Stroke-associated pneumonia (SAP), a highly lethal complication following stroke, is closely linked to dysregulation of the "brain-gut-lung axis." Accumulating evidence indicates that stroke triggers intestinal alterations through the brain-gut axis, while multiple studies confirm that gut-derived changes can mediate pneumonia through the gut-lung axis. However, the mechanisms connecting stroke-induced intestinal dyshomeostasis to SAP remain incompletely elucidated, and the multiorgan interaction mechanisms of the "brain-gut-lung axis" in SAP pathogenesis require further exploration.

This systematic literature review systematically searched databases, including PubMed, using the keywords "stroke," "gastrointestinal microbiome," and "bacterial pneumonia," incorporating 80 mechanistic studies. Key findings reveal that stroke initiates a cascade of "neuro-microbial-immune" pathway interactions along the brain-gut-lung axis, leading to intestinal dyshomeostasis characterized by microbiota and metabolite alterations, barrier disruption, immune dysregulation, inflammatory responses, and impaired gut motility. These intestinal perturbations ultimately disrupt pulmonary immune homeostasis, promoting SAP development. In addition, stroke directly induces vagus nerve injury through the brain-gut axis, resulting in impaired swallowing and cough reflexes that exacerbate aspiration-related pulmonary infection risks.

Elucidating the role of the brain-gut-lung axis in SAP pathogenesis provides critical insights into its underlying mechanisms. This paradigm highlights intestinal homeostasis modulation and vagus nerve stimulation as promising therapeutic strategies for SAP prevention and management, advancing a multitargeted approach to mitigate poststroke complications.

Circadian rhythms are innate biological systems that control everyday behavior and physiology. Furthermore, bilateral interaction between the host's circadian rhythm and the gut microbes influences a variety of health ramifications, including metabolic diseases, obesity, and mental health including GALT physiology and the microbiome population. Therefore, we are studying the correlation between differential gene expression in the chicken brain and microbiota abundance during circadian rhythms. To understand this, we raised freshly hatched chicks under two photoperiod treatments: normal photoperiod (NP = 12/12 LD) and extended photoperiod (EP 23/1 LD). The chicks were randomly assigned to one of two treatments. After 21 days of circadian entrainment, the chicks were euthanized at nine time points spaced six hours apart over 48 h to characterize the brain transcriptomes. Each sample's RNA was extracted, and 36 mRNA libraries were generated and sequenced using Illumina technology, followed by data processing, count data generation, and differential gene expression analysis. We generated an average of 17.5 million reads per library for 237.9 M reads. When aligned to the Galgal6 reference genome, 11,867 genes had detectable expression levels, with a common dispersion value of 0.105. To identify the genes that follow 24 h rhythms, counts per million data were performed in DiscoRhythm. We discovered 577 genes with Cosinor and 417 with the JTK cycle algorithm that exhibit substantial rhythms. We used weighted gene co-expression network analysis (WGCNA) to analyze the correlation between differentially expressed genes and microbiota abundance. The most enriched pathways included aldosterone-regulated sodium reabsorption, endocrine and other factor-regulated calcium reabsorption, GABAergic synapse, oxidative phosphorylation, serotonergic synapse, dopaminergic synapse and circadian entrainment. This study builds on our previous study, and adds new findings about the specific interactions and co-regulation of the brain transcriptome and the gut microbiota. The interaction between gut microbiota and host gene expression highlights the potential benefits of microbiome-modulation approaches to improve gut health and performance in poultry.

Music intervention is gaining recognition as a cost-effective therapeutic for improving human health. Despite its growing application, the mechanisms through which music exerts beneficial health effects remain largely unexplored. Here, we show that music can exert beneficial effects in mice through modulating gut microbiome composition. Adult mice were exposed to ambient noise, Mozart's Flute Quartet in D Major, K. 285, or white noise over a three-week period. Afterward, we observed treatment-specific changes in the community of gut commensal bacteria in these animals. Upon subsequent challenge with the bacterial pathogen Salmonella typhimurium, control groups exhibited significant weight loss and increased Salmonella colonization, whereas the Mozart-treated group did not. 16S ribosomal RNA gene sequencing revealed that the Mozart group showed a significant increase in Lactobacillus salivarius, a probiotic known for its antibacterial properties. Further experiments confirmed that L. salivarius mitigated Salmonella infection in mice and that L. salivarius acidified local environments in in vitro culture, thus inhibiting Salmonella growth. Additionally, mice exposed to Mozart consumed more food but showed similar body weight compared to the control groups. Behavioral assessments, including open field and object location tests, revealed that Mozart-treated mice were more active, less anxious, and exhibited enhanced spatial memory. Finally, Mozart exposure was shown to significantly boost colonization of administered L. salivarius and alter gut metabolite profiles. These findings suggest that music exposure fosters healthier gut microbiota, enhancing resistance to bacterial infections and highlighting the potential of music therapy as a novel strategy to combat drug-resistant pathogen infections.

Music therapy is increasingly recognized as a low-cost approach to improving health, but how it works remains unclear. Our study demonstrates that music can positively influence health by altering the gut microbiome. In a mouse model, exposure to Mozart's Flute Quartet in D Major enhanced the gut microbiota, specifically increasing levels of the beneficial bacterium Lactobacillus salivarius. This probiotic protected mice from Salmonella infection by creating an acidic environment that inhibited pathogen growth. Mozart-treated mice also showed reduced anxiety, better spatial memory, and higher food intake without weight gain, suggesting the benefits of music exposure. These findings reveal a novel link between music, gut health, and disease resistance, suggesting that music therapy could be a promising strategy for enhancing gut microbiota and combating infections, including those caused by drug-resistant bacteria.

