Search Results (699)

Inflammatory bowel diseases (IBD) are increasingly acknowledged not merely as confined gastrointestinal disorders but as systemic immunometabolic syndromes. Central to this paradigm is the gut microbiota including non-bacterial components such as the virome, whose functional disruption marked by reduced short-chain fatty acids (SCFAs), increasingly implicated in pathogenic processes extending beyond intestinal mucosa. This review outlines how these alternations compromise the epithelial barrier and immune regulation, increasing the risk of recurrent Clostridioides difficile infections to anemia, neuropsychiatric comorbidities, and extraintestinal manifestations. We critically evaluate emerging microbiota-targeted strategies, including fecal microbiota transplantation (FMT), live biotherapeutic products (LBPs), and precision postbiotics, positioning them as potential adjuncts to conventional immunosuppression. Finally, we discuss the current barriers to clinical translation, such as safety and heterogeneity, and propose a future framework for personalized, functionally integrated IBD care aimed at restoring long-term microbiota homeostasis. Full article

Fecal microbiota transplantation (FMT) has demonstrated potential in reshaping gut microbiota to improve animal phenotypes, yet its application in lean-type to obese-type pigs like Ningxiang (NX) pigs remains unclear. To address this, we investigated the effects of Lean Duroc × Landrace × Yorkshire (DLY) pig-derived fecal microbiota on the growth, gut microbiota composition, and serum metabolism of obese NX pigs. Thirty-six 50-day-old castrated male NX pigs of similar initial body weight were randomly assigned to either a control group or FMT group. The trial lasted for 35 days. Results indicated that FMT significantly improved the average daily gain and increased nutrient digestibility. Serum biochemical analysis revealed elevated levels of globulin and total protein and reduced low-density lipoprotein cholesterol in the FMT group. In addition, 16S rRNA sequencing demonstrated that FMT modified gut microbiota composition and diversity, enriching beneficial genera such as Blautia, Agathobacter, Faecalibacterium, and Eubacterium_coprostanoligenes_group. Untargeted serum metabolomics further revealed altered metabolite profiles linked to lipid and amino acid metabolism. Correlation analysis further revealed a link between these enriched bacteria and metabolites changes. Overall, these findings demonstrate that transplantation of the fecal microbiota from lean DLY pigs significantly improved the growth performance of obese NX pigs by improving nutrient digestibility and modulating the gut microbiota–host metabolic axis. Full article

Fucoidan improves host health by enriching beneficial taxa such as Bacteroides and Parabacteroides, yet the underlying mechanisms remain unclear. This study validated the association between these two genera and fucoidan-mediated mitigation of intestinal inflammation in mice. Subsequently, the effects of Parabacteroides goldsteinii and Bacteroides finegoldii were evaluated in colitis mice, and the contributions of microbiota-associated metabolites spermidine and betaine were investigated in vitro. Both strains reduced IL-6 (32–36%), TNF-α (30–37%), and IL-1β (40–45%) levels and increased levels of catalase (25–35%) and glutathione peroxidase (31–45%) in the colon. Mechanically, these strains suppressed activation of the NF-κB and MAPK pathways and preserved tight junction integrity by inhibiting myosin light chain kinase activation. These effects were associated with alterations of gut microbiota, characterized by decreased Proteobacteria and increased Bacteroidota, resulting in increased betaine (45–60%) and spermidine (90–112%). In vitro, betaine and spermidine alleviated LPS-induced inflammation and oxidative damage by regulating macrophage polarization. These results suggest that Bacteroides and Parabacteroides contribute to fucoidan-induced improvement of host health through betaine- and spermidine-related pathways. Future studies should clarify the origins of key metabolites and validate their causality and translational relevance using approaches such as fecal microbiota transplantation, metabolite tracing, and human-relevant systems. Full article

