Search Results (582)

The respiratory tract is a dynamic biological interface where microbiome, environmental exposure, epithelial integrity, and host metabolic regulation converge to maintain pulmonary homeostasis. Once considered sterile, the lung is now recognized as a low-biomass yet structured microbial ecosystem that contributes to immune calibration, colonization resistance, epithelial barrier function, and tissue resilience. Disruption of this equilibrium, known as pulmonary dysbiosis, has been increasingly associated with acute and chronic lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, idiopathic pulmonary fibrosis, asthma, bronchiectasis, and lung cancer. In parallel, mitochondria have emerged as central regulators of pulmonary cell function, extending beyond ATP production to control redox signaling, apoptosis, innate immunity, epithelial repair, and inflammatory responses. This review examines the bidirectional crosstalk between the respiratory microbiome and mitochondria as an integrated pathogenic axis in lung disease. Dysbiotic microbial communities and respiratory pathogens can induce mitochondrial stress through toxins, virulence factors, microbial metabolites, and pattern-recognition receptor activation, leading to mitochondrial alteration and the release of mitochondrial damage-associated molecular patterns. Conversely, dysfunctional mitochondria reshape the pulmonary microenvironment by altering oxygen consumption, nutrient availability, cytokine production, redox balance, and barrier repair, thereby favoring pathogen persistence and chronic inflammation. Understanding mitochondria–microbiome interactions may support precision medicine strategies that integrate microbial, metabolic, inflammatory, and bioenergetic biomarkers to improve the diagnosis, prognosis, and treatment of inflammatory-related lung diseases. Full article

(1) Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with gut microbiota dysbiosis and metabolic perturbations. Although Liubao tea (LBT) has gastroprotective benefits, the precise mechanisms by which LBT extract (LBTE) alleviates UC by orchestrating microbial and metabolic homeostasis remain poorly understood. (2) Methods: A DSS-induced UC mouse model was used to evaluate LBTE efficacy. Serum pharmacochemistry, untargeted metabolomics, 16S rRNA sequencing, and targeted SCFA metabolomics were integrated to characterize absorbable active constituents, metabolic shifts, and gut microbiota landscapes. SCFA- and arachidonic acid metabolism-related targets were validated by RT-qPCR and Western blotting. PGF models and FMT were used to assess the causal role of gut microbiota in LBTE-mediated efficacy. (3) Results: LBTE preserved colon length and mucosal integrity while reducing IL-6, TNF-α, IL-1β, and oxidative stress. It enriched SCFA-producing genera and increased colonic butyric and valeric acids, activating GPR41/GPR109A signaling, upregulating ZO-1 and occludin, and strengthening the intestinal barrier. LBTE also downregulated PTGS2 and ALOX5, restored PTGS1 and CYP3A11, and inhibited NF-κB signaling. These effects were weakened in PGF mice but reproduced by FMT from LBTE-treated donors, confirming microbiota-dependent protection. (4) Conclusions: LBTE may serve as a complementary strategy for UC prevention and management. Full article