The gut microbiota-brain axis is a complex system that links the bacteria in our gut with our brain, it plays a part in what way we respond to stress. This chapter explores how stress affects the types of bacteria in the gut and shows the two-way connection between them. Stress can change the bacteria in our gut, which can cause various problems related to stress, like depression, anxiety, and irritable bowel syndrome (IBS). Figuring out how these interactions may help us develop new treatments that focus on the connection between gut bacteria and the brain. This chapter looks at how gut bacteria could help identify stress-related problems. It also discusses the difficulties and possibilities of using this research in medical practice. In the end, the chapter talks about what comes next in this quickly changing area. It highlights how important it is to include research about the gut-brain connection in overall public health plans.

The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain-gut-microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior. Emerging evidence suggests that the gut microbiome regulates brain function and behavior, particularly through microbial influences on tryptophan metabolism and the serotonergic system, both of which are essential for normal functioning. Additionally, sex differences exist in multiple aspects of serotonin-mediated modulation within the brain-gut-microbiome axis, affecting feeding and affective behaviors. This review summarizes the current knowledge from human and animal studies on the influence of tryptophan and its metabolite serotonin on metabolic and behavioral regulation involving the brain and gut microbiome, with a focus on sex differences and the role of sex hormones. We speculate that gut-derived tryptophan and serotonin play essential roles in the pathophysiology that modifies neural circuits, potentially contributing to eating and affective disorders. We propose the gut microbiome as an appealing therapeutic target for metabolic and affective disorders, emphasizing the importance of understanding sex differences in metabolic and behavioral regulation influenced by the brain-gut-microbiome axis. The therapeutic targeting of the gut microbiota and its metabolites may offer a viable strategy for treating serotonin-related disorders, such as eating and affective disorders, with potential differences in treatment efficacy between men and women. This review would promote research on sex differences in metabolic and behavioral regulation impacted by the brain-gut-microbiome axis.

Deciphering the gastrointestinal microbial response to oral SS DNA vaccines with different doses is helpful for identifying the mechanism for effective utilization of the vaccine for improving animal production. Here, we conduct a comparative study with different doses of vaccine (control: empty plasmid; low dose: 1 × 107 CFU vaccine; high dose: 1 × 1012 CFU vaccine) using goat as a case to investigate the potential of somatostatin vaccination from the entire gastrointestinal microbiota perspective. Our results show that body weight gain and slaughter rate are greater in the L_SS group than in the C_SS group. Compared with the C_SS group, the GH concentration is reduced, while the SS concentration is elevated in the cecum of L_SS goats. Moreover, the SCFAs concentration is elevated in the L_SS goats, the acetate molar proportion is lower in the rumen, the proportion of the acetate is decreased, and propionate is increased in the cecum of L_SS goats. Our data indicate that the low-dose somatostatin vaccine possesses a more efficient improvement in the productivity of goats, emphasizing that the dosage should be considered to reach its optimal effect on the host. Moreover, we find that different doses of the SS vaccination select distinct microbial communities in the gastrointestinal tract. Beta diversity analysis shows a significant interaction. Microorganisms capable of converting nutrients, including Ruminococcacease, Butyrivibrio, Akkermansia, and Lachnospiraceae are enriched, altering the gastrointestinal fermentation response to SS DNA vaccination of ruminants. Moreover, the correlation analysis results revealing these biomarkers have a close association with the phenotypes of productivity. These results imply that somatostatin immunoneutralization might directly alter the gastrointestinal tract commensal bacterial structure, improving gastrointestinal homeostasis, and, thus, modifying the fermentability and effected hormone level to improve the productivity of goats. Our study extends the understanding of the somatostatin vaccine regulation of ruminants' growth through the entire gastrointestinal microbial perspective.

Huntington's disease (HD) is a currently incurable neurogenerative disorder and is typically characterized by progressive movement disorder (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which is depression), and peripheral symptoms (including gastrointestinal dysfunction). There are currently no approved disease-modifying therapies available for HD, with death usually occurring approximately 10-25 years after onset, but some therapies hold promising potential. HD subjects are often burdened by chronic diarrhea, constipation, esophageal and gastric inflammation, and a susceptibility to diabetes. Our understanding of the microbiota-gut-brain axis in HD is in its infancy and growing evidence from preclinical and clinical studies suggests a role of gut microbial population imbalance (gut dysbiosis) in HD pathophysiology. The gut and the brain can communicate through the enteric nervous system, immune system, vagus nerve, and microbiota-derived-metabolites including short-chain fatty acids, bile acids, and branched-chain amino acids. This review summarizes supporting evidence demonstrating the alterations in bacterial and fungal composition that may be associated with HD. We focus on mechanisms through which gut dysbiosis may compromise brain and gut health, thus triggering neuroinflammatory responses, and further highlight outcomes of attempts to modulate the gut microbiota as promising therapeutic strategies for HD. Ultimately, we discuss the dearth of data and the need for more longitudinal and translational studies in this nascent field. We suggest future directions to improve our understanding of the association between gut microbes and the pathogenesis of HD, and other 'brain and body disorders'.

We provide an overview of the field of microbiome research, the current understanding of the microbiome-gut-brain axis, and the most recent updates on the interplay between migraine and the gut microbiome.

