Search Results (180)

Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder characterized by high mortality and limited therapeutic options. Alginate oligosaccharide (AOS), a marine-derived bioactive polysaccharide, exhibits prebiotic, anti-inflammatory and antioxidant properties that are effective against various inflammatory diseases. In this study, a mouse model of SAP was established by intraperitoneal injection of cerulein (100 μg/kg) and lipopolysaccharide (5 mg/kg), and the mice were pretreated with AOS (200 mg/kg) by gavage for 4 consecutive weeks to explore the potential protective efficacy and underlying mechanisms. The results shown that AOS attenuated the severity of SAP, as evidenced by reduced serum amylase and lipase levels, as well as alleviated histopathological injury in both pancreatic and ileal tissues. AOS suppressed the overproduction of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in serum, pancreas, and ileum at protein or mRNA levels. Moreover, AOS effectively diminished pancreatic and ileal inflammatory infiltration and oxidative stress in SAP mice, accompanied by inhibited the TLR4/MyD88/NF-κB pathway and activated the Nrf2/HO-1 antioxidant axis. Furthermore, AOS restored intestinal barrier integrity, as manifested by upregulated expression of tight junction proteins (claudin-1, occludin, ZO-1), reduced serum diamine oxidase, and decreased bacterial translocation from the gut to the pancreas. It was revealed by 16S rRNA sequencing that AOS ameliorated SAP-induced gut dysbiosis by restoring microbial diversity, normalizing the Firmicutes/Bacteroidetes ratio, enriching beneficial genera (Lactobacillus, Blautia), and enhancing cecal short-chain fatty acid (acetic, propionic, butyric acid) production. Collectively, our findings demonstrate that AOS exerts comprehensive protective effects against SAP through suppression of inflammatory signaling and oxidative stress, as well as restoring gut homeostasis. These results suggest that AOS may serve as a promising prebiotic-based nutritional strategy for the management of SAP. Full article

Titanium dioxide nanoparticles (TiO₂-NPs) are widely produced and persist in aquatic ecosystems, yet their indirect effects on host–microbe interactions remain poorly defined. By using zebrafish (Danio rerio) as a sentinel species, this study investigated the effects of subchronic 5 mg/L TiO₂-NP exposure. Dynamic light scattering was utilized to characterize the bimodal aggregates (peaks at 917 and 46,841 nm; surface charge: +22.08 mV) that define the environmental state of TiO₂-NPs. Parallel 16S rRNA metagenomic profiling on Day 6, prior to mortality, revealed profound gut dysbiosis. A marked increase in Chao1 richness (p < 0.01), alongside a catastrophic 333-fold reduction in beneficial Cetobacterium and an 856-fold enrichment of pathogenic Mycobacterium, was observed. Beta-diversity and hierarchical clustering analyses revealed a striking convergence between gut and gill microbial signatures, supporting a gut-to-gill translocation model. These results suggest that TiO₂-NPs exposure induces intestinal dysbiosis, facilitating opportunistic bacterial migration via internal (gut–blood–gill) or external (fecal–water–gill) pathways. This study identifies dysbiosis-driven secondary infection as a novel, overlooked mechanism of nanoparticle toxicity, necessitating a shift in ecological risk assessments toward host–microbe interactions. Full article

Hypertriglyceridemic acute pancreatitis (HTG-AP) progresses rapidly with poor prognosis. Intestinal barrier dysfunction and excessive oxidative stress contribute to its pathogenesis, but specific mediators linking gut injury, oxidative stress and pancreatic damage remain unclear. Here, we identify endogenous phenyllactic acid (PLA) as a critical metabolite regulating intestinal barrier integrity and oxidative homeostasis in HTG-AP. We noted serum PLA, a disease-associated metabolite whose reduction correlates with gut dysbiosis and pancreatic inflammation in HTG-AP. PLA supplementation in HTG-AP mice attenuated intestinal barrier dysfunction and mitigated intestinal oxidative stress, as evidenced by improved gut dysbiosis, reduced reactive oxygen species accumulation, restored superoxide dismutase activity, restored barrier integrity, reduced bacterial translocation to the pancreas, and decreased serum lipopolysaccharide levels, ultimately mitigating pancreatic injury. RNA sequencing of colonic tissue revealed peroxisome proliferator-activated receptor (PPAR) signaling as one of the most significantly altered pathways in HTG-AP. PPARγ expression was markedly reduced in colonic epithelial cells and upregulated upon PLA treatment. Knockdown of colonic epithelial PPARγ via adeno-associated virus abrogated the beneficial effects of PLA on intestinal barrier integrity, oxidative stress and pancreatic injury in HTG-AP mice. The protective effects of PLA were phenocopied by the PPARγ agonist rosiglitazone. Collectively, these findings identified gut microbiota-derived PLA as an endogenously derived metabolite modulating intestinal oxidative stress and barrier function. Using male C57BL/6J mice to establish an HTG-AP model, we further revealed that PLA exerts protective effects against HTG-AP by targeting colonic PPARγ to modulate the gut–pancreas axis, highlighting PLA as a promising candidate for targeted intervention in HTG-AP. Full article