Background: To date, several studies have confirmed the fact that over 700 species of microbiota interacts with host, modulating immunity, controlling the homeostasis environment, and thus maintaining systemic condition. Dysbiosis in the subgingival biofilm can initiate chronic inflammation of the gingiva, potentially progressing to periodontitis. Advances in DNA sequencing analysis of the subgingival microbial community have shown that periodontal treatment causes a microbial shift in subgingival plaque, affecting the taxonomic composition (disease- and health-associated taxa). Yet, none of these have been investigated in Indonesia. Objective: The objective was to profile the composition of oral microbiome in Indonesian population with healthy, gingivitis, and periodontitis status. Further, we analyzed the subgingival bacterial alteration following the therapy in periodontitis group. Methods: Twelve subjects consisting of healthy, gingivitis, and periodontitis patients were included. Additionally, the periodontitis group was observed at baseline, 1-month, and 3-month. Subgingival dental plaque were sampled and 16S rRNA NGS analysis was performed. Alpha (Chao1, Shannon, and Simpson indices) and beta diversity (PCoA plots based on Bray–Curtis dissimilarity) were observed. Microbiota composition at the genus and species levels was analyzed. Results: No statistically significant differences (p > 0.05) were found for Chao1, Shannon, and Simpson indices amongst groups and in periodontitis patients across the observation. At the genus level, PCoA plots based on Bray–Curtis dissimilarity revealed that the clinical status accounted for 21.9% of the total variation (R² = 0.219, p = 0.197), while at the species level, it accounted for 19.8% (R²= 0.198, p = 0.281). Periodontitis samples across all timepoints showed no distinct clustering at either the genus 7.6% (R² = 0.076 p = 0.097) or species levels 9.7% (R² = 0.097 p = 0.995). Top five subgingival microbiota at the genus and species levels in all groups showed definite pattern of composition. Although no significant association was found (p > 0.05), it described that Veillonella parvula, Campylobacter gracilis, and Capnocytophaga granulosa were more abundant in healthy subjects than in gingivitis and periodontitis. Prevotella oris and Selenomonas noxia were less abundant in healthy subject than in gingivitis and periodontitis. In periodontitis subjects, Prevotella intermedia was increased by the therapy at 1 month and reduced again at 3 months. On the other hand, Capnocytophaga granulosa was increased by the therapy at 1 and 3 months. Hoylesella loescheii was reduced by the time. Porphyromonas gingivalis was reduced at 1 month and increased again at 3 months. Discussion: The result showed that the number of alpha diversity was notably higher in the gingivitis and periodontitis groups compared to health group, supporting a trend toward increased community richness and evenness in diseases states. The microbial richness and evenness remained relatively stable across the evaluated periods within periodontitis cohort. Oral microbial composition defines the periodontal status and disease. More abundance of Red Complex bacteria is associated with disease-associated condition. Pathogen re-colonization may occur 3 months after the therapy. Conclusions: These findings suggest that maintaining health-associated microbiome may be beneficial to the clinical status. Periodontal recall may be addressed from 1 to 3 months after the therapy to avoid bacterial re-colonization. Suppressing bacterial dysbiosis and regulating periodontal homeostasis are the main key in managing periodontal treatment. Full article

Antibiotic-induced dysbiosis can cause persistent alterations in gut microbial composition and fermentative metabolism, yet the long-term role of mushroom β-glucan-based prebiotics in supporting post-antibiotic microbiota modulation remains poorly defined. To address this gap, the present study evaluated the modulatory effects of ColonX, a mushroom β-glucan-based formulation, during a 60-day in vitro simulation of post-antibiotic gut microbiota modulation. Quantitative PCR (qPCR) was used to monitor key bacterial groups, while UHPLC-DAD analysis was applied to characterize fermentation-derived organic acids. ColonX administration produced a selective, time-dependent increase in Bifidobacterium spp., with limited effects on Lactobacillus spp. and no stimulation of opportunistic bacteria such as Escherichia coli. This response became more evident after prolonged administration, suggesting progressive adaptation of the dysbiotic microbiota. Metabolomic analysis showed increased production of short-chain fatty acids and other fermentation-derived organic acids, indicating enhanced saccharolytic activity and functional metabolic remodeling. The accumulation of succinic acid further suggested ongoing microbial metabolic restructuring during recovery, while comparison with individual excipients indicated that resistant dextrin contributed to the fermentative response. Overall, this study addresses an important gap by linking prolonged mushroom β-glucan administration with both taxonomic modulation and functional metabolic recovery markers in a post-antibiotic dysbiosis model. These findings support ColonX as a promising nutraceutical strategy to promote gut microbiota restoration following antibiotic exposure. Full article