Pre-clinical studies suggest that gut microbiota is required for normal pain sensation. There is also evidence in rodent models that there is potential application of food, herbal medicines, probiotics, and short chain fatty acids (SCFAs) as novel therapies for migraine. Evidence from human cohorts suggests that there is altered gut microbiota in people with migraine, and that the microbiome dysbiosis is from both compositional and functional aspects. Recent metagenome-wide association studies (MWAS) that employ Mendelian Randomization support the causal association between gut microbiota and migraine. The connection between migraine and the gut microbiome remains underexplored, but recent preclinical and clinical studies support the association between gut microbiota and the development of migraine.

This article aims to explore the role of the human gut microbiota (GM) in the pathogenesis of neurological, psychiatric, and neurodevelopmental disorders, highlighting its influence on health and disease, and investigating potential therapeutic strategies targeting GM modulation.

A comprehensive analysis of the gut microbiota's composition and its interaction with the human body, particularly, its role in neurological and psychiatric conditions, is provided. The review discusses factors influencing GM composition, including birth mode, breastfeeding, diet, medications, and geography. Additionally, it examines the GM's functions, such as nutrient absorption, immune regulation, and pathogen defense, alongside its interactions with the nervous system through the gut-brain axis, neurotransmitters, and short-chain fatty acids (SCFAs).

Alterations in the GM are linked to various disorders, including Parkinson's disease, multiple sclerosis, depression, schizophrenia, ADHD, and autism. The GM influences cognitive functions, stress responses, and mood regulation. Antibiotic use disrupts GM diversity, increasing the risk of metabolic disorders, obesity, and allergic diseases. Emerging therapies such as probiotics, prebiotics, and microbiota transplantation show promise in modulating the GM and alleviating symptoms of neurological and psychiatric conditions.

The modulation of the GM represents a promising approach for personalized treatment strategies. Further research is needed to better understand the underlying mechanisms and to develop targeted therapies aimed at restoring GM balance for improved clinical outcomes.

Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively.

This research aimed to investigate the pharmacological components for liver stagnation and spleen deficiency syndrome (LSSDS) of Evodia rutaecarpa (also called Yu HuangLian [YHL]) by exploring the spectrum-effect relationship between fingerprints and pharmacological actions. The fingerprints of 17 batches of YHL with different preparation conditions according to Box-Behnken Design were generated and analyzed to identify the common peaks by HPLC and FT-IR. Vasoactive intestinal peptide (vip), substance P, and 5-HT levels in colon sample were measured by ELISA. Gray degree correlation and orthogonal partial least squares were employed to explore the correlation degree between components and pharmacologic activity. The presumed pharmacological components were further confirmed by network pharmacology, molecular docking, and qRT-PCR. The columbamine, jatrorrhizine, coptisine, berberine, rutecarpine, and evodiamine of the 14 common peaks in HPLC fingerprints were significantly correlated with the pharmacological indexes. Similarly, there was a strong correlation with -OH, δNC-H, and νC-O-C of the 10 common peaks in FT-IR fingerprints. PTGS2 and CHRM3 were the main targets intervening LSSDS, and the presumed pharmacological components could markedly increase the expression of CHRM3 and obviously reduce the expression of PTGS2 compared with the model group.

The importance of the gut microbiome for human health and well-being is generally accepted, and elucidating the signaling pathways between the gut microbiome and the host offers novel mechanistic insight into the (patho)physiology and multifaceted aspects of healthy aging and human brain functions.

The gut microbiome is tightly linked with the nervous system, and gut microbiota are increasingly emerging as important regulators of emotional and cognitive performance. They send and receive signals for the bidirectional communication between gut and brain via immunological, neuroanatomical, and humoral pathways. The composition of the gut microbiota and the spectrum of metabolites and neurotransmitters that they release changes with increasing age, nutrition, hypoxia, and other pathological conditions. Changes in gut microbiota (dysbiosis) are associated with critical illnesses such as cancer, cardiovascular, and chronic kidney disease but also neurological, mental, and pain disorders, as well as chemotherapies and antibiotics affecting brain development and function.

Dysbiosis and a concomitant imbalance of mediators are increasingly emerging both as causes and consequences of diseases affecting the brain. Understanding the microbiota's role in the pathogenesis of these disorders will have major clinical implications and offer new opportunities for therapeutic interventions.

Tachykinins are short neuropeptides, such as substance P and neurokinin B, that have been shown to interact with Alzheimer's β-amyloid (Aβ) peptide. Neurokinin A (NKA) is a secreted tachykinin neuropeptide that binds to neurokinin receptors and with an emerging role in the brain-gut axis. NKA shares the brain niche with Aβ; thus, we investigate whether and how NKA and Aβ peptide interact. We have used a combination of computational and experimental biophysics to assess the interaction of both peptides in vitro. Using Phe-to-Trp substitution, we have shown that Phe in the FXGLM signature in NKA is important for such interaction and for the modulation of the Aβ peptide amyloid cascade. Besides, cellular experiments have shown that the NKA-Aβ interaction decreases the Aβ peptide toxicity. Altogether, our work raises the intriguing possibility that NKA balance and the NKA-Aβ peptide interplay are relevant in the aggregation process in Alzheimer's disease.