Chronic kidney disease (CKD), which affects over 850 million individuals globally, is increasingly regarded as a systemic condition in which the gut microbiota represents a key pathogenic node. This review provides an integrated overview of mechanistic, translational and clinical data implicating the gut–kidney axis in CKD. The CKD-associated microbiota displays a characteristic dysbiosis, marked by depletion of short-chain fatty acid–producing commensals, overgrowth of proteolytic and urease-expressing taxa and disruption of epithelial barrier integrity. These disturbances favor the generation and systemic accumulation of gut-derived uremic toxins, most notably indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid and trimethylamine-N-oxide, which promote endothelial dysfunction, vascular calcification, fibrosis and chronic inflammation, thereby hastening renal function loss and heightening cardiovascular risk. Microbiome-directed interventions, including dietary modification, prebiotics, probiotics, synbiotics, intestinal dialysis, fecal microbiota transplantation, gut-acting sorbents and nephroprotective phytochemicals, are summarized with emphasis on their effects on uremic toxin burden and clinical surrogates. System-level implications of the gut–kidney axis for cardiovascular disease, immunosenescence and sarcopenia are discussed, together with future priorities for integrating multi-omics profiling and precision microbiome-based strategies into nephrology practice. Full article

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care. Full article

Background and Objectives: Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with an increasing global incidence. Gut microbiota dysbiosis is believed to be playing a role in ASD pathogenesis. Fecal microbiota transplantation (FMT) is emerging as a potential therapeutic strategy to alleviate ASD-related and gastrointestinal symptoms, but data in pediatric ASD populations remain limited. Materials and Methods: We conducted a prospective, single-center, open-label controlled study to evaluate the efficacy of colonoscopic FMT in children with ASD. Participants were allocated to two groups: an intervention group that underwent a single FMT procedure and a control group. Gastrointestinal Symptoms Rating Scale (GSRS), Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Child Behavior Checklist (CBCL), and Parent Global Impression (PGI-R) scales were assessed for both groups at baseline and at set time points. Results: 30 participants were enrolled, with 15 in each group. At 8 weeks, no significant between-group differences were observed for the prespecified primary endpoint, change in ADOS scores. The intervention group showed significantly greater improvements in CARS (p < 0.001), PGI-R (p < 0.001), CBCL Internalizing Problems (p = 0.001), and GSRS (p = 0.037) compared with controls; CARS and PGI-R improvements persisted at 6 months. Within the intervention group, sustained improvements were noted in CARS, GSRS, and PGI-R up to 18 months. No serious adverse events were observed; three mild, self-limited adverse events were recorded following FMT. Conclusions: Colonoscopic FMT was associated with significant short-term improvements in gastrointestinal and caregiver-reported ASD symptoms (CARS), but not in ADOS scores. Some effects persisted long-term. However, due to a lack of blinding and possible selection bias, these findings should be interpreted as exploratory. Larger randomized controlled trials are needed to confirm efficacy and optimize protocols. Full article

The microbiota–gut–brain axis (MGBA) comprises a complex bidirectional communication network integrating neural, immune, metabolic, and endocrine pathways. Dopamine, traditionally viewed as a central neurotransmitter, also plays essential roles in the gastrointestinal (GI) tract, where it regulates motility, secretion, barrier homeostasis, and mucosal immunity. Growing evidence indicates that the gut microbiota significantly contributes to intestinal dopamine metabolism through specialized enzymatic pathways, particularly tyrosine decarboxylase in Enterococcus species and catechol dehydroxylase in Eggerthella species. These microbial reactions compete with host processes, alter dopaminergic tone, and degrade orally administered levodopa (L-DOPA), providing a mechanistic explanation for the variability in treatment response in Parkinson’s disease (PD). Beyond PD, microbially mediated alterations in dopaminergic signaling have been implicated in mood disorders, neurodevelopmental conditions, metabolic dysfunction, and immune-mediated diseases. This review synthesizes current mechanistic and translational evidence on the dopamine–microbiota interface, outlines microbial pathways shaping dopaminergic activity, and highlights therapeutic opportunities including microbiota modulation, dietary strategies, fecal microbiota transplantation, and targeted inhibitors of microbial dopamine metabolism. Understanding this interface offers a foundation for developing personalized approaches in neurogastroenterology and neuromodulatory therapies. Full article

