Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the interactome concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.

Inflammatory bowel disease (IBD) is a chronic autoimmune condition whose pathogenesis has not been fully elucidated, and current treatments are not definitive and often carry several side effects. The Complementary and Alternative Medicine (CAM) offers a new approach to conventional medicine. However, their clinical application and mechanisms remain limited.Objective: The aim of this review is to evaluate the anti-inflammatory, impact on microbiota and antioxidant efficacy of currently available CAM for IBD.Methods: The literature collection was obtained from Google Scholar, MEDLINE, PubMed and Web of Science (WOS). Studies in both human and animal models, published in English language between 2018 and 2024, were selected. Sixty-seven studies were included in the current review after inclusion and exclusion screening processes.Results: Mostly, studies showed significant anti-inflammatory, gut microbiota restoring, antioxidant effects of polyphenols, polysaccharides, emodin, short-chain fatty acids (SCFA; including butyrate, propionate and acetate), and probiotics although some contrasting results were noted. Current evidence shows that polyphenols exhibit the most consistent result in alleviating IBD pathophysiology, primarily due to their significant SCFA-elevating effect.Discussion: Future studies may focus on human studies, narrowing down on individual factors which may change natural product's metabolism. Further research studies are also essential to obtain therapeutic recommendations.

According to the criteria established by the International League Against Epilepsy (ILAE), epilepsy is defined as a disorder characterized by at least two unprovoked seizures occurring more than 24 h apart. Its pathogenesis is closely related to various physiological and pathological factors. Advances in high-throughput metagenomic sequencing have increasingly highlighted the role of gut microbiota dysbiosis in epilepsy. Short-chain fatty acids (SCFAs), the major metabolites of the gut microbiota and key regulators of the gut-brain axis, support physiological homeostasis through multiple mechanisms. Recent studies have indicated that SCFAs not only regulate seizures by maintaining intestinal barrier integrity and modulating intestinal immune responses, but also affect the structure and function of the blood-brain barrier (BBB) and regulate neuroinflammation. This review, based on current literatures, explores the relationship between SCFAs and epilepsy, emphasizing how SCFAs affect epilepsy by modulating the intestinal barrier and BBB. In-depth studies on SCFAs may reveal their therapeutic potential and inform the development of gut microbiota-targeted epilepsy treatments.

Schizophrenia (SCZ) is a complex disorder characterized by acute symptom exacerbations. Amisulpride, an antipsychotic, has shown effects beyond its primary neurochemical actions, suggesting an influence on the gut microbiome, cytokine modulation, and short-chain fatty acid (SCFA) metabolism. This study aims to investigate these broader effects by examining changes in serum SCFA levels and gene expression profiles in peripheral blood mononuclear cells (PBMCs) following amisulpride treatment. Patients with SCZ undergoing a four-week amisulpride regimen were enrolled. Serum SCFA levels were quantified by gas chromatography, and gene expression profiling was performed in PBMCs using real-time quantitative polymerase chain reaction to assess treatment-associated changes. Results revealed that treatment with amisulpride resulted in a significant increase in serum acetate levels. Gene expression analysis revealed upregulation of G-protein coupled receptor 109a (GPR109a), histone deacetylase 1 (HDAC1), G-protein coupled receptor 43 (GPR43), Toll-like receptor 2 (TLR2), soluble CD14 (sCD14), and N-methyl-d-aspartate receptor (NMDAR), while Toll-like receptor 4 (TLR4) and pregnane X receptor (PXR) were downregulated. These findings suggest that amisulpride may modulate acetate metabolism and immune signaling pathways in SCZ, potentially contributing to anti-inflammatory effects and neuroimmune regulation. The observed increase in acetate, a key microbial metabolite, and the altered expression of immune-related genes suggest a possible link between metabolic shifts and immunomodulatory responses in SCZ pathophysiology. However, direct evidence linking these changes to gut-brain axis mechanisms remains insufficient. Further research is needed to elucidate the therapeutic implications of these metabolic and immunological alterations and their potential role in symptom modulation.

Emerging evidence supports gut microbiota's association with mental distress, particularly depression and anxiety, the microbiota-gut-brain axis was the believed to be the underlying mechanism. This study investigated the causal relationships between specific gut microbiota and depression and anxiety disorders using large-scale genome-wide association study (GWAS) data.

A two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal effects of 211 microbial taxa on depression and anxiety across three large GWAS databases: FinnGen, Pan-UKBB, and PGC. Sensitive analyses were followed to validate the robustness of results. Random-effect meta-analysis was further performed to enhance the statistical power.

The MR analysis revealed that the Bifidobacteriales (IVW: OR 0.90, 95 %CI 0.83 to 0.98) and Bifidobacteriaceae (IVW: OR 0.90, 95 %CI 0.83 to 0.98) had a protective effect against depression. Clostridiales (cML-MA: OR 0.88, 95 %CI 0.81 to 0.95) and Parasutterella (cML-MA: OR 0.75, 95 %CI 0.64 to 0.88) showed negative associations with depression. Increased abundance of Oxalobacteraceae (cML-MA: OR 1.78, 95 %CI 1.24 to 2.56), Deltaproteobacteria (cML-MA: OR 2.17, 95 %CI 1.38 to 3.40), and Desulfovibrionales (cML-MA: OR 2.22, 95 %CI 1.41 to 3.49) was associated with a higher risk of depression. For anxiety, protective effects were found for Actinobacteria (phylum: IVW: OR 0.83, 95 %CI 0.76 to 0.87; class: IVW: OR 0.84, 95 %CI 0.75 to 0.93), Bifidobacteriales (IVW: OR 0.80, 95 %CI 0.75 to 0.85), Bifidobacteriaceae (IVW: OR 0.80, 95 %CI 0.75 to 0.85) and Bifidobacterium [g] (IVW: OR 0.79, 95 %CI 0.74 to 0.84). Lactobacillaceae [f] (cML-MA: OR 1.18, 95 %CI 1.08 to 1.28), Clostridia [c] (cML-MA: OR 1.15, 95 %CI 0.1.06 to 1.26) and Clostridiales [o] (IVW: OR 1.15, 95 %CI 1.05 to 1.27) were associated with increased anxiety risk. Meta-analysis results indicated significant associations, particularly the protective effects of Actinobacteria (OR 0.90, 95 % CI, 0.83 to 0.98) and Clostridiaceae1 (OR 0.91, 95 % CI, 0.83 to 0.99) on depression and several taxa on anxiety. No significant instrumental variables for depression or anxiety on gut microbiota were identified.

