OBJECTIVE: Irritable bowel syndrome (IBS) is a diagnosis defined by gastrointestinal (GI) symptoms like abdominal pain and changes associated with defecation. The condition is classified as a disorder of the gut-brain interaction (DGBI), and patients with IBS commonly experience psychological distress. The present study focuses on this distress, defined from reports of fatigue, anxiety, depression, sleep disturbances, and performance on cognitive tests. The aim was to investigate the joint contribution of these features of psychological distress in predicting IBS versus healthy controls (HCs) and to disentangle clinically meaningful subgroups of IBS patients.
METHODS: IBS patients ( n = 49 ) and HCs ( n = 28 ) completed the Chalder Fatigue Scale (CFQ), the Hamilton Anxiety and Depression Scale (HADS), and the Bergen Insomnia Scale (BIS), and performed tests of memory function and attention from the Repeatable Battery Assessing Neuropsychological Symptoms (RBANS). An initial exploratory data analysis was followed by supervised (Random Forest) and unsupervised (K-means) classification procedures.
RESULTS: The explorative data analysis showed that the group of IBS patients obtained significantly more severe scores than HCs on all included measures, with the strongest pairwise correlation between fatigue and a quality measure of sleep disturbances. The supervised classification model correctly predicted belongings to the IBS group in 80% of the cases in a test set of unseen data. Two methods for calculating feature importance in the test set gave mental and physical fatigue and anxiety the strongest weights. An unsupervised procedure with K = 3 showed that one cluster contained 24% of the patients and all but two HCs. In the two other clusters, their IBS members were overall more impaired, with the following differences. One of the two clusters showed more severe cognitive problems and anxiety symptoms than the other, which experienced more severe problems related to the quality of sleep and fatigue. The three clusters were not different on a severity measure of IBS and age.
CONCLUSIONS: The results showed that psychological distress is an integral component of IBS symptomatology. The study should inspire future longitudinal studies to further dissect clinical patterns of IBS to improve the assessment and personalized treatment for this and other patient groups defined as disorders of the gut-brain interaction. The project is registered at https://classic.
RESULTS: gov/ct2/show/NCT04296552 20/05/2019.

This perspective explores the current understanding of the gut microbiota\'s impact on cognitive function in apparently healthy humans and in individuals with metabolic disease. We discuss how alterations in gut microbiota can influence cognitive processes, focusing not only on bacterial composition but also on often overlooked components of the gut microbiota, such as bacteriophages and eukaryotes, as well as microbial functionality. We examine the mechanisms through which gut microbes might communicate with the central nervous system, highlighting the complexity of these interactions. We provide a comprehensive overview of the emerging field of microbiota-gut-brain interactions and its significance for cognitive health. Additionally, we summarize novel therapeutic strategies designed to promote cognitive resilience and reduce the risk of cognitive disorders, focusing on interventions that target the gut microbiota. An in-depth understanding of the microbiome-brain axis is imperative for developing innovative treatments aimed at improving cognitive health.

The gastrointestinal (GI) tract, home to the largest microbial population in the human body, plays a crucial role in overall health through various mechanisms. Recent advancements in research have revealed the potential implications of gut-brain and vice-versa communication mediated by gut-microbiota and their microbial products in various diseases including type-2 diabetes and Alzheimer\'s disease (AD). AD is the most common type of dementia where most of cases are sporadic with no clearly identified cause. However, multiple factors are implicated in the progression of sporadic AD which can be classified as non-modifiable (e.g., genetic) and modifiable (e.g. Type-2 diabetes, diet etc.). Present review focusses on key players particularly the modifiable factors such as Type-2 diabetes (T2D) and diet and their implications in microbiota-gut-brain (MGB) and brain-gut (BG) communication and cognitive functions of healthy brain and their dysfunction in Alzheimer\'s Disease. Special emphasis has been given on elucidation of the mechanistic aspects of the impact of diet on gut-microbiota and the implications of some of the gut-microbial products in T2D and AD pathology. For example, mechanistically, HFD induces gut dysbiosis with driven metabolites that in turn cause loss of integrity of intestinal barrier with concomitant colonic and systemic chronic low-grade inflammation, associated with obesity and T2D. HFD-induced obesity and T2D parallel neuroinflammation, deposition of Amyloid β (Aβ), and ultimately cognitive impairment. The review also provides a new perspective of the impact of diet on brain-gut and microbiota-gut-brain communication in terms of transcription factors as a commonly spoken language that may facilitates the interaction between gut and brain of obese diabetic patients who are at a higher risk of developing cognitive impairment and AD. Other commonality such as tyrosine kinase expression and functions maintaining intestinal integrity on one hand and the phagocytic clarence by migratory microglial functions in brain are also discussed. Lastly, the characterization of the key players future research that might shed lights on novel potential pharmacological target to impede AD progression are also discussed.

