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Search Results (1,125)

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20 pages, 2076 KiB  
Article
Numerical Modeling of Gentamicin Transport in Agricultural Soils: Implications for Environmental Pollution
by Nami Morales-Durán, Sebastián Fuentes, Jesús García-Gallego, José Treviño-Reséndez, Josué D. García-Espinoza, Rubén Morones-Ramírez and Carlos Chávez
Antibiotics 2025, 14(8), 786; https://doi.org/10.3390/antibiotics14080786 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives: In recent years, the discharge of antibiotics into rivers and irrigation canals has increased. However, few studies have addressed the impact of these compounds on agricultural fields that use such water to meet crop demands. Methods: In this study, the transport of [...] Read more.
Background/Objectives: In recent years, the discharge of antibiotics into rivers and irrigation canals has increased. However, few studies have addressed the impact of these compounds on agricultural fields that use such water to meet crop demands. Methods: In this study, the transport of two types of gentamicin (pure gentamicin and gentamicin sulfate) was modeled at concentrations of 150 and 300 μL/L, respectively, in a soil with more than 60 years of agricultural use. Infiltration tests under constant head conditions and gentamicin transport experiments were conducted in acrylic columns measuring 14 cm in length and 12.7 cm in diameter. The scaling parameters for the Richards equation were obtained from experimental data, while those for the advection–dispersion equation were estimated using inverse methods through a nonlinear optimization algorithm. In addition, a fractal-based model for saturated hydraulic conductivity was employed. Results: It was found that the dispersivity of gentamicin sulfate is 3.1 times higher than that of pure gentamicin. Based on the estimated parameters, two simulation scenarios were conducted: continuous application of gentamicin and soil flushing after antibiotic discharge. The results show that the transport velocity of gentamicin sulfate in the soil may have short-term consequences for the emergence of resistant microorganisms due to the destination of wastewater containing antibiotic residues. Conclusions: Finally, further research is needed to evaluate the impact of antibiotics on soil physical properties, as well as their effects on irrigated crops, animals that consume such water, and the soil microbiota. Full article
(This article belongs to the Special Issue Impact of Antibiotic Residues in Wastewater)
20 pages, 4612 KiB  
Article
Effect of a Gluten-Free Diet on the Intestinal Microbiota of Women with Celiac Disease
by M. Mar Morcillo Serrano, Paloma Reche-Sainz, Daniel González-Reguero, Marina Robas-Mora, Rocío de la Iglesia, Natalia Úbeda, Elena Alonso-Aperte, Javier Arranz-Herrero and Pedro A. Jiménez-Gómez
Antibiotics 2025, 14(8), 785; https://doi.org/10.3390/antibiotics14080785 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, [...] Read more.
Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article
(This article belongs to the Special Issue Antibiotic Resistance: A One-Health Approach, 2nd Edition)
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24 pages, 2329 KiB  
Article
Flavonoid Extract of Senecio Scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-κB Signaling Pathway
by Xiaolin Zhu, Lulu Zhang, Xuan Ni, Jian Guo, Yizhuo Fang, Jianghan Xu, Zhuo Chen and Zhihui Hao
Nutrients 2025, 17(15), 2540; https://doi.org/10.3390/nu17152540 (registering DOI) - 1 Aug 2025
Abstract
Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated [...] Read more.
Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4+/CD8+ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article
(This article belongs to the Section Nutrition and Metabolism)
29 pages, 6541 KiB  
Article
Lacticaseibacillus paracasei L21 and Its Postbiotics Ameliorate Ulcerative Colitis Through Gut Microbiota Modulation, Intestinal Barrier Restoration, and HIF1α/AhR-IL-22 Axis Activation: Combined In Vitro and In Vivo Evidence
by Jingru Chen, Linfang Zhang, Yuehua Jiao, Xuan Lu, Ning Zhang, Xinyi Li, Suo Zheng, Bailiang Li, Fei Liu and Peng Zuo
Nutrients 2025, 17(15), 2537; https://doi.org/10.3390/nu17152537 (registering DOI) - 1 Aug 2025
Abstract
Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracasei L21 (L. paracasei L21) and its ability to ameliorate colitis [...] Read more.
Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracasei L21 (L. paracasei L21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracasei L21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracasei L21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracasei L21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracasei L21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article
(This article belongs to the Special Issue Probiotics, Postbiotics, Gut Microbiota and Gastrointestinal Health)
13 pages, 310 KiB  
Review
Microbiome Shifts in Bladder Cancer: A Narrative Review of Urobiome Composition, Progression, and Therapeutic Impact
by Raul-Dumitru Gherasim, Călin Chibelean, Daniel Porav-Hodade, Ciprian Todea-Moga, Sabin-Octavian Tătaru, Tibor-Lorand Reman, Arpad-Oliver Vida, Maria-Veronica Ghirca, Matteo Ferro and Orsolya Katalyn Ilona Martha
Medicina 2025, 61(8), 1401; https://doi.org/10.3390/medicina61081401 (registering DOI) - 1 Aug 2025
Abstract
Background/Objectives: Bladder cancer is a common malignancy with a high rate of recurrence and progression. Recent studies have identified that the urinary microbiome can be a key factor in tumor pathogenesis, progression, and outcomes. This narrative review is designed to summarize current [...] Read more.
Background/Objectives: Bladder cancer is a common malignancy with a high rate of recurrence and progression. Recent studies have identified that the urinary microbiome can be a key factor in tumor pathogenesis, progression, and outcomes. This narrative review is designed to summarize current evidence regarding the urobiome and explore its diagnostic and therapeutic potential. Methods: Studies between 2019 and 2024 were identified through the PubMed/MEDLINE and Google Scholar databases. Case reports and non-English-language articles were excluded. Results: The main findings revealed that specific bacteria, viruses, and taxa are linked to bladder cancer presence, progression, and response to immunotherapy treatment. Urinary microbiota differ by tumor type, sex, smoking status, and occupational exposure to toxins. Conclusions: Urinary microbiome and certain types of viruses present in urine may serve as promising tools to enhance bladder cancer diagnosis and predict treatment response. However, larger longitudinal studies are needed to confirm and establish these findings. Furthermore, integration of the urinary microbiome in clinical practice and public health strategies may reduce disease-related burden. Full article
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11 pages, 1139 KiB  
Article
Effect of Akkermansia muciniphila on GLP-1 and Insulin Secretion
by Ananta Prasad Arukha, Subhendu Nayak and Durga Madhab Swain
Nutrients 2025, 17(15), 2516; https://doi.org/10.3390/nu17152516 - 31 Jul 2025
Viewed by 59
Abstract
Background/Objectives: Gut microbiota research has gained momentum in recent years broadening knowledge of microbial components and their potential effects on health and well-being. Strong association between explicit microbes and metabolic diseases associated with obesity and type 2 diabetes mellitus, gastrointestinal disorders, neurodegenerative diseases, [...] Read more.
Background/Objectives: Gut microbiota research has gained momentum in recent years broadening knowledge of microbial components and their potential effects on health and well-being. Strong association between explicit microbes and metabolic diseases associated with obesity and type 2 diabetes mellitus, gastrointestinal disorders, neurodegenerative diseases, and even cancers have been established. Akkermansia muciniphila is a budding next-generation probiotic that plays an important role in systemic metabolism, intestinal health, and immune regulation, establishing strong implications for its use as a potent therapeutic intervention in diverse diseases. This project aimed at evaluating whether bacterial cell extracts of VH Akkermansia muciniphila (Vidya Strain; VS) can stimulate insulin secretion in INS-1 pancreatic beta cells and GLP-1 secretion in NCI-H716 human L-cells, both established in vitro models for studying metabolic regulation. Methods: Cultured VH Akkermansia muciniphila extracts were administered in a dose-dependent manner on INS-1 cells, and glucose-stimulated insulin secretion (GSIS) was measured via ELISA. Treated Human L-cell lines (NCI-H716) were analyzed for GLP-1 secretion. Results: Our study demonstrated that VH Akkermansia muciniphila extracts modestly increase insulin secretion from INS-1 beta cells and, more notably, induce a robust, dose-dependent rise in GLP-1 secretion from NCI-H716 L-cells, with the highest dose achieving over a 2000% increase comparable to glutamine. Conclusions: These findings suggest that VH A. muciniphila extracts may offer metabolic benefits by enhancing GLP-1 release, highlighting their potential for managing type 2 diabetes and obesity. Full article
(This article belongs to the Section Prebiotics and Probiotics)
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15 pages, 1360 KiB  
Systematic Review
Prebiotics Improve Blood Pressure Control by Modulating Gut Microbiome Composition and Function: A Systematic Review and Meta-Analysis
by Abdulwhab Shremo Msdi, Elisabeth M. Wang and Kevin W. Garey
Nutrients 2025, 17(15), 2502; https://doi.org/10.3390/nu17152502 - 30 Jul 2025
Viewed by 241
Abstract
Background: Ingestion of dietary fibers (DFs) is a safe and accessible intervention associated with reductions in blood pressure (BP) and cardiovascular mortality. However, the mechanisms underlying the antihypertensive effects of DFs remain poorly defined. This systematic review and meta-analysis evaluates how DFs influence [...] Read more.