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic metabolic disorders. However, the mechanisms underlying CIH-induced intestinal dysfunction remain unclear. In this study, we investigated the effects of CIH on intestinal barrier integrity, gut microbiota, and host metabolism using a multi-omics approach. Male C57BL/6J mice were exposed to six weeks of CIH or normoxia. Colonic barrier integrity was assessed by histological and molecular analyses. Gut microbiota was profiled by full-length 16S rRNA gene sequencing. Untargeted metabolomics was performed on fecal and serum samples, followed by integrated microbiome–metabolome analysis. CIH markedly impaired colonic barrier integrity, as evidenced by disrupted crypt architecture, reduced goblet cell abundance, and decreased expression of ZO-1, Occludin, and Claudin-5. CIH also induced gut microbial dysbiosis, characterized by depletion of the beneficial mucin-associated bacterium Akkermansia muciniphila and enrichment of several anaerobic taxa. Metabolomic analysis revealed opposite alterations of PC (20:2/0:0) and LysoPE (20:5/0:0) between feces and serum, whereas melatonin was consistently decreased in both compartments. Integrated multi-omics analysis further revealed close associations between microbial dysbiosis and metabolic remodeling. Collectively, these findings demonstrate that CIH disrupts intestinal homeostasis through coordinated alterations in barrier integrity, gut microbiota composition, and host metabolism, providing new insights into the intestinal mechanisms underlying OSA-associated systemic dysfunction. Full article

High-throughput metagenomic sequencing and advances in mucosal immunology have refuted the traditional physiological concept of a sterile respiratory tract. The oral cavity has been recognized as a dynamic determinant of systemic health. As in other parts of the body, recent studies also suggest that pulmonary health may be linked to oral health. Under eubiotic conditions, the oral microbiome maintains local immunological homeostasis and colonization resistance. Oral dysbiosis, characterized by sequential shifts in microbial communities and the proliferation of the pathogenic red complex (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia), induces a state of chronic systemic inflammation, potentially involved in an infectious axis between the oral cavity and the lung. This review evaluates the tripartite systemic pathways of metastatic infection, metastatic injury, and metastatic inflammation that govern the translocation of oral pathobionts and their bioactive components, including lipopolysaccharides, outer membrane vesicles, and matrix metalloproteinases, to the lower respiratory tract via microaspiration and hematogenous circulation. The clinical implications across the chronic respiratory disease spectrum are examined, with a focus on how deficits in oral microbial diversity influence chronic obstructive pulmonary disease (COPD) pathogenesis, modulate the pulmonary virome and mycobiome, and stimulate maladaptive trained immunity. Furthermore, the contribution of biological aging is assessed, highlighting the roles of immunosenescence, inflammaging, and physiological reflex decline within the broader mucosal continuum. Finally, the clinical translation of this axis is analyzed, emphasizing the integration of saliva-based point-of-care nano-theranostics, metatranscriptomic profiling, and targeted interventions—such as professional oral biofilm management in intensive care settings and precision microbiome engineering—to preserve respiratory function and restore immune homeostasis. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disorder characterized by intestinal inflammation and gut microbiota dysbiosis, but current therapies remain limited by adverse effects and suboptimal long-term efficacy. Methods: Here, using a dextran sulfate sodium (DSS)-induced mouse model of IBD-like colitis, we investigated the protective effects of Yakuchinone B (YB)—a diarylheptanoid derived from Alpinia oxyphylla with reported anti-inflammatory and antioxidant activities—against inflammatory bowel disease (IBD). Results: YB supplementation significantly alleviated colitis symptoms, as evidenced by reduced body weight loss, lower disease activity index scores, attenuated colonic shortening, and ameliorated histopathological damage. YB also decreased the colonic and serum levels of TNF-α, IL-1β, and IL-6. Microbiome profiling showed that YB restored gut microbial diversity and reshaped microbial composition, with increased abundances of Alistipes and Duncaniella and reduced overgrowth of Akkermansia. Untargeted metabolomics revealed that YB modulated colitis-associated pathways, including purine metabolism, alanine, aspartate, and glutamate metabolism, and steroid hormone biosynthesis. Targeted analysis further showed that YB increased acetate, propionate, and butyrate levels. Conclusions: These results collectively suggest that YB ameliorates DSS-induced colitis by attenuating inflammation, associated with modulation of the gut microbiota-host metabolism axis, and promoting short-chain fatty acid production, supporting its potential as a promising functional dietary candidate for IBD management. Full article

