that microbial balances could be a reproducible method for identifying BD/SSD-specific microbial signatures, with potential diagnostic and prognostic applications. Notably, Lachnoclostridium and Eggerthella emerge as frequently occurring bacteria in BD/SSD. Last, our study reaffirms the previously established link between Klebsiella and antipsychotic medication use and identifies a novel association between Anaeromassilibacillus and lithium use. [ABSTRACT FROM AUTHOR]

Functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) are common clinical disorders characterized by recurrent diarrhea and abdominal pain. Although their pathogenesis has not been fully clarified, disruptions in intestinal motility and immune function are widely accepted as contributing factors to both conditions, and the brain-gut axis plays a key role in these processes. Traditional Chinese Medicine (TCM) employs a holistic approach to treatment, considers spleen and stomach impairments and liver abnormality the main pathogenesis of these two diseases, and offers a unique therapeutic strategy that targets these interconnected pathways. Clinical evidence shows the great potential of TCM in treating FGIDs and IBD. This study presents a systematic description of the pathological mechanisms of FGIDs and IBD in the context of the brain-gut axis, discusses clinical and preclinical studies on TCM and acupuncture for the treatment of these diseases, and summarizes TCM targets and pathways for the treatment of FGIDs and IBD, integrating ancient wisdom with contemporary biomedical insights. The alleviating effects of TCM on FGID and IBD symptoms are mainly mediated through the modulation of intestinal immunity and inflammation, sensory transmission, neuroendocrine-immune network, and microbiota and their metabolism through brain-gut axis mechanisms. TCM may be a promising treatment option in controlling FGIDs and IBD; however, further high-quality research is required. This review provides a reference for an in-depth exploration of the interventional effects and mechanisms of TCM in FGIDs and IBD, underscoring TCM's potential to recalibrate the dysregulated brain-gut axis in FGIDs and IBD. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The study of the brain-gut axis and its impact on cognitive function and in the development of neurodegenerative diseases is a very timely topic of interest to researchers. This review summarizes information on the basic mechanisms of gut-brain communication. We then discuss the roles of the gut microbiome as a neuroprotective factor in neurodegeneration. The gut microbiota is extremely important in maintaining the body's homeostasis, shaping the human immune system and the proper functioning of the brain. The intestinal microflora affects the processes of neuroplasticity, synaptogenesis, and neuronal regeneration. This review aims to explain changes in the composition of the bacterial population of the intestinal microflora among patients with Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Abnormalities in gut microflora composition are also noted in stress, depression, or autism spectrum development. New observations on psychobiotic supplementation in alleviating the symptoms of neurodegenerative diseases are also presented.

Major depressive disorder (MDD) is a common mental illness. Currently, nearly 16% of the global population is affected by depression-related symptoms, while the diagnosis and treatment rate of MDD patients in China is only 9.5%. MDD is characterised by high morbidity and low recovery rate, and how to effectively improve its therapeutic effect has been a hot research topic in recent years. Antidepressants, as the main treatment for MDD, have the disadvantages of many adverse effects and slow onset of action, prompting people to pay attention to the non-pharmacological treatments of MDD. Dietary intervention is a kind of non-pharmacological treatment by changing dietary structures and rhythms; the current application of dietary intervention to psychiatry is very extensive, and it has been proved to be effective in the treatment of depression. Recent research suggests that dietary interventions can treat and ameliorate depressive symptoms by influencing brain-gut axis-related eating mechanisms. This article reviews the multidimensional exploration of dietary interventions in the treatment of depression: dietary structure interventions, dietary rhythm interventions, and the role of intestinal flora. It details the modalities of dietary interventions and the related mechanisms involved, and provides reference for dietary interventions in the treatment of depression-related symptoms.

Abstract Background Existing evidence suggests that alterations in the gut microbiome are closely associated with major depressive disorder (MDD). We aimed to reveal the causal relationships between MDD and various microbial taxa in the gut. Methods We used the two-sample Mendelian randomization (TSMR) to explore the bidirectional causal effects between gut microbiota and MDD. The genome-wide association studies summary results of gut microbiota were obtained from two large consortia, the MibioGen consortium and the Dutch Microbiome Project, which we analyzed separately. Results Our TSMR analysis identified 10 gut bacterial taxa that were protective against MDD, including phylum Actinobacteria, order Clostridiales, and family Bifidobacteriaceae (OR: 0.96 ∼ 0.98). Ten taxa were associated with an increased risk of MDD, including phyla Firmicutes and Proteobacteria, class Actinobacteria, and genus Alistipes (OR: 1.01 ∼ 1.09). On the other hand, MDD may decrease the abundance of 12 taxa, including phyla Actinobacteria and Firmicutes, families Bifidobacteriaceae and Defluviitaleaceae (OR: 0.63 ∼ 0.88). MDD may increase the abundance of 8 taxa, including phylum Bacteroidetes, genera Parabacteroides, and Bacteroides (OR: 1.12 ∼ 1.43). Conclusions Our study supports that there are mutual causal relationships between certain gut microbiota and the development of MDD suggesting that gut microbiota may be targeted in the treatment of MDD.

