Search Results (18)

Background/Objectives: High-fat-diet (HFD) consumption drives chronic liver injury via gut dysbiosis and metabolic disturban. Apple cider vinegar, rich in polyphenols and organic acids, shows potential in metabolic regulation. This study aimed to investigate whether apple cider vinegar powder (ACVP) alleviates HFD-induced liver injury by modulating the gut–liver axis. Methods: For 12 weeks, C57BL/6 J mice received daily ACVP gavage while being fed a HFD. A series of biological assessments were conducted, including systemic metabolic evaluations (body weight, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and lipid/glucose levels), hepatic steatosis (hematoxylin and eosin (H&E) staining), intestinal microbiome characterization (16S rRNA gene genomic analysis), and comprehensive metabolite profiling of cecal contents (non-targeted metabolomics). Pearson correlation networks integrated multi-omics data. Results: ACVP attenuated HFD-induced weight gain by 26.3%, hepatomegaly and dyslipidemia, as well as reduced hepatic lipid vacuoles and serum ALT (48%)/AST (21.5%). ACVP restored gut microbiota diversity, enriching Muribaculaceae. Cecal metabolomics identified 38 HFD-perturbed metabolites reversed by ACVP, including indolelactate, hyocholate, and taurocholic acid. the Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed ACVP-mediated recovery of linoleic acid metabolism. Correlation networks linked Akkermansia to anti-inflammatory metabolites (e.g., trans-ferulic), while Desulfobacterota correlated with pro-inflammatory oxylipins (e.g., 12,13-dihydroxy-9Z-octadecenoic acid (DHOME)). Conclusions: ACVP mitigates HFD-induced liver injury by remodeling gut microbiota, restoring microbial metabolites, and enhancing gut–liver crosstalk. Full article

Background and aim: Neurobehavioral changes associated with food allergies have been reported, but the therapeutic effects of probiotics have not been fully explored. Our study aimed to investigate the impact of multi-strain probiotics on neurobehavioral outcomes and to elucidate the underlying mechanism via the microbiota-gut-brain axis. Methods: C57BL/6J Male mice were randomly divided into the following three groups: (1) control group; (2) OVA-sensitized group; (3) OVA-sensitized group treated with multi-strain probiotics (OVA + P). Anaphylactic reactions and behavioral abnormalities were assessed by histological, immunological, and behavioral analyses. To further elucidate the underlying mechanisms, the prefrontal cortex was collected for microglial morphological analysis, while serum and fecal samples were obtained for untargeted metabolomic profiling and 16S rDNA-based gut microbiota analysis, respectively. Results: Multi-strain probiotics significantly alleviated anaphylactic reactions in OVA-sensitized mice, as evidenced by reduced serum IgE levels, decreased Th2 cytokines, and reduced epithelial damage. Meanwhile, neurobehavioral symptoms were alleviated, including anxiety-like and depression-like behaviors, repetitive behaviors, social avoidance, and impaired attention. Mechanistically, probiotics administration suppressed production of inflammatory cytokines (TNF-α, IL-1β and IL-6) and inhibited activation of M1 microglia in the prefrontal cortex, which might contribute to neuron recovery. Furthermore, multi-omics analysis revealed that amino acid metabolism restoration in OVA + P mice, particularly carboxylic acids and derivatives, which was remarkably correlated with alterations in gut microbiota and behaviors related to FA. Conclusions: Gut microbiota and its amino acid metabolites mediate the therapeutic effects of multi-strain probiotics on FA-induced behavioral abnormalities. These effects occur alongside the suppression of neuroinflammation and microglial activation in the prefrontal cortex. Our findings highlight the neuroimmune regulatory role of the gut-microbiota-brain axis and support the potential use of probiotics as an intervention for FA-induced brain dysfunctions. Full article