Our findings highlight specific gut microbiota that are associated with depression and anxiety, underscoring the causal relationships between these intestinal microbes and psychiatric disorders. These results suggest potential strategies for mitigating disease symptoms and improving quality of life through microbiome-targeted therapies. Further studies, including randomized controlled trials and investigations into sex-specific effects, are essential to validate and expand upon these findings.

The tumour microenvironment (TME) exerts a profound influence on cancer progression and treatment outcomes. Recent investigations have elucidated the crucial role of intratumoural microbiota and their metabolites in shaping the TME and modulating anti-tumour immunity. This review critically assesses the influence of intratumoural microbial metabolites on the TME and cancer immunotherapy. We systematically analyse how microbial-derived glucose, amino acid, and lipid metabolites modulate immune cell function, cytokine secretion, and tumour growth. The roles of specific metabolites, including lactate, short-chain fatty acids, bile acids, and tryptophan derivatives, are comprehensively examined in regulating immune responses and tumour progression. Furthermore, we investigate the potential of these metabolites to augment the efficacy of cancer immunotherapies, with particular emphasis on immune checkpoint inhibitors. By delineating the mechanisms through which microbial metabolites influence the TME, this review provides insights into novel microbiome-based therapeutic strategies, thereby highlighting a promising frontier in personalised cancer medicine.

In the present study, an inulin-type fructan (ITF) with the degree polymerization (DP) of 21 was isolated from Codonopsis pilosula roots and its structure was characterized by FT-IR, MALDI-TOF-MS and NMR. The immunomodulatory and intestinal protective effects of ITF were investigated on immunosuppressive mice. Male BALB/c mice were pretreated with cyclophosphamide (Cy) for 3 days to establish an immunosuppressive model followed by ITF treatment. The results demonstrated that compared with the model group, ITF administration significantly increased immune organ index (P<0.05), alleviated intestinal villus damage, stimulated serum cytokine secretion including Ig G, IL-4, IL-6, IL-2, TNF-α, and INF-γ (P<0.05), upregulated the expression of Occludin and Claudin-1 (P<0.05), and increased CD4+ and CD8+ T cells of ileum in Cy-induced mice (P<0.05). Furthermore, ITF restored the intestinal microbiota dysbiosis caused by Cy by increasing the abundance of Muribaculaceae, Blautia, Odoribacter, Lactobacillus and decreasing the abundance of Lachnospiraceae_NK4A136_group (P<0.05). Meanwhile, ITF increased the production of short-chain fatty acids (SCFAs) including acetic acid, propionic acid and butyric acid (P<0.05). These results indicated that ITF can ameliorate cyclophosphamide-induced immunosuppression and intestinal barrier injury, and restore gut microbiota dysbiosis. This study provided important evidences for the immunomodulatory and intestinal protective effects of the ITF from C. pilosula.

Short-chain fatty acids (SCFAs) have attracted considerable interest as potential biomarkers, therapeutic targets, and nutritional factors in athletic training. SCFAs are typically produced by the intestinal microbiome and exhibit various structural forms, including linear- and branched-chain types. In particular, branched-chain SCFAs have been associated with muscle metabolism during exercise loading. Consequently, accurate and efficient analytical methods are essential for identifying these biomarkers. Liquid chromatography-tandem mass spectrometry is a suitable and accurate technique for SCFA analysis; however, stable isotope calibrations are required for all analytes. Because of technological limitations, the available species are restricted to certain types of SCFAs. To address this issue, this study performed a simple conversion reaction involving the incorporation of 18O into the carboxyl group. Specifically, oxygen atoms in the carboxyl groups were substituted with 18O sourced from commercially available H218O. An SCFA mixture standard solution was successfully labeled under optimized conditions, and the SIL purity and amount were sufficient for isotope dilution (95.2-96.9%, 250 assays using 10 μL of H218O). Moreover, no reversion to 16O was observed during storage or analysis. Analytical validation was performed in human serum using the substituted isotopic standard mixture, achieving good accuracy (90-110%) and precision (<10% relative standard deviation) across three concentration levels. Finally, changes in SCFA patterns were examined in athletes during exercise loading.

Inflammatory bowel disease (IBD) is a serious chronic condition marked by persistent and recurrent intestinal ulcers. Although the exact cause of IBD remains unclear, it is generally accepted that a complex interaction among dietary factors, gut microbiota, and immune responses in genetically predisposed individuals contributes to its development. Pyroptosis, an inflammatory form of programmed cell death activated by inflammasomes, is marked by the rupture of cell membranes and the subsequent release of inflammatory mediators. Emerging evidence indicates that pyroptosis plays a crucial role in the pathogenesis of IBD. Moderate pyroptosis activation can enhance intestinal immune defenses, while excessive inflammasome activation can trigger an inflammatory cascade, resulting in increased damage to intestinal tissues. This article reviews the molecular mechanisms underlying pyroptosis and highlights its role in the onset and progression of IBD. Furthermore, We explore recent advancements in IBD treatment, focusing on small molecule compounds that specifically target and inhibit pyroptosis.