Cheese is a complex fermented dairy food containing bioactive nutrients and microorganisms that can influence host physiology. However, most existing evidence of its health effects derives from observational studies or investigations of isolated components rather than the whole food matrix. The present study examined the impact of low-fat Cheddar cheese as a whole food on the gut microbiota using a human microbiota–associated (HMA) mouse model. Germ-free C57BL/6 mice were colonized with human fecal microbiota and randomly assigned to either a control diet or a diet supplemented with low-fat Cheddar cheese (7.5% w/w) for six weeks. Fecal samples were collected longitudinally and analyzed by 16S rRNA gene (V3–V4 region) amplicon sequencing. Human microbiota transplantation successfully established a stable, human-like gut microbial community in the mice. Cheese supplementation significantly increased alpha diversity (Shannon and Chao1 indices) and altered microbial composition, characterized by a higher relative abundance of Firmicutes and a reduction in Bacteroidetes (p < 0.001). At the genus level, Lactococcus and Streptococcus were enriched in cheese-fed mice, reflecting potential viable transfer of cheese-derived lactic acid bacteria. These findings provide experimental evidence that low-fat Cheddar cheese can beneficially influence the human-derived gut microbiota in an animal model and highlight the need for further clinical research to validate these effects in humans. Full article

Background/Objectives: The pathogenesis of ulcerative colitis (UC) is complex, and there is an urgent need for effective therapeutic agents with low side effects. Recent studies highlight the critical roles of abnormal bile acid (BA) metabolism and gut microbiota dysbiosis in UC progression. However, there is a significant knowledge gap about the relation between BA and gut microbiota. The BA derivative T3K exerts good anti-UC effect, and its mechanism is still unknown. In this study, we investigate how its anti-UC mechanism is involved in the modulation of the gut microbiota-BA axis and BA metabolism. Methods: Gene expression microarray GSE92415 of UC from the Gene Expression Omnibus was used to analyze BA metabolism. DSS-induced colitis mouse model, Caco-2 and IEC6 cells were used to confirm the anti-UC of T3K using intestinal permeability assay with FITC, Western-blot, immunohistochemical staining, immunofluorescenc and so on in vitro and in vivo. The changes in bile acid and microbiota were measured by 16S rRNA sequencing and bile acid analysis combined with pseudo-germ-free (PGF) models and fecal microbiota transplantation (FMT). Results: T3K demonstrated strong therapeutic effects, including reduced weight loss, lower disease activity index (DAI), and increased colon length. T3K also enhanced the expression of Occludin and Mucin2, and restored gut barrier integrity. Furthermore, T3K improved intestinal dysbiosis and abnormal BA metabolism in colitis mice. Through PGF models and FMT, we confirmed that T3K modulates BA metabolism via the gut microbiota. T3K specifically promotes the growth of beneficial bacteria, such as Akkermansia muciniphila, increases levels of hydrophilic BAs like muricholic acid (MCA), lithocholic acid (LCA) and its derivatives isoLCA and then repairs damaged intestinal mucosa. Conclusions: Bile acid derivative T3K, as a potential anti-UC candidate, effectively restores gut barrier integrity and then ameliorates colitis by improving gut microbiota composition and regulating BA metabolism, including increasing hydrophilic BAs. Full article