Abstract Background Necrotizing enterocolitis (NEC) and intracranial hemorrhage are severe emergencies in the neonatal period. The two do not appear to be correlated. However, our report suggests that parenchymal brain hemorrhage in full-term newborns may put patients at risk for NEC by altering intestinal function through the brain-gut axis. Case presentation We present a case of spontaneous parenchymal cerebral hemorrhage in a full-term newborn who developed early-stage NEC on Day 15. Conclusions It is possible to consider brain parenchymal hemorrhage as a risk factor for the appearance of NEC. Clinicians should be highly cautious about NEC in infants who have experienced parenchymal hemorrhage. This article is the first to discuss the relationship between parenchymal hemorrhage and NEC in full-term newborns.

Objective: To investigate effect of Yiqi Huoxue Huazhuo Jiedu Prescription （YHHJP） on inflammatory factors of brain tissues, tight junction between brain and colon tissues, intestinal flora and bacterial metabolites in cerebral ischemia reperfusion injury （CIRI） rats based on brain-gut axis. Methods: Fifty male SD rats of SPF grade were randomly divided into sham-operation group （Sham）, model group （MCAO）, low, medium, high doses YHHJP groups （TCM-L/TCM-M/TCM-H）. Middle cerebral artery occlusion model was established according to Zea Longa methods. Neurological function defects were detected 3 days after administration. TTC staining was used to calculate infarct size of brain tissue. Pathological changes of brain tissue were observed by Nissl staining, and pathological changes of brain and colon tissues were observed by HE staining. IL-1β, IL-6, TNF-α in brain tissue and LPS content in serum were detected by ELISA, and D-LA content in serum was detected by biochemical method. Gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1, Claudin-1 in colon tissue were studied by Real-time fluorescent quantitative PCR. Intestinal flora were detected by 16S rDNA high-throughput sequencing. Results: Compared with Sham group, pathological damage of brain and colon tissue were serious in MCAO group, intestinal flora structure was significantly different, neural function impairment was aggravated, infarct size was increased, IL-1β, IL-6, TNF-α contents in brain tissue, and LPS, D-LA contents in serum were increased, gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1 and Claudin-1 in colon tissue were decreased significantly （P<0.05）. Compared with MCAO group, pathological damage of brain and colon tissue of rats were relieved in TCM-L, TCM-M, TCM-H groups, disturbance of intestinal microflora microecology was improved, neurological function impairment and infarct size were markedly decreased, IL-1β, IL-6, TNF-α contents in brain tissue were decreased, gene expressions of ZO-1 and Claudin-1 in colon tissue were increased significantly （P<0.05）; LPS and D-LA contents in serum were decreased in YHHJP medium and high doses groups, while gene expressions of ZO-1 and Claudin-5 in brain tissue were increased significantly （P< 0.05）. Conclusion: YHHJP has a good effect on improving CIRI, whose mechanism may be related to regulating diversity of intestinal flora, reducing release of intestinal bacterial metabolites LPS and D-LA, increasing gene expressions of tight junction proteins ZO-1, Claudin-5 and Claudin-1, and down-regulating secretion of proinflammatory cytokine. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a common mental illness. Currently, nearly 16% of the global population is affected by depression-related symptoms, while the diagnosis and treatment rate of MDD patients in China is only 9.5%. MDD is characterised by high morbidity and low recovery rate, and how to effectively improve its therapeutic effect has been a hot research topic in recent years. Antidepressants, as the main treatment for MDD, have the disadvantages of many adverse effects and slow onset of action, prompting people to pay attention to the non-pharmacological treatments of MDD. Dietary intervention is a kind of non-pharmacological treatment by changing dietary structures and rhythms; the current application of dietary intervention to psychiatry is very extensive, and it has been proved to be effective in the treatment of depression. Recent research suggests that dietary interventions can treat and ameliorate depressive symptoms by influencing brain-gut axis-related eating mechanisms. This article reviews the multidimensional exploration of dietary interventions in the treatment of depression: dietary structure interventions, dietary rhythm interventions, and the role of intestinal flora. It details the modalities of dietary interventions and the related mechanisms involved, and provides reference for dietary interventions in the treatment of depression-related symptoms. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Health Science Yuksek Ihtisas University / Yüksek İhtisas Üniversitesi Sağlık Bilimleri Dergisi is the property of Journal of Health Science Yuksek Ihtisas University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The human reward network consists of interconnected brain regions that process stimuli associated with satisfaction and modulate pleasure-seeking behaviors. Impairments in reward processing have been implicated in several medical and psychiatric conditions, and there is a growing interest in disentangling the underlying pathophysiological mechanisms. The brain–gut axis plays a regulatory role in several higher-order neurophysiological pathways, including reward processing. In this context, the aim of the current review was to critically appraise research findings on the contribution of the brain–gut axis to the human reward system. Enteric neuropeptides, which are implicated in the regulation of hunger and satiety, such as ghrelin, PYY3–36, and glucagon-like peptide 1 (GLP-1), have been associated with the processing of food-related, alcohol-related, and other non-food-related rewards, maintaining a delicate balance between the body's homeostatic and hedonic needs. Furthermore, intestinal microbiota and their metabolites have been linked to differences in the architecture and activation of brain reward areas in obese patients and patients with attention deficit and hyperactivity disorder. Likewise, bariatric surgery reduces hedonic eating by altering the composition of gut microbiota. Although existing findings need further corroboration, they provide valuable information on the pathophysiology of reward-processing impairments and delineate a novel framework for potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary tumor of the brain, accounting for 81 % of central nervous system (CNS) malignant tumors. The degree of malignancy is high, and the current treatment methods are limited. In recent years, with the in-depth study of intestinal flora and brain-gut axis, it has been found that the diversity of gut microbiota plays an important role in the regulation of glioma. The mechanism is that the intestinal flora affects the development of glioma through the role of immune regulation and metabolites. In addition, it has been confirmed that there is a certain correlation between some probiotics and glioma, which provides a new application prospect for the treatment of glioma. This paper discusses the main intestinal bacteria that regulate gliomas as well as the role and regulatory mechanisms of intestinal flora in the development of gliomas, and provides ideas for the discovery of new targets for glioma treatment and further improvement of treatment options. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke (AIS) remains a major cause of mortality and long-term disability worldwide, driven by complex and multifaceted etiological factors. Metabolic dysregulation, gastrointestinal microbiome alterations, and systemic inflammation are emerging as significant contributors to AIS pathogenesis. This review addresses the critical need to understand how these factors interact to influence AIS risk and outcomes. We aim to elucidate the roles of dysregulated adipokines in obesity, the impact of gut microbiota disruptions, and the neuroinflammatory cascade initiated by lipopolysaccharides (LPS) in AIS. Dysregulated adipokines in obesity exacerbate inflammatory responses, increasing AIS risk and severity. Disruptions in the gut microbiota and subsequent LPS-induced neuroinflammation further link systemic inflammation to AIS. Advances in neuroimaging and biomarker development have improved diagnostic precision. Here, we highlight the need for a multifaceted approach to AIS management, integrating metabolic, microbiota, and inflammatory insights. Potential therapeutic strategies targeting these pathways could significantly improve AIS prevention and treatment. Future research should focus on further elucidating these pathways and developing targeted interventions to mitigate the impacts of metabolic dysregulation, microbiome imbalances, and inflammation on AIS. [ABSTRACT FROM AUTHOR]