High fructose diet (HFrD) has been approved to be involved in the pathogenesis of insulin resistance. Mesenchymal stem cells have a vital role in the treatment of various diseases including metabolic disturbances. We investigated the effect of Adipose-derived mesenchymal stem cells (ADMSCs) against HFrD-induced metabolic disorders and the molecular mechanisms for this effect. Rats were divided into 3 groups; control, HFrD, and combined HFrD with ADMSCs. We assessed liver functions, gut microbiota activity, oxidative stress, adiponectin, and IL10 levels. Also, we measured SREBP-1, IRS-1 expression using Western blot, and Malat1 expression using rt-PCR. ADMSCs antagonized metabolic abnormalities induced by HFrD in the form of improvement of liver functions and alleviation of oxidative stress. In addition, ADMSCs ameliorated gut microbiota activity besides the elevation of adiponectin and IL10 levels. ADMSCs attenuated insulin resistance through upregulation of IRS1 and downregulation of SREBP-1 and Malat1. ADMSCs can protect against HFrD-induced metabolic hazards.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and emotional instability, primarily resulting from the abnormal accumulation of mutant huntingtin protein. Growing research highlights the role of intestinal microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), in modulating HD progression. SCFAs, including acetate, propionate, and butyrate, are produced by gut bacteria through dietary fiber fermentation and are recognized for their neuroprotective properties. Evidence suggests that SCFAs regulate neuroinflammation, neuronal communication, and metabolic functions within the central nervous system (CNS). In HD, these compounds may support neuronal health, reduce oxidative stress, and enhance blood-brain barrier (BBB) integrity. Their mechanisms of action involve binding to G-protein-coupled receptors (GPCRs) and modulating gene expression through epigenetic pathways, underscoring their therapeutic potential. This analysis examines the significance of SCFAs in HD, emphasizing the gut-brain axis and the benefits of dietary interventions aimed at modifying gut microbiota composition and promoting SCFA production. Further research into these pathways may pave the way for novel HD management strategies and improved therapeutic outcomes.

Polysaccharides, as complex carbohydrates, play a pivotal role in immune modulation and interactions with the gut microbiota. The diverse array of dietary polysaccharides influences gut microbial ecology, impacting immune responses, metabolism, and overall well-being. Despite their recognized benefits, there is limited understanding of the precise mechanisms by which polysaccharides modulate the immune system through the gut microbiota. A comprehensive search of Web of Science, PubMed, Google Scholar, and Embase up to May 2024 was conducted to identify relevant studies. This study employs a systematic approach to explore the interplay between polysaccharides and the gut microbiota, focusing on cytokine-mediated and short-chain fatty acid (SCFA)-mediated pathways. The findings underscore the significant role of polysaccharides in shaping the composition and function of the gut microbiota, thereby influencing immune regulation and metabolic processes. However, further research is necessary to elucidate the detailed molecular mechanisms and translate these findings into clinical applications.

In the current era, metabolic dysfunction-associated steatotic liver disease (MASLD) has gradually developed into a major type of chronic liver disease that is widespread globally. Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD. Currently, the gut microbiota has become one of the important entry points for the research of this disease. Therefore, the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD, including the changes and differences in the microbiota between the healthy liver and the diseased liver. Meanwhile, considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis (such as mild fibrosis and severe fibrosis) during the disease progression, we also conduct a comparison of the microbiota in these states and use them as markers of disease progression. It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota, and the impact of lipopolysaccharide from Gram-negative bacteria on the disease. In addition, the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics (including new-generation probiotics) will be explored, which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota. This will achieve important progress in preventing and combating this disease.

Background: COPD is a heterogenous disease of the respiratory tract caused by diverse genetic factors along with environmental and lifestyle-related effects such as industrial dust inhalation and, most frequently, cigarette smoking. These factors lead to airflow obstruction and chronic respiratory symptoms. Additionally, the increased risk of infections exacerbates airway inflammation in COPD patients. As a consequence of the complex pathomechanisms and difficulty in treatment, COPD is among the leading causes of mortality both in the western countries and in the developing world. Results: The management of COPD is still a challenge for the clinicians; however, alternative interventions such as smoking cessation and lifestyle changes from a sedentary life to moderate physical activity with special attention to the diet may ameliorate patients' health. Here, we reviewed the effects of different dietary components and supplements on the conditions of COPD. Conclusions: COPD patients are continuously exposed to heavy metals, which are commonly present in cigarette smoke and polluted air. Meanwhile, they often experience significant nutrient deficiencies, which affect the detoxification of these toxic metals. This in turn can further disrupt nutritional balance by interfering with the absorption, metabolism, and utilization of essential micronutrients. Therefore, awareness and deliberate efforts should be made to check levels of micronutrients, with special attention to ensuring adequate levels of antioxidants, vitamin D, vitamin K2, magnesium, and iron, as these may be particularly important in reducing the risk of COPD development and limiting disease severity.