The human gut microbiome is essential for immune regulation and mucosal homeostasis, functions that are profoundly disrupted during HIV infection. Early viral replication in the gut-associated lymphoid tissue (GALT) triggers a self-reinforcing cycle of CD4⁺ T-cell depletion, epithelial barrier breakdown, and increased microbial translocation. This persistent immune activation continues even under effective antiretroviral therapy (ART). A growing body of evidence indicates that HIV infection is consistently associated with alterations in gut microbial communities. This dysbiosis is typically characterized by fewer beneficial butyrate-producing commensal bacteria and an enrichment of pro-inflammatory microbial taxa. It also involves disturbances in key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan catabolites. Such changes not only exacerbate systemic inflammation but may also contribute to incomplete immune reconstitution and the persistence of latent viral reservoirs despite long-term ART. In this review, we summarize current knowledge of microbiome–HIV interactions, with particular emphasis on the mechanisms through which gut dysbiosis contributes to immune dysfunction and viral persistence. We discuss recent advances in multi-omics technologies, as well as experimental systems such as gnotobiotic and humanized mouse models and intestinal organoid platforms that are helping to elucidate these complex interactions. Furthermore, we evaluate emerging microbiome-targeted interventions—including probiotics, prebiotics, fecal microbiota transplantation, and engineered bacterial therapeutics—and consider their potential role as adjunctive strategies in HIV treatment and cure research. By integrating microbiological, immunological, and clinical perspectives, this review highlights key knowledge gaps and outlines future research directions aimed at harnessing the gut microbiome as a novel therapeutic avenue in HIV management and eradication. Full article

Male infertility contributes to approximately half of all infertility cases, with a substantial proportion remaining idiopathic. Emerging evidence implicates the gut microbiome as a regulator of male reproductive health through a proposed gut–testis axis. Few studies have shown that gut microbial dysbiosis may impair sperm quality via multiple mechanisms, including disruption of endocrine function (e.g., reduced testosterone production), alterations in microbial-derived metabolites, and impaired testicular energy metabolism. Increased intestinal permeability and systemic inflammation may further compromise the blood–testis barrier, while translocation of bacterial endotoxins may also contribute to testicular damage. Collectively, these processes can disrupt spermatogenesis and negatively affect sperm parameters, such as concentration, motility, and morphology. Interventions that restore microbial balance, including dietary modulation, have shown potential in reversing these effects and improving reproductive outcomes. This review summarizes and evaluates current literature linking gut microbial dysbiosis to male reproductive dysfunction. Key methodological limitations and knowledge gaps are highlighted, providing a foundation for advancing the development of gut microbiome-based interventions to improve male reproductive health. Full article

Background: The gut microbiota and its metabolite short-chain fatty acids (SCFAs) regulate host physiology, but whether butyrate, a key SCFA, protects against myocardial injury via the gut–heart axis remains unclear. Objectives: This study aimed to investigate the cardioprotective effect of butyrate in a rat model of isoproterenol (ISO)-induced myocardial injury and to explore its underlying gut–heart mechanism. Methods: In this experimental study, male Sprague-Dawley rats received intragastric butyrate pre-treatment followed by ISO injection to induce myocardial injury. Cardiac function, myocardial remodeling, gut–heart homeostasis, intestinal barrier integrity, and the expression of Tas2r, GPR41/43, and NLRP3 pyroptosis pathway components were assessed. Results: Butyrate pre-treatment significantly restored cardiac function (LVEF increased by 19.67 units; 95% CI, 11.17–28.16; p < 0.001) and ameliorated electrophysiological abnormalities (QTc shortened by 63.21 ms; 95% CI, 45.45–80.97; p < 0.0001). Mechanistically, butyrate suppressed aberrant myocardial Tas2r signaling (Tas2r137 reduced by 1.06 units; 95% CI, 0.37–1.74; p < 0.01), upregulated GPR41/43, inhibited NLRP3 inflammasome activation (NLRP3 reduced by 1.23 units; 95% CI, 0.13–2.33; p < 0.05), and repaired intestinal barrier integrity, thereby reducing bacterial translocation and secondary injury. Conclusions: Butyrate ameliorates ISO-induced myocardial injury through a simultaneous gut–heart mechanism, acting on both the cardiac Tas2r137/GPR41/43-NLRP3 pathway and intestinal barrier protection. These findings identify butyrate as a key functional molecule in gut–heart crosstalk and suggest its potential as a therapeutic agent for myocardial injury. Full article