Bioactive peptides (BPs) are increasingly recognized for modulating the gut microbiome, metabolome, and brain function via the gut–brain axis. Kapi-pla, a traditional Thai fermented freshwater fish paste rich in proteins and peptides, is widely consumed in Southern Thailand. This study profiled the peptides of Phatthalung Kapi-pla (PK) and Songkhla Kapi-pla (SK) and investigated their impacts on gut microbiota and metabolome using a simulated colonic fermentation model with fecal samples from patients with Alzheimer’s disease (AD). Microbial composition and metabolites were assessed by 16S rRNA sequencing and LC–MS/MS, respectively. After 24 h fermentation, PK modestly increased Shannon diversity relative to the unsupplemented control, with richness indices unchanged, reduced Proteobacteria abundance and opportunistic pathogens such as Escherichia–Shigella and Klebsiella, and selectively increased short- and branched-chain fatty acids, including acetate, propionate, butyrate, and iso-valerate. PK further enhanced neuroactive metabolites relevant to AD pathology, underscoring its potential as a functional food ingredient to ameliorate AD-associated dysbiosis and support gut–brain axis health. Full article

Obesity is a chronic metabolic disorder closely associated with dyslipidemia, insulin resistance, low-grade inflammation, and gut microbiota dysbiosis. Mulberry leaves are rich in bioactive proteins, but whether mulberry leaf albumin-type protein can improve diet-induced obesity remains unclear. In this study, ultrafiltered mulberry leaf albumin-type protein (UMP) was prepared and its anti-obesity effects were evaluated in high-fat diet (HFD)-fed C57BL/6J mice. UMP contained 87.12 ± 0.52 g/100 g protein, 2.52 ± 0.00 g/100 g polyphenols, and 8.21 ± 1.49 g/100 g polysaccharides, with two major albumin-type protein bands of approximately 14 and 52 kDa. Structural analysis showed that UMP was mainly composed of β-turns and α-helices. In HFD-fed mice, daily administration of UMP for 16 weeks reduced body weight gain by 3.85 g and 5.63 g in the low- and high-dose groups, respectively, without affecting food intake. Biochemical assays, glucose and insulin tolerance tests, and histological analysis showed that UMP improved insulin responsiveness, alleviated serum dyslipidemia, reduced hepatic lipid accumulation, and decreased circulating alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide levels. Histological analysis and nuclear magnetic resonance-based short-chain fatty acid quantification further showed that UMP protected colonic morphology and increased colonic short-chain fatty acid levels. Gut microbiota analysis showed that UMP restored microbial diversity, reduced the Firmicutes/Bacteroidota ratio, and enriched potentially beneficial genera, including Ileibacterium and norank_f_Muribaculaceae. Fecal biochemical assays suggested that UMP promoted fecal free fatty acid excretion and partially improved bile acid-related metabolic alterations. Untargeted serum metabolomics revealed that UMP reshaped metabolic pathways related to lipid turnover, bile acid signaling, glucose utilization, and glucuronidation. Correlation analysis linked UMP-enriched bacterial taxa with key metabolites involved in fatty acid and energy metabolism. Together, these findings indicate that UMP attenuates HFD-induced obesity through coordinated regulation of gut microbiota, intestinal metabolites, and systemic metabolic homeostasis. UMP may therefore represent a promising functional dietary protein for the prevention of obesity-related metabolic disorders. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that arises from a complex interplay of genetic susceptibility, immune dysregulation, environmental exposures, and altered host–microbiome interactions. Increasing evidence identifies the gut microbiota as a central component of IBD pathogenesis. In healthy individuals, the intestinal microbiota supports epithelial integrity, metabolic homeostasis, immune education, colonization resistance, and bidirectional gut–brain communication. In IBD, this ecosystem is disrupted by reduced microbial diversity, expansion of pathobionts, and broader functional alterations affecting community stability and metabolic output. Importantly, these changes are increasingly viewed not merely as consequences of inflammation, but as active contributors to disease development and persistence. Dysbiosis may also influence neuroimmune signaling through the gut–brain axis, linking microbial metabolites, intestinal barrier dysfunction, enteric nervous system activity, and psychological comorbidities frequently observed in patients with IBD. This review provides a comprehensive overview of the role of the gut microbiota in IBD, beginning with its physiological functions in intestinal homeostasis and the evidence linking dysbiosis to disease pathogenesis, followed by a critical evaluation of current microbiome-based therapeutic strategies, their translational challenges, and prospects for personalized microbiota-directed interventions. Approaches such as fecal microbiota transplantation (FMT), probiotics, live biotherapeutic products, and genetically engineered bacteria aim to restore microbial balance and modulate intestinal inflammation. Among these, FMT has provided the strongest proof-of-concept for microbiome restoration, whereas probiotic efficacy remains variable and strain-dependent. Emerging defined microbial consortia and engineered bacterial platforms offer improved standardization and mechanistic precision, but their clinical application remains limited by challenges related to engraftment, durability of response, safety, and treatment optimization. Collectively, current evidence supports gut microbiota as both a key determinant of IBD pathogenesis and a promising therapeutic target, underscoring the need for more precise and personalized microbiota-directed approaches in IBD management. Full article