Children diagnosed with autism spectrum disorder (ASD) are at an increased risk of experiencing gastrointestinal (GI) discomfort, which has been linked to dysfunctions in the microbiome-gut-brain axis. The bidirectional communication between gut and brain plays a crucial role in the overall health of individuals, and alterations in the gut microbiome can contribute to immune activation and gut-brain dysfunction in ASD. Despite the limited and controversial results of pre-/probiotic applications in ASD, this review comprehensively maps the association between ASD clinical symptoms and specific bacterial taxa and evaluates the efficacy of pre-/probiotics in modulating microbiota composition, reducing inflammatory biomarkers, alleviating difficulties in GI distress, sleep problems, core and other ASD-associated symptoms, as well as relieving parental concerns, separately, in individuals with ASD. Beyond simply targeting core ASD symptoms, this review highlights the potential of pre-/probiotic supplementations as a strategy to modulate gut homeostasis and immune response, and to delineate the potential mechanisms by which its direct or mediating effects can alleviate gut-brain dysfunction and poor nutritional status in ASD management. Further well-designed randomized controlled trials are needed to strengthen the existing evidence and establish optimal protocols for the use of pre-/probiotics in the context of ASD.

Alzheimer\'s disease (AD) is a neurodegenerative process responsible for almost 70% of all cases of dementia. The clinical signs consist in progressive and irreversible loss of memory, cognitive, and behavioral functions. The main histopathological hallmark is the accumulation of amyloid-ß (Aß) peptide fibrils in the brain. To date, the origin of Aß has not been determined. Recent studies have shown that the gut microbiota produces Aß, and dysbiotic states have been identified in AD patients and animal models of AD. Starting from the hypothesis that maintaining or restoring the microbiota\'s eubiosis is essential to control Aß\'s production and deposition in the brain, we used a mixture of probiotics and prebiotics (symbiotic) to treat APPPS1 male and female mice, an animal model of AD, from 2 to 8 months of age and evaluated their cognitive performances, mucus secretion, Aβ serum concentration, and microbiota composition. The results showed that the treatment was able to prevent the memory deficits, the reduced mucus secretion, the increased Aβ blood levels, and the imbalance in the gut microbiota found in APPPS1 mice. The present study demonstrates that the gut-brain axis plays a critical role in the genesis of cognitive impairment, and that modulation of the gut microbiota can ameliorate AD\'s symptomatology.

The role of human microbiota in mental health and the underlying mechanisms of psychobiotics, which can modulate mood and behavior through the microbiota-gut-brain axis, has been a focus of scientific scrutiny. This work presents a bibliometric analysis to uncover research trends and insights in psychobiotics literature. The Clarivate Analytics Web of Science database served as the source for articles and reviews on psychobiotics spanning the years 2012 to 2023. Bibliometric network visualization and graphing were conducted using VOSviewer, Microsoft Excel for Windows 10, and Datawrapper software. A total of 348 publications were included, and it has been determined that the number of publications and citations shows an increasing trend from 2012 to 2023. The most active authors on psychobiotics, in order, were Dinan TG, Cryan JF, and Tsai YC. The most active organizations have been identified as University College Cork, National Yang Ming Chiao Tung University, and Bened Biomedical Co. Ltd. The most active countries in psychobiotic research were China, Ireland, and United States of America, while the most active journals were Nutrients, International Journal of Molecular Sciences, and Probiotics and Antimicrobial Proteins. The most commonly used keywords were \"psychobiotics,\" \"probiotics,\" and \"gut-brain axis.\" This bibliometric analysis has revealed the growing academic interest in psychobiotics, indicating that the relationship between gut microbiota and mental health will increasingly be supported by scientific evidence in the years ahead.