Background: Ingestion of dietary fibers (DFs) is a safe and accessible intervention associated with reductions in blood pressure (BP) and cardiovascular mortality. However, the mechanisms underlying the antihypertensive effects of DFs remain poorly defined. This systematic review and meta-analysis evaluates how DFs influence BP regulation by modulating gut microbial composition and enhancing short-chain fatty acid (SCFA) production. Methods: MEDLINE and EMBASE were systematically searched for interventional studies published between January 2014 and December 2024. Eligible studies assessed the effects of DFs or other prebiotics on systolic BP (SBP) and diastolic BP (DBP) in addition to changes in gut microbial or SCFA composition. Results: Of the 3010 records screened, nineteen studies met the inclusion criteria (seven human, twelve animal). A random-effects meta-analysis was conducted on six human trials reporting post-intervention BP values. Prebiotics were the primary intervention. In hypertensive cohorts, prebiotics significantly reduced SBP (−8.5 mmHg; 95% CI: −13.9, −3.1) and DBP (−5.2 mmHg; 95% CI: −8.5, −2.0). A pooled analysis of hypertensive and non-hypertensive patients showed non-significant reductions in SBP (−4.5 mmHg; 95% CI: −9.3, 0.3) and DBP (−2.5 mmHg; 95% CI: −5.4, 0.4). Animal studies consistently showed BP-lowering effects across diverse etiologies. Prebiotic interventions restored bacterial genera known to metabolize DFs to SCFAs (e.g., Bifidobacteria, Akkermansia, and Coprococcus) and increased SCFA levels. Mechanistically, SCFAs act along gut–organ axes to modulate immune, vascular, and neurohormonal pathways involved in BP regulation. Conclusions: Prebiotic supplementation is a promising strategy to reestablish BP homeostasis in hypertensive patients. Benefits are likely mediated through modulation of the gut microbiota and enhanced SCFA production. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics: Past, Present and Future)
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25 pages, 2693 KiB  
Article
Adipokine and Hepatokines in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Current and Developing Trends
by Salvatore Pezzino, Stefano Puleo, Tonia Luca, Mariacarla Castorina and Sergio Castorina
Biomedicines 2025, 13(8), 1854; https://doi.org/10.3390/biomedicines13081854 - 30 Jul 2025
Viewed by 231
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article
(This article belongs to the Special Issue Advances in Hepatology)
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22 pages, 1013 KiB  
Review
Genomic Alterations and Microbiota Crosstalk in Hepatic Cancers: The Gut–Liver Axis in Tumorigenesis and Therapy
by Yuanji Fu, Jenny Bonifacio-Mundaca, Christophe Desterke, Íñigo Casafont and Jorge Mata-Garrido
Genes 2025, 16(8), 920; https://doi.org/10.3390/genes16080920 - 30 Jul 2025
Viewed by 98
Abstract
Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and [...] Read more.
Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and gut microbiota in liver cancer development and progression. This review aims to integrate emerging knowledge on the interplay between host genomic changes and gut microbial dynamics in the pathogenesis and treatment of hepatic cancers. Methods: We conducted a comprehensive review of current literature on genetic and epigenetic drivers of HCC and CCA, focusing on commonly mutated genes such as TP53, CTNNB1, TERT, IDH1/2, and FGFR2. In parallel, we evaluated studies addressing the gut–liver axis, including the roles of dysbiosis, microbial metabolites, and immune modulation. Key clinical and preclinical findings were synthesized to explore how host–microbe interactions influence tumorigenesis and therapeutic response. Results: HCC and CCA exhibit distinct but overlapping genomic landscapes marked by recurrent mutations and epigenetic reprogramming. Alterations in the gut microbiota contribute to hepatic inflammation, genomic instability, and immune evasion, potentially enhancing oncogenic signaling pathways. Furthermore, microbiota composition appears to affect responses to immune checkpoint inhibitors. Emerging therapeutic strategies such as probiotics, fecal microbiota transplantation, and precision oncology based on mutational profiling demonstrate potential for personalized interventions. Conclusions: The integration of host genomics with microbial ecology provides a promising paradigm for advancing diagnostics and therapies in liver cancer. Targeting the gut–liver axis may complement genome-informed strategies to improve outcomes for patients with HCC and CCA. Full article
(This article belongs to the Special Issue Feature Papers in Microbial Genetics and Genomics)
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16 pages, 636 KiB  
Review
The Gut–Endometriosis Axis: Genetic Mechanisms and Public Health Implications
by Efthalia Moustakli, Nektaria Zagorianakou, Stylianos Makrydimas, Emmanouil D. Oikonomou, Andreas Miltiadous and George Makrydimas
Genes 2025, 16(8), 918; https://doi.org/10.3390/genes16080918 - 30 Jul 2025
Viewed by 248
Abstract
Background/Objectives: Endometriosis is a chronic, estrogen-driven gynecological disorder affecting approximately 10% of reproductive-aged women worldwide, with significant physical, psychosocial, and socioeconomic impacts. Recent research suggests a possible involvement of the gut microbiome in endometriosis disease mechanisms through immune manipulation, estrogen metabolism, and [...] Read more.
Background/Objectives: Endometriosis is a chronic, estrogen-driven gynecological disorder affecting approximately 10% of reproductive-aged women worldwide, with significant physical, psychosocial, and socioeconomic impacts. Recent research suggests a possible involvement of the gut microbiome in endometriosis disease mechanisms through immune manipulation, estrogen metabolism, and inflammatory networks. This narrative review aims to summarize current evidence on gut microbiota changes in endometriosis patients, explore the mechanisms by which gut dysbiosis contributes to disease progression, and examine epidemiological links between gastrointestinal health and endometriosis risk. Methods: A narrative review was conducted to synthesize available literature on the compositional changes in gut microbiota associated with endometriosis. The review also evaluated studies investigating potential mechanisms and epidemiological patterns connecting gut health with endometriosis development and severity. Results: Alterations in gut microbiota composition were observed in endometriosis patients, suggesting roles in immune dysregulation, estrogen metabolism, and inflammation. Potential gut-oriented interventions, including dietary changes, probiotics, and lifestyle modifications, emerged as promising management options. However, methodological variability and research gaps remain barriers to clinical translation. Conclusions: Integrating gut microbiome research into endometriosis management holds potential for improving early diagnosis, patient outcomes, and healthcare system sustainability. The study emphasizes the need for further research to address existing challenges and to develop public health strategies that incorporate microbiome-based interventions in population-level endometriosis care. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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15 pages, 1216 KiB  
Review
Biomolecular Aspects of Reelin in Neurodegenerative Disorders: An Old Candidate for a New Linkage of the Gut–Brain–Eye Axis
by Bijorn Omar Balzamino, Filippo Biamonte and Alessandra Micera
Int. J. Mol. Sci. 2025, 26(15), 7352; https://doi.org/10.3390/ijms26157352 - 30 Jul 2025
Viewed by 188
Abstract
Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in [...] Read more.
Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut–brain–eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin’s potential relation with the gut–brain and gut–brain–eye axes and providing novel attractive hypotheses on the gut–brain–eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss. Full article
(This article belongs to the Section Molecular Immunology)
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13 pages, 982 KiB  
Article
Salivary pH Modulation and Antimicrobial Properties of Oregano-Oil Jelly in Relation to Menstrual and Menopausal Status
by Georgiana Ioana Potra Cicalău, Gabriela Ciavoi, Ioana Scrobota, Ionut Daniel Venter, Madalin Florin Ganea, Marc Cristian Ghitea, Evelin Claudia Ghitea, Maria Flavia Gîtea, Timea Claudia Ghitea, Csaba Nagy, Diana Constanta Pelea, Luciana Dobjanschi, Octavia Gligor, Corina Moisa and Mariana Ganea
Nutrients 2025, 17(15), 2480; https://doi.org/10.3390/nu17152480 - 29 Jul 2025
Viewed by 165
Abstract
Background: Salivary pH plays a critical role in oral health by influencing enamel demineralization, buffering capacity, and the ecology of oral microbiota. Essential oils such as Origanum vulgare (oregano) possess well-documented antimicrobial properties that may reduce acidogenic bacterial activity. However, the effects of [...] Read more.
Background: Salivary pH plays a critical role in oral health by influencing enamel demineralization, buffering capacity, and the ecology of oral microbiota. Essential oils such as Origanum vulgare (oregano) possess well-documented antimicrobial properties that may reduce acidogenic bacterial activity. However, the effects of edible delivery systems like jellies on salivary pH modulation and their potential interactions with hormonal states remain poorly understood. Methods: This study evaluated the in vitro antimicrobial activity of an oregano-oil-based jelly formulation against standard bacterial (Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli) and fungal (Candida albicans) strains using the Kirby–Bauer disc diffusion method. Additionally, a human trial (n = 91) measured salivary pH before and after administration of the oregano-oil jelly. Participants were characterized by age, smoking status, menopausal status, and presence of menstruation. Multiple linear regression was used to identify predictors of final salivary pH. Results: The oregano-oil jelly demonstrated strong in vitro antimicrobial activity, with inhibition zones up to 8 mm for E. coli and C. albicans. In vivo, mean unstimulated salivary pH increased from 6.94 to 7.07 overall, indicating a mild alkalinizing effect. However, menstruating participants showed a significant decrease in final pH (from 7.03 to 6.78). Multiple regression identified menstruation as a significant negative predictor (β = −0.377, p < 0.001) and initial pH as a positive predictor (β = +0.275, p = 0.002). Menopausal status was not a significant predictor, likely due to the small sample size. Conclusions: Oregano-oil jellies may represent a promising natural approach to support oral health by increasing salivary pH and providing strong antimicrobial activity. However, physiological states such as menstruation can significantly modulate this response, underscoring the importance of personalized or phase-aware oral care strategies. Further studies with larger, diverse cohorts and controlled hormonal assessments are needed to validate these findings and optimize product formulations. Full article
(This article belongs to the Section Nutrition and Metabolism)
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17 pages, 1908 KiB  
Article
BDE-47 Disrupts Gut Microbiota and Exacerbates Prediabetic Conditions in Mice: Therapeutic Potential of Grape Exosomes and Antioxidants
by Zaoling Liu, Fang Cao, Aerna Qiayimaerdan, Nilupaer Aisikaer, Zulipiya Zunong, Xiaodie Ma and Yale Yu
Toxics 2025, 13(8), 640; https://doi.org/10.3390/toxics13080640 - 29 Jul 2025
Viewed by 140
Abstract
Background: BDE-47, a pervasive environmental pollutant detected in >90% of human serum samples, is increasingly linked to metabolic disorders. This study investigates the specific impact of BDE-47 exposure on the gut microbiota in prediabetic mice and evaluates the efficacy of therapeutic interventions [...] Read more.