Background/Objectives: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, with its development influenced by diet, obesity, and gut microbiota (GM) alterations. This study aimed to evaluate the impact of human fecal microbiota transplantation (FMT) on the progression of CRC in a murine model. Methods: CRC was chemically induced in BALB/c mice using azoxymethane/dextran sulfate sodium (AOM/DSS). Mice were transferred with GM via FMT and divided into two experimental groups according to the microbiota source (healthy donors or CRC patients). A positive control group (AOM/DSS without FMT) and a negative control group (no CRC induction or FMT) were included. Clinical parameters, histopathological analyses, and cytokine profiling were performed. Results: Mice receiving FMT, particularly from CRC patients, exhibited increased mitotic activity, dysplasia, neoplastic proliferation, structural alterations in the colon, and more pronounced GALT hyperplasia. At the immunological level, both FMT groups (healthy and CRC-derived) showed modulation of IL-1β, IL-4, IL-6, IL-10, IL-17A, and TNF-α compared to the positive control. Conclusions: Human GM transplantation modulated the colonic microenvironment through histopathological and immunological changes, influencing CRC progression in this murine model. These findings highlight the role of GM in shaping CRC development and suggest that human-derived microbiota may significantly impact tumor dynamics. Full article

Alcohol-associated liver disease, particularly severe alcoholic-associated hepatitis (AH), remains a major cause of morbidity and mortality worldwide. Conventional treatments, including corticosteroids, offer limited short-term benefit and are contraindicated in many patients, necessitating exploration of alternative therapies. Fecal microbiota transplant (FMT) has emerged as a novel therapeutic intervention, targeting the gut–liver axis that is disrupted in AH. This review synthesizes the current literature on FMT in the management of alcohol-induced liver injury, examining its pathophysiological basis, clinical efficacy, and implementation challenges. Dysbiosis and increased gut permeability in patients with alcohol use disorder contribute to systemic endotoxemia and hepatic inflammation. FMT aims to restore microbiota diversity and gut barrier integrity, mitigating the progression of liver injury. Some clinical trials have demonstrated encouraging survival benefits and modulation of gut microbiota composition in patients with severe AH. These studies report improved one-year survival rates and reductions in pathogenic bacterial taxa following FMT. However, the field remains nascent, with unresolved questions regarding optimal donor selection, sample preparation, administration routes, and long-term safety. Despite limited large-scale randomized data, FMT shows potential as an adjunct or alternative to existing therapies. Continued research is needed to establish standardized protocols and fully elucidate its role in the treatment algorithm for AH. Given the high mortality associated with untreated severe AH and limitations of current therapies, FMT represents a promising frontier in the management of alcohol-associated liver disease. Full article

Given the limited efficacy of current interventions and the complexity of chronic pain, identifying perpetuating factors is crucial for uncovering new mechanistic pathways and treatment targets. The oral and gut microbiome has emerged as a potential modulator of pain through immune, metabolic, and neural mechanisms. Contemporary evidence indicates that chronic pain populations exhibit altered oral and gut microbiota, characterized by reduced short-chain fatty acid (SCFA)-producing taxa and an overrepresentation of pro-inflammatory species. These compositional changes affect metabolites such as SCFAs, bile acids, and microbial cell wall components, which interact with host receptors to promote peripheral and central sensitization. Microbiota-derived metabolites modulate peripheral sensitization by altering nociceptive neuron excitability and stimulating immune cells to release pro-inflammatory cytokines that increase blood–brain barrier permeability, activate microglia, and amplify neuroinflammation. Activated microglia further disrupt the balance between excitatory and inhibitory neurotransmission by enhancing glutamatergic activity and weakening GABAergic signaling, thereby contributing to the induction and maintenance of central sensitization. While observational studies establish associations between dysbiosis and chronic pain, animal models and early human fecal microbiota transplantation studies suggest a potential causal role of dysbiosis in pain, although human evidence remains preliminary and influenced by diet, lifestyle, and comorbidities. Overall, microbiota appears to regulate pain via peripheral and central mechanisms, and targeting it through specific interventions, such as dietary modulation to enhance SCFA production, alongside broader lifestyle measures like sleep, physical activity, stress management, and oral hygiene, may represent a new therapeutic strategy for the management of chronic pain. Full article