Neuropeptides are the most ubiquitous neurotransmitters in the immune system, regulating various biological processes. Neuropeptides play a significant role for the discovery of new drugs and targets for nervous system disorders. Traditional experimental methods for identifying neuropeptides are time-consuming and costly. Although several computational methods have been developed to predict the neuropeptides, the accuracy is still not satisfactory due to the representability of the extracted features. In this work, we propose an efficient and interpretable model, NeuroPpred-SHE, for predicting neuropeptides by selecting the optimal feature subset from both hand-crafted features and embeddings of a protein language model. Specially, we first employed a pre-trained T5 protein language model to extract embedding features and twelve other encoding methods to extract hand-crafted features from peptide sequences, respectively. Secondly, we fused both embedding features and hand-crafted features to enhance the feature representability. Thirdly, we utilized random forest (RF), Max-Relevance and Min-Redundancy (mRMR) and eXtreme Gradient Boosting (XGBoost) methods to select the optimal feature subset from the fused features. Finally, we employed five machine learning methods (GBDT, XGBoost, SVM, MLP, and LightGBM) to build the models. Our results show that the model based on GBDT achieves the best performance. Furthermore, our final model was compared with other state-of-the-art methods on an independent test set, the results indicate that our model achieves an AUROC of 97.8 % which is higher than all the other state-of-the-art predictors. Our model is available at: https://github.com/wenjean/NeuroPpred-SHE.

Aquatic animals frequently undergo feed deprivation and starvation stress. It is well-known that the gut microbiota and the gut-brain short neuropeptide F (sNPF) play essential roles in diet restriction. Therefore, investigating the responses of the gut microbiota and sNPF can enhance our understanding of physiological adaptations to feed deprivation and starvation stress. In this study, we examined the alterations in the gut microbiota of juvenile mud crabs under feed deprivation and starvation conditions. The results reveal differences in the richness and diversity of gut microbiota among the satisfied, half food, and starvation groups. Moreover, the microbial composition was affected by starvation stress, and more than 30 bacterial taxa exhibited significantly different abundances among the three feeding conditions. These results indicate that the diversity and composition of the gut microbiota are influenced by diet restriction, potentially involving interactions with the gut-brain sNPF. Subsequently, we detected the location of sNPF in the brains and guts of mud crabs through immunofluorescence and investigated the expression profile of sNPF under different feeding conditions. The results suggest that sNPF is located in both the brains and guts of mud crabs and shows increased expression levels among different degrees of diet restriction during a 96 h period. This study suggested a potential role for sNPF in regulating digestive activities and immunity through interactions with the gut microbiota. In conclusion, these findings significantly contribute to our understanding of the dynamic changes in gut microbiota and sNPF, highlighting their interplay in response to diet restriction.

Obesity, a global health challenge, necessitates innovative approaches for effective management. Targeting gut peptides in the development of anti-obesity pharmaceuticals has already demonstrated significant efficacy. Ghrelin, peptide YY (PYY), cholecystokinin (CCK), and amylin are crucial in appetite regulation offering promising targets for pharmacological interventions in obesity treatment using both peptide-based and small molecule-based pharmaceuticals. Ghrelin, a sole orexigenic gut peptide, has a potential for anti-obesity therapies through various approaches, including endogenous ghrelin neutralization, ghrelin receptor antagonists, ghrelin O-acyltransferase, and functional inhibitors. Anorexigenic gut peptides, peptide YY, cholecystokinin, and amylin, have exhibited appetite-reducing effects in animal models and humans. Overcoming substantial obstacles is imperative for translating these findings into clinically effective pharmaceuticals. Peptide YY and cholecystokinin analogues, characterized by prolonged half-life and resistance to proteolytic enzymes, present viable options. Positive allosteric modulators emerge as a novel approach for modulating the cholecystokinin pathway. Amylin is currently the most promising, with both amylin analogues and dual amylin and calcitonin receptor agonists (DACRAs) progressing to advanced stages of clinical trials. Despite persistent challenges, innovative pharmaceutical strategies provide a glimpse into the future of anti-obesity therapies.

Neuropsychiatric disorders are clinical conditions that affect cognitive function and emotional stability, often resulting from damage or disease in the central nervous system (CNS). These disorders are a worldwide concern, impacting approximately 12.5% of the global population. The gut microbiota has been linked to neurological development and function, implicating its involvement in neuropsychiatric conditions. Due to their interaction with gut microbial communities, probiotics offer a natural alternative to traditional treatments such as therapeutic drugs and interventions for alleviating neuropsychiatric symptoms. Introduced by Metchnikoff in the early 1900s, probiotics are live microorganisms that provide various health benefits, including improved digestion, enhanced sleep quality, and reduced mental problems. However, concerns about their safety, particularly in immunocompromised patients, warrant further investigation; this has led to the concept of "paraprobiotics", inactivated forms of beneficial microorganisms that offer a safer alternative. This review begins by exploring different methods of inactivation, each targeting specific cellular components like DNA or proteins. The choice of inactivation method is crucial, as the health benefits may vary depending on the conditions employed for inactivation. The subsequent sections focus on the potential mechanisms of action and specific applications of probiotics and paraprobiotics in neuropsychiatric therapy. Probiotics and paraprobiotics interact with gut microbes, modulating the gut microbial composition and alleviating gut dysbiosis. The resulting neuropsychiatric benefits primarily stem from the gut-brain axis, a bidirectional communication channel involving various pathways discussed in the review. While further research is needed, probiotics and paraprobiotics are promising therapeutic agents for the management of neuropsychiatric disorders.

