Search Results (1,056)

The interaction between the gut microbiota and the host immune system is pivotal in maintaining health or driving disease pathogenesis. The gut microbiota directly or indirectly modulates immune cells activation and inflammatory cytokines secretion through microbial metabolites, including short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and polyamines. Conversely, the immune system regulates microbial community composition by maintaining the integrity of the epithelial barrier. In addition, antibiotics and probiotics can further regulate the inflammatory response by altering gut microbiota structure and microbial metabolites levels. This review systematically examines the bidirectional regulatory mechanisms among the gut microbiota, microbial metabolites, and inflammatory cytokines, and explores the impact of antibiotics and probiotics on this interaction network. These insights provide new targets for immune-related diseases. Full article

The small brown planthopper (SBPH), Laodelphax striatellus, transmits rice stripe virus (RSV), a devastating pathogen that causes significant yield losses in rice. The components of the gut microbiota in SBPH and the effects of RSV infection on gut microorganisms are unclear. In this study, high-throughput sequencing of 16S rRNA was utilized to evaluate the composition of gut microorganisms in SBPH. The gut microbiota of SBPH was primarily composed of Proteobacteria, Firmicutes and Bacteroidetes at ratios of 94.79%, 3.04% and 1.39%, respectively; furthermore, the composition of bacteria in the gut microbiota was relatively conserved with differences at the genus level. To elucidate the response of the SBPH gut microbiota to RSV infection, we compared its composition and abundance in viruliferous and naïve SBPH. Interestingly, RSV infection was associated with increased diversity in the SBPH gut microbiota. Comparative analysis demonstrated that RSV infection elevated the relative abundance of Proteobacteria while reducing that of Firmicutes. Population counts demonstrated that RSV infection reduced the gut loads of Stenotrophomonas, Brevundimonas, and Brevibacillus, whereas the gut load of Staphylococcus was significantly increased. Further functional predictive assays revealed that RSV infection enhanced the functions of the SBPH gut microbiota in terms of metabolism, cellular processes, genetic and environmental information processing, and organismal systems. Our results indicate that RSV reshapes the composition, abundance, and functions of the SBPH gut microbiota, offering insights into virus–host–microbiome interactions. Full article

Major depressive disorder (MDD) is a multifaceted psychiatric disorder that has been a longstanding focus of research. However, its underlying mechanisms remain underexplored. Recently, the inflammatory hypothesis has gained attention, highlighting inflammation’s role in MDD progression. Potential contributors to increased systemic inflammation in MDD include hyperactivation of the hypothalamic–pituitary–adrenal axis, dysregulation of the sympathetic nervous system, gut microbiota imbalances, the “pathogen host defense” hypothesis, and damage-associated molecular patterns. Traditional pathways explaining how systemic inflammation affects the central nervous system (CNS) do not fully account for the observed desynchrony between systemic and neuroinflammation in most depressed individuals. Alternative models suggest mechanisms such as reduced blood–brain barrier permeability and the involvement of immune cells from the skull. This review examines the link between inflammation and MDD, focusing on systemic and neuroinflammation interactions, with special emphasis on the heterogeneity of MDD symptoms and the potential impact of dysfunction in the brain’s lymphatic system. Gaining insight into the origins of inflammation in both the central nervous system and the peripheral body, along with their interactions, offers an important understanding of the inflammatory mechanisms associated with MDD for future treatment. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have achieved striking clinical efficacy in the subset of CRCs with mismatch repair deficiency/high microsatellite instability (dMMR/MSI-H), the vast majority of patients—those with proficient mismatch repair/microsatellite-stable (pMMR/MSS) tumors—derive little benefit from current immunotherapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lethal accumulation of lipid peroxides, has emerged as a promising antitumor mechanism that can interact with and modulate antitumor immunity. Concurrently, the gut microbiota exerts powerful control over host metabolism and immune tone through microbial community structure and metabolite production; accumulating evidence indicates that microbiota-derived factors can either sensitize tumors to ferroptosis (for example, via short-chain fatty acids) or confer resistance (for example, indole-3-acrylic acid produced by Peptostreptococcus anaerobius acting through the AHR→ALDH1A3→FSP1/CoQ axis). In this review we synthesize mechanistic data linking microbial ecology, iron and lipid metabolism, and immune regulation to ferroptotic vulnerability in CRC. We discuss translational strategies to exploit this “microbiota–ferroptosis” axis—including precision microbiome modulation, dietary interventions, pharmacologic ferroptosis inducers, and tumor-targeted delivery systems—and we outline biomarker frameworks and trial designs to evaluate combinations with ICIs. We also highlight major challenges, such as interindividual microbiome variability, potential collateral harm to ferroptosis-sensitive immune cells, adaptive antioxidant compensation (e.g., NRF2/FSP1 activation), and safety/regulatory issues for live biotherapeutics. In summary, this review highlights that targeting the microbiota-ferroptosis axis may represent a rational and potentially transformative approach to reprogramming the tumor microenvironment and overcoming immune checkpoint resistance in pMMR/MSS colorectal cancer; however, further research is essential to validate this concept and address existing challenges. Full article

