The emergence of new viral pathogens necessitates innovative antiviral therapies and vaccines. Traditional approaches, such as monoclonal antibodies and vaccines, are often hindered by resistance, limited effectiveness, and high costs. Here, we develop an engineered probiotic-based antiviral platform using Escherichia coli Nissle 1917 (EcN), capable of providing both mucosal and systemic immunity via oral administration. EcN was engineered to display anti-spike nanobodies or express the Spike-Receptor Binding Domain on its surface. Our findings reveal that EcN with nanobodies effectively inhibits the interaction between spike protein-expressing pseudoviruses and the ACE2 receptor. Furthermore, we observed the translocation of nanobodies to distant organs, facilitated by outer membrane vesicles (OMVs). The oral administration of EcN expressing spike proteins induced a robust immune response characterized by the production of both IgG and IgA, antibodies that blocked the pseudovirus-ACE2 interaction. While SARS-CoV-2 served as a model, this versatile probiotic platform holds potential for developing customizable biotherapeutics against a wide range of emerging pathogens such as influenza virus or respiratory syncytial virus (RSV) by engineering EcN to express viral surface protein or neutralizing nanobodies demonstrating its versatility as a next-generation mucosal vaccine strategy.

The pathogenesis of cancer is closely related to the disruption of homeostasis in the human body. The gut microbiome plays crucial roles in maintaining the homeostasis of its host throughout lifespan. In recent years, a large number of studies have shown that dysbiosis of the gut microbiome is involved in the entire process of cancer initiation, development, and prognosis by influencing the host immune system and metabolism. Some specific intestinal bacteria promote the occurrence and development of cancers under certain conditions. Conversely, some other specific intestinal bacteria suppress the oncogenesis and progression of cancers, including inhibiting the occurrence of cancers, delaying the progression of cancers and boosting the therapeutic effect on cancers. The promoting effects of the gut microbiome on cancers have been comprehensively discussed in the previous review. This article will review the latest advances in the roles and mechanisms of gut microbiome in cancer suppression, providing a new perspective for developing strategies of cancer prevention and treatment.

Selenium (Se) is linked to physiological homeostasis. Male mice (n = 8/group) were fed control (AIN93G) or diets enriched in sodium selenite (NaSe, 5.6 ppm), methylselenocysteine (Met, 4.7 ppm), diphenyl diselenide (DPDS, 14.2 ppm), or nanoselenium (NanoSe, 2.7 ppm); dietary Se ascertained by inductively-coupled plasma mass spectrometry. At 4 weeks testes, sperm, thyroids, blood and stool were collected to assess histoarchitecture, circulating hormones (thyroxine, T4; triiodothyronine, T3; thyroid stimulating hormone, TSH) and gut microbiome (16S rRNAV3-V4 amplicon sequencing). Supplemented NaSe, Met, and NanoSe increased plasma testosterone and testis glutathione peroxidases (GPx-1/4) while testicular superoxide dismutase and catalase increased slightly in the NanoSe group indicating a selective antioxidant response. Overall, NanoSe and NaSe enhanced male reproductive factors. All thyroids isolated from Se-supplemented mice contained marginal vacuoles and a lower follicle area vs control. Nano-Se enhanced thyroidiodothyronine deiodinase-1 (DIO1) expression however, thyroid GPx-1/4 remained unchanged. Supplemented NaSe and DPDSl increased plasma T3/T4 ratio, while plasma TSH was unchanged. Microbiome analyses showed that NanoSe was most efficacious in altering composition (judged by α-diversity, Shannon index and taxon richness) while the NaSe diet showed the greatest overall change in α-diversity. Dietary Se supplementation, particularly encapsulated NanoSe, may improve male fertility factors by enhancing the gut-thyroid-fertility axis.

The gut microbiome has emerged as a potential influencer of muscle health; however, its role in hospitalized patients remains unclear. This study aimed to investigate the association between gut microbiome diversity and skeletal muscle mass, strength, and quality in hospitalized post-stroke patients.

We conducted a cross-sectional study of post-stroke patients admitted to a rehabilitation facility. Gut microbiome diversity was assessed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing, calculating Operational Taxonomic Unit (OTU) Richness, Faith's Phylogenetic Diversity (PD), and Shannon index. Muscle health was evaluated using skeletal muscle index (SMI) for muscle mass, handgrip strength (HGS) for muscle strength, and bioimpedance analysis-derived phase angle (PhA) for muscle quality. Multiple linear regression analyses were performed, adjusting for potential confounders.

A total of 156 patients (mean age 78.4 years; 55.7 % male) were analyzed. OTU Richness showed significant positive associations with SMI (β = 0.197, p = 0.025), HGS (β = 0.180, p = 0.005), and PhA (β = 0.178, p = 0.022). The Shannon index was also positively associated with SMI (β = 0.120, p = 0.041), HGS (β = 0.140, p = 0.028), and PhA (β = 0.164, p = 0.032). Faith's PD did not demonstrate significant associations with muscle health parameters.

Higher gut microbiome diversity, assessed by OTU Richness and Shannon index, is associated with better muscle mass, strength, and quality in post-stroke patients. These findings suggest a potential role for gut microbiota in muscle health during stroke rehabilitation.

Symbiotic microbiota in vertebrates play critical roles in establishing and enhancing host resistance to pathogenic infections as well as maintaining host homeostasis. The interactions and mechanisms of commensal microbiota-mediated mucosal immune systems have been extensively studied in mammals and, to a lesser extent, in birds. However, despite several studies emphasizing the role of mucosal microbiota in controlling pathogen infections in teleost fish, limited knowledge exists regarding the core microbiota and the mechanisms by which they contribute to resistance against viral infections.