Background: Depression and anxiety are common in UC patients due to gut microbiota dysbiosis and increased proinflammatory markers. Butyrate, a short-chain fatty acid, participates in the regulation of gut microbiota and inflammation and has neuroprotective effects in neurodegenerative disease. Therefore, we assessed the effects of sodium butyrate supplementation on the disease severity, inflammation, and psychological factors in active UC patients. Methods: This study was a randomized, parallel, double-blind controlled trial. Participants in the intervention (n = 18) and control (n = 18) groups received 600 mg/kg of sodium butyrate or rice starch as a placebo with their main meal, respectively, for 12 weeks. The partial Mayo score was used to evaluate disease severity, while the Westergren method was employed to assess the erythrocyte sedimentation rate (ESR). NLR and PLR were determined using an automated analyzer (XS-500i, Sysmex). Moreover, the psychological factors were assessed by the hospital anxiety depression scale (HADS) and the general health questionnaire (GHQ). Results: In comparison with placebo, sodium-butyrate supplementation significantly decreased the ESR level (-6.66 ± 1.56 vs. 3.00 ± 2.11, p=0.01), NLR (-0.24 ± 0.1 vs. 0.33 ± 0.23, p=0.02), Mayo score (-2.33 ± 0.41 vs. 0.22 ± 0.40, p < 0.001), HADS anxiety score (-2.77 ± 0.64 vs. 0.94 ± 0.63, p=0.001), HADS depression score (-2.38 ± 0.47 vs. 0.61 ± 0.33, p < 0.001), and GHQ total score (-12.11 ± 1.48 vs. 3.55 ± 1.39, p < 0.001). Conclusion: Butyrate could serve as an effective adjuvant treatment for reducing disease severity and alleviating psychological symptoms. This trial was registered on the Research Ethics Committee of Shiraz University of Medical Sciences, with the reference number IR.SUMS.SCHEANUT.REC.1400.037. Trial Registration: Iranian Registry of Clinical Trials: IRCT20211214053401N1.

Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.

Anti-tumor immunity, including innate and adaptive immunity is critical in inhibiting tumorigenesis and development of tumor. The adaptive immunity needs specific lymph organs such as tertiary lymphoid structures (TLSs), which are highly correlated with improved survival outcomes in many cancers. In recent years, with increasing attention on the TLS in tumor microenvironment, TLSs have emerged as a novel target for anti-tumor therapy. Excitingly, studies have shown the contribution of TLSs to the adaptive immune responses. However, it is unclear how TLSs to form and how to more effectively defense against tumor through TLS formation. Recent studies have shown that the inflammation plays a critical role in TLS formation. Interestingly, studies have also found that gut microbiota can regulate the occurrence and development of inflammation. Therefore, we here summarize the potential effects of gut microbiota- mediated inflammation or immunosuppression on the TLS formation in tumor environments. Meanwhile, this review also explores how to manipulate mature TLS formation through regulating gut microbiota/metabolites or gut microbiota associated signal pathways for anti-tumor immunity, which potentially lead to a next-generation cancer immunotherapy.

This study aimed to explore the potential mechanism of Xiexin Tang in improving type 2 diabetes mellitus from the perspective of intestinal barrier function. The results indicated that Xiexin Tang could notably promote the expression of GPRs while suppressing the expression of HDACs in colon epithelial cells, then significantly elevate the levels of TGF-β1 and IL-18 to regulate the differentiation of T cells and further maintain the intestinal immune homeostasis. Meanwhile, it could markedly inhibit the inflammatory signaling pathway to improve intestinal barrier function, relieving type 2 diabetes mellitus.

Metabolic disease is rising along with both global industrialization and the use of new commercial, agricultural, and industrial chemicals and food additives. Exposure to these compounds may contribute to aspects of metabolic diseases such as obesity, diabetes, and fatty liver disease. Ingesting compounds in the food supply is a key route of human exposure, resulting in the interaction between toxicants or additives and the intestinal microbiota. Toxicants can influence the composition and function of the gut microbiota, and these microbes can metabolize and transform toxicants and food additives. Microbe-toxicant interactions in the intestine can alter host mucosal barrier function, immunity, and metabolism, which may contribute to the risk or severity of metabolic disease development. Targeting the connection between toxicants, food, and immunity in the gut using strategies such as fermentable fiber (i.e., inulin) may mitigate some of the effects of these compounds on host metabolism. Understanding causative factors in the microbe-host relationship that promote toxicant-induced dysmetabolism is an important goal. This review highlights the role of common toxicants (i.e., persistent organic pollutants, pesticides, and fungicides) and food additives (emulsifiers and artificial sweeteners) found in our food supply that alter the gut microbiota and promote metabolic disease development.

The human gut, with a complex community of microbes, is essential for maintaining overall health. This gut microbiota engages in two-way communication with the central nervous system, collectively known as the gut microbiota-brain axis. Alterations in gut microbiota have been associated with various neurological disorders, and disruptions to the blood-brain barrier (BBB) may be crucial, though the exact mechanisms remain unknown. In the current study, we investigated the impacts of short-chain fatty acids (SCFAs) on the integrity of the BBB, which was compromised by orally administered antibiotics in rhesus monkeys and C57BL/6n mice. Our results showed that SCFA supplementation notably enhanced BBB integrity in rhesus monkeys with gut dysbiosis. Similar outcomes were observed in mice with gut dysbiosis, accompanied by decreased cortical claudin-5 mRNA levels. In particular, propionate, but not acetate or butyrate, could reverse the antibiotic-induced BBB permeability increase in mice. Additionally, in vitro studies demonstrated that propionate boosted the expression of tight junction proteins in brain endothelial cells. These results suggest that the propionate can maintain BBB integrity through a free fatty acid receptor 2-dependent mechanism. This study offers new insights into the gut-brain axis and underscores potential therapeutic targets for interventions based on gut microbiota.