Background: High-dose γ-ray exposure (≥7 Gy) in nuclear emergencies induces life-threatening acute radiation syndrome, characterized by rapid hematopoietic collapse (leukocytes <0.5 × 10⁹/L) and gastrointestinal barrier failure. While clinical biomarkers like leukocyte depletion guide current therapies targeting myelosuppression, the concomitant metabolic disturbances and gut microbiota dysbiosis—critical determinants of delayed mortality—remain insufficiently profiled across the 28-day injury-recovery continuum. Methods: This study investigates the effects of ⁶⁰Co γ-ray irradiation on metabolic characteristics and gut microbiota in Sprague Dawley rats using untargeted metabolomics and 16S rRNA sequencing. Meanwhile, body weight and complete blood counts were measured. Results: Body weight exhibited significant fluctuations, with the most pronounced deviation observed at 14 days. Blood counts revealed a rapid decline in white blood cells, red blood cells, and platelets post-irradiation, reaching nadirs at 7–14 days, followed by gradual recovery to near-normal levels by 28 days. Untargeted metabolomics identified 32 upregulated and 33 downregulated plasma metabolites at 14 days post-irradiation, while fecal metabolites showed 47 upregulated and 18 downregulated species at 3 days. Key metabolic pathways impacted included Glycerophospholipid metabolism, alpha-linolenic acid metabolism, and biosynthesis of unsaturated fatty acids. Gut microbiota analysis demonstrated no significant change in α-diversity but significant β-diversity shifts (p < 0.05), indicating a marked alteration in the compositional structure of the intestinal microbial community following radiation exposure. Principal coordinate analysis confirmed distinct clustering between control and irradiated groups, with increased abundance of Bacteroidota and decreased Firmicutes in irradiated rats. These findings highlight dynamic metabolic and microbial disruptions post-irradiation, with recovery patterns suggesting a 28-day restoration cycle. Spearman’s rank correlation analysis explored associations between the top 20 fecal metabolites and 50 abundant bacterial taxa. Norank_f_Muribaculaceae, Prevotellaceae_UCG-001, and Bacteroides showed significant correlations with various radiation-altered metabolites, highlighting metabolite–microbiota relationships post-radiation. Conclusions: This study provides insights into potential biomarkers for radiation-induced physiological damage and underscores the interplay between systemic metabolism and gut microbiota in radiation response. Full article

Antibiotics are commonly used to aid in the remission of gastrointestinal diseases, but usage may lead to prolonged dysbiosis. The objective of this study was to evaluate the effects of metronidazole on fecal microbiota, fecal metabolites, and serum bile acids and uremic toxins of healthy adult cats. Twelve healthy adult cats (4.7 ± 0.4 yr) received metronidazole (20 mg/kg BW PO BID) for 14 days (day 0–14) and were monitored during a 28-day recovery period (day 15–42). Fecal and blood samples were collected at baseline (day 0), after metronidazole (day 14), and weekly during recovery (on days 21, 28, 35, and 42). Fecal samples were analyzed for microbiota and bacterial metabolites. Serum samples were analyzed for bile acids and uremic toxins. Metronidazole increased dysbiosis index and fecal lactate concentrations (p < 0.0001) and decreased fecal propionate, butyrate, and secondary bile acid concentrations (p < 0.0001) for up to 28 days. Prolonged dysbiosis and Peptacetobacter (Clostridium) hiranonis reductions were observed in 10/12 (83%) cats. Serum uremic toxins were also reduced (p < 0.0001) after metronidazole administration. The observed changes after metronidazole administration illustrate how changes in the gut microbiome alter microbial metabolism and its relation to host dysmetabolism. In conclusion, metronidazole is a potent antibiotic with persistent effects observed in the microbiome and metabolome, even up to one month after administration. Full article

Background: Critical illness induces profound metabolic alterations, characterized by a hypermetabolic state, insulin resistance, protein catabolism, and gut barrier dysfunction, which contribute to increased morbidity and mortality. Emerging evidence highlights the role of the gut microbiome and its metabolites in modulating systemic inflammation and immune responses during critical illness. This narrative review explores the metabolic evolution of critically ill patients, the impact of gut dysbiosis on disease progression, and the potential role of nutrition in modulating metabolism and improving patient outcomes. Methods: A comprehensive literature search was conducted across PubMed and Google Scholar for articles published up to February 2025. Search terms included “critical illness”, “metabolism”, “gut microbiota”, “nutrition”, and related keywords. Articles published in English addressing metabolic alterations, microbiome changes, and nutritional strategies in critically ill patients were included. After screening for eligibility, relevant articles were synthesized to outline current knowledge and identify gaps. Results: Metabolic changes in critical illness progress through distinct phases, from catabolism-driven hypermetabolism to gradual recovery. Gut dysbiosis, characterized by a loss of microbial diversity and increased gut permeability, contributes to systemic inflammation and organ dysfunction. Nutritional strategies, including enteral nutrition, probiotics, prebiotics, and metabolomics-driven interventions, may help restore microbial balance, preserve gut barrier integrity, and modulate immune and metabolic responses. Future nutrition therapy should focus on metabolic modulation rather than solely addressing nutrient deficits. Conclusions: Advances in gut microbiome research and metabolomics offer new avenues for personalized nutrition strategies tailored to the metabolic demands of critically ill patients. Integrating these approaches may improve clinical and functional recovery while mitigating the long-term consequences of critical illness. Full article