The gastrointestinal (GI) barrier is a highly coordinated, multilayered defence system that maintains intestinal homeostasis by separating the luminal microbiota from the internal milieu. In liver cirrhosis, this barrier undergoes profound structural and functional disruption, emerging as a central driver of bacterial translocation and infection-related complications. Among these, spontaneous bacterial peritonitis (SBP) represents a major determinant of morbidity, mortality, and disease progression. Barrier failure in cirrhosis is not attributable to a single defect but results from the convergence of multiple interconnected mechanisms. Structural alterations include disruption of epithelial tight junctions and deterioration of the mucus layer, leading to increased intestinal permeability and loss of spatial compartmentalisation. These changes are compounded by microbial dysbiosis, characterised by reduced diversity, depletion of short-chain fatty acid-producing taxa, and expansion of pathobionts. In parallel, cirrhosis-associated immune dysfunction impairs both mucosal and systemic antimicrobial defences, while gut–vascular barrier disruption facilitates systemic dissemination of bacteria and microbial products. The resulting increase in bacterial translocation plays a pivotal role in the pathogenesis of SBP and contributes to systemic inflammation, circulatory dysfunction, and acute decompensation. Importantly, this process establishes a self-amplifying pathogenic loop in which barrier dysfunction, dysbiosis, and immune dysregulation mutually reinforce each other. Recent advances have identified key molecular pathways involved in barrier regulation, including bile acid–FXR signalling and microbiome-derived metabolites, providing novel targets for therapeutic intervention. While current management relies largely on antibiotics and supportive care, emerging strategies aim to restore barrier integrity and modulate the gut–liver axis. A deeper understanding of GI barrier dysfunction offers new opportunities to prevent bacterial translocation and improve clinical outcomes in patients with liver cirrhosis. Full article

Cardiac amyloidosis is a rare and progressive condition characterized by the extracellular deposition of amyloid fibrils in multiple organs. Wild-type transthyretin amyloidosis (ATTR-wt) is the most common type affecting subjects above 60 years old. Recent and growing evidence suggests a potential link between GM and cardiac amyloidosis. In this scenario, the aim of the present study is to characterize the gut microbiota (GM), related metabolites and inflammatory biomarkers in ATTR-wt patients. In the ATTR patients we identified Prevotella_9 as the core OTUs (Operational Taxonomic Unit) of this group, alongside Prevotella 7, Prevotellaceae_UCG-003 and Prevotellaceae_NK3B31. In addition, there were increased levels of long fatty acids, including tetradecanoic, hexadecanoic and octadecanoic acids, in the ATTR group. The data obtained suggest that ATTR patients have an altered gut microbiota that could be used as a potential biomarker in metabolic and cardiovascular diseases, as well as a potential predictor of adverse prognosis in ATTR patients. In addition, the intestinal dysbiosis in ATTR patients could be associated with low-grade endotoxemia promoting a pro-inflammatory state due to the translocation of bacterial components, such as LPS (lipopolysaccharide), into blood circulation. Full article

Necrotizing enterocolitis (NEC) and sepsis/late-onset sepsis (LOS) are significant contributors to preterm infant morbidity and mortality, with prematurity and low birth weight representing major risk factors for these interconnected conditions. Although the pathogenesis of NEC and LOS is not fully understood, there is a clear association with an immature intestinal mucosal barrier, which may enable bacterial invasion and translocation, resulting in an inflammatory cascade. Increasing recognition of the gut microbiome as a marker for health and disease has driven interest in probiotics, particularly Bifidobacterium spp. and Lactobacillus spp., as potential adjunctive agents for the prevention and management of NEC and LOS in preterm infants, which is the area of focus of this review. The focus of this paper was to analyze clinical studies using different probiotic strains, and compare single-strain versus multi-strain probiotic formulations. Several studies support that probiotic supplementation in preterm infants has the potential to decrease NEC incidence and, to a lesser extent, sepsis/LOS. Nonetheless, inconsistent results due to strain differences and clinical heterogeneity limit the widespread adoption of this mode of therapy, as do safety concerns in this vulnerable population. Further high-quality standardized studies are necessary to establish consistent guidelines for probiotic use in preterm infants. Full article