Our findings suggest that viral infections shape clinical manifestations of varying severity in infected fish. An increased abundance of Bacillus spp. in the mild phenotype indicates its crucial role in influencing fish immunity during viral infections. To confirm that Bacillus spp. act as a core contributor against viral infection in fish, we isolated a representative strain of Bacillus spp. from largemouth bass (Micropterus salmoides), which was identified as Bacillus velezensis (Bv), and subsequently conducted feeding trials. Our study demonstrated that dietary supplementation with Bv significantly reduced mortality from largemouth bass virus (LMBV) infection in bass by enhancing host immunity and metabolism as well as by regulating the microbial community. Furthermore, multi-omics analysis elucidated the mechanism by which Bacillus spp. confer resistance to viral infections by regulating the production of diglyceride (DG) during lipid metabolism.

Our study provides the first evidence that Bacillus spp. are a core microbiota for combating viral infections in teleost fish, shedding light on the conserved functions of probiotics as a core microbiota in regulating microbial homeostasis and mucosal immunity across the vertebrate lineage.

Preeclampsia is a leading cause of morbidity and mortality in pregnant women, affecting 5-8% of gestations worldwide. Its development is influenced by maternal immune abnormalities, metabolic disorders, and gut dysbiosis. In this study, we show that gut dysbiosis in pregnant C57BL/6J dams leads to increased fetal resorption, impaired placental development and altered vascularization. These adverse outcomes are associated with key pathological features of preeclampsia, including hypoxia, endoplasmic reticulum (ER) stress and reduction in uterine natural killer (NK) cell numbers. Furthermore, gut dysbiosis significantly perturbs placental carbohydrate metabolism, which impairs NK cell IFN-γ secretion. Notably, glucose supplementation restores placental NK cell function and reduces fetal resorption, suggesting that the observed impairment is reversible and dependent on a lower glycolytic rate. These findings highlight maternal gut microbiota as a key player in carbohydrate metabolism, with a pivotal role in modulating placental immunity and pregnancy outcome. The results provide valuable insights into potential metabolic biomarkers and suggest that targeting the gut microbiota may offer a strategy for preventing preeclampsia.

Neurodevelopmental disorders (NDDs) and epileptic syndromes are complex neurological conditions linked by shared abnormal neurobiological processes. Existing therapies mostly target symptoms, rather than addressing the underlying causes of the disease, leaving a burden of unmet clinical needs.

Emerging evidence suggests a significant role for the gut microbiota and associated immune responses in influencing brain development and function, changing the paradigm of a brain-centric origin of NDDs. This review discusses the pivotal interactions within the gut-immune-brain axis, highlighting how microbial dysbiosis and immune signaling contribute to neurological pathologies. We also explore the potential of microbial management and immunomodulation as novel therapeutic avenues, emphasizing the need for a shift towards addressing the root causes of these disorders rather than just their symptoms.

This integrated perspective offers new insights into the biological underpinnings of NDDs and epilepsy, proposing innovative biomarkers and therapeutic strategies.

The gut microbiome significantly influences autoimmune diseases, including systemic lupus erythematosus (SLE). This study aimed to characterize the gut microbiome and metabolome in SLE and evaluate the therapeutic potential of specific microbial supplementation in MRL/lpr mice.

MRL/lpr mice, a well-established model for SLE, were used to analyze gut microbiome changes before and after SLE symptom onset. 16S rRNA sequencing and GC-MS-based metabolic profiling were performed to identify key microbial species and associated metabolites. Selected microbes were supplemented in MRL/lpr mice for 10 weeks, and their effects on SLE symptoms and Th17/Treg balance were evaluated.

Eisenbergiella massiliensis, Lacrimispora saccharolytica, and Hungatella xylanolytica were significantly decreased in MRL/lpr mice following the onset of SLE symptoms. These microbes were strongly correlated with specific metabolites, including 5-cholestanol, cholesterol, p-cresol, and indole. Supplementation with these microbes alleviated SLE symptoms and modulated the Th17/Treg balance.

This study highlights the critical role of gut microbiota in immune regulation and SLE symptom relief. Targeted microbial supplementation may serve as a novel therapeutic strategy for managing SLE.

The study evaluated the effectiveness of a synbiotic blend containing Lactococcus lactis KA-FF 1-4 and Fibersol-2 in modulating gut microbiota and inhibiting vancomycin-resistant Enterococcus (VRE). Compared to probiotic or prebiotic treatments alone, the synbiotic blend significantly altered the gut microbiota composition, increasing beneficial bacteria like Blautia, Clostridium, Parabacteroides, Prevotella, and Roseburia, while reducing VRE abundance. Moreover, the synbiotic treatment showed an increase in short-chain fatty acid (SCFA) concentrations, particularly acetate, propionate, and butyrate. Correlation analysis revealed that enriched taxa in the synbiotic treatment were positively associated with higher SCFA levels. These findings highlight the potential of synbiotic formulations in improving gut microbiota balance and combating antibiotic-resistant pathogens like VRE.

The gastrointestinal (GI) tract plays a critical role in nutrient absorption, immune responses, and overall health. Traditional models such as two-dimensional cell cultures have provided valuable insights but fail to replicate the dynamic and complex microenvironment of the human gut. Gut-on-a-chip platforms, which incorporate cells located in the gut into microfluidic devices that simulate peristaltic motion and fluid flow, represent a significant advancement in modeling GI physiology and diseases. This review discusses the evolution of gut-on-a-chip technology, from simple cellular mono-cultures models to more sophisticated systems incorporating bi-cultures and tri-cultures that enable studies of drug metabolism, disease modeling, and gut-microbiome interactions. Although challenges remain, including maintaining long-term cell viability and replicating immune responses, these platforms hold great potential for advancing personalized medicine and improving drug discovery efforts targeting gastrointestinal disorders.