Background: Dysbiosis, mucosal inflammation and increased intestinal permeability have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Objective: To evaluate the effectiveness of a sequential butyrate–probiotic administration in reducing symptoms and improving stool consistency in patients with diarrhea-predominant (IBS-D) or mixed-type IBS (IBS-M). Methods: Two hundred adult patients were allocated to intervention (n = 105) or control (n = 95). The intervention group received ColonLife formulation (Εuro-Pharma S.r.l., Torino—Italy), consisting of two distinct capsules: the first containing butyric acid and grapefruit seed extract, and the second containing microencapsulated probiotic strains together with fructooligosaccharides (FOSs). Symptom severity, quality of life and stool consistency (Bristol Stool Scale) were assessed at baseline and three follow-up visits. Results: Baseline characteristics were comparable between groups (p > 0.05). Diarrhea severity decreased significantly in the intervention group (3.78 ± 1.01 to 3.31 ± 1.21; Δ − 0.47) compared with minimal change in controls (3.71 ± 1.05 to 3.62 ± 1.14; Δ − 0.08; p = 0.015). Stool consistency improved more in the intervention group (−1.18 ± 1.46 vs. −0.64 ± 1.41; p = 0.028), with normal stools increasing from 1.0% to 65.7% versus 4.2% to 36.8% in controls (p < 0.001). The degree of change in pain scores was similar between the two groups (p > 0.05). The degree of reduction in bloating scores was also similar between groups (p > 0.05). Quality of life improved in both groups (intervention: +0.68 ± 1.43; control: +0.71 ± 1.64; both p < 0.01), with no significant difference between groups (p > 0.05). Conclusions: Sequential butyrate–probiotic administration significantly improves diarrhea, stool consistency and gastrointestinal symptoms in IBS-D and IBS-M, supporting its role as a microbiota-targeted treatment. Full article

Excessive consumption of ultra-processed foods (UPFs) containing non-nutritive sweeteners (NNS) has been implicated in inflammatory bowel disease (IBD), yet the effects of erythritol on intestinal inflammation remain poorly understood. In this study, we assessed NNS-containing UPF exposure in patients with IBD and healthy controls, and then investigated the effects of erythritol in a dextran sulfate sodium (DSS)-induced colitis. Food frequency questionnaire (FFQ) results showed that patients with IBD, particularly those with active disease, had a higher proportion of NNS-containing UPF categories among total UPFs consumed. In mice, erythritol administration exacerbated DSS-induced colitis, as evidenced by sustained body weight loss, increased disease activity index, impaired intestinal barrier integrity, and elevated inflammatory cytokine expression. Transcriptomic analysis revealed significant enrichment of ferroptosis-related pathways in the colonic mucosa of erythritol-treated colitic mice. Furthermore, erythritol markedly altered gut microbial composition, characterized by increased abundance of potentially pathogenic bacteria and enrichment of Alistipes sp. CHKCI003. Untargeted metabolomics demonstrated alteration of tryptophan metabolism. Consistently, erythritol aggravated depression-like behavior in DSS-induced mice. Collectively, these findings suggest that erythritol exacerbates experimental colitis and depression-like behavior, potentially through microbiota dysbiosis, ferroptosis-associated alterations, and disrupted tryptophan metabolism. Full article