Global consumer demand for probiotic-enriched functional foods has increased as consumers become increasingly aware of the connection between what they eat and its role in their long-term health. Compared with conventional foods that primarily deliver fundamental nutrients, functional foods include biologically active compounds capable of influencing physiological processes. While traditionally used probiotic strains like Lactobacillus and Bifidobacterium are still at the center of this trend, there is growing interest in the exploration of emerging and novel microbial candidates that harbor new functional properties. This review addresses the characterization, modes of action, technological limitations, regulatory guidelines, and prospective health benefits of new probiotic strains in functional foods. The review further highlights the need for precise strain selection, novel encapsulation technologies for viability, and strict safety assessments in accordance with EFSA’s QPS (Qualified Presumption of Safety) and the United States FDA GRAS (Generally Recognized As Safe) specifications. Current research focuses on the classical benefits of probiotics, including gut microbiota modulation, immunomodulation, antimicrobial activity, lowering of cholesterol, and mental health. However, long-term clinical validation, strain specificity, personalized application, and effective communication to consumers are some areas where gaps remain. Addressing these challenges through the incorporation of omics technologies, synthetic biology, and more detailed microbiome–host interaction studies will be the key to unlocking the full potential of next-generation probiotics and sustaining consumer trust in this emerging market. Full article

The structure and assembly mechanism of wild animal gut microbiota represent persistent research hotspots. Among, the impact of geographic factors on the bacterial co-occurrence network characteristics and assembly mechanism of the gut microbiome remains unclear. Therefore, this study analyzed the gut microbiome of Niviventer confucianus and Apodemus agrarius from Anhui and Hubei provinces. The same alpha diversity pattern was found in the gut microbiome of species from the same region. The gut microbiome of the two rodent species in Anhui region exhibited “small world” characteristics, such as nodes with more local connections to allow interaction information (such as metabolites) to rapidly spread throughout the entire microbial community. In addition, dispersal limitations and heterogeneous selection accounted for higher proportions of the gut microbiome in the rodents from the Anhui and Hubei regions, respectively. The higher proportion of heterogeneous selection may exacerbate selection pressure in the Hubei region. Multiple regression on distance matrices analysis revealed that geographic region exerted a limited but significant influence (0 < R² < 0.2, * p < 0.05) on the gut microbiome, surpassing the effects of host phylogeny, gender, and weight. Nevertheless, the roles of regional factors—such as environmental microbes, pollutants, and diet—remain unexamined, and their potential as key drivers of microbiota variation in these rodents warrants further investigation. Full article

The gut microbiota, a complex community of trillions of microorganisms residing in the gastrointestinal tract, plays a vital role in maintaining host health and regulating a wide range of physiological functions. Advances in molecular biology have greatly expanded our understanding of the dynamic interactions between the gut microbiome and the immune system. Disruption of this microbial community, known as dysbiosis, can compromise epithelial barrier integrity, trigger aberrant immune activation, and lead to the production of proinflammatory metabolites. These changes are increasingly recognized as contributing factors in the pathogenesis of chronic inflammatory diseases. Emerging research highlights the gut microbiota as a key modulator of immune homeostasis, influencing both local and systemic inflammatory processes during the initiation and progression of these diseases. Understanding the mechanisms underlying gut microbiota-immune interactions will offer new avenues for therapeutic interventions. This review focuses on six representative chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, asthma, and vasculitis, all of which are characterized by dysregulated immune responses and persistent inflammation. Our goal is to synthesize the recent research on the role of gut microbiome in the pathogenesis of the diseases listed above and provide insights into the development of microbiota-based therapies, particularly fecal microbiota transplant, dietary modifications, prebiotic and probiotic interventions, for their treatment. Full article

The gut microbiota of Drosophila melanogaster offers a simplified yet powerful system to study conserved mechanisms of host–microbe interactions. Unlike the highly complex mammalian gut microbiota, which includes hundreds of species, the fly gut harbors a small and defined community dominated by Lactobacillus and Acetobacter. Despite its low diversity, this microbiota exerts profound effects on host physiology. Commensal bacteria modulate nutrient acquisition, regulate insulin/TOR signaling, and buffer dietary imbalances to support metabolic homeostasis and growth. They also influence neural and behavioral traits, including feeding preferences, mating, and aggression, through microbial metabolites and interactions with host signaling pathways. At the immune level, microbial molecules such as peptidoglycan, acetate, uracil, and cyclic dinucleotides activate conserved pathways including Imd, Toll, DUOX, and STING, balancing antimicrobial defense with tolerance to commensals. Dysbiosis disrupts this equilibrium, accelerating aging, impairing tissue repair, and contributing to tumorigenesis. Research in Drosophila demonstrates how a low-diversity microbiota can shape systemic host biology, offering mechanistic insights relevant to human health and disease. Full article