Hibernation poses significant physiological challenges to the animals, making it an excellent model for investigating the impacts of extreme environment changes on animal health. This study explored the gut microbiota and host metabolism in hibernating snakes using 16S rRNA gene sequencing and untargeted metabolomics. Ten king ratsnakes were divided into active and hibernating groups, and their gut microbial compositions and serum metabolomic profiles were analyzed. Results demonstrated a significant reduction in gut microbial diversity during hibernation, with the abundance of Cetobacterium increasing dramatically from 5.57 % to 49.56 %, establishing it as the predominant genus in hibernating snakes. Metabolomic analysis revealed significant alterations in lipid and amino acid metabolism, with 69 metabolites downregulated during hibernation. Correlation analyses identified Cetobacterium as a central hub in the correction networks, influencing numerous gut microorganisms and showing a strong association with host metabolic depression. In addition to the recognized ability to produce vitamin B12 and short-chain fatty acids, this study further confirmed the robust antioxidant ability of snake-derived Cetobacterium somerae strains. These findings highlight the potential role of Cetobacterium in the physiological adaptation of snakes during hibernation and provide a foundation for exploring its applications in reptilian health management.

Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis. Recently, the role of gut microbiota in psoriasis has attracted increasing attention. A systematic bibliometric analysis of relevant literature is necessary to understand better the current state and development trends in this field.

The Web of Science Core Collection database was searched for literature indexed from 2004 to October 15, 2024. Bibliometric analysis was conducted using Bibliometrix, CiteSpace (version 6.3.R1), R 4.2.2 with the Bibliometrix package, Scimago Graphica 1.0.45, and VOSviewer (version 1.6.20.0) to visualize publication types, years, authors, countries, institutions, journal sources, references, and keywords.

The development of psoriasis and gut microbiota research can be divided into two phases: slow growth (2004-2014) and rapid development (2014-2024). Lidia Rudnicka is the most active and influential author. China produced the highest number of publications, followed by the United States, which had the highest number of citations per article. The International Journal of Molecular Sciences published the most articles. In contrast, articles in the Journal of Investigative Dermatology, British Journal of Dermatology, and Journal of Allergy and Clinical Immunology were cited over 1,000 times. Keyword and co-citation analyses identified evolving research hotspots. Early studies focused on the association between gut microbiota and comorbid inflammatory diseases. Recent research has delved into specific mechanisms, such as disruption of gut barrier function, short-chain fatty acid metabolism alterations, impaired regulatory T-cell function, and excessive activation of Th17 cells. These mechanisms highlight how gut dysbiosis exacerbates psoriasis patients' systemic inflammation and skin lesions.

The field of psoriasis and gut microbiota research is developing rapidly despite uneven research distribution. This bibliometric evaluation assesses the current state of research and provides new perspectives for understanding the complex interactions between microbes and the host. Future efforts should strengthen international collaboration to deeply explore the mechanisms of gut microbiota's role in psoriasis, especially its potential applications in disease diagnosis and treatment.

Metabolites, particularly those derived from gut microbiota, play crucial roles in modulating immune responses, but the impact of most metabolites on immune cells remains unexplored. To systematically investigate the effect of metabolites on immune cells, we treated peripheral blood mononuclear cells (PBMCs) with 364 endogenous and gut microbiota metabolites and analyzed their impact on the PBMC transcriptome using RNA sequencing (RNA-seq). Clustering analysis revealed three distinct metabolite groups (Cluster 0, 1, 2), each exerting unique immunomodulatory effects. Cluster 1 metabolites, enhanced inflammatory pathways (e.g., cytokine signaling, neutrophil migration) and suppressed ferroptosis, potentially prolonging immune cell activity. In contrast, Cluster 0 metabolites promoted antigen presentation and extracellular matrix repair, while Cluster 2 metabolites upregulated autophagy-related pathways (e.g., GTPase signaling, ubiquitin-protein regulation), suggesting anti-inflammatory and tissue-homeostatic functions. Immune deconvolution highlighted Cluster 1-driven monocyte-to-M0 macrophage differentiation and elevated activated dendritic/mast cells, aligning with pro-inflammatory outcomes. Metabolites in Clusters 0/2 were enriched in the TCA cycle and alanine/aspartate metabolism, whereas Cluster 1 metabolites correlated with beta-alanine and branched-chain amino acid pathways. Gut microbiota analysis identified 23 species overrepresented in Cluster 1, linking dysbiosis to inflammatory metabolite profiles. Together, this high-throughput atlas elucidates how bloodborne metabolites shape PBMC function, offering insights into metabolic-immune crosstalk and potential therapeutic targets for inflammatory and autoimmune disorders.

Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.

Bile acid sequestrants (BAS) are an emerging option for treatment of pouchitis. We aimed to compare BAS monotherapy, antibiotics, and combination therapy with both in the treatment of pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC).

We conducted a retrospective cohort study using the US-Collaborative TriNetX database to identify patients with acute pouchitis and UC. Treatment groups were divided into BAS (cholestyramine, colesevelam, colestipol), antibiotics (ciprofloxacin and/or metronidazole), and combination therapy of both BAS and antibiotics. Primary outcomes were failure of initial therapy (early relapse or nonresponse) and the development of recurrent pouchitis in the first 12 months after an initial episode of pouchitis.