The prevalence of gastrointestinal disorders caused by alcohol, Helicobacter pylori, non-steroidal anti-inflammatory drugs, chronic stress and sedentary lifestyle is on the rise. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, has emerged as a protective factor against various gastrointestinal issues. Despite its known benefits, the dual role of CGRP in gastrointestinal damage remains unclear. Discovered 30 years ago through alternative RNA processing of the calcitonin gene, CGRP is known to be a potent vasodilator involved in crucial defensive mechanisms for both physiological and pathological conditions. Promising evidences from preclinical research have attracted the interest of scientists for the exploration of CGRP as a therapeutic neuropeptide. Numerous evidences suggest that this neuropeptide is secreted by the neurons under the influence of endogenous as well as exogenous stimuli. CGRP repairs the gastric mucosal barrier and maintain mucosal integrity by suppressing NF-κB activation, thereby reducing tumour necrosis factor-alpha expression. In addition, recent studies suggest that CGRP modulates immune responses and enhances epithelial cell proliferation, further contributing to its cytoprotective effects. Consequently, CGRP and the CGRP secretagogues represent promising novel targets for clinical applications. This review aims to elucidate the role of CGRP and CGRP secretagogues in the management of gastrointestinal disorders, highlighting its potential as a therapeutic agent in the context of evidence-based modern gastroenterology.

A diverse array of microbial organisms colonizes the human body, collectively known as symbiotic microbial communities. Among the various pathogen infections that hosts encounter, viral infections represent one of the most significant public health challenges worldwide. The gut microbiota is considered an important biological barrier against viral infections and may serve as a promising target for adjuvant antiviral therapy. However, the potential impact of symbiotic microbiota on viral infection remains relatively understudied. In this review, we discuss the specific regulatory mechanisms of gut microbiota in antiviral immunity, highlighting recent advances in how gut microbiota regulate the host immune response, produce immune-related molecules, and enhance the host's defense against viruses. Finally, we also discuss the antiviral potential of oral probiotics.

Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4+ intraepithelial lymphocytes (IELs). The influence of dietary fibers on MHC-II expression is mediated by its metabolic product, acetate, and its receptor, free fatty acid receptor 2 (FFAR2). While acetate activation of FFAR2 on epithelial cells helps resist CDI, it does not directly regulate MHC-II expression. Instead, MHC-II is regulated by FFAR2 in type 3 innate lymphoid cells (ILC3s). Acetate enhances interleukin-22 (IL-22) production by ILC3s, which then suppresses MHC-II expression on the colonic epithelium. In conclusion, a low-fiber diet reduces acetate-induced IL-22 production by ILC3s, leading to increased MHC-II on the colonic epithelium. This change affects recovery from CDI by expanding the population of pathogenic CD4+ IELs.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. Recent research has highlighted the significant role of gut microbiota in the pathogenesis and treatment of UC. This review aims to provide a comprehensive overview of the current understanding of the relationship between gut microbiota and UC. We discuss the involvement of gut microbiota in the onset of UC, including the dysbiosis observed in patients and its potential mechanisms. Additionally, the role of extra-intestinal microbiota in UC pathogenesis is explored, which has been less studied but is gaining attention. The influence of gut microbiota on the efficacy of biological immunotherapy for UC is also examined, highlighting how microbial composition can influence treatment outcomes. Furthermore, we review microbiota transplantation, and their potential benefits in UC management. Finally, we consider the combined use of antibiotics and biological agents in UC treatment, discussing their synergistic effects and potential drawbacks. This review underscores the importance of gut microbiota in UC and suggests that targeting microbial communities could offer new avenues for effective treatment.

The gut microbiota is firmly associated with the progression of ulcerative colitis (UC). Beneficial microbial metabolites, such as butyrate, exert vital roles in maintaining intestinal homeostasis. The Sea buckthorn berry is a traditional Chinese medicine homologous to food and medicine which is widely applied in the prevention and treatment of UC in clinic practice. Recent studies have exhibited the potential function of Sea buckthorn on regulating the gut microbiota, however, the mechanism underlying its anti-colitis effects and the key gut microbes mediating its efficacy are still unclear.

This study is intended to explore the pharmacological mechanism of the efficacy of Sea buckthorn berries extract (SBE) in alleviating UC from the perspective of the gut microbial regulation.

The effect of SBE on UC was evaluated on dextran sulfate sodium (DSS)-induced murine model by assessing the body weight change, colon length, disease activity index (DAI), histopathological staining and the transcriptional expression of genes associated with inflammation and mucosal integrity. The dependence of the gut microbiota in the therapeutical effects of SBE on UC was confirmed by pseudo-germ-free mice and the co-housing experiment. The differential gut microbes altered by SBE were discovered by 16S rRNA sequencing and qPCR. The levels of short chain fatty acids (SCFAs) in bacterial medium and colonic contents were determined by GC-MS/MS. Bacterial colonization was conducted to estimate the effects of the bacteria on UC and to verify the involvement of the functional bacteria in the efficacy of SBE. A butyrate receptor G protein-coupled receptor (GPR)109A antagonist mepenzolate bromide (MPN) was used to validate the important role of butyrate and GPR109A in the anti-colitis effects of SBE and functional bacteria on UC. Two-way ANOVA was employed for multiple curve comparison and One-way ANOVA and Brown-Forsythe ANOVA test were used for multiple group comparison. Statistical significance was defined as p< 0.05.

SBE treatment significantly alleviated DSS-induced UC and its therapeutical effects was impaired in pseudo-germ-free mice. Moreover, the co-housing experiment exhibited that SBE-altered microbiota could effectively ameliorate UC. Further research demonstrated that Faecalibaculum rodentium was obviously increased by SBE and could be transferable by co-housing. Moreover, butyrate, a product of F. rodentium, dramatically decreased in UC mice while could be recovered by SBE administration. Abolishment of F. rodentium using vancomycin deprived the efficacy of SBE, but this could be reversed by recolonization of F. rodentium. Finally, blockage of the butyrate's receptor GPR109A weakened the effects of F. rodentium, indicating the indispensability of butyrate and GPR109A in the anti-colitis effects of F. rodentium.