Chlamydia trachomatis (CT) remains the most commonly reported bacterial sexually transmitted infection (STI) globally, with particularly high incidence among adolescents and young adults. In Europe, CT cases have continued to rise over the past decade, despite ongoing public health efforts in prevention and screening. Screening coverage, however, remains inconsistent across countries. CT infections are often asymptomatic, especially in women, yet can lead to serious CT-related reproductive complications if left untreated, including pelvic inflammatory disease (PID), tubal factor infertility, and ectopic pregnancy. Emerging evidence highlights the cervicovaginal microbiota as a key factor influencing susceptibility to STIs, including CT infection, its progression, and associated outcomes. A Lactobacillus-dominated microbiota, particularly L. crispatus, is well-known to be a protective factor against CT acquisition, whereas vaginal dysbiosis, characterized by a depletion of these species and an overgrowth of anaerobes, such as Gardnerella vaginalis, Atopobium vaginae, and Prevotella spp., has been linked to increased CT acquisition risk, reduced immune control, and impaired infection resolution. Interaction between microbial communities and host immunity may modulate whether CT infections spontaneously clear, persist, or progress into pathological conditions. This review explores the natural history of CT genital infection in women, emphasizing the role of cervicovaginal dysbiosis in disease progression and reproductive sequelae. By integrating current knowledge about resident cervicovaginal microbes, host-microbe interaction, and CT-related reproductive outcomes, we discuss how microbiota-targeted strategies, including probiotic or microbiome-modulating strategies, may complement current CT prevention, diagnosis, and treatment approaches. Full article

The interaction between the gut microbiota and the skeletal system has evolved into a new research focus. Studies underscore the role of bioactive metabolites in sustaining systemic balance via the “gut microbiota–endocrine–skeleton” axis, where they modulate metabolic processes and organ morphology through intracellular signaling. A key bidirectional relationship exists with the gut: shifts in gut microbiota affect host metabolism and subsequent metabolite profiles, while these metabolites can, in turn, reshape the intestinal microenvironment. This review explores how short-chain fatty acids (SCFAs), estrogen, and vitamin D modulate osteoporosis via the gut–bone axis. It synthesizes evidence of their signaling pathways and metabolic roles, identifies research gaps from recent clinical studies, and evaluates gut microbiota-targeted therapeutic strategies for potential clinical translation. Full article

The gut microbiome has emerged as a pivotal player in shaping host immune responses, with significant implications for vaccine efficacy and safety. Rather than detailing all influencing factors, this review focuses on the most critical and translational aspects of microbiome–vaccine interactions. Increasing evidence shows that the composition and functionality of the intestinal microbiota can influence both the magnitude and durability of vaccine-induced immunity. For instance, Bifidobacterium longum supplementation was shown to enhance influenza vaccine seroconversion rates by approximately 30% in clinical and preclinical models, underscoring the translational potential of microbiome modulation. Here, we provide a concise synthesis of mechanistic insights and key clinical findings that connect gut microbial composition and metabolism with vaccine outcomes. We further highlight microbiome-targeted interventions—such as probiotics, prebiotics, and postbiotics—that hold promise for optimizing vaccine responses in diverse populations. By emphasizing actionable evidence over descriptive variability, the review aims to clarify how microbiome modulation can be strategically harnessed to improve vaccine performance. Integrating microbiome modulation into vaccination strategies may enhance global immunization equity and effectiveness, offering a feasible pathway toward more durable and inclusive protection worldwide. Full article

Background: The accumulation of glycosidic polymers in Lilium brownii var. viridulum Baker (Lv) bulbs fundamentally governs the nutritional and medicinal properties. Methods: In this study, metabolomic, transcriptomic, and microbiome analyses were integrated to elucidate the differential mechanisms of glycoside accumulation between the elite ‘Xuefeng’ (Lv, X) and ‘Longya’ (Lv, L), each comprising three biological replicates. Results: The results demonstrate significantly elevated diversity and abundance of glycosides in X bulbs, with glucose derivatives constituting the predominant fraction. Differential expression genes (DEGs) associated with carbohydrate metabolism were primarily enriched in starch/sucrose metabolism and amino sugar metabolic pathways. Planctomycetes in rhizospheric soil, combined with Acidobacteriia and Rhodanobacteraceae in non-rhizospheric soil, were identified as key microbial taxa associated with glycoside accumulation. Variation partitioning analysis (VPA) revealed that synergistic genetic microbiota–host interactions collectively accounted for 86.8% of the metabolic variance. Conclusions: Consequently, X exhibits superior potential as a medicinal/edible cultivar and as a breeding material due to its enhanced biosynthesis of glycosidic polymers. This work, for the first time, systematically deciphers the regulatory framework of glycoside accumulation in Lv bulbs, highlighting microbiota–host synergy, and provides critical insights for the refining of biosynthetic pathways and targeted crop enhancement. Full article