Our analysis included 1,136 patients (mean age: 37.8 ± 15.4 years, and 45.9% female) of whom 727 (64%) were diagnosed with recurrent pouchitis. After adjusting for confounders by propensity-score matching, there was no significant difference in the odds of early relapse or nonresponse with BAS compared with antibiotic monotherapy (aOR: 0.74; 95% CI: 0.40-1.38; p = 0.34) or combination therapy (aOR: 0.94; 95% CI: 0.47-1.88; p = 0.86). Patients treated with BAS had a statistically significant lower recurrent pouchitis rate (aHR: 0.57; 95% CI: 0.42-0.79; p < 0.001) compared with patients treated with antibiotics. Patients treated with BAS had a statistically significant longer time (median: 225 days) to recurrent pouchitis (p < 0.001) compared to antibiotics (median: 99 days).

Using real-world evidence regarding treatment of pouchitis compared to standard antibiotic therapy, BAS monotherapy was not inferior for initial treatment response and significantly prolonged time to recurrent pouchitis.

Tire wear particles (TWPs), as a pervasive environmental pollutant, pose significant risks to aquatic ecosystems. This study investigates the effects of small (HS) and large (HL) TWPs produced by heavy vehicles on zebrafish, focusing on physiological, microbial, and transcriptomic levels, as well as their intergenerational consequences, under short-term (15 days) and long-term (90 days) exposure. Short-term exposure to small particles (HS15) significantly reduced body width and triggered widespread oxidative stress, while long-term exposure to large particles (HL90) increased gut weight and decreased gill weight, reflecting respiratory and digestive disruptions. Tissue-level analyses revealed that smaller particles accumulated more readily in internal organs, whereas larger particles caused localized physiological stress. Gut microbiota profiling indicated a marked decline in microbial diversity, compositional shifts, and network simplification, with HL15 enriched in Acinetobacter and xenobiotic metabolism pathways, and HS15 exhibiting Proteobacteria-dominated dysbiosis and enrichment of LPS biosynthesis genes. Liver transcriptomics revealed group-specific responses: HL15 exposure activated innate immunity via the NOD-MAPK axis, while HS15 induced atypical PI3K-NF-κB signaling, potentially linked to microbial LPS. Notably, all TWP-exposed groups showed enrichment of the herpes simplex virus 1 (HSV-1) infection pathway, suggesting a conserved antiviral-like host response. Transgenerational effects were evidenced by impaired growth and significant downregulation of GH/IGF signaling and upregulation of apoptotic genes in offspring, despite only subtle transcriptomic changes in long-term exposed parents. These findings underscore the importance of particle size, exposure duration, and microbiota-gut-liver axis interactions in mediating TWP toxicity and highlight potential transgenerational risks associated with environmental microplastic exposure.

This narrative review presents the role of antioxidants in regulating the gut microbiota and the impact on the gut-brain axis, with a particular focus on neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). These diseases are characterised by cognitive decline, motor dysfunction, and neuroinflammation, all of which are significantly exacerbated by oxidative stress. This review elucidates the contribution of oxidative damage to disease progression and explores the potential of antioxidants to mitigate these pathological processes through modulation of the gut microbiota and associated pathways. Based on recent studies retrieved from reputable databases, including PubMed, Web of Science, and Scopus, this article outlines the mechanisms by which antioxidants influence gut health and exert neuroprotective effects. Specifically, it discusses how antioxidants, including polyphenols, vitamins, and flavonoids, contribute to the reduction in reactive oxygen species (ROS) production and neuroinflammation, thereby promoting neuronal survival and minimising oxidative damage in the brain. In addition, the article explores the role of antioxidants in modulating key molecular pathways involved in oxidative stress and neuroinflammation, such as the NF-κB, Nrf2, MAPK, and PI3K/AKT pathways, which regulate ROS generation, inflammatory cytokine expression, and antioxidant responses essential for maintaining cellular homeostasis in both the gut and the central nervous system. In addition, this review explores the complex relationship between gut-derived metabolites, oxidative stress, and neurodegenerative diseases, highlighting how dysbiosis-an imbalance in the gut microbiota-can exacerbate oxidative stress and contribute to neuroinflammation, thereby accelerating the progression of such diseases as AD and PD. The review also examines the role of short-chain fatty acids (SCFAs) produced by beneficial gut bacteria in modulating these pathways to attenuate neuroinflammation and oxidative damage. Furthermore, the article explores the therapeutic potential of microbiota-targeted interventions, including antioxidant delivery by probiotics and prebiotics, as innovative strategies to restore microbial homeostasis and support brain health. By synthesising current knowledge on the interplay between antioxidants, the gut-brain axis, and the molecular mechanisms underlying neurodegeneration, this review highlights the therapeutic promise of antioxidant-based interventions in mitigating oxidative stress and neurodegenerative disease progression. It also highlights the need for further research into antioxidant-rich dietary strategies and microbiota-focused therapies as promising avenues for the prevention and treatment of neurodegenerative diseases.

The physiology of a transplanted kidney is affected from the moment it is separated from the donor. The risk of complications arising from surgery are highly associated with ischemic-reperfusion injury (IRI) due to the effects of hypoxia and oxidative stress during the procurement, preservation and reperfusion procedures. Hypoxia promotes the formation of reactive oxygen species (ROS) and it seems apparent that finding ways of optimising the metabolic milieu for the transplanted kidney would improve recovery and graft survival. Studies have demonstrated the benefits of nutrition and antioxidant compounds in mitigating the disturbance of energy supply to cells post-transplant and at improving long-term graft survival. Particularly in patients who may be nutritionally deficient following long-term dialysis. Despite the high incidence of allograft failure, a search of the literature and grey literature reveals no medical nutriti on therapy guidelines on beneficial nutrient intake to aid transplant recovery and survival. This narrative review aims to summarise current knowledge of specific macro and micronutrients and their effect on allograft recovery and survival in the perioperative period, up to 1-year post transplant, to optimise the metabolic environment and mitigate risk to graft injury.