SBE has potent therapeutical efficacy on UC including relieving inflammation and enhancing intestinal epithelial integrity, which is mediated by the gut F. rodentium-regulated butyrate-GPR109A axis.

The gut microbiota plays a crucial role in the communication between the gut, liver, and brain through the production of short chain fatty acids (SCFAs). SCFAs serve as key mediators in the Gut-Liver-Brain Axis, influencing various physiological processes and contributing to overall health. SCFAs are produced by bacterial fermentation of dietary fiber in the gut, and they exert systemic effects by signaling through various pathways. In the Gut-Liver axis, SCFAs regulate liver metabolism through peroxisome proliferator-activated receptor-γ (PPAR-γ), AMP-activated protein kinase (AMPK) and other pathways, promotes fat oxidation, modulate inflammation through mTOR pathway, and impact metabolic health. In the Gut-Brain axis, SCFAs influence brain function, behavior, and may have implications for neurological disorders, in which G-protein coupled receptors (GPCRs) play an essential role, along with other pathways such as hypothalamic-pituitary-adrenal (HPA) pathway. Understanding the mechanisms by which SCFAs mediate communication between the gut, liver, and brain is crucial for elucidating the complex interplay of the Gut-Liver-Brain Axis. This review aims to provide insight into the role of gut microbiota-derived SCFAs as mediators of the Gut-Liver-Brain Axis and their potential therapeutic implications. Further research in this area will be instrumental in developing novel strategies to target the Gut-Liver-Brain Axis for the prevention and treatment of various health conditions.

Metabolic syndrome (Mets) is an important contributor to morbidity and mortality in cardiovascular, liver, neurological, and reproductive diseases. Short-chain fatty acid (SCFA), an organismal energy donor, has recently been demonstrated in an increasing number of studies to be an important molecule in ameliorating immuno-inflammation, an important causative factor of Mets, and to improve lipid distribution, blood glucose, and body weight levels in animal models of Mets. This study reviews recent research advances on SCFA in Mets from an immune-inflammatory perspective, including complications dominated by chronic inflammation, as well as the fact that these findings also contribute to the understanding of the specific mechanisms by which gut flora metabolites contribute to metabolic processes in humans. This review proposes an emerging role for SCFA in the inflammatory Mets, followed by the identification of major ambiguities to further understand the anti-inflammatory potential of this substance in Mets. In addition, this study proposes novel strategies to modulate SCFA for the treatment of Mets that may help to mitigate the prognosis of Mets and its complications.

B-lymphocyte-induced maturation protein 1 (Blimp-1) is a transcription factor that, among other functions, modulates metabolism and helps to regulate antioxidant pathways, which is important in the context of chronic inflammatory diseases like diabetes, cardiovascular disease, and autoimmune disease. In immune cell function, Blimp-1 has a modulatory role in the orchestration of metabolic reprogramming and as a promoter of anti-inflammatory cytokines, including IL-10, responsible for modulating oxidative stress and immune homeostasis. Moreover, Blimp-1 also modulates key metabolic aspects, such as glycolysis and fatty acid oxidation, which regulate reactive oxygen species levels, as well as tissue protection. This review depicts Blimp-1 as an important regulator of antioxidant defenses and anti-inflammation and suggests that the protein could serve as a therapeutic target in chronic inflammatory and metabolic dysregulation conditions. The modulation of Blimp-1 in diseases such as diabetic coronary heart disease and atherosclerosis could alleviate oxidative stress, augment the protection of tissues, and improve disease outcomes. The therapeutic potential for the development of new treatments for these chronic conditions lies in the synergy between the regulation of Blimp-1 and antioxidant therapies, which are future directions that may be pursued. This review emphasizes Blimp-1's emerging importance as a novel regulator in the pathogenesis of inflammatory diseases, providing new opportunities for therapeutic intervention.

Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

Akkermansia muciniphila is a bacterium commonly found in the human gastrointestinal tract that has received considerable interest as a potential probiotic for the improvement of gut health and overall metabolic function. A. muciniphila is enriched in the mucus layer of the intestinal lining, where it degrades mucin and plays a significant role in gut barrier maintenance and immune regulation. A higher abundance of A. muciniphila has been observed in the gut of healthy individuals relative to those with metabolic disorders, and multiple metabolic benefits, including improved glucose management, reduced body fat, and reduced inflammation have been linked to A. muciniphila. Current research on A. muciniphila primarily relies on mouse models, with limited human interventional studies available. While these animal studies offer valuable insights into the potential roles of A. muciniphila in health and disease, further clinical investigations in humans are needed to fully understand its impact. Here, we explore the current scope of A. muciniphila research and its potential as a therapeutic agent to improve gut and metabolic health while also emphasizing the need to optimize techniques to further improve studies of this organism.

Recent developments in microbiome research suggest that the gut microbiome may remotely modulate central and peripheral neuronal processes, ranging from early brain development to age-related changes. Dysbiotic microbiome configurations have been increasingly associated with neurological disorders, such as neurodegeneration, but causal understanding of these associations remains limited. Most mechanisms explaining how the microbiome may induce such remote neuronal effects involve microbially modulated metabolites that influx into the 'sterile' host. Some metabolites are able to cross the blood-brain barrier (BBB) to reach the central nervous system, where they can impact a variety of cells and processes. Alternatively, metabolites may directly signal to peripheral nerves to act as neurotransmitters or exert modulatory functions, or impact immune responses, which, in turn, modulate neuronal function and associated disease propensity. Herein, we review the current knowledge highlighting microbiome-modulated metabolite impacts on neuronal disease, while discussing unknowns, controversies and prospects impacting this rapidly evolving research field.