This study employed Mendelian randomization (MR) analysis to systematically investigate the potential connections between gut microbiota and the risk of glioblastoma (GBM). We identified 12 microbial groups closely associated with the incidence risk of GBM. Subsequently, MR analysis was conducted on 1,091 blood metabolites and 309 metabolite ratios, revealing 19 metabolites that exert an impact on the occurrence of GBM. Hypothesizing that gut microbiota may influence the risk of glioblastoma multiforme by modulating these metabolites, we performed MR analyses, considering each microbial group as exposure and each metabolite as an outcome. Through these analyses, we constructed a regulatory network encompassing gut microbiota, metabolites, and GBM, providing a novel perspective for a deeper understanding of the role of the gut-brain axis in the pathogenesis of GBM. This research offers crucial insights into how gut microbiota may affect the risk of GBM by regulating specific metabolites. The identified regulatory network of the gut-brain axis may play a significant role in the formation and development of GBM, providing valuable information for future research and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Existing evidence suggests that alterations in the gut microbiome are closely associated with major depressive disorder (MDD). We aimed to reveal the causal relationships between MDD and various microbial taxa in the gut. Methods: We used the two-sample Mendelian randomization (TSMR) to explore the bidirectional causal effects between gut microbiota and MDD. The genome-wide association studies summary results of gut microbiota were obtained from two large consortia, the MibioGen consortium and the Dutch Microbiome Project, which we analyzed separately. Results: Our TSMR analysis identified 10 gut bacterial taxa that were protective against MDD, including phylum Actinobacteria, order Clostridiales, and family Bifidobacteriaceae (OR: 0.96 ∼ 0.98). Ten taxa were associated with an increased risk of MDD, including phyla Firmicutes and Proteobacteria, class Actinobacteria, and genus Alistipes (OR: 1.01 ∼ 1.09). On the other hand, MDD may decrease the abundance of 12 taxa, including phyla Actinobacteria and Firmicutes, families Bifidobacteriaceae and Defluviitaleaceae (OR: 0.63 ∼ 0.88). MDD may increase the abundance of 8 taxa, including phylum Bacteroidetes, genera Parabacteroides, and Bacteroides (OR: 1.12 ∼ 1.43). Conclusions: Our study supports that there are mutual causal relationships between certain gut microbiota and the development of MDD suggesting that gut microbiota may be targeted in the treatment of MDD. [ABSTRACT FROM AUTHOR]