Background: Growing interest in the gut mycobiome has renewed focus on Candida spp. in inflammatory bowel disease (IBD). Yet, fecal detection remains difficult to interpret, given its uncertain relationship with intestinal inflammation. This narrative review synthesizes historical, mechanistic, observational, and interventional evidence to distinguish colonization, relative abundance, mucosal invasion, virulence transitions, and potential contributions to IBD. Methods: PubMed, Scopus, the Cochrane Library, and Google Scholar were searched, focusing on human studies and major mechanistic or interventional contributions. The final synthesis included 43 studies, 41 research articles, and two historical monographs. Results: Fungal alterations in IBD are heterogeneous and method-dependent across studies. Longitudinal cohorts have associated increased relative abundance of the genus Candida with active disease, but findings have not been consistently replicated across populations. Experimental evidence suggests that fungal expansion, morphology, and strain-specific virulence may trigger inflammation in selected settings, although stool sequencing cannot establish viability, invasion, morphology, or causality. Antifungal therapy, fecal microbiota transplantation, and nutraceutical approaches may modify microbial or inflammatory markers, but consistent clinical benefits remain unproven. Conclusions: Fecal detection of Candida spp. should generally be interpreted as a context-dependent signal of disrupted bacterial–fungal–immune interactions, not as evidence of infection or a compelling indication for antifungal treatment. Full article

Background: Diets high in fat and carbohydrates, like fructose, trigger colon inflammation, increase intestinal permeability, and drive dysbiosis. However, the effects of obesogenic diets on gut microbiota, including Clostridium and Bacteroides, remain unknown. Understanding how these diets damage the colon is critical. Methods: Using a controlled preclinical obesity model, we compared the effects over time of High-Fat Diet (HFD), High-Fructose Diet (HFrD), and their combination (HFHFrD). Diet-induced dysbiosis was assessed at 4 and 8 weeks via qPCR using primers specific to bacterial phyla and species. In addition, intestinal inflammation, atrophy, and mucin production were evaluated by digital pathology after 8 weeks of diet exposure. Results: both HFrD and HFHFrD mice exhibited marked intestinal inflammation, atrophy, and damage, alongside altered production of neutral and mixed mucins. HFD-fed mice displayed a 15-fold surge in Clostridium/Bacteroides ratio at 4 weeks. At 8 weeks, HFrD-fed mice showed a striking 10-fold rise in microbial relative abundance compared to the other diets. Both HFrD and HFHFrD triggered an early increase in Bacteroides species, but significance emerged only at 8 weeks. Conclusions: Although all obesogenic diets induced inflammation, atrophy, epithelial damage, and altered mucin patterns, HFrD and HFHFrD caused pronounced disruptions to barrier function and dysbiosis. Critically, HFD consistently raised the Firmicutes/Bacteroidetes ratio at 4 and 8 weeks, while the Clostridium/Bacteroides ratio spiked only at 4 weeks. Obesogenic diets fundamentally shifted microbial load and diversity. Therefore, bacterial ratios, such as Clostridium/Bacteroides, may signal dysbiosis and tissue damage from obesogenic diets, but further research is required for confirmation. Full article

Cheonggukjang (CGJ) exerts anti-obesity and lipid-lowering effects; however, its effects on gut microbiota-derived short-chain fatty acid (SCFA) production, adipose G protein-coupled receptor (GPCR) expression, and the mechanistic associations between them have not been investigated. Thus, the current study aimed to investigate these relationships in relation to lipid metabolism in white adipose tissue (WAT). Two distinct CGJ samples were administered to high-fat/high-cholesterol diet-induced (HCFD) obese mice. CGJ slightly lowered body weight gain and significantly improved dyslipidemia and hepatic lipid accumulation, also improving WAT lipid metabolism-related gene expression. Additionally, CGJ reversed gut microbiota dysbiosis, increased the abundance of genera associated with SCFA production, and increased colonic SCFA levels. Adipose Gpr41 and Gpr109a expressions were upregulated, and their mRNA levels were strongly correlated with systemic lipid indicators and WAT lipid-metabolism genes. To the best of our knowledge, this is the first study to provide evidence that CGJ modulates gut microbiota-derived SCFA levels and elevates adipose GPCR gene expression, suggesting that CGJ may exert anti-obesity and lipid-metabolism-alleviating effects through the gut microbiota–SCFA–adipose GPCR–WAT lipid metabolism axis. Full article