Tonic immobility (TI) serves as an indicator of innate stress response recovery in poultry. Broilers with different TI phenotypes exhibit varying levels of aggressive behavior, which can significantly impact their welfare. However, the influences of TI phenotypes on broiler aggression remain largely unexplored. In this study, broiler chickens were stratified into two distinct phenotypic groups based on the TI duration: short TI (STI) and long TI (LTI). The impacts of TI phenotypes on broiler aggression were investigated by analyzing cecal intestinal morphology, cecal bacteria, plasma metabolites, and corticosterone levels. Compared to LTI broilers, STI broilers showed significantly reduced plasma corticosterone (CORT) levels (p < 0.05) and a decreased frequency of aggressive behaviors, including dominant and subdominant types (p < 0.01). Histological analysis revealed that STI broilers have an increased duodenal villus height and villus-height-to-crypt-depth ratio (p < 0.01), a decreased jejunal crypt depth with an increased villus-height-to-crypt-depth ratio (p < 0.01), and a reduced ileal crypt depth and villus height (p < 0.01) compared to LTI broilers. 16S rDNA sequencing and Linear discriminant analysis effect size (LefSe) identified differential cecal bacterial abundance, notably in the genus cc115 belonging to Firmicutes. Specific microbiota in LTI broilers exhibited significant positive correlations with aggressive behavior and plasma corticosterone, while those in STI broilers showed significant negative correlations. Untargeted plasma metabolomics revealed 21 downregulated and 17 upregulated metabolites between TI phenotypes. Correlation analysis showed that the genus cc115 and 10 plasma metabolites were positively correlated with aggressive behavior, whereas 8 metabolites were negatively correlated. LTI broilers have higher plasma corticosterone content and more intense aggressive behavior than STI broilers. The distinct behavioral and physiological profiles observed in broilers with different TI phenotypes are strongly correlated with their specific gut microbiota and differential plasma metabolite profiles. The identified gut microbial signatures serve as key biomarkers for regulating aggressive behavior in broilers, while the differential plasma metabolites represent potential early indicators for detecting stress and behavioral issues in poultry farming. Full article

Background/Objectives: Ulcerative colitis (UC) is a chronic and easily recurrent inflammatory bowel disease. The gut microbiota and plasma metabolites play pivotal roles in the development and progression of UC. Therefore, therapeutic strategies targeting the intestinal flora or plasma metabolites offer promising avenues for the treatment of UC. Luteolin (Lut), originating from a variety of vegetables and fruits, has attracted attention for its potent anti-inflammatory properties and potential to modulate intestinal flora. Methods: The therapeutic efficacy of Lut was evaluated in an established dextran sodium sulfate (DSS)-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination and the evaluation of the epithelial barrier function, microbiome, and metabolomics. Results: The findings revealed that Lut administration at a dose of 25 mg/kg significantly ameliorated systemic UC symptoms in mice, effectively reduced the systemic inflammatory response, and significantly repaired colonic barrier function. Furthermore, Lut supplementation mitigated gut microbiota dysbiosis in a UC murine model, increasing the abundance of Muribaculaceae, Rikenella, and Prevotellaceae while decreasing Escherichia_Shigella and Bacteroides levels. These alterations in gut microbiota also influenced plasma metabolism, significantly increasing phosphatidylcholine (PC), 6′-Deamino- 6′-hydroxyneomycin C, and gamma-L-glutamyl-butyrosine B levels and decreasing Motapizone and Arachidoyl-Ethanolamide (AEA) levels. Conclusions: This study reveals that Lut supplementation modulates intestinal inflammation by restoring the gut microbiota community structure, thereby altering the synthesis of inflammation-related metabolites. Lut is a potential nutritional supplement with anti-inflammatory properties and offers a novel alternative for UC intervention and mitigation. In addition, further studies are needed to ascertain whether specific microbial communities or metabolites can mediate the recovery from UC. Full article