Epilepsy is a common neurological disorder that affects approximately 10.5 million children worldwide. Approximately 33% of affected patients exhibit resistance to all available antiseizure medications, but the underlying mechanisms are unknown and there is no effective treatment. Increasing evidence has shown that an abnormal gut microbiota may be associated with epilepsy. The gut microbiota can influence the function of the brain through multiple pathways, including the neuroendocrine, neuroimmune, and autonomic nervous systems. This review discusses the interactions between the central nervous system and the gastrointestinal tract (the brain-gut axis) and the role of the gut microbiota in the pathogenesis of epilepsy. However, the exact gut microbiota involved in epileptogenesis is unknown, and no consistent results have been obtained based on current research. Moreover, the target that should be further explored to identify a novel antiseizure drug is unclear. The role of the gut microbiota in epilepsy will most likely be uncovered with the development of genomics technology. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of disorders of gut–brain interaction (DGBI) in children is exclusively based on clinical criteria called the Rome criteria. The inter‐rater reliability (IRR) measures how well two raters agree with a diagnosis using the same diagnostic tool. Previous versions of the Rome criteria showed only fair to moderate IRR. There have been no studies assessing the IRR of the current edition of the pediatric Rome criteria (Rome IV). This study sought to investigate the IRR of the pediatric Rome IV criteria and compare its reliability with the previous versions of the Rome criteria. We hypothesized that changes made to Rome IV would result in higher IRR than previous versions. Methods: This study used the same methodology as the previous studies on Rome II and III, including identical clinical vignettes, number of raters, and levels of expertise. Participants included 10 pediatric gastroenterology fellows and 10 pediatric gastroenterology specialists. IRR was assessed using the percentage of agreement and Cohen's kappa coefficient to account for possible agreement by chance. Results: The average IRR percentage of agreement using the Rome IV criteria was 55% for pediatric gastroenterologists and 48.5% for fellows, indicating moderate agreement (k = 0.54 for specialists, k = 0.47 for fellows). The results demonstrated higher percentages of agreement and kappa coefficients compared to the Rome II and III criteria. Conclusions: The findings demonstrate improved reliability in Rome IV compared to Rome II and III, suggesting that the changes incorporated into the Rome IV criteria have enhanced diagnostic consistency. Despite the advancements, the reliability is still moderate, indicating the need for further refinement of future versions of the Rome criteria. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to assess the knowledge level of students in the Faculty of Medicine and the Faculty of Nutrition and Dietetics at Bahçeşehir University (BAU) regarding the role of nutrition and gut microbiota in Alzheimer's disease (AD). Materials and Methods: A descriptive research design was employed to measure the knowledge level of first- and second-year students from the Faculties of Medicine and Nutrition and Dietetics at BAU regarding the role of nutrition and gut microbiota in AD. A 23-question questionnaire was administered, divided into five sections: (1) Demographic characteristics, (2) Understanding of AD, (3) Understanding of the relationship between nutrition and AD, (4) Understanding of the relationship between nutrition and gut microbiota, and (5) Understanding of the relationship between gut microbiota and AD. The questionnaire included two types of closed-ended questions: (1) Dichotomous and (2) Multiple-choice questions. Results: Medical students demonstrated a higher overall knowledge level compared to Nutrition and Dietetics students. However, within both faculties, firstyear students exhibited a greater understanding of the relationship between gut microbiota and AD than second-year students. Conclusion: These findings underscore the importance of early education in establishing a strong knowledge foundation. Addressing these knowledge gaps will better prepare future healthcare professionals to understand the impact of nutrition and gut microbiota on AD. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common and burdensome disorder characterized by chronic recurrent abdominal pain and altered bowel habits. IBS remains misunderstood, leading to delayed diagnosis, impaired quality of life, and substantial healthcare costs. Advancing clinicians' understanding of this complex biopsychosocial process, using a positive diagnostic strategy rather than a diagnosis of exclusion, and incorporating a multimodal treatment approach expedite time to diagnosis, facilitate symptom relief, and reduce financial expenditure. [ABSTRACT FROM AUTHOR]

This study delves into the pivotal role of the gut microbiota and the brain-gut axis in Parkinson’s Disease (PD), a neurodegenerative disorder with significant motor and non-motor implications. It posits that disruptions in gut microbiota—dysbiosis—and alterations in the brain-gut axis contribute to PD’s pathogenesis. Our findings highlight the potential of the gastrointestinal system’s early involvement in PD, suggested by the precedence of gastrointestinal symptoms before motor symptoms emerge. This observation implies a possible gut-originated disease pathway. The analysis demonstrates that dysbiosis in PD patients leads to increased intestinal permeability and systemic inflammation, which in turn exacerbates neuroinflammation and neurodegeneration. Such insights into the interaction between gut microbiota and the brain-gut axis not only elucidate PD’s underlying mechanisms but also pave the way for novel therapeutic interventions. We propose targeted treatment strategies, including dietary modifications and fecal microbiota transplantation, aimed at modulating the gut microbiota. These approaches hold promise for augmenting current PD treatment modalities by alleviating both motor and non-motor symptoms, thereby potentially improving patient quality of life. This research underscores the significance of the gut microbiota in the progression and treatment of PD, advocating for an integrated, multidisciplinary approach to develop personalized, efficacious management strategies for PD patients, combining insights from neurology, microbiology, and nutritional science. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) and intracranial hemorrhage are severe emergencies in the neonatal period. The two do not appear to be correlated. However, our report suggests that parenchymal brain hemorrhage in full-term newborns may put patients at risk for NEC by altering intestinal function through the brain-gut axis. Case presentation: We present a case of spontaneous parenchymal cerebral hemorrhage in a full-term newborn who developed early-stage NEC on Day 15. Conclusions: It is possible to consider brain parenchymal hemorrhage as a risk factor for the appearance of NEC. Clinicians should be highly cautious about NEC in infants who have experienced parenchymal hemorrhage. This article is the first to discuss the relationship between parenchymal hemorrhage and NEC in full-term newborns. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is caused by the misfolding and aggregation of α-synuclein in neurons into toxic oligomers and fibrils that have prion-like properties allowing them to infect healthy neurons and to be transmitted to animal models of PD by injection or oral exposure. Given α-synuclein fibrils' potential transmission on the gut-brain axis, α-synuclein may be transmitted through colonoscopy procedures. Objective: This study examines a possible association between colonoscopy and PD. Methods: Longitudinal health insurance data of 250,000 individuals aged 50+ from 2004–2019 was analyzed. Cox proportional hazard and competing risk models with death as a competing event were estimated to calculate the risk of PD. Colonoscopy was categorized as never receiving colonoscopy, colorectal cancer (CRC) screening without or with biopsy, destruction or excision (BDE), and diagnostic colonoscopy without or with BDE. Results: We identified 6,422 new cases of PD among 221,582 individuals. The Cox model revealed a significantly increased risk of PD for patients who ever had a diagnostic colonoscopy without or with BDE (HR = 1.31; 95% CI: [1.23–1.40]; HR = 1.32 [1.22–1.42]) after adjustment for age and sex. After controlling for covariates and death, persons who ever underwent CRC screening had a 40% reduced risk of PD (CRHR = 0.60 [0.54–0.67]), while persons who underwent diagnostic colonoscopy had a 20% reduced risk of PD (CRHR = 0.81 [0.75–0.88]). Conclusions: Colonoscopy does not increase the risk of PD, after adjusting for death and covariates. Individuals who underwent only CRC screening had the lowest risk of PD, which may be a result of a more health-conscious lifestyle. [ABSTRACT FROM AUTHOR]