A widely recognized benefit of gut microbiota is that it provides colonization resistance against enteric pathogens. The gut microbiota and their products can protect the host from invading microbes directly via microbe-pathogen interactions and indirectly by host-microbiota interactions, which regulate immune system function. In contrast, enteric pathogens have evolved mechanisms to utilize microbiota-derived metabolites to overcome colonization resistance and increase their pathogenic potential. This review will focus on recent studies of metabolism-mediated mechanisms of colonization resistance and virulence strategies enteric pathogens use to overcome them, along with how induction of inflammation by pathogenic bacteria changes the landscape of the gut and enables alternative metabolic pathways. We will focus on how intestinal pathogens counteract the protective effects of microbiota-derived metabolites to illustrate the growing appreciation of how metabolic factors may serve as crucial virulence determinants and overcome colonization resistance.

Cerebral ischemia-reperfusion injury (CIRI) is clinically characterized by high rates of morbidity, disability, mortality, and recurrence as well as high economic burden. The clinical manifestations of CIRI are often accompanied by gastrointestinal symptoms such as intestinal bacterial dysbiosis and gastrointestinal bleeding. Gut microbiota plays an important role in the pathogenesis of CIRI, and its potential biological effects have received extensive attention. The gut microbiota not only affects intestinal barrier function but also regulates gastrointestinal immunity and host homeostasis. Traditional Chinese medicine (TCM), a multi-component and multi-targeted drug, has shown remarkable effects and few adverse reactions in the prevention and treatment of CIRI. Notably, the effect of TCM on CIRI by regulating gut microbiota and maintaining gastrointestinal homeostasis has gradually become a hot topic. This review summarizes the functional role of the gut microbiota in the development and progression of CIRI and the therapeutic effects of TCM on CIRI by improving gut microbiota dysbiosis, affecting gut microbiota metabolism, and maintaining host immunity. The active ingredients of TCM used for the treatment of CIRI in relevant studies were saponins, triterpenoids, phenolics, and alkaloids. In addition, the clinical effects of TCM used to treat CIRI were briefly discussed. This review established the clinical significance and development prospects of TCM-based CIRI treatments and provided the necessary theoretical support for the further development of TCM resources for the treatment of CIRI.

Treatment methods in traditional Chinese medicine (TCM) are foundational to their theoretical, methodological, formulaic, and pharmacological systems, significantly contributing to syndrome differentiation and therapy. The principle of "promoting urination to regulate bowel movements" is a common therapeutic approach in TCM. The core concept is "promoting the dispersion and drainage of water dampness, regulating urination to relieve diarrhea," yet its scientific underpinning remains unclear. Modern medical treatment for watery diarrhea primarily focuses on electrolyte replenishment, as diuretics may lead to dehydration and other side effects. Some reports suggest that this TCM approach lacks scientific validity. Microecology, an area associated with the origins of TCM, is closely related to the development, diagnosis, and treatment of diarrhea. The renal-intestinal axis offers a molecular biological basis for examining associated pathological mechanisms, advancing therapeutic targets such as "treating the intestine to address kidney issues" and highlighting the interactions within the "renal-intestinal microbiota-liquid metabolism" framework, thus providing an endogenous mechanism to support "treating the intestine through the kidney." An increasing number of studies have shown that the intestinal microbiota and its metabolites, as unique mediators, are involved in the physiological and pathological changes of the body. Therefore, this study explores the relationship between fluid metabolism and diarrhea from the perspective of the intestinal microbiota and its metabolites, aiming to elucidate the biological mechanisms underlying the "promoting urination to regulate bowel movements" therapeutic approach and to clarify the scientific basis for treating diarrhea via the renal-intestinal axis. This research provides new insights for the study of TCM microbiology.

Lactobacillus helveticus LZ-R-5 (R-5), a strain with high epithelial adhesion and bioactive exopolysaccharide production, was isolated from Tibetan kefir grains. This study investigated its potential to alleviate intestinal inflammation using a DSS-induced colitis model in BALB/c mice. We integrated microbial diversity and serological analyses to assess changes in gut flora and cytokines following the R-5 treatment. Pathological assessments showed that R-5 reduced crypt distortion in the proximal colon and mitigated hepatic immune challenges by enhancing gut barrier function. The increased relative expression of TGF-β1 and the downregulation of NLRP3-related inflammatory factors were conducive to preventing organ damage in the thymus and spleen of mice with colitis. Additionally, R-5 stimulated GPR43 expression and improved epithelial nutrition, promoting mucin production to prevent enterotoxin leakage. It also modulated the gut microbiota by suppressing Bacteroides and Erysipelatoclostridium, leading to a microbiota composition more akin to that of normal flora.

The role of gut microbiota in inflammatory disease development and progression has been recognized more recently. Inflammasome-mediated pyroptosis in involved in these diseases. This complex relationship between gut microbiota and inflammasome-mediated pyroptosis provides an important field of research. Bibliometric analysis provides a comprehensive understanding of this relationship, offering valuable insights into emerging research trends.

Leveraging data spanning from 2014 to 2023 sourced from the Web of Science Core Collection, our analysis was conducted using advanced tools such as SCImago Graphica, VOSviewer, and CiteSpace software. Visualizations were created using GraphPad Prism software. We explored the nuanced aspects of research hotspots, collaborative networks, and developing trends in this field.