In order to investigate the potential mechanisms of probiotic-fermented coconut water in treating enteritis, this study conducted a comprehensive analysis of the effects of probiotic intervention on the recovery from Dextran Sodium Sulfate-induced acute enteritis in Wenchang chicks. The analysis encompassed the assessment of growth performance, serum indicators, intestinal tissue structure, and metagenomic and metabolomic profiles of cecal contents in 60 Wenchang chicks subjected to intervention. This approach aimed to elucidate the impact of probiotic intervention on the recovery process from acute enteritis at both the genetic and metabolic levels in the avian model. The results revealed that intervention with Saccharomyces cerevisiae Y301 improved the growth rate of chicks. and intervention with Lactiplantibacillus plantarum MS2c regulated the glycerophospholipid metabolism pathway and reshaped the gut microbiota structure in modeling chicks with acute enteritis, reducing the abundance of potentially pathogenic bacteria from the Alistipes and increasing the abundance of potentially beneficial species from the Christensenellaceae. This intervention resulted in the production of specific gut metabolites, including Gentamicin C and polymyxin B2, recognized for their therapeutic effects on acute enteritis. The combined intervention of S. cerevisiae Y301 and L. plantarum MS2c not only enhanced growth performance but also mitigated intestinal wall damage and increased the abundance of gut metabolites such as gentamicin C and polymyxin B2, thereby mitigating symptoms of enteritis. Furthermore, this combined intervention reduced the levels of serum immune markers, including IL-10, IL-6, TNF-α, IFN-γ, and D-lactic acid, thus mitigating intestinal epithelial cell damage and promoting acute enteritis recovery. This study provides crucial insights into the mechanisms of action of probiotics and probiotic-fermented coconut water in acute enteritis recovery, offering new perspectives for sustainable farming practices for Wenchang chicken. Full article

An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies. Full article

Accumulated clinical and biomedical evidence indicates that the gut microbiota and their metabolites affect brain function and behavior in various central nervous system disorders. This study was performed to investigate the changes in brain metabolites and composition of the fecal microbial community following injection of amyloid β (Aβ) and donepezil treatment of Aβ-injected mice using metataxonomics and metabolomics. Aβ treatment caused cognitive dysfunction, while donepezil resulted in the successful recovery of memory impairment. The Aβ + donepezil group showed a significantly higher relative abundance of Verrucomicrobia than the Aβ group. The relative abundance of 12 taxa, including Blautia and Akkermansia, differed significantly between the groups. The Aβ + donepezil group had higher levels of oxalate, glycerol, xylose, and palmitoleate in feces and oxalate, pyroglutamic acid, hypoxanthine, and inosine in brain tissues than the Aβ group. The levels of pyroglutamic acid, glutamic acid, and phenylalanine showed similar changes in vivo and in vitro using HT-22 cells. The major metabolic pathways in the brain tissues and gut microbiota affected by Aβ or donepezil treatment of Aβ-injected mice were related to amino acid pathways and sugar metabolism, respectively. These findings suggest that alterations in the gut microbiota might influence the induction and amelioration of Aβ-induced cognitive dysfunction via the gut–brain axis. This study could provide basic data on the effects of Aβ and donepezil on gut microbiota and metabolites in an Aβ-induced cognitive impairment mouse model. Full article

Dietary intake of fermented soymilk is associated with hypotensive effects, but the mechanisms involved have not been fully elucidated. We investigated the anti-hypertensive effects of soymilk fermented by L. rhamnosus AC1 on DOCA-salt hypertension from the point of view of oxidative stress, inflammatory response and alteration of the gut microbiome. The antioxidant assays in vitro indicated the ethanol extract (EE) of L. rhamnosus AC1 fermented soymilk showed better antioxidative effects than the water extract (WE). Those extracts displayed a hypotensive effect using a tail-cuff approach to measuring blood pressure and improved nitric oxide (NO), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α) and interleukin factor-6 (IL-6) on DOCA-salt hypertensive rats. Furthermore, cardiac and renal fibrosis were attenuated by those extracts. The gut microbiota analysis revealed that they significantly reduced the abundance of phylum Proteobacteria, its family Enterobacteriaceae and genus Escherichia-Shigella. Moreover, metabolomic profiling revealed several potential gut microbiota-related metabolites which appeared to involve in the development and recovery of hypertension. In conclusion, fermented soymilk is a promising nutritional intervention strategy to improve hypertension via reducing inflammation and reverting dysbiotic microbiota. Full article

Antibiotics cause gut dysbiosis and bile acid dysmetabolism in dogs. The effect of fecal microbiota transplantation (FMT) on microbiome and metabolome recovery is unknown. This prospective, randomized, placebo-controlled study included sixteen healthy purpose-bred dogs. All dogs received tylosin 20 mg/kg PO once daily (days 1–7) and were randomly assigned to either receive one FMT via enema (day 8), daily oral FMT capsules (days 8–21), or daily placebo capsules (days 8–21). Fecal samples were frozen at regular intervals until day 42. Quantitative PCR for 8 bacterial taxa was performed to calculate the fecal dysbiosis index (FDI) and fecal concentrations of unconjugated bile acids (UBA) were measured using gas chromatography-mass spectrometry. Tylosin altered the abundance of most evaluated bacteria and induced a significant decrease in secondary bile acid concentrations at day 7 in all dogs. However, most parameters returned to their baseline by day 14 in all dogs. In conclusion, tylosin markedly impacted fecal microbiota and bile acid concentrations, although return to baseline values was quick after the antibiotic was discontinued. Overall, FMT did not accelerate recovery of measured parameters. Further studies are warranted to confirm the value of FMT in accelerating microbiota recovery in antibiotic-associated dysbiosis in dogs. Full article