BACKGROUND: Depression post-myocardial infarction (MI) is becoming more prevalent. The gut-brain axis (GBA), influenced by the gut microbiota, is a critical component in understanding depression post-MI. Despite the well-established connection between gut microbiota and depression post-MI, this relationship remains incompletely understood.
METHODS: This protocol will follow the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) 2020 statement. Beginning from inception to October 2023, a systematic search will be conducted across eight electronic databases, including PubMed, MEDLINE, Scopus, Embase, Cochrane Clinical Trials Database, Web of Science, China National Knowledge Infrastructure, and China Biomedical Literature Database. Pre-selected studies will be independently assessed by two researchers following a standard inclusion, data extraction and quality assessment protocol. The primary outcome measures are differences in the profile of gut microbiota and rating scale scores for depression. Fixed-effects models will be used when both clinical heterogeneity and statistical heterogeneity are low, otherwise random-effects models will be used. Furthermore, subgroup analyses will be conducted on the depression severity of the participants using the same psychiatric scales employed, study type and geographic region. Random forest plot runs and research-related statistical analyses will be carried out using Rev Man V.5.3 software.
RESULTS: This study will identify the association between the gut microbiota and the onset of depression post-MI, and provide evidence for the use of probiotics as an adjunctive treatment for depression post-MI.
BACKGROUND: Prospero registration number: CRD42023444026.

BACKGROUND: Chronic stress induces cognitive deficits. There is a well-established connection between the enteric and central nervous systems through the microbiota-gut-brain (MGB) axis. However, the effects of the gut microbiota on cognitive deficits remain unclear. The present study aimed to elucidate the microbiota composition in cognitive deficits and explore its potential in predicting chronic stress-induced cognitive deficits.
METHODS: Mice were randomly divided into control and chronic restraint stress (CRS) groups. The mice subjected to CRS were further divided into cognitive deficit (CRS-CD) and non-cognitive deficit (CRS-NCD) groups using hierarchical cluster analysis of novel object recognition test results. The composition and diversity of the gut microbiota were analyzed.
RESULTS: After being subjected to chronic restraint distress, the CRS-CD mice travelled shorter movement distances (p = 0.034 vs. CRS-NCD; p < 0.001 vs. control) and had a lower recognition index than the CRS-NCD (p < 0.0001 vs. CRS-NCD; p < 0.0001 vs. control) and control mice. The results revealed that 5 gut bacteria at genus levels were significantly different in the fecal samples of mice in the three groups. Further analyses demonstrated that Muricomes were not only significantly enriched in the CRS-CD group but also correlated with a decreased cognitive index. The area under the receiver operating curve of Muricomes for CRS-induced cognitive deficits was 0.96.
CONCLUSIONS: Our study indicates that the composition of the gut microbiota is involved in the development of cognitive deficits induced by chronic restraint stress. Further analysis revealed that Muricomes have the potential to predict the development of chronic stress-induced cognitive deficits in mice.

Depression is a highly prevalent disorder and a leading cause of disability worldwide. It has a major impact on the affected individual and on society as a whole. Regrettably, current available treatments for this condition are insufficient in many patients. In recent years, the gut microbiome has emerged as a promising alternative target for treating and preventing depressive disorders. However, the microbes that form this ecosystem do not act alone but are part of a complicated network connecting the gut and the brain that influences our mood. Host cells that are in intimate contact with gut microbes, such as the epithelial cells forming the gut barrier and the immune cells in their vicinity, play a key role in the process. These cells continuously shape immune responses to maintain healthy communication between gut microbes and the host. In this article, we review how the interplay among epithelial cells, the immune system, and gut microbes mediates gut-brain communication to influence mood. We also discuss how advances in our knowledge of the mechanisms underlying the gut-brain axis could contribute to addressing depression. SIGNIFICANCE STATEMENT: This review does not aim to systematically describe intestinal microbes that might be beneficial or detrimental for depression. We have adopted a novel point of view by focusing on potential mechanisms underlying the crosstalk between gut microbes and their intestinal environment to control mood. These pathways could be targeted by well defined and individually tailored dietary interventions, microbes, or microbial metabolites to ameliorate depression and decrease its important social and economic impact.

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.