Background: BDE-47, a pervasive environmental pollutant detected in >90% of human serum samples, is increasingly linked to metabolic disorders. This study investigates the specific impact of BDE-47 exposure on the gut microbiota in prediabetic mice and evaluates the efficacy of therapeutic interventions in mitigating these effects. Objectives: To determine whether BDE-47 exposure induces diabetogenic dysbiosis in prediabetic mice and to assess whether dietary interventions, such as grape exosomes and an antioxidant cocktail, can restore a healthy microbiota composition and mitigate diabetes risk. Methods: In this study, a prediabetic mouse model was established in 54 male SPF-grade C57BL/6J mice through a combination of high-sugar and high-fat diet feeding with streptozotocin injection. Oral glucose tolerance tests (OGTT) were conducted on day 7 and day 21 post-modeling to assess the establishment of the model. The criteria for successful model induction were defined as fasting blood glucose levels below 7.8 mmol/L and 2 h postprandial glucose levels between 7.8 and 11.1 mmol/L. Following confirmation of model success, a 3 × 3 factorial design was applied to allocate the experimental animals into groups based on two independent factors: BDE-47 exposure and exosome intervention. The BDE-47 exposure factor consisted of three dose levels—none, high-dose, and medium-dose—while the exosome intervention factor included three modalities—none, Antioxidant Nutrients Intervention, and Grape Exosomes Intervention. Fresh fecal samples were collected from mice two days prior to sacrifice. Cecal contents and segments of the small intestine were collected and transferred into 1.5 mL cryotubes. All sequences were clustered into operational taxonomic units (OTUs) based on defined similarity thresholds. To compare means across multiple groups, a two-way analysis of variance (ANOVA) was employed. The significance level was predefined at α = 0.05, and p-values < 0.05 were considered statistically significant. Bar charts and line graphs were generated using GraphPad Prism version 9.0 software, while statistical analyses were performed using SPSS version 20.0 software. Results: The results of 16S rDNA sequencing analysis of the microbiome showed that there was no difference in the α diversity of the intestinal microbiota in each group of mice (p > 0.05), but there was a difference in the Beta diversity (p < 0.05). At the gate level, the abundances of Proteobacteria, Campylobacterota, Desulfobacterota, and Fusobacteriota in the medium-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Patellar bacteria was lower than that of the model control group (p < 0.05). The abundances of Proteobacteria and Campylobacterota in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Planctomycetota and Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Campylobacterota in the grape exosome group was higher than that of the model control group (p < 0.05). The abundance of Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Firmicutes and Fusobacteriota in the antioxidant nutrient group was higher than that of the model control group (p < 0.05). However, the abundance of Verrucomicrobiota and Patescibacteria was lower than that of the model control group (p < 0.05). At the genus level, the abundances of Bacteroides and unclassified Lachnospiraceae in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Lachnospiraceae NK4A136_group and Lactobacillus was lower than that of the model control group (p < 0.05). The abundance of Veillonella and Helicobacter in the medium-dose BDE-7 group was higher than that in the model control group (p < 0.05), while the abundance of Lactobacillus was lower (p < 0.05). The abundance of genera such as Lentilactobacillus and Faecalibacterium in the grape exosome group was higher than that in the model control group (p < 0.05). The abundance of Alloprevotella and Bacteroides was lower than that of the model control group (p < 0.05). In the antioxidant nutrient group, the abundance of Lachnospiraceae and Hydrogenophaga was higher than that in the model control group (p < 0.05). However, the abundance of Akkermansia and Coriobacteriaceae UCG-002 was significantly lower than that of the model control group (p < 0.05). Conclusions: BDE-47 induces diabetogenic dysbiosis in prediabetic mice, which is reversible by dietary interventions. These findings suggest that microbiota-targeted strategies may effectively mitigate the diabetes risk associated with environmental pollutant exposure. Future studies should further explore the mechanisms underlying these microbiota changes and the long-term health benefits of such interventions. Full article
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21 pages, 2030 KiB  
Article
Restoring Balance: Probiotic Modulation of Microbiota, Metabolism, and Inflammation in SSRI-Induced Dysbiosis Using the SHIME® Model
by Marina Toscano de Oliveira, Fellipe Lopes de Oliveira, Mateus Kawata Salgaço, Victoria Mesa, Adilson Sartoratto, Kalil Duailibi, Breno Vilas Boas Raimundo, Williams Santos Ramos and Katia Sivieri
Pharmaceuticals 2025, 18(8), 1132; https://doi.org/10.3390/ph18081132 - 29 Jul 2025
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Abstract
Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus [...] Read more.