The pathogenesis of inflammatory bowel disease (IBD) is driven by an interplay among intestinal dysbiosis and aberrant mucosal immune responses. This review centers on the microbiota as a pivotal pathogenic hub, systematically dissecting how three hallmark features of dysbiosis—reduced microbial alpha diversity, depletion of immunomodulatory commensals, and expansion of pro-inflammatory pathobionts—collectively compromise epithelial barrier function, promote bacterial translocation, and sustain chronic mucosal inflammation. We further integrate emerging evidence implicating bidirectional gut-brain axis communication in amplifying both peripheral inflammation and central nervous system (CNS)-mediated behavioral comorbidities. Building on this mechanistic framework, we critically evaluate next-generation microbiota-targeted interventions: standardized fecal microbiota transplantation (FMT), rationally designed live biotherapeutic products (LBPs), precision phage cocktails targeting defined pathobionts, and microbiome-informed dietary strategies. Collectively, these approaches represent a paradigm shift—from broad-spectrum immunosuppression toward mechanism-guided, ecosystem-level modulation—thereby advancing the goal of precision medicine in IBD. Full article

Escherichia coli, Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans are microorganisms capable of causing severe infections, particularly in patients with underlying comorbidities or immune dysfunction. We report a rare clinical case of a 65-year-old man with advanced cardiac and hepatic disease who developed severe diarrheal syndrome followed by septic shock, rapid clinical deterioration, and death. Microbiological examination of autopsy specimens from the intestinal wall and spleen identified Escherichia coli O128 with an enterotoxigenic profile (lt+, st+, eae−), together with Streptococcus equi subsp. zooepidemicus, Klebsiella oxytoca, and Enterococcus durans. Histopathological analysis demonstrated catarrhal enteritis with fibrinous deposits, mucosal edema, vascular congestion, and inflammatory infiltration. Although the microbiological findings were partly derived from autopsy material and postmortem bacterial translocation cannot be completely excluded, the concordance between clinical presentation, laboratory findings, and morphological changes supports the presence of a clinically significant infectious process. To our knowledge, this is the first reported human case of fatal polymicrobial infection involving these four pathogens. The case highlights the potential severity of polymicrobial infections in patients with cirrhosis-associated immune dysfunction and underscores the importance of integrated microbiological and molecular diagnostics for accurate etiological assessment. Full article

Liver cirrhosis represents the end stage of chronic liver disease arising from diverse etiologies and is characterized by persistent hepatic injury, architectural distortion, extensive fibrosis, and nodular regeneration. While decompensated cirrhosis is commonly associated with overt, life-threatening complications such as hepatic encephalopathy, hepatorenal syndrome and gastrointestinal bleeding, less apparent manifestations—including sarcopenia and metabolic disturbances—have emerged as major determinants of prognosis. Sarcopenia, defined by the progressive loss of skeletal muscle mass and function, is highly prevalent in cirrhotic patients and is closely linked to frailty, increased morbidity, mortality, and adverse liver transplantation outcomes. Increasing data support the role of gastrointestinal dysfunction in the pathogenesis of sarcopenia in liver cirrhosis. In chronic liver disease, intestinal dysfunction is exacerbated by portal hypertension, which promotes increased intestinal permeability and bacterial translocation. Furthermore, gut dysbiosis, a key feature of advanced liver disease, contributes to impaired digestion, malabsorption of macro- and micronutrients, increased intestinal permeability, malnutrition and systemic inflammation. These alterations promote negative energy balance, reduce muscle protein synthesis and enhance muscle catabolism, thereby accelerating muscle wasting. Despite increasing recognition of the individual roles of gut dysbiosis, malabsorption, and sarcopenia in cirrhosis, their complex interrelationship has not been comprehensively addressed. This narrative review synthesizes current evidence on the interplay between gut dysbiosis, malabsorption and sarcopenia in patients with liver cirrhosis. We discuss underlying pathophysiological mechanisms, clinical implications and potential therapeutic strategies, while highlighting existing knowledge gaps and future research directions. Improved understanding of the gut-liver-muscle axis may offer novel opportunities for early intervention and optimization of outcomes in this high-risk patient population. Full article