There is growing interest in gut microbiota and health outcomes. However, the relationship between systemic inflammation and gut microbiota diversity in hospitalized patients remains unclear. This study aimed to investigate the association in post-stroke rehabilitation patients.

A cross-sectional study was conducted on post-stroke patients admitted to a rehabilitation hospital. Systemic inflammation was assessed using the modified Glasgow Prognostic Score (mGPS). Gut microbiota diversity was evaluated using three indices: Shannon index, Operational Taxonomic Unit (OTU) richness, and Faith's Phylogenetic Diversity (PD). Multiple linear regression analyses were performed to examine the relationship between mGPS and gut microbiota diversity indices, adjusting for potential confounders.

A total of 156 patients (mean age 78.4 years; 55.7% men) were analyzed. The median mGPS was 0 (interquartile range: 0-1), with GPS distribution: 61.8% scored 0, 25.7% scored 1, and 12.5% scored 2. After adjusting for confounders, mGPS was significantly and negatively associated with the Shannon index (B = -0.143, 95% CI -0.288 to -0.002, β = -0.177) and OTU richness (B = -17.832, 95% CI -24.349 to -3.951, β = -0.208). However, no significant association was observed between mGPS and Faith's PD (B = -1.155, 95% CI -2.464 to 0.189, β = -0.155).

This study demonstrates a significant negative association between systemic inflammation and both quantitative and qualitative gut microbiota diversity in post-stroke patients.

The gut microbiota significantly influence host health by impacting metabolism, immune function and development. Understanding bacterial behaviours in intestinal folds is crucial owing to their role in biofilm formation, which protects bacteria from immune responses and antibiotics and is associated with colorectal cancer. In this study, we observed the behaviours of Escherichia coli bacteria in the intestinal folds of zebrafish larvae (Danio rerio). It is found that E. coli swims in the intestinal folds for extended periods and is confined in a groove on the wall. In order to clarify the mechanism of the confinement, we further performed numerical simulations using a boundary element method. Our simulations demonstrate that bacterial movement in the groove is constrained by hydrodynamic and steric forces. The groove configuration significantly influences bacterial confinement, with bacteria in a deep groove escaping more easily in the presence of background flow. Based on the aggregation rate of E. coli in the intestinal folds of zebrafish larvae, it is indicated that the groove trapping significantly reduces cell flux away from the wall. These findings enhance our understanding of bacterial accumulation and biofilm formation in the gut, with implications for other environments with geometric constraints.

Malaria is caused by protozoan parasites in the genus Plasmodium. Over time individuals slowly develop clinical immunity to malaria, but this process occurs at variable rates, and the mechanism of protection is not fully understood. We have recently demonstrated that in genetically identical C57BL/6N mice, gut microbiota composition dramatically impacts the quality of the humoral immune response to Plasmodium yoelii and subsequent protection against a lethal secondary challenge with Plasmodium berghei ANKA in C57BL/6N mice. Here, we utilize this genetically identical, gut microbiome-dependent model to investigate how the gut microbiota modulate immunological memory, hypothesizing that the gut microbiome impacts the formation and functionality of immune memory. In support of this hypothesis, P. yoelii hyperparasitemia-resistant C57BL/6N mice exhibit increased protection against P. berghei ANKA-induced experimental cerebral malaria (ECM) compared to P. yoelii hyperparasitemia-susceptible C57BL/6N mice. Despite differences in protection against ECM, P. yoelii-resistant and -susceptible mice accumulate similar numbers of memory B cells (MBCs) and memory T cells. Following challenge with P. berghei ANKA, P. yoelii-resistant mice generated more rapid germinal center reactions; however, P. yoelii-resistant and -susceptible mice had similar titers of P. yoelii- and P. berghei-specific antibodies. In contrast, P. yoelii-resistant mice had an increased number of regulatory T cells in response to secondary challenge with P. berghei ANKA, which may dampen the immune-mediated breakdown of the blood-brain barrier and susceptibility to P. berghei-induced ECM. These findings demonstrate the ability of the gut microbiome to shape immune memory and the potential to enhance resistance to severe malaria outcomes.

Glioblastoma (GBM) remains the most aggressive primary brain tumor, with poor survival outcomes and treatment limited to maximal safe surgical resection, chemotherapy with temozolomide, and radiotherapy. While immunotherapy and targeted treatments show promise, therapeutic resistance and disease progression remain major challenges. This is partly due to GBM's classification as a "cold tumor" with low mutational burden and a lack of distinct molecular targets for drug delivery that selectively spare healthy tissue. Emerging evidence highlights the gut microbiota as a key player in cancer biology, influencing both glioma development and treatment response. This review explores the intersectionality between the gut microbiome and GBM, beginning with an overview of microbiota composition and its broader implications in cancer pathophysiology. We then examine how specific microbial populations contribute to glioma oncogenesis, modulating immune responses, inflammation, and metabolic pathways that drive tumor initiation and progression. Additionally, we discuss the gut microbiome's role in glioma therapeutic resistance, including its impact on chemotherapy, radiotherapy, and immunotherapy efficacy. Given its influence on treatment outcomes, we evaluate emerging strategies to modulate gut flora, such as probiotics, dietary interventions, and microbiota-based therapeutics, to enhance therapy response in GBM patients. Finally, we address key challenges and future directions, emphasizing the need for standardized methodologies, mechanistic studies, and clinical trials to validate microbiota-targeted interventions in neuro-oncology. By integrating gut microbiome research into GBM treatment paradigms, we may unlock novel therapeutic avenues to improve patient survival and outcomes.