Background: Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)‐like symptoms. Although these symptoms cause significant reductions in quality of life, evidence‐based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS‐like symptoms in IBD patients with quiescent disease. Methods: We performed a single‐center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 μg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS‐like symptoms in IBD patients. Key Results: A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0–82.0) 63.3 per 1000 person‐years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. Conclusions & Inferences: Mood disorder and Crohn's disease were positively associated with IBS‐like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS‐like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS‐like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

The holobiont theory of evolution explains how individuals are deeply symbiotic with their gut microbes, such that microbes are adapted to influence host metabolism, immunity and behaviour, as signalled from the gut to the brain. For eusocial taxa like the Western honey bee (Apis mellifera), this brain-gut axis may scale up from the individual to affect entire colonies. Here, we examine how microbial supplementation of honey bee feeds could manipulate the brain-gut axis to affect hygienic and other social behaviours relevant to beekeeping, such as foraging, recruitment (dance language) and defence. To illustrate this concept, we focus on various lactic acid-producing bacteria that can synthesize neurotransmitters such as octopamine, dopamine, serotonin and γ-aminobutyric acid, which can influence an individual bee’s behavioural cycles and responsiveness to environmental cues. If the behaviour of a worker bee can be deliberately manipulated, and this effect multiplied across many workers, microbial neurotherapeutics could conceivably render colonies more behaviourally responsive to symptoms of disease, or more motivated to forage or possibly less aggressive towards beekeepers. Drawing from the scientific literature, we infer how microbial supplements, such as neurostimulatory or neurosuppressive probiotics, could be applied or even engineered to co-opt the brain-gut axis to bolster colony health or improve performance. The mechanistic link between the gut microbiota and the collective social behaviour of single colonies remains an understudied aspect of honey bee social biology with relevance to apiculture.

Abstract As a prevalent psychiatric disorder, the etiology of depression remains largely elusive, necessitating further investigation into its pathophysiological underpinnings. Notably, the comorbidity of depression with other mental health conditions and chronic diseases often presents alongside gastrointestinal symptoms. Research on the microbiome‐gut‐brain axis (MGBA) has emerged as a promising avenue for elucidating the pathophysiology of depression. In this study, bibliometric analysis tools, including HistCite, VOSviewer, CiteSpace, and the bibliometrix R package, were employed to comprehensively explore the MGBA‐depression connection. A comprehensive survey identified 980 relevant publications concerning the MGBA‐depression relationship, with a significant increase in research output observed since 2014. This analysis pinpointed five key factors within the MGBA‐depression domain: cytokines, maternal separation, neuroinflammation, probiotics, and the vagus nerve. The insights presented herein offer valuable perspectives on prevailing research models that investigate the intricate interplay among the microbiome, gastrointestinal system, and brain within the context of depression. Based on these findings, future investigations should prioritize developing microbial‐based interventions and innovative therapeutic modalities aimed at alleviating depression. By leveraging interdisciplinary collaboration and enhancing our understanding of MGBA–depression connections, we can pave pathways toward more effective treatments. Furthermore, improving outcomes for individuals with depression may be achieved by deepening our comprehension of the complex relationships between depression itself, the gut‐brain axis, and gastrointestinal microbiota.