Gut-derived uremic toxins may play a key role in neurodevelopmental conditions such as autism spectrum disorder (ASD) via host-microbe metabolic interactions. We evaluated five uremic toxins—p-cresyl sulfate (PCS), indoxyl sulfate (IS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in urine samples of 97 children with ASD and 71 neurotypical controls, stratified by Bristol Stool Chart (BSC) consistency types. Four of these toxins (PCS, IS, TMAO, ADMA) were integrated into a novel composite biomarker called the Metabolic Index of Gut Dysfunction (MIGD), while SDMA was measured as a complementary renal function marker. While individual metabolite levels showed no statistically significant differences, group-wise analysis by stool phenotype revealed distinct trends. ASD children with hard stools (BSC 1–2) showed elevated PCS levels and the MIGD score (median 555.3), reflecting phenolic fermentation dominance with reduced indolic detoxification. In contrast, children with loose stools (BSC 6–7) had the lowest MIGD values (median 109.8), driven by higher IS and lower ADMA concentrations, suggestive of enhanced indole metabolism. These findings indicate that MIGD may serve as a novel biomarker to stratify metabolic phenotypes in ASD, linking urinary metabolite patterns to gut function. Further validation in larger and longitudinal cohorts is warranted to confirm its potential utility in precision microbiota-targeted interventions. Full article

Periodontitis (PD) is a multifactorial, progressive inflammatory disease affecting the teeth-supporting tissues, characterized by an imbalance of the oral microbiota and the presence of bacterial biofilms leading to host response. Nowadays, reliable biochemical markers for early and objective diagnosis, and for predicting disease progression, are still lacking. Our previous proteomic investigations revealed the significant overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in periodontal pocket tissue, gingival crevicular fluid (GCF), and tooth-surface-collected material (TSCM) from PD patients in comparison to periodontally healthy controls, proposing it as a possible biomarker of PD. This study aimed to evaluate the expression of GAPDH in saliva, a more accessible, non-invasive, and clinically relevant oral sample. The whole saliva was analyzed by a preliminary mass spectrometry-based proteomic approach, identifying significantly increased levels of GAPDH also in salivary samples from periodontal-affected subjects. These data were further validated by enzyme-linked-immunosorbent assay (ELISA). Additionally, protein–protein interaction networks were generated through the Human Protein Atlas database, using different datasets (OpenCell, IntAct, and BioGRID). Bioinformatic analysis provided noteworthy GAPDH-associated networks potentially relevant to periodontal pathology. The scientific significance of this study lies in the detection of salivary GAPDH as a novel strategy to advance periodontal clinical diagnostics from the perspective of a non-invasive screening test. In correlation with other protein markers, salivary GAPDH could constitute a promising set of distinctive and predictive targets to enhance early diagnosis of PD, disease monitoring, and treatment planning in periodontology. Full article

Butyrate is a key short-chain fatty acid (SCFA) essential for maintaining colon health, immune homeostasis, and metabolic balance. Its synthesis primarily depends on the fermentation of dietary substrates by the gut microbiota. In a healthy state, carbohydrate fermentation sustains the stability of the gut microbiota; however, in chronic diseases, the diversity of the microbiota decreases, and the metabolic pathway shifts from carbohydrate fermentation to protein fermentation, thereby inhibiting butyrate production. Polysaccharides and proteins play key roles in regulating butyrate synthesis. As fermentable carbon sources, polysaccharides promote the proliferation of probiotics, lower colonic pH, and inhibit anaerobic fermentation of proteins. However, excessive protein fermentation produces branched-chain fatty acid (BCFA), ammonia, phenols, and other metabolites that inhibit butyrate production. The structural characteristics of polysaccharides and the digestibility of proteins can determine the substrate selection of gut microbiota. This review systematically elucidates the biosynthetic pathways of butyrate in the gut and the host metabolic signaling pathways in which it participates, focusing on the interactions between dietary proteins and polysaccharides and their key regulatory mechanisms affecting butyrate production by the gut microbiota. Full article