A growing body of evidence underscores a significant association between neurological disorders, particularly migraines, and the gut microbiota. However, a research gap persists in understanding the cause-and-effect dynamics between these elements. Therefore, we employed robust methodologies aimed at thoroughly exploring the causal relationship between the gut microbiome and migraines.

Employing bidirectional Two Sample Mendelian Randomization (TSMR) analysis, we investigated the causal association between the composition of the gut microbiota and migraines. Data summarizing the relationship between gut microbiota and migraines were extracted from one or more genome-wide association studies. The TSMR analysis employed five methods to assess the correlation between the gut microbiota and migraines, with the inverse variance-weighted method serving as the primary approach for analyzing causal links. Sensitivity analyses were applied to address horizontal pleiotropy and heterogeneity. Simultaneously, a meta-analysis was performed to strengthen the robustness of the findings. Additionally, a reverse TSMR was carried out to explore potential occurrences of reverse causal relationships.

The ongoing TSMR analysis identified a collection of 14 bacterial taxa connected to migraines. Among these, 8 taxa exhibited a protective effect, while 5 taxa had a detrimental impact, and 1 taxon maintained a neutral relationship. The reverse Mendelian randomization analysis highlighted stable outcomes for only one bacterial taxonomic group.

The study confirms a causal relationship between the gut microbiota and migraines, offering a new perspective for migraine research. Strategically targeting specific bacterial taxa with dysregulation may be effective in both preventing and treating migraines, thus opening new avenues for therapeutic strategies.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease.

Entered the keywords "Dry eye", "Microbiota", "Bacteria" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary.

Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models.

By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.

Migraine is a common and debilitating neurological disorder characterized by the recurrent attack of pulsating headaches typically localized on one side of the head associated with other disabling symptoms, such as nausea, increased sensitivity to light, sound and smell and mood changes. Various clinical factors, including the excessive use of migraine medication, inadequate acute treatment and stressful events, can contribute to the worsening of the condition, which may evolve to chronic migraine, that is, a headache present on >15 days/month for at least 3 months. Chronic migraine is frequently associated with various comorbidities, including anxiety and mood disorders, particularly depression, which complicate the prognosis, response to treatment and overall clinical outcomes. Emerging research indicates a connection between alterations in the composition of the gut microbiota and mental health conditions, particularly anxiety and depression, which are considered disorders of the gut-brain axis. This underscores the potential of modulating the gut microbiota as a new avenue for managing these conditions. In this context, it is interesting to investigate whether migraine, particularly in its chronic form, exhibits a dysbiosis profile similar to that observed in individuals with anxiety and depression. This could pave the way for interventions aimed at modulating the gut microbiota for treating difficult-to-manage migraines.

Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called "therapy-resistant depression". The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a "patient fingerprint", which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.

Ischemic stroke, a disease with high mortality and disability rate worldwide, currently has no effective treatment. The systemic inflammation response to the ischemic stroke, followed by immunosuppression in focal neurologic deficits and other inflammatory damage, reduces the circulating immune cell counts and multiorgan infectious complications such as intestinal and gut dysfunction dysbiosis. Evidence showed that microbiota dysbiosis plays a role in neuroinflammation and peripheral immune response after stroke, changing the lymphocyte populations. Multiple immune cells, including lymphocytes, engage in complex and dynamic immune responses in all stages of stroke and may be a pivotal moderator in the bidirectional immunomodulation between ischemic stroke and gut microbiota. This review discusses the role of lymphocytes and other immune cells, the immunological processes in the bidirectional immunomodulation between gut microbiota and ischemic stroke, and its potential as a therapeutic strategy for ischemic stroke.

Hepatic lipid homeostasis is not only essential for maintaining normal cellular and systemic metabolic function but is also closely related to the steatosis of the liver. The controversy over the nomenclature of non-alcoholic fatty liver disease (NAFLD) in the past three years has once again sparked in-depth discussions on the pathogenesis of this disease and its impact on systemic metabolism. Pituitary-targeted gland axes (PTGA), an important hormone-regulating system, are indispensable in lipid homeostasis. This review focuses on the roles of thyroid hormones, adrenal hormones, sex hormones, and their receptors in hepatic lipid homeostasis, and summarizes recent research on pituitary target gland axes-related drugs regulating hepatic lipid metabolism. It also calls on researchers and clinicians to recognize the concept of endocrine-associated fatty liver disease (EAFLD) and to re-examine human lipid metabolism from the macroscopic perspective of homeostatic balance.

Growing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to observe the effect of electroacupuncture (EA) on gut microbiota in rats that showed depressive-like behavior.

The rats were randomly divided into normal group, chronic unpredictable mild stress model (CUMS) group, CUMS + electroacupuncture (EA) group, and CUMS + sham-electroacupuncture (Sham) group. The CUMS+EA rats were treated with EA stimulation at bilateral Zusanli (ST36) and Tianshu (ST25) acupoints for 2 weeks (0.7 mA, 2/100 Hz, 30 min/day). The rats in the sham EA group were treated with the same conditions without inserting needles and electrical stimulation. Behavioral tests were conducted by forced swimming test (FST), open field test (OFT), and sucrose preference test (SPT) to assess depression-like behavior in rats. The relative abundance of intestinal bacteria in rat feces was detected by 16S rRNA analysis. The expression of calcitonin-gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SST), and adrenocorticotropic hormone (ACTH) in serum was detected by ELISA kit, and VIP, CGRP, and SST in the colon were detected by qRT-PCR and Western blot.