Interest in the microbiome and its correlation with different neurological diseases has grown significantly over the past decade. The gut microbiome contains a vast array of diverse organisms living in the gastrointestinal (GI) tract. Predominantly composed of bacteria, the gut microbiome helps regulate homeostasis and metabolism in the host, aiding in immune system development as well as vitamin and nutrient absorption. Studies suggest that, in addition to providing humans with these physiological benefits, the gut microbiome is also linked to and communicates with the brain via the gut-brain axis (GBA). Long-standing research on the GBA has demonstrated that the GI tract and the central nervous system are interconnected through both neurological and immunological signaling pathways. Recent research is expanding our understanding of the microbiome and the GBA, revealing correlations between the microbiome impact on the GBA and neurological conditions such as Alzheimer’s dementia and Lewy body dementia, going as far as to identify and highlight specific microbial species that may serve as risk or protective factors for various forms of dementia. This letter aims to highlight the current findings and recommend the use of tools such as microbial cell-free DNA testing to gain a better understanding of the role of gut dysbiosis in dementia patients.

Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

Dougho Park,1,2 Hyoung Seop Kim,3 Jong Hun Kim4 1Medical Research Institute, Pohang Stroke and Spine Hospital, Pohang, Republic of Korea; 2Department of Medical Science and Engineering, School of Convergence Science and Technology, Pohang University of Science and Technology, Pohang, Republic of Korea; 3Department of Physical Medicine and Rehabilitation, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea; 4Department of Neurology, National Health Insurance Service Ilsan Hospital, Goyang, Republic of KoreaCorrespondence: Jong Hun Kim, Department of Neurology, National Health Insurance Service Ilsan Hospital, 100 Ilsan-ro, Goyang, 10444, Republic of Korea, Tel +82-31-900-0213, Fax +82-31-900-0343, Email jh7521@naver.comPurpose: Clinical studies on dysbiosis and stroke outcomes has been insufficient to establish clear evidence. This study aimed to investigate the effects of pre-antibiotic use before a stroke event on secondary outcomes using a longitudinal population-level database.Patients and Methods: This retrospective cohort study included adults aged 55 years or older diagnosed with acute ischemic stroke (AIS) and acute hemorrhagic stroke (AHS) between 2004 and 2007. Patients were followed-up until the end of 2019, and the target outcomes were secondary AIS, AHS, and all-cause mortality. Multivariable Cox regression analyses were applied, and we adjusted covariates such as age, sex, socioeconomic status, hypertension, diabetes, and dyslipidemia. Pre-antibiotic use was identified from 7 days to 1 year before the acute stroke event.Results: We included 159,181 patients with AIS (AIS group) and 49,077 patients with AHS (AHS group). Pre-antibiotic use significantly increased the risk of secondary AIS in the AIS group (adjusted hazard ratio [aHR], 1.03; 95% confidence interval [CI], 1.01– 1.05; p = 0.009) and secondary AHS in the AHS group (aHR, 1.08; 95% CI, 1.03– 1.12; p < 0.001). Furthermore, pre-antibiotic use in the AIS group was associated with a lower risk of mortality (aHR, 0.95; 95% CI, 0.94– 0.96; p < 0.001).Conclusion: Our population-based longitudinal study revealed that pre-antibiotic use was associated with a higher risk of secondary stroke and a lower risk of mortality in the AIS and AHS groups. Further studies are needed to understand the relationship between dysbiosis and stroke outcomes.Keywords: brain-gut axis, dysbiosis, mortality, stroke

Abstract Objective The purpose of this study is to investigate the connection of pre-competition anxiety with gut microbiota and metabolites in wrestlers with different sports performances. Methods One week prior to a national competition, 12 wrestlers completed anxiety questionnaires. Faecal and urine samples were collected for the analysis of gut microbiota and metabolites through the high-throughput sequencing of the 16 S rRNA gene in conjunction with untargeted metabolomics technology. The subjects were divided into two groups, namely, achievement (CP) and no-achievement (CnP) wrestlers, on the basis of whether or not their performances placed them in the top 16 at the competition. The relationship amongst the variations in gut microbiota, metabolites, and anxiety indicators was analyzed. Results (1) The CP group exhibited significantly higher levels of “state self-confidence,” “self-confidence,” and “somatic state anxiety” than the CnP group. Conversely, the CP group displayed lower levels of “individual failure anxiety” and “sports competition anxiety” than the CnP group. (2) The gut microbiota in the CP group was more diverse and abundant than that in the CnP group. Pre-competition anxiety was linked to Oscillospiraceae UCG_005, Paraprevotella, Ruminococcaceae and TM7x. (3) The functions of differential metabolites in faeces and urine of the CP/CnP group were mainly enriched in caffeine metabolism, lipopolysaccharide biosynthesis and VEGF and mTOR signaling pathways. Common differential metabolites in feces and urine were significantly associated with multiple anxiety indicators. Conclusions Wrestlers with different sports performance have different pre-competition anxiety states, gut microbiota distribution and abundance and differential metabolites in faeces and urine. A certain correlation exists between these psychological and physiological indicators.

The brain-gut axis refers to the communication between the central nervous system and the gastrointestinal tract, with the gut microbiome playing a crucial role. While our understanding of the interaction between the gut microbiome and the host's physiology is still in its nascent stage, evidence suggests that the gut microbiota can indeed modulate host behavior. Understanding the specific mechanisms by which the gut microbiota community modulates the host's behavior remains the focus of present and future neuro-gastroenterology studies. This paper reviews several pieces of evidence from the literature on the impact of gut microbiota on host behavior across animal taxa. We explore the different pathways through which this modulation occurs, with the aim of deepening our understanding of the fascinating relationship between the gut microbiome and the central nervous system.