A global bibliometric analysis identified 520 relevant studies spanning 41 countries and 887 institutions. Over the past decade, publication trends have shown consistent growth, with China and the United States leading the research output. Southern Medical University and Nanjing Medical University in China emerged as leading institutions in this filed. Prominent contributors include Jia Sun, Yuan Zhang, Wei Chen, Jing Wang, and Hongtao Liu from China, alongside Eicke Latz from Germany. High-impact journals such as Frontiers in Immunology and Nature Communications have been pivotal in disseminating research in this domain. Keyword analysis highlighted a primary focus on gut microbiota, NLRP3 inflammasome, pyroptosis pathways, and inflammatory diseases, themes that persist in recent studies. Furthermore, burst keyword analysis identified "butyrate" as the sole term currently experiencing a marked increase in research interest.

Research has been deeply focused on the gut microbiota and inflammasome triggered pyroptosis in years. Over the past decade, the exploration of how gut microbiota and NLRP3 or NLRP6 inflammasome-mediated pyroptosis has been an area of interest. Future investigations in this filed may primarily revolve around understanding the correlation between butyrate and NLRP3 inflammasome induced pyroptosis in relation to conditions. However, an in-depth analysis, through studies is crucial to uncover and elucidate the complex mechanisms linking these elements.

Free-caged rearing modes, which prioritize animal welfare, are believed to enhance the quality of animal products. The impact of rearing modes on meat quality may play a key role in the superior quality of local chicken breeds. This study analyzed the cecal contents of free-range and caged black-bone chickens at different ages using metagenomic and metabolomic sequencing. We identified 32 metabolites and 367 microbial species significantly affected by the rearing mode. Linear discriminant analysis Effect Size (LefSe) highlighted five key microorganisms, Gemmiger formicilis, Bacteria unclassified, Bacteroides sp. ET225, Massilistercora timonensis, and Bacteroidales unclassified, that showed distinct abundance patterns across all age points. Among them, Bacteroides sp. ET225 and Massilistercora timonensis were positively associated with certain phospholipids and plant-derived metabolites, while negatively correlated with others like demissidine and acylcarnitine. Functional analysis revealed that rearing modes impact gut metabolites involved in gut metabolism as well as broader processes such as signal transduction, protein digestion, and autophagy. This study offers new insights into how rearing modes influence gut microbiota and metabolites, shedding light on the study of rearing mode-mediated muscle development and fat deposition.

Diabetes mellitus is a common chronic metabolic disease characterized by a high incidence and disability rate. Intestinal flora refers to the microbial community that lives in the intestines and plays a crucial role in maintaining intestinal health and the human immune system. In recent years, an increasing body of research has revealed a close relationship between intestinal flora and diabetes. The pathophysiological mechanisms between them have also been constantly uncovered, and the regulation of intestinal flora has shown promising efficacy in the adjuvant treatment of diabetes. This study mainly summarized the characteristics and mechanisms of intestinal flora in patients with diabetes in recent years, as well as the methods of regulating intestinal flora to prevent and treat diabetes, and prospected the future research direction. This will offer a theoretical basis for the clinical adjuvant treatment of diabetes with intestinal flora and the development of new drugs.

Bioactive lipids have a multifaceted role in health and disease and are recognized to play an important part in gut immunity and disease conditions such as inflammatory bowel disease and colon cancer. Advancements in lipidomics, enabled by mass spectrometry and chromatographic techniques, have enhanced our understanding of lipid diversity and functionality. Bioactive lipids, including short-chain fatty acids, saturated fatty acids, omega-3 fatty acids, and sphingolipids, exhibit diverse effects on inflammation and immune regulation. Short-chain fatty acids like butyrate demonstrate anti-inflammatory properties, enhancing regulatory T cell function, gut barrier integrity, and epigenetic regulation, making them promising therapeutic targets for inflammatory bowel disease and colon cancer. Conversely, saturated fatty acids promote inflammation by disrupting gut homeostasis, triggering oxidative stress, and impairing immune regulation. Omega-3 lipids counteract these effects, reducing inflammation and supporting immune balance. Sphingolipids exhibit complex roles, modulating immune cell trafficking and inflammation. They can exert protective effects or exacerbate colitis depending on their source and context. Additionally, eicosanoids can also prevent pathology through prostaglandin defense against damage to epithelial barriers. This review underscores the importance of dietary lipids in shaping gut health and immunity and also highlights the potential use of lipids as therapeutic strategies for managing inflammatory conditions and cancer.

Cactus contains dietary fiber and minerals and is expected to have preventive effects against diabetes, arteriosclerosis, and other diseases. Additionally, cactus intake induces the production of short-chain fatty acids derived from the gut microbiota, which might influence immune functions. In this study, we examined the effects of a cactus (Nopalea cochenillifera: NC)-supplemented diet on lipopolysaccharide (LPS)-induced immune responses and intestinal barrier function.

Male C3H/HeN mice were randomly divided into three groups-no fiber (NF), cellulose-containing fiber (Cellu), and cactus-added (NC) diets-for 6 weeks. The TNF-α and IL-10 responses to LPS, antibody titers, and intestinal barrier function, as well as the fecal microbiota, were analyzed.

The plasma TNF-α but not the IL-10 concentrations were significantly higher in the NC group than in the NF and Cellu groups. Furthermore, the plasma IgG antibody titers were significantly higher in the NC group than in the other groups. The NC group showed higher mucin content and IgA antibody titers in their feces compared with the Cellu group. The succinate and lactate contents, which induce a reduction in TNF-α secretion by macrophages, in the cecum of the NC group were significantly lower than those in the Cellu and NF groups. In contrast, the butyrate content was significantly higher in the cecum of the NC group compared to that of the Cellu group, with a significantly higher relative abundance of butyrate-producing bacteria.

Taken together, we found that cactus intake regulates innate and adaptive immune function via the gut microbiota in mice. Therefore, cactus supplementation might serve as a strategy to develop novel functional foods with dietary fiber.