Traumatic brain injury (TBI) heavily impacts the body: it damages the brain tissue and the peripheral nervous system and shifts homeostasis in many types of tissue. An acute brain injury compromises the “brain–gut-microbiome axis”, a well-balanced network formed by the brain, gastrointestinal tract, and gut microbiome, which has a complex effect: damage to the brain alters the composition of the microbiome; the altered microbiome affects TBI severity, neuroplasticity, and metabolic pathways through various bacterial metabolites. We modeled TBI in rats. Using a bioinformatics approach, we sought to identify correlations between the gut microbiome composition, TBI severity, the rate of neurological function recovery, and blood metabolome. We found that the TBI caused changes in the abundance of 26 bacterial genera. The most dramatic change was observed in the abundance of Agathobacter species. The TBI also altered concentrations of several metabolites, specifically citrulline and tryptophan. We found no significant correlations between TBI severity and the pre-existing gut microbiota composition or blood metabolites. However, we discovered some differences between the two groups of subjects that showed high and low rates of neurological function recovery, respectively. The present study highlights the role of the brain–gut-microbiome axis in TBI. Full article

Crocetin is one of the major active constituents of saffron (Crocus sativus L.) which has a reputation for facilitating blood circulation and dispersing blood stasis in traditional Chinese medicine. However, there is little evidence showing the relationship between crocetin intake and the risk of gastrointestinal diseases such as colitis. In order to investigate the effect of crocetin on the regulation of intestinal barrier function and intestinal microbiota composition, mice were treated with crocetin after 3% dextran sulfate sodium (DSS) administration for one week. We found that crocetin intake at 10 mg/kg aggravated colitis in mice, showing increased weight loss and more serious histological abnormalities compared with the DSS group. The 16s rDNA sequencing analysis of the feces samples showed that mice treated with 10 mg/kg crocetin had lower species diversity and richness than those treated with DSS. At the genus level, a higher abundance of Akkermansia and Mediterraneibacter, and a lower abundance of Muribaculaceae, Dubosiella, Paramuribaculum, Parasutterella, Allobaculum, Duncaniella, Candidatus Stoquefichus, and Coriobacteriaceae UCG-002 were observed in the crocetin group. Untargeted metabolomic analyses revealed that crocetin reduced the levels of primary and secondary bile acids such as 12-ketodeoxycholic acid, 7-ketodeoxycholic acid, 3-sulfodeoxycholic acid, 6-ethylchenodeoxycholic acid, chenodeoxycholate, glycochenodeoxycholate-7-sulfate, glycocholate, and sulfolithocholic acid in the colon. In conclusion, crocetin intake disturbed intestinal homeostasis and prolonged recovery of colitis by promoting inflammation and altering gut microbiota composition and its metabolic products in mice. Our findings suggest that patients with gastrointestinal diseases such as inflammatory bowel disease should use crocetin with caution. Full article

The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fecal microbiota transplant (FMT) engraftment in conventional mice are yet to be established. Conventional BALB/c mice were randomized to receive 3-day (3d) or 3-week (3w) antibiotic (ABX) regimen in their drinking water followed by 1 or 5-daily FMTs from a human donor. Fecal samples were collected longitudinally and characterized using 16S ribosomal RNA (rRNA) sequencing. Semi-targeted metabolomic profiling of fecal samples was also done with liquid chromatography–mass spectrometry (LC-MS). Lastly, we sought to confirm our findings in BKS mice. Recovery of baseline diversity scores were greatest in the 3d groups, driven by re-emergence of mouse commensal microbiota, whereas the most resemblance to donor microbiota was seen in the 3w + 5-FMT group. Amplicon sequence variants (ASVs) that were linked to the input material (human ASVs) engrafted to a significantly greater extent when compared to mouse ASVs in the 3-week groups but not the 3-day groups. Lastly, comparison of metabolomic profiles revealed distinct functional profiles by ABX regimen. These results indicate successful model optimization and emphasize the importance of ABX duration and frequency of FMT dosing; the most stable and reliable colonization by donor ASVs was seen in the 3wk + 5-FMT group. Full article