Chronic unpredictable mild stress model rats exhibited depressive-like behaviors and had differential abundance vs. control rats. CUMS significantly decreased the relative abundance of Bifidobacterium and Streptococcus at the genus level, CGRP in plasma (p < 0.05), and significantly increased the intestine propulsion rate, the mRNA and protein expression of VIP, SST, and mRNA in the colon, and ATCH in plasma (p < 0.05). EA rats with microbial profiles were distinct from CUMS rats. EA markedly reduced the depressive-like behaviors, significantly increased the intestine propulsion rate, the relative abundance of Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level, Bifidobacterium and Streptococcus at the genus level, and VIP and CGRP in plasma (p < 0.05), and significantly decreased Firmicutes, the ratio of Firmicutes to Bacteroidetes at the phylum level, ACTH and SST in plasma, and SST mRNA in the colon (p < 0.05).

The antidepressant effect of EA at ST36 and ST25 is related to regulating intestinal flora and the neurotransmitter system. Our study suggests that EA contributes to the improvement of depression, and gut microbiota may be one of the mechanisms of EA effect.

The gut microbiota (GM) of the human body comprises several species of microorganisms. This microorganism plays a significant role in the physiological and pathophysiological processes of various human diseases.

The literature review includes studies that describe causative factors that influence GM. The GM is sensitive to various factors like circadian rhythms, environmental agents, physical activity, nutrition, and hygiene that together impact the functioning and composition of the gut microbiome. This affects the health of the host, including the psycho-neural aspects, due to the interconnectivity between the brain and the gut. Hence, this paper examines the relationship of GM with neurodegenerative disorders in the context of these aforesaid factors.

Future studies that identify the regulatory pathways associated with gut microbes can provide a causal link between brain degeneration and the gut at a molecular level. Together, this review could be helpful in designing preventive and treatment strategies aimed at GM, so that neurodegenerative diseases can be treated.

Gut microbiota plays several roles in the host organism's metabolism and physiology. This phenomenon holds across different species from different kingdoms and classes. Different species across various classes engage in continuous crosstalk via various mechanisms with their gut microbiota, ensuring homeostasis of the host. In this Review, the diversity of the microflora, the development of the microflora in the host, its regulations by the host, and its functional implications on the host, especially in the context of dysbiosis, are discussed across different organisms from sponges to humans. Overall, our review aims to address the indispensable nature of the microbiome in the host's survival, fitness, and protection against invading pathogens.

A correlation between gut microbiota and brain structure, referring to as a component of the gut-brain axis, has been observed in observational studies. However, the causality of this relationship and its specific bacterial taxa remains uncertain. To reveal the causal effects of gut microbiota on subcortical brain volume, we applied Mendelian randomization (MR) studies in this study. Genome-wide association study data were obtained from the MiBioGen Consortium (n = 18,340) and the Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium (n = 13,170). The primary estimate was obtained utilizing the inverse-variance weighted, while heterogeneity and pleiotropy were assessed using the Cochrane Q statistic, MR Pleiotropy RESidual Sum and Outlier, and MR-Egger intercept. Our findings provide strong evidence that a higher abundance of the genus Parasutterella is causally correlated with a decrease in intracranial volume (β = -30,921.33, 95% CI -46,671.78 to -15,170.88, P = 1.19 × 10-4), and the genus FamilyXIIIUCG001 is associated with a decrease in thalamus volume (β = -141.96, 95% CI: -214.81 to -69.12, P = 1.0× 10-4). This MR study offers novel perspectives on the intricate interplay between the gut microbiota and subcortical brain volume, thereby lending some support to the existence of the microbiota-gut-brain axis.

The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.

Podophyllotoxin (PPT) is a naturally occurring aryltetralin lignan. However, its clinical application has been limited due to its neurotoxicity, the mechanism of which remains unclear. This study aimed to investigate the potential involvement of the microbiota-gut-brain (MGB) axis in PPT-induced neurotoxicity using the toxicological evidence chain concept. Our approach included behavioral testing in rats, evaluation of colon and hippocampal pathological changes, examination of proinflammatory factors, brain-gut peptides, and an in-depth analysis of gut microbiome and metabolic profiles. Our results demonstrated that PPT exposure compromised cognitive functions, induced damage to the colon and hippocampus, and increased intestinal permeability in rats. Furthermore, it elevated proinflammatory factors, particularly TNF-α and IL-6, while causing disruptions in the gut microbiota, favoring Escherichia-Shigella over Lactobacillus. Significant alterations in metabolic profiles in feces, serum, and hippocampus, particularly in tryptophan metabolism with a correlation to inflammatory factors and Escherichia-Shigella, were also observed. Our findings suggest that PPT promotes the enrichment of Escherichia-Shigella leading to inflammatory factor production and alterations in kynurenine metabolism in the hippocampus, potentially contributing to neurotoxicity. The study provides novel insights into the mechanistic pathways of PPT-induced neurotoxicity, emphasizing the role of the MGB axis and offering avenues for therapeutic interventions.