The gut–mammary axis represents a promising therapeutic target for mastitis. Although plant-derived polysaccharides exhibit immunomodulatory properties, their capacity to modulate this axis—and specifically to ameliorate dysbiosis-induced mastitis—remains unexplored. Here, we investigated the therapeutic potential of Taraxacum kok-saghyz leaf-derived polysaccharides (TKP-L) against mastitis in a murine model of gut dysbiosis, with dysbiosis induced by fecal microbiota transplantation (FMT) from donor cows. Pregnant mice (n = 60) with antibiotic-depleted microbiota received FMT suspensions prepared from the feces of healthy dairy cows or cows with clinical mastitis (based on somatic cell count). Mice were randomly divided into five groups: Control (vehicle), M-FMT (mastitis-cow FMT, disease model), H-FMT (healthy-cow FMT), TKP-L (M-FMT + oral TKP-L, 500 mg/kg/day), and Ciprofloxacin (M-FMT + ciprofloxacin, positive Control). After FMT establishment, TKP-L or ciprofloxacin was administered for 14 days. We assessed histopathology, pro-inflammatory mediators (IL-6, IL-1β, TNF-α, MPO), tight junction proteins (occludin, ZO-1, Claudin-3), and bacterial translocation using GFP-E. coli, and gut/milk microbiota via 16S rRNA sequencing. Compared to the M-FMT group, TKP-L treatment significantly alleviated mammary inflammation and pathology, inhibited pro-inflammatory cytokine expression, and enhanced the expression of tight junction proteins in both intestinal and mammary tissues, correlating with reduced bacterial translocation to the mammary gland. Microbiota analysis showed that TKP-L restored microbial homeostasis in the gut and milk, concurrently increasing the relative abundance of beneficial bacteria such as Limosilactobacillus. TKP-L alleviates gut dysbiosis-induced mastitis in mice by concurrently modulating the gut–mammary axis through microbial remodeling, enhancement of epithelial barriers, and anti-inflammatory actions. These findings highlight TKP-L as a promising gut microbiota-targeting candidate for mastitis intervention. Full article

Colorectal cancer (CRC) cachexia is a multifactorial, treatment-limiting syndrome characterized by progressive loss of skeletal muscle with or without loss of fat mass, accompanied by systemic inflammation, anorexia, metabolic dysregulation, and impaired treatment tolerance. Despite decades of work, cachexia remains clinically underdiagnosed and therapeutically underserved, in part because canonical models treat tumor-derived factors and host inflammatory mediators as a largely ‘host-only’ network. In parallel, CRC is strongly linked to intestinal dysbiosis, barrier disruption, and microbial translocation. Extracellular vesicles (EVs)—host small EVs, tumor-derived EVs, and bacterial extracellular vesicles (including outer membrane vesicles)—may provide a mechanistically plausible, information-dense route by which these domains could be coupled. Here, we synthesize emerging evidence suggesting that cross-kingdom EV signaling may operate as a vesicular ecosystem spanning gut lumen, mucosa, circulation, and peripheral organs. We propose the “vesicular intersection layer” as a unifying framework for how heterogeneous EV cargos converge on shared host decoding hubs (e.g., pattern-recognition receptors and stress-response pathways) to potentially contribute to muscle catabolism. We critically evaluate what is known—and what remains unproven—about EV biogenesis, trafficking, and causal mechanisms in CRC cachexia, highlight methodological constraints in microbial EV isolation and attribution, and outline minimum evidentiary standards for cross-kingdom claims. Finally, we translate the framework into actionable hypotheses for EV-informed endotyping, biomarker development (including stool EV assays), and therapeutic strategies targeting shared signaling nodes (e.g., TLR4–p38) and endocrine mediators that are predominantly soluble but may be fractionally vesicle-associated (e.g., GDF15). By reframing CRC cachexia as an emergent property of tumor–host–microbiota vesicular communication, this review provides a roadmap for mechanistic studies and clinically tractable interventions. Full article

Background: Coronary heart disease (CHD) is the leading cause of death and disability worldwide. The human microbiota, particularly gut bacteria, plays a role in the development of CHD. However, determining the contribution of gut bacteria translocation to systemic circulation in the progression of atherosclerosis remains challenging. Methods and Results: In this exploratory study, we conducted 16S rRNA–based metagenomic analysis to characterize systemic bacterial profiles in a cohort of 27 patients with CHD (9 with severe coronary artery stenosis and 18 with mild to moderate stenosis). We compared microbial diversity between arterial and venous blood and across different blood fractions. For the first time, we observed higher microbial diversity in plasma than in serum. We also identified differences in microbial richness among arterial whole blood, venous whole blood, arterial plasma, venous plasma, arterial serum, and venous serum, with 15, 22, 43, 10, 4, and 3 genera showing significant differences, respectively. Many of the detected blood taxa belonged to genera typically found in intestinal, oral, or skin microbiota, although their precise source cannot be determined from this study. Conclusions: Our study provides preliminary evidence of distinct bacterial profiles between arterial and venous blood fractions in patients with CHD, as determined by 16S rRNA sequencing. These findings should be interpreted with caution given the small sample size and the absence of a healthy control group, and they warrant confirmation in larger, controlled studies. Full article