This work aims to (1) identify microbial and metabolic alterations and (2) reveal a shift in phenylalanine production-consumption equilibrium in individuals with HIV. We conducted extensive searches in multiple databases [MEDLINE, Web of Science (including Cell Press, Oxford, HighWire, Science Direct, IOS Press, Springer Nature, PNAS, and Wiley), Google Scholar, and Embase] and selected two case-control 16S data sets (GenBank IDs: SRP039076 and EBI ID: ERP003611) for analysis. We assessed alpha and beta diversity, performed univariate tests on genus-level relative abundances, and identified significant microbiome features using random forest. We also utilized the MICOM model to simulate growth and metabolic exchanges within the microbiome, focusing on the Metabolite Exchange Score (MES) to determine key metabolic interactions. We found that L-phenylalanine had a higher MES in HIV-uninfected individuals compared with their infected counterparts. The flux of L-phenylalanine consumption was significantly lower in HIV-infected individuals compared with healthy controls, correlating with a decreased number of consuming species in the chronic HIV stage. Prevotella, Roseburia, and Catenibacterium were demonstrated as the most important microbial species involving an increase in L-phenylalanine production in HIV patients, whereas Bacteroides, Faecalibacterium, and Blautia contributed to a decrease in L-phenylalanine consumption. We also found significant alterations in both microbial diversity and metabolic exchanges in people living with HIV. Our findings shed light on why HIV-1 patients have elevated levels of phenylalanine. The impact on essential amino acids like L-phenylalanine underscores the effect of HIV on gut microbiome dynamics. Targeting the restoration of these interactions presents a potential therapeutic avenue for managing HIV-related dysbiosis.

The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.

The intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host-microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host-microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ-free and gnotobiotic mouse technology, in which causal disease-driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease-driving mechanisms can be dissected. A better understanding of the health-modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ-free and gnotobiotic experiments, including considerations around germ-free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research.

Background: Type 1 diabetes (T1D) is a severe chronic T-cell mediated autoimmune disease that attacks the insulin-producing beta cells of the pancreas. The multifactorial nature of T1D involves both genetic and environmental components, with recent research focusing on the gut microbiome as a crucial environmental factor in T1D pathogenesis. The gut microbiome and its metabolites play an important role in modulating immunity and autoimmunity. In recent years, studies have revealed significant alterations in the taxonomic and functional composition of the gut microbiome associated with the development of islet autoimmunity and T1D. These changes include reduced production of short-chain fatty acids, altered bile acid and tryptophan metabolism, and increased intestinal permeability with consequent perturbations of host (auto)immune responses. Methods/Results: In this review, we summarize and discuss recent observational, mechanistic and etiological studies investigating the gut microbiome in T1D and elucidating the intricate role of gut microbes in T1D pathogenesis. Moreover, we highlight the recent advances in intervention studies targeting the microbiota for the prevention or treatment of human T1D. Conclusions: A deeper understanding of the evolution of the gut microbiome before and after T1D onset and of the microbial signals conditioning host immunity may provide us with essential insights for exploiting the microbiome as a prognostic and therapeutic tool.

The prebiotic properties of human milk oligosaccharides (HMOs) and emerging evidence of immunomodulatory effects suggest their potential therapeutic value in allergy management. 2'-Fucosyllactose (2'-FL) has been reported to alleviate food allergies, while the effect of other fucosylated HMOs on food allergy remains unclear. In this study, we assess the effect of two HMOs, 2'-FL and 3-fucosyllactose (3-FL), on symptomatology and immunological responses in an ovalbumin (OVA)-sensitized mouse model of food allergy as well as their influence on gut microbiota. The assessment of allergic symptoms, specific immunoglobulin E (IgE), and related gene expression levels in sensitized mice indicated that 3-FL was as effective as 2'-FL in alleviating food allergy. 2'-FL and 3-FL significantly decreased serum levels of OVA-specific IgE, mouse mast cell protease (mMCP-1) and IL-4 while increasing the levels of IFN-γ. Additionally, 2'-FL and 3-FL down-regulated gene expression of allergy-related cytokines in the small intestine and improved intestinal barrier damage. Furthermore, both 2'-FL and 3-FL treatment positively influenced the gut microbial profiles, in particular by enhancing the proportion of beneficial bacteria such as Lactobacillus and Bifidobacterium and decreasing the percentage of Turicibacter and Lachnospiraceae NK4A136 group, thereby modulating the immune system. Therefore, this study can provide insights into 2'-FL and 3-FL to alleviate OVA-induced allergy.

Emerging research indicates that gut microbiota and the associated immune responses are crucial in the development of chronic inflammatory skin diseases. This investigation employs Mendelian Randomization (MR) and Bayesian weighting to elucidate the causal links between gut microbiota, immune cells, and psoriasis, with a specific emphasis on CD8 + T cells. We leveraged summary statistics from genome-wide association studies (GWAS) related to gut microbiota, immune cells, and psoriasis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs) to evaluate causal relationships through various MR methods, such as inverse variance weighted (IVW), MR Egger, weighted median, and simple mode. Additionally, Bayesian weighting was used to validate results and account for potential pleiotropy. The IVW analysis revealed significant associations between certain gut microbiota and psoriasis, notably identifying a protective link between Escherichia coli and psoriasis. Further MR analysis demonstrated that Escherichia coli had a causal relationship with CD8 + T cells. Increased levels of CD8 + T cells were associated with a higher risk of psoriasis. BWMR analysis confirmed these findings, showing that CD8 + T cells mediated 10.09% of the protective effect of Escherichia coli on psoriasis. This study underscores the significant role of Escherichia coli and CD8 + T cells in psoriasis, suggesting both protective and exacerbating effects. Understanding these microbiota-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.