BackgroundEvidence supports a role for the gut-brain axis in Parkinson's disease (PD). Mice overexpressing human wild type α- synuclein (Thy1-haSyn) exhibit slow colonic transit prior to motor deficits, mirroring prodromal constipation in PD. Identifying molecular changes in the gut could provide both biomarkers for early diagnosis and gut-targeted therapies to prevent progression.ObjectiveTo identify early molecular changes in the gut-brain axis in Thy1-haSyn mice through gene expression profiling.MethodsGene expression profiling was performed on gut (colon) and brain (striatal) tissue from Thy1-haSyn and wild-type (WT) mice aged 1 and 3 months using 3' RNA sequencing. Analysis included differential expression, gene set enrichment and weighted gene co-expression network analysis (WGCNA).ResultsAt one month, differential expression (Thy1-haSyn vs. WT) of mitochondrial genes and pathways related to PD was discordant between gut and brain, with negative enrichment in brain (enriched in WT) but positive enrichment in gut. Linear regression of WGCNA modules showed partial independence of gut and brain gene expression changes. Thy1-haSyn-associated WGCNA modules in the gut were enriched for PD risk genes and PD-relevant pathways including inflammation, autophagy, and oxidative stress. Changes in gene expression were modest at 3 months.ConclusionsOverexpression of haSyn acutely disrupts gene expression in the colon. While changes in colon gene expression are highly related to known PD-relevant mechanisms, they are distinct from brain changes, and in some cases, opposite in direction. These findings are in line with the emerging view of PD as a multi-system disease.

Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia. Herein, after briefly reviewing the classification of acetylcholine-activated receptors and the role that nicotinic and muscarinic cholinergic signaling plays in normal digestive function, we consider the mechanics of acetylcholine synthesis and release by neuronal and non-neuronal cells in the gastrointestinal microenvironment, and current methodology and challenges in measuring serum and tissue acetylcholine levels accurately. Then, we critically evaluate the evidence that constitutive and ligand-induced activation of acetylcholine-activated receptors plays a role in promoting gastrointestinal neoplasia. We focus primarily on adenocarcinomas of the stomach, pancreas, and colon, because these cancers are particularly common worldwide and, when diagnosed at an advanced stage, are associated with very high rates of morbidity and mortality. Throughout this comprehensive review, we concentrate on identifying novel ways to leverage these observations for prognostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

The luminal environment is rich in macronutrients coming from our diet and resident microbial populations including their metabolites. Together, they have the capacity to modulate unique cell surface receptors, known as G‐protein coupled receptors (GPCRs). Along the entire length of the gut epithelium, enteroendocrine cells express GPCRs to interact with luminal contents, such as GPR93 and the calcium sensing receptor to sense proteins, FFA2 and GPR84 to sense fatty acids, and SGLT1 and T1R to sense carbohydrates. Nutrient–receptor interaction causes the release of hormonal stores such as glucagon‐like peptide 1, peptide YY, and cholecystokinin, which further regulate gut function. Existing data show the role of luminal components and microbial fermentation products on gut function. However, there is a lack of understanding in the mechanistic interactions between diet‐derived luminal components and microbial products and nutrient‐sensing receptors and downstream gastrointestinal modulation. This review summarizes current knowledge on various luminal components and describes in detail the range of nutrients and metabolites and their interaction with nutrient receptors in the gut epithelium and the emerging impact on immune cells. [ABSTRACT FROM AUTHOR]

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The brain- and body-first models of Lewy body disorders predict that aggregated alpha-synuclein pathology usually begins in either the olfactory system or the enteric nervous system. In both scenarios the pathology seems to arise in structures that are closely connected to the outside world. Environmental toxicants, including certain pesticides, industrial chemicals, and air pollution are therefore plausible trigger mechanisms for Parkinson's disease and dementia with Lewy bodies. Here, we propose that toxicants inhaled through the nose can lead to pathological changes in alpha-synuclein in the olfactory system that subsequently spread and give rise to a brain-first subtype of Lewy body disease. Similarly, ingested toxicants can pass through the gut and cause alpha-synuclein pathology that then extends via parasympathetic and sympathetic pathways to ultimately produce a body-first subtype. The resulting spread can be tracked by the development of symptoms, clinical assessments, in vivo imaging, and ultimately pathological examination. The integration of environmental exposures into the brain-first and body-first models generates testable hypotheses, including on the prevalence of the clinical conditions, their future incidence, imaging patterns, and pathological signatures. The proposed link, though, has limitations and leaves many questions unanswered, such as the role of the skin, the influence of the microbiome, and the effects of ongoing exposures. Despite these limitations, the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson's disease and open the door toward the ultimate goal –prevention. [ABSTRACT FROM AUTHOR]

Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain‐gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA‐ and DR‐related drugs for digestive system diseases. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD), characterized by the loss of dopaminergic neurons, is a progressive neurodegenerative disorder. Recent research has revealed a significant connection between gut microbiota and PD. To gain insight into research interests, disciplinary contexts, and potential future directions, a comprehensive bibliometric analysis was conducted on the brain-gut axis and PD literature published between 2014 and 2023. Methods: Relevant literature records were gathered from the Web of Science Core Collection on August 11, 2023. The data were then analyzed by Biblioshiny R packages and VOSviewer (version 1.6.19). Results: The dataset revealed an upward trend in annual scientific publications on the brain-gut axis and PD, with an annual growth rate of 50.24%. China, the United States, and Italy were the top three most productive countries/regions. The journal "International Journal Of Molecular Sciences" published the most articles, while "Movement Disorders" received the highest number of citations. Professor Keshavarzian A emerged as the most prolific author, while Professor Scheperjans F held the highest h-index. Keyword analysis highlighted "alphasynuclein" as the most frequent term, with "mouse model," "inflammation," and "risk" as emerging research topics. Additionally, "central nervous system" and "intestinal bacterial overgrowth" attracted increasing attention. Conclusion: This study examined current trends and hotspots in the bibliometric landscape of the brain-gut axis and PD research. Future research directions should explore the functional and metabolic activities of gut microbiota. Additionally, transitioning from observational to interventional study designs offers the potential for personalized interventions and disease prediction. These findings can guide researchers in navigating the latest developments and shaping the future directions of this field. [ABSTRACT FROM AUTHOR]

Injuries and subclinical effects from exposure to blasts are of significant concern in military operational settings, including tactical training, and are associated with self-reported concussion-like symptomology and physiological changes such as increased intestinal permeability (IP), which was investigated in this study. Time-series gene expression and IP biomarker data were generated from "breachers" exposed to controlled, low-level explosive blast during training. Samples from 30 male participants at pre-, post-, and follow-up blast exposure the next day were assayed via RNA-seq and ELISA. A battery of symptom data was also collected at each of these time points that acutely showed elevated symptom reporting related to headache, concentration, dizziness, and taking longer to think, dissipating ~16 h following blast exposure. Evidence for bacterial translocation into circulation following blast exposure was detected by significant stepwise increase in microbial diversity (measured via alpha-diversity p = 0.049). Alterations in levels of IP protein biomarkers (i.e., Zonulin, LBP, Claudin-3, I-FABP) assessed in a subset of these participants (n = 23) further evidenced blast exposure associates with IP. The observed symptom profile was consistent with mild traumatic brain injury and was further associated with changes in bacterial translocation and intestinal permeability, suggesting that IP may be linked to a decrease in cognitive functioning. These preliminary findings show for the first time within real-world military operational settings that exposures to blast can contribute to IP. [ABSTRACT FROM AUTHOR]

Psychiatric disorders represent a primary source of disability worldwide, manifesting as disturbances in individuals' cognitive processes, emotional regulation, and behavioral patterns. In the quest to discover novel therapies and expand the boundaries of neuropharmacology, studies from the field have highlighted the gut microbiota's role in modulating these disorders. These alterations may influence the brain's processes through the brain–gut axis, a multifaceted bidirectional system that establishes a connection between the enteric and central nervous systems. Thus, probiotic and prebiotic supplements that are meant to influence overall gut health may play an insightful role in alleviating psychiatric symptoms, such as the cognitive templates of major depressive disorder, anxiety, or schizophrenia. Moreover, the administration of psychotropic drugs has been revealed to induce specific changes in a microbiome's diversity, suggesting their potential utility in combating bacterial infections. This review emphasizes the intricate correlations between psychiatric disorders and the gut microbiota, mentioning the promising approaches in regard to the modulation of probiotic and prebiotic treatments, as well as the antimicrobial effects of psychotropic medication. [ABSTRACT FROM AUTHOR]

Introduction and Purpose. Parkinson’s Disease (PD) is a chronic neurodegenerative disorder caused by dopamine deficiency due to neuronal degeneration, leading to motor and non-motor symptoms. Gastrointestinal symptoms are common and often precede motor symptoms. There is increasing evidence that imbalanced gut microbiota may influence the gut-brain axis and contribute to motor and non-motor PD symptoms. Fecal microbiota transplantation (FMT) may have the potential to restore gut flora and improve PD symptoms. The study aims to explore the current knowledge on the impact of FMT on PD symptoms, acknowledging existing reviews and highlighting new studies not yet reviewed. Understanding the underlying causes of PD could lead to better treatment, diagnostics, and prevention. State of knowledge. PD patients suffer from specific gut dysbiosis which leads to imbalance in the produced pro- and anti-inflammatory substances in the intestinal lumen resulting in aggreviation of α-synuclein in gut nervous cells which may hypothetically transfer via vagal nerve to CNS causing PD. In animal research FMT showed promising results in alleviating PD symptoms. Case reports showed reduction of both motor and non-motor dysfunctions, especially in constipation. DuPont et al. showed improvements in constipation, motor deficits, overall Parkinson’s symptoms, and some non-motor disorders. Cheng et al. showed improvements in MDS-UPDRS, scores of GI tract symptoms scales, PD-related autonomic symptoms and the stool frequency. Bruggeman et al. showed better MDS-UPDRS part 3 scores and better colon transit, but no significant differencies in any other tested domains. Conclusions. As there is yet no standarized protocol for FMT, all of the past research used different techniques and showed slightly different outcomes, but all have shown that FMT have some positive effects on PD symptoms.