The microbiota–gut–organ axis is widely recognized as a pivotal mediator of systemic health, primarily through gut-derived immune, metabolic, and inflammatory signaling. Fucoidans, a class of fucose-containing sulfated polysaccharides predominantly composed of L-fucose and exclusively found in brown seaweeds, have been demonstrated to modulate gut microbiota composition and function, resulting in the enrichment of beneficial bacteria and the suppression of harmful species. They enhance the production of beneficial metabolites, such as short-chain fatty acids and specific bile acids, while suppressing harmful metabolites, including lipopolysaccharide, thereby ameliorating organ damage via key mechanisms such as the mitigation of oxidative stress and inhibition of inflammatory responses. Furthermore, fucoidan supplementation was found to restore intestinal barrier integrity. Using disease models including Parkinson’s disease, alcoholic liver disease, diabetic kidney disease, and obesity, the mechanisms through which fucoidans ameliorate extraintestinal diseases via the microbiota–gut–organ axis were elucidated. Microbiota-dependent mechanisms have been confirmed via experimental approaches such as fecal microbiota transplantation and specific bacterial strain supplementation. Fucoidans represent promising prebiotic agents for the restoration of microbial ecology and the treatment of extraintestinal diseases, highlighting the need for further clinical investigation. Full article

The interplay between the oral and gut microbiota and systemic health has garnered significant attention in recent years, particularly concerning hematological malignancies. Multiple myeloma and other hematological cancers are characterized by immune dysfunction, creating a bidirectional relationship with microbial communities. Dysbiosis, defined as an imbalance in microbial composition, may influence disease progression, treatment response, and overall prognosis. This narrative review is based on a non-systematic search of PubMed and Scopus (2010–2024) using terms related to oral microbiota, gut microbiota, dysbiosis, hematological malignancies, multiple myeloma, immune modulation, and treatment-related complications. Studies were selected for relevance to pathogenesis, immune regulation, clinical implications, and therapeutic interactions. As this is a narrative review, no quantitative synthesis or formal grading of evidence strength was performed; findings are therefore interpreted qualitatively based on the available literature. The role of microbial-derived metabolites, their effects on immune modulation, and their potential as biomarkers for disease and treatment outcomes have been explored. Specific attention is given to the implications of dysbiosis in chemotherapy-induced complications, such as mucositis and infections, and emerging therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation. Additionally, the influence of anticancer therapies on microbial ecosystems has been highlighted and the bidirectional impact of host–microbe interactions in shaping disease trajectory has been discussed. Understanding these complex interactions could lead to novel diagnostic and therapeutic approaches, ultimately improving patient outcomes. This review aims to provide clinicians and researchers with a comprehensive overview of current knowledge and future perspectives on the role of oral and gut microbiota in the context of hematological malignancies. Full article

Background: Obesity has emerged as a significant public health challenge largely attributed to excessive dietary fat consumption. A growing body of evidence indicates that soluble dietary fiber (SDF) can prevent high-fat-diet (HFD)-induced obesity by modulating the gut microbiota. Our previous studies have shown that SDF derived from highland barley bran exhibits favorable lipid-lowering activity in vitro, but its lipid-lowering effect in vivo remains to be elucidated. Methods: This study aimed to investigate the lipid-lowering effects of SDF from highland barley bran in HFD-fed mice based on the gut microbiota. Mice were fed an HFD, and the intervention effects of SDF on hepatic lipid metabolism and its underlying molecular mechanisms were systematically evaluated using liver lipidomics, 16S rDNA sequencing, molecular biological techniques, and fecal microbiota transplantation (FMT). Results: Liver lipidomics analysis revealed that potential lipid biomarkers responsive to barley bran-derived SDF included phosphatidylethanolamines (PE, 18:2–20:3), phosphatidylserine (PS, 18:0–18:2), and PS (18:1–22:3). Furthermore, SDF modulated the composition and structure of the gut microbiota in HFD-fed mice. Notably, SDF increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Dubosiella, as well as elevated SCFA levels. Conclusions: The increase in SCFAs activated the hepatic AMP-activated protein kinase α (AMPK) signaling pathway, thereby ameliorating HFD-induced disturbances in lipid metabolism, reducing hepatic lipid accumulation, and lowering serum lipid concentrations. Full article