The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.

Osteoarthritis (OA) is one of the most common degenerative diseases, and the number of patients has been constantly increasing. Non-steroidal anti-inflammatory drugs, glucocorticosteroids, opioids, etc., and surgical procedures, e.g. arthroplasty, are among the most common methods of treatment. There are reasons to believe that the gut microbiome (GMB) may influence inflammatory processes occurring in the pathomechanism of OA. The inflammatory processes occurring in the intestines may lead to disruption of tight junctions and increased concentrations of pro-inflammatory cytokines, resulting in increased permeability of intestines, causing low-grade inflammation, including in the joints. Methods of altering the GMB composition to reduce the inflammatory and joint degenerative processes are known only to some extent, and long-term research is required. Osteoarthritis, a particularly well-known and very widespread disease due to the aging population, is characterized by moderate and local inflammation. It occurs due to the effects of biomechanical cartilage wear with damage of joint structures, primarily through degenerative processes. OA represents a therapeutic challenge, and any element that can influence its inhibition is highly sought after. Therefore, these methods seem to offer a promising additional approach to treatment.

Type 2 diabetes mellitus (T2DM) poses a significant global health challenge due to various lifestyle factors contributing to its prevalence and associated complications. Chronic low-grade inflammation, characterized by elevated levels of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), plays a pivotal role in the pathogenesis of T2DM. Modulation of the gut microbiota through microbiome-targeted therapy (MTT), including probiotics, prebiotics, and synbiotics, has emerged as a potential strategy to mitigate inflammation and improve metabolic outcomes in T2DM.

A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the impact of MTT on inflammatory markers in patients with T2DM. Searches were performed in PubMed, Scopus, and Web of Science databases up to June 2024, with inclusion criteria limited to English-language meta-analyses of randomized controlled trials (RCTs) assessing the effects of probiotics, prebiotics, or synbiotics on inflammatory markers in T2DM patients.

Ten meta-analyses met the inclusion criteria, comprising studies investigating the effects of various MTT interventions on CRP, IL-6, and TNF-α levels in T2DM patients. Meta-analysis results indicated significant reductions in CRP (SMD: -0.070; 95 % CI: -0.119 to -0.020) and TNF-α (SMD: -0.370; 95 % CI: -0.554 to -0.186) levels following MTT, while IL-6 reductions (SMD: -0.070; 95 % CI: -0.269 to 0.129) did not reach statistical significance. However, heterogeneity in study quality, intervention protocols, and participant demographics posed challenges in interpretation.

While improvements in inflammatory markers with MTT have been observed, significant limitations-such as heterogeneity in study quality and variation in intervention protocols-highlight the need for further research to confirm its efficacy and clarify underlying mechanisms. Future studies should aim to address these limitations by exploring variations in dosage, supplement formulations, and bacterial strains, which are crucial for improving the reliability and broader applicability of MTT in the management of T2DM.

Prostate cancer (PCa) is the most commonly detected malignancy in men worldwide. PCa is a slow-growing cancer with the absence of symptoms at early stages. The pathogenesis has not been entirely understood including the key risk factors related to PCa development like diet and microbiota derived metabolites. Microbiota may influence the host's immunological responses, inflammatory responses, and metabolic pathways, which may be crucial for the development and metastasis. Similarly, short-chain fatty acids, methylamines, hippurate, bile acids, and other metabolites generated by microbiota may have potential roles in cancer inflammation and progression of cancer. Most studies have focused on the role of metabolites and their pathways involved in chronic inflammation, tumor initiation, proliferation, and progression. In summary, the review discusses the role of microbiota and microbial-derived metabolite-built strategies in inflammation and progression of the PCa.

For a long time, traditional medicine has acknowledged the gut's impact on general health. Contemporary science substantiates this association through investigations of the gut microbiota, the extensive community of microorganisms inhabiting our gastrointestinal system. These microscopic residents considerably improve digestive processes, nutritional absorption, immunological function, and pathogen defense. Nevertheless, a variety of gastrointestinal and extra-intestinal disorders can result from dysbiosis, an imbalance of the microbial composition of the gut microbiota. A groundbreaking discovery is the gut-brain axis, a complex communication network that links the enteric and central nervous system (CNS). This bidirectional communication allows the brain to influence gut activities and vice versa, impacting mental health and mood disorders like anxiety and depression. The gut microbiota can influence this communication by creating neurotransmitters and short-chain fatty acids, among other biochemical processes. These factors may affect our mental state, our ability to regulate our emotions, and the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to explore the complex interrelationships between the brain and the gut microbiota. We also conducted a thorough examination of the existing understanding in the area of how microbiota affects social behaviors, including emotions, stress responses, and cognitive functions. We also explored the potential of interventions that focus on the connection between the gut and the brain, such as using probiotics to treat diseases of the CNS. This research opens up new possibilities for addressing mental health and neurological conditions in an innovative manner.