Increasing evidence links the gut microbiome and the nervous system in health and disease. This narrative review discusses current views on the interaction between the gut microbiota, the intestinal epithelium, and the brain, and provides an overview of the communication routes and signals of the bidirectional interactions between gut microbiota and the brain, including circulatory, immunological, neuroanatomical, and neuroendocrine pathways. Similarities and differences in healthy gut microbiota in humans and mice exist that are relevant for the translational gap between non-human model systems and patients. There is an increasing spectrum of metabolites and neurotransmitters that are released and/or modulated by the gut microbiota in both homeostatic and pathological conditions. Dysbiotic disruptions occur as consequences of critical illnesses such as cancer, cardiovascular and chronic kidney disease but also neurological, mental, and pain disorders, as well as ischemic and traumatic brain injury. Changes in the gut microbiota (dysbiosis) and a concomitant imbalance in the release of mediators may be cause or consequence of diseases of the central nervous system and are increasingly emerging as critical links to the disruption of healthy physiological function, alterations in nutrition intake, exposure to hypoxic conditions and others, observed in brain disorders. Despite the generally accepted importance of the gut microbiome, the bidirectional communication routes between brain and gut are not fully understood. Elucidating these routes and signaling pathways in more detail offers novel mechanistic insight into the pathophysiology and multifaceted aspects of brain disorders.

Probiotics are beneficial microorganisms shown to improve human health when consumed regularly and in sufficient quantities. Numerous health benefits can be attained by possessing important metabolites with nutritional and medicinal qualities. It has been shown through scientific research that these living microbial consortiums can influence a variety of mental health outcomes, including but not limited to anxiety, depression, cognitive processes, stress responses, and behavioral patterns. Selected strains of bacteria and yeasts control how the central nervous system (CNS) communicates with the gut-brain axis (GBA) through neuronal, humoral, and metabolic pathways to ease mood. Psychobiotics are substances that can affect the digestive system as well as mood and anxiety. There is scant evidence to validate the beneficial effects of psychiatric drugs in treating neurological diseases or disorders. The therapeutic method of research into psychobiotics opens exciting prospects for the future of the field of development. This review compiles the current evidence available in the scientific literature on the use of probiotics to influence neurological disorders.

Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC), show an increased incidence of anxiety and depression; however, the association between UC-associated psychiatric disorders and the gut microbiota is unclear. This study aimed to examine whether gut microbiota from patients with UC can alter colonic gene expression, leading to anxiety- and depression-like behavior in mice receiving fecal microbiota transplantation (FMT). RNA sequencing transcriptome analyses revealed a difference in colonic gene expression between mice receiving FMT from patients with UC (UC-FMT mice) and those receiving FMT from healthy controls (HC-FMT mice). Gene ontology analysis revealed the downregulation of neuropeptide signaling pathways, including neuropeptide Y (NPY) expression, in the colons of UC-FMT mice. The protein levels of NPY also decreased in the colon and plasma of UC-FMT mice compared to those in HC-FMT mice. The oral administration of Enterococcus mundtii (EM), a bacterium isolated from the feces of patients with UC, reduced NPY expression in the colons of mice and induced intestinal inflammation, anxiety, and depression-like behavior. Reduced NPY protein levels were also observed in the plasma and hippocampus of EM-treated mice. Intraperitoneal administration of NPY significantly alleviated anxiety- and depressive-like behaviors induced by EM in mice. Capsular polysaccharide in EM was associated with EM-induced NPY downregulation in the colon. Analysis of Gene Expression Omnibus datasets showed markedly reduced NPY expression in the inflamed colons of patients with UC compared with that in the colons of healthy controls. In summary, EM-induced reduction in the colonic expression of NPY may be associated with a decrease in hippocampal NPY and anxiety- and depression-like behavior in mice.

Among the factors incriminated in the appearance of eating disorders, intestinal microbiota has recently been implicated. Now there is evidence that the composition of gut microbiota is different in anorexia nervosa. We gathered many surveys on the changes in the profile of gut microbiota in patients with anorexia nervosa. This review comprehensively examines the contemporary experimental evidence concerning the bidirectional communication between gut microbiota and the brain. Drawing from recent breakthroughs in this area of research, we propose that the gut microbiota significantly contributes to the intricate interplay between the body and the brain, thereby contributing to overall healthy homeostasis while concurrently impacting disease risk, including anxiety and mood disorders. Particular attention is devoted to elucidating the structure and functional relevance of the gut microbiota in the context of Anorexia Nervosa.

Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.

The intestinal microbiota is an "invisible organ" in the human body, with diverse components and complex interactions. Homeostasis of the intestinal microbiota plays a pivotal role in maintaining the normal physiological process and regulating immune homeostasis. By reviewing more than one hundred related studies concerning HIV infection and intestinal microbiota from 2011 to 2023, we found that human immunodeficiency virus (HIV) infection can induce intestinal microbiota dysbiosis, which not only worsens clinical symptoms but also promotes the occurrence of post-sequelae symptoms and comorbidities. In the early stage of HIV infection, the intestinal mucosal barrier is damaged and a persistent inflammatory response is induced. Mucosal barrier damage and immune injury play a pivotal role in promoting the post-sequelae symptoms caused by HIV infection. This review summarizes the relationship between dysbiosis of the intestinal microbiota and mucosal barrier damage during HIV infection and discusses the potential mechanisms of intestinal barrier damage induced by intestinal microbiota dysbiosis and inflammation. Exploring these molecular mechanisms might provide new ideas to improve the efficacy of HIV treatment and reduce the incidence of post-sequelae symptoms.