Background/Objectives: Selective serotonin reuptake inhibitors (SSRIs), widely prescribed for anxiety disorders, may negatively impact the gut microbiota, contributing to dysbiosis. Considering the gut–brain axis’s importance in mental health, probiotics could represent an effective adjunctive strategy. This study evaluated the effects of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on microbiota composition, metabolic activity, and immune markers in fecal samples from patients with anxiety on SSRIs, using the SHIME® (Simulator of the Human Intestinal Microbial Ecosystem) model. Methods: The fecal microbiotas of four patients using sertraline or escitalopram were inoculated in SHIME® reactors simulating the ascending colon. After stabilization, a 14-day probiotic intervention was performed. Microbial composition was assessed by 16S rRNA sequencing. Short-chain fatty acids (SCFAs), ammonia, and GABA were measured, along with the prebiotic index (PI). Intestinal barrier integrity was evaluated via transepithelial electrical resistance (TEER), and cytokine levels (IL-6, IL-8, IL-10, TNF-α) were analyzed using a Caco-2/THP-1 co-culture system. The statistical design employed in this study for the analysis of prebiotic index, metabolites, intestinal barrier integrity and cytokines levels was a repeated measures ANOVA, complemented by post hoc Tukey’s tests to assess differences across treatment groups. For the 16S rRNA sequencing data, alpha diversity was assessed using multiple metrics, including the Shannon, Simpson, and Fisher indices to evaluate species diversity, and the Chao1 and ACE indices to estimate species richness. Beta diversity, which measures microbiota similarity across groups, was analyzed using weighted and unweighted UniFrac distances. To assess significant differences in beta diversity between groups, a permutational multivariate analysis of variance (PERMANOVA) was performed using the Adonis test. Results: Probiotic supplementation increased Bifidobacterium and Lactobacillus, and decreased Klebsiella and Bacteroides. Beta diversity was significantly altered, while alpha diversity remained unchanged. SCFA levels increased after 7 days. Ammonia levels dropped, and PI values rose. TEER values indicated enhanced barrier integrity. IL-8 and TNF-α decreased, while IL-6 increased. GABA levels remained unchanged. Conclusions: The probiotic combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 modulated gut microbiota composition, metabolic activity, and inflammatory responses in samples from individuals with anxiety on SSRIs, supporting its potential as an adjunctive strategy to mitigate antidepressant-associated dysbiosis. However, limitations—including the small pooled-donor sample, the absence of a healthy control group, and a lack of significant GABA modulation—should be considered when interpreting the findings. Although the SHIME® model is considered a gold standard for microbiota studies, further clinical trials are necessary to confirm these promising results. Full article
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34 pages, 1059 KiB  
Review
Autism Spectrum Disorder: From Experimental Models to Probiotic Application with a Special Focus on Lactiplantibacillus plantarum
by Giusi Sabatini, Ilenia Boccadoro, Roberta Prete, Natalia Battista and Aldo Corsetti
Nutrients 2025, 17(15), 2470; https://doi.org/10.3390/nu17152470 - 29 Jul 2025
Viewed by 234
Abstract
Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) encompasses several neurodevelopmental disorders, whose onset is correlated to genetic and environmental factors. Although the etiopathogenesis is not entirely clear, the involvement of inflammatory processes, the endocannabinoid system, and alterations in the permeability and composition of the intestinal microbiota are known to occur. Methods: This review systematically explores the literature available to date on the most widely used murine models for the study of ASD, the main biomarkers investigated for the diagnosis of ASD, and the therapeutic potential of probiotics, with a particular focus on the use of strains of Lactiplantibacillus (Lpb.) plantarum in in vivo models and clinical trials for ASD. Results: Several studies have demonstrated that targeting multifactorial biomarkers in animal models and patients contributes to a more comprehensive understanding of the complex mechanisms underlying ASD. Moreover, accumulating evidence supports the beneficial effect of probiotics, including Lpb. plantarum, as a promising alternative therapeutic strategy, capable of modulating gut–brain axis communication. Conclusions: Probiotic supplementation, particularly with selected Lpb. plantarum strains, is emerging as a potential complementary approach for ameliorating ASD-related gastrointestinal and behavioral symptoms. However, further large-scale clinical studies are essential to validate their efficacy and determine optimal treatment protocols and dietary strategies. Full article
(This article belongs to the Special Issue The Effect of Nutrition Interventions on Neuropsychiatric Diseases)
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