Sleep deprivation is a prevalent issue in contemporary society, with significant ramifications for both physical and mental well-being. Emerging scientific evidence illuminates its intricate interplay with the gut-brain axis, a vital determinant of neurological function. Disruptions in sleep patterns disturb the delicate equilibrium of the gut microbiota, resulting in dysbiosis characterized by alterations in microbial composition and function. This dysbiosis contributes to the exacerbation of neurological disorders such as depression, anxiety, and cognitive decline through multifaceted mechanisms, including heightened neuroinflammation, disturbances in neurotransmitter signalling, and compromised integrity of the gut barrier. In response to these challenges, there is a burgeoning interest in therapeutic interventions aimed at restoring gut microbial balance and alleviating neurological symptoms precipitated by sleep deprivation. Probiotics, dietary modifications, and behavioural strategies represent promising avenues for modulating the gut microbiota and mitigating the adverse effects of sleep disturbances on neurological health. Moreover, the advent of personalized interventions guided by advanced omics technologies holds considerable potential for tailoring treatments to individualized needs and optimizing therapeutic outcomes. Interdisciplinary collaboration and concerted research efforts are imperative for elucidating the underlying mechanisms linking sleep, gut microbiota, and neurological function. Longitudinal studies, translational research endeavours, and advancements in technology are pivotal for unravelling the complex interplay between these intricate systems.

Recently, researchers have been interested in the potential connection between gut microbiota composition and various neuropsychological disorders. Dementia significantly affects the socioeconomics of families. Gut microbiota is considered as a probable factor in its pathogenesis. Multiple bacterial metabolites such as short-chain fatty acids, lipopolysaccharides, and various neurotransmitters that are responsible for the incidence and progression of dementia can be produced by gut microbiota. Various bacterial species such as Bifidobacterium breve, Akkermansia muciniphila, Streptococcus thermophilus, Escherichia coli, Blautia hydrogenotrophica, etc. are implicated in the pathogenesis of dementia. Gut microbiota can be a great target for imitating or inhibiting their metabolites as an adjunctive therapy based on their role in its pathogenesis. Therefore, some diets can prevent or decelerate dementia by altering the gut microbiota composition. Moreover, probiotics can modulate gut microbiota composition by increasing beneficial bacteria and reducing detrimental species. These therapeutic modalities are considered novel methods that are probably safe and effective. They can enhance the efficacy of traditional medications and improve cognitive function.

Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var. boulardii (Sb), a probiotic yeast with high genetic tractability and innate anticancer activity, to secrete "miniature" antibody variants that target programmed death ligand 1 (Sb_haPD-1). When tested in an ICI-refractory colorectal cancer (CRC) mouse model, Sb_haPD-1 significantly reduced intestinal tumor burden and resulted in significant shifts to the immune cell profile and microbiome composition. This oral therapeutic platform is modular and highly customizable, opening new avenues of targeted drug delivery that can be applied to treat a myriad of gastrointestinal malignancies.

Calcineurin Inhibitors (CNIs), including tacrolimus and cyclosporine A, are the most widely used immunosuppressive drugs in solid organ transplantation. Those drugs play a pivotal role in preventing graft rejection and reducing autoimmunity. However, recent studies indicate that CNIs can disrupt the composition of gut microbiota or result in "gut dysbiosis". This dysbiosis has been shown to be a significant factor in reducing host immunity by decreasing innate immune cells and impairing metabolic regulation, leading to lipid and glucose accumulation. Several in vivo and clinical studies have demonstrated a mechanistic link between gut dysbiosis and the side effects of CNI. Those studies have unveiled that gut dysbiosis induced by CNIs contributes to adverse effects such as hyperglycemia, nephrotoxicity, and diarrhea. These adverse effects of the induced gut dysbiosis require interventions to restore microbial balance. Probiotics and dietary supplements have emerged as potential interventions to mitigate the side effects of gut dysbiosis caused by CNIs. In this complex relationship between CNI treatment, gut dysbiosis, and interventions, several types of gut microbiota and host immunity are involved. However, the mechanisms underlying these relationships remain elusive. Therefore, the aim of this review is to comprehensively summarize and discuss the major findings from in vivo and clinical data regarding the impact of treatment with CNIs on gut microbiota. This review also explores interventions to mitigate dysbiosis for therapeutic approaches of the side effects of CNIs. The possible underlying mechanisms of CNIs-induced gut dysbiosis with or without interventions are also presented and discussed.

Chronic gastrointestinal disorders such as inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS) impose significant health burdens globally. IBDs, encompassing Crohn's disease and ulcerative colitis, are multifactorial disorders characterized by chronic inflammation of the gastrointestinal tract. On the other hand, IBS is one of the principal gastrointestinal tract functional disorders and is characterized by abdominal pain and altered bowel habits. Although the precise etiopathogenesis of these disorders remains unclear, mounting evidence suggests that non-coding RNA molecules play crucial roles in regulating gene expression associated with inflammation, apoptosis, oxidative stress, and tissue permeability, thus influencing disease progression. miRNAs have emerged as possible reliable biomarkers, as they can be analyzed in the biological fluids of patients at a low cost. This review explores the roles of miRNAs in IBDs and IBS, focusing on their involvement in the control of disease hallmarks. By an extensive literature review and employing bioinformatics tools, we identified the miRNAs frequently studied concerning these diseases. Ultimately, specific miRNAs could be proposed as diagnostic biomarkers for IBDs and IBS. Their ability to be secreted into biofluids makes them promising candidates for non-invasive diagnostic tools. Therefore, understanding molecular mechanisms through the ways in which they regulate gastrointestinal inflammation and immune responses could provide new insights into the pathogenesis of IBDs and IBS and open avenues for miRNA-based therapeutic interventions.