Obesity is a public health crisis, presenting a huge burden on health care and the economic system in both developed and developing countries. According to the WHO's latest report on obesity, 39% of adults of age 18 and above are obese, with an increase of 18% compared to the last few decades. Metabolic energy imbalance due to contemporary lifestyle, changes in gut microbiota, hormonal imbalance, inherent genetics, and epigenetics is a major contributory factor to this crisis. Multiple studies have shown that probiotics and their metabolites (postbiotics) supplementation have an effect on obesity-related effects in vitro, in vivo, and in human clinical investigations. Postbiotics such as the SCFAs suppress obesity by regulating metabolic hormones such as GLP-1, and PPY thus reducing feed intake and suppressing appetite. Furthermore, muramyl di-peptides, bacteriocins, and LPS have been tested against obesity and yielded promising results in both human and mice studies. These insights provide an overview of targetable pharmacological sites and explore new opportunities for the safer use of postbiotics against obesity in the future.

Irritable bowel syndrome (IBS) and bladder pain syndrome/interstitial cystitis (BPS/IC) are comorbid visceral pain disorders seen commonly in women with unknown etiology and limited treatment options and can involve visceral organ cross-sensitization. Calcitonin gene-related peptide (CGRP) is a mediator of nociceptive processing and may serve as a target for therapy. In three rodent models, we employed a monoclonal anti-CGRP F(ab')2 to investigate the hypothesis that visceral organ cross-sensitization is mediated by abnormal CGRP signaling. Visceral organ cross-sensitization was induced in adult female rats via transurethral infusion of protamine sulfate (PS) into the urinary bladder or infusion into the colon of trinitrobenzene sulfonic acid (TNBS). Colonic sensitivity was assessed via the visceromotor response to colorectal distension (CRD). Bladder sensitivity was assessed as the frequency of abdominal withdrawal reflexes to von Frey filaments applied to the suprapubic region. PS- or TNBS-induced changes in colonic and bladder permeability were investigated in vitro via quantification of transepithelial electrical resistance (TEER). Peripheral administration of an anti-CGRP F(ab')2 inhibited PS-induced visceral pain behaviors and colon hyperpermeability. Similarly, TNBS-induced pain behaviors and colon and bladder hyperpermeability were attenuated by anti-CGRP F(ab')2 treatment. PS into the bladder or TNBS into the colon significantly increased the visceromotor response to CRD and abdominal withdrawal reflexes to suprapubic stimulation and decreased bladder and colon TEER. These findings suggest an important role of peripheral CGRP in visceral nociception and organ cross-sensitization and support the evaluation of CGRP as a therapeutic target for visceral pain in patients with IBS and/or BPS/IC. SIGNIFICANCE STATEMENT: A monoclonal antibody against calcitonin gene-related peptide (CGRP) was found to reduce concomitant colonic and bladder hypersensitivity and hyperpermeability. The results of this study suggest that CGRP-targeting antibodies, in addition to migraine prevention, may provide a novel treatment strategy for multiorgan abdominopelvic pain following injury or inflammation.

Migraine, a prevalent neurological condition and the third most common disease globally, places a significant economic burden on society. Despite extensive research efforts, the precise underlying mechanism of the disease remains incompletely comprehended. Nevertheless, it is established that the activation and sensitization of the trigeminal system are crucial during migraine attacks, and specific substances have been recognized for their distinct involvement in the pathomechanism of migraine. Recently, an expanding body of data indicates that migraine attacks can be prevented and treated through dietary means. It is important to highlight that the various diets available pose risks for patients without professional guidance. This comprehensive overview explores the connection between migraine, the gut microbiome, and gastrointestinal disorders. It provides insight into migraine-triggering foods, and discusses potential diets to help reduce the frequency and severity of migraine attacks. Additionally, it delves into the benefits of using pre- and probiotics as adjunctive therapy in migraine treatment.

Regular high-intensity exercise can cause changes in athletes' gut microbiota, and the extent and nature of these changes may be affected by the athletes' exercise patterns. However, it is still unclear to what extent different types of athletes have distinct gut microbiome profiles and whether we can effectively monitor an athlete's inflammatory risk based on their microbiota. To address these questions, we conducted a multi-cohort study of 543 fecal samples from athletes in three different sports: aerobics (n = 316), wrestling (n = 53), and rowing (n = 174). We sought to investigate how athletes' gut microbiota was specialized for different types of sports, and its associations with inflammation, diet, anthropometrics, and anaerobic measurements. We established a microbiota catalog of multi-cohort athletes and found that athletes have specialized gut microbiota specific to the type of sport they engaged in. Using latent Dirichlet allocation, we identified 10 microbial subgroups of athletes' gut microbiota, each of which had specific correlations with inflammation, diet, and anaerobic performance in different types of athletes. Notably, most inflammation indicators were associated with Prevotella-driven subgroup 7. Finally, we found that the effects of sport types and exercise intensity on the gut microbiota were sex-dependent. These findings shed light on the complex associations between physical factors, gut microbiota, and inflammation in athletes of different sports types and could have significant implications for monitoring potential inflammation risk and developing personalized exercise programs. IMPORTANCE This study is the first multi-cohort investigation of athletes across a range of sports, including aerobics, wrestling, and rowing, with the goal of establishing a multi-sport microbiota catalog. Our findings highlight that athletes' gut microbiota is sport-specific, indicating that exercise patterns may play a significant role in shaping the microbiome. Additionally, we observed distinct associations between gut microbiota and markers of inflammation, diet, and anaerobic performance in athletes of different sports. Moreover, we expanded our analysis to include a non-athlete cohort and found that exercise intensity had varying effects on the gut microbiota of participants, depending on sex.