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22 pages, 1986 KiB  
Article
Predictive Microbial Markers Distinguish Responders and Non-Responders to Adalimumab: A Step Toward Precision Medicine in Ulcerative Colitis
by Shaghayegh Baradaran Ghavami, Arfa Moshiri, Carola Bonaretti, Maryam Farmani, Margherita Squillario, Eddi Di Marco, Shabnam Shahrokh, Hedieh Balaii, Maria Valeria Corrias, Mirco Ponzoni, Amir Sadeghi and Roberto Biassoni
Microorganisms 2025, 13(8), 1941; https://doi.org/10.3390/microorganisms13081941 - 20 Aug 2025
Abstract
Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon, often associated with gut microbial dysbiosis. Although anti-TNF-α agents, such as Adalimumab (Cinnora®), are used to treat moderate-to-severe UC, the treatment response is highly variable. Identifying early microbial biomarkers [...] Read more.
Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon, often associated with gut microbial dysbiosis. Although anti-TNF-α agents, such as Adalimumab (Cinnora®), are used to treat moderate-to-severe UC, the treatment response is highly variable. Identifying early microbial biomarkers of response could help support personalized therapeutic strategies and prevent unnecessary exposure to ineffective treatments. However, the long-term effects of anti-TNF therapy on both stool and mucosal microbiota remain poorly understood. This prospective longitudinal study included 23 corticosteroid-refractory or -dependent UC patients who started Adalimumab after endoscopy-confirmed flare-ups. Stool samples and inflamed colonic biopsies were collected at baseline, and 3 and 6 months. Microbiota profiling was performed using 16S rRNA sequencing. Microbial changes were analyzed over time and compared between responders (Mayo score 0–1) and non-responders (Mayo score ≥ 2). Sixty percent of patients achieved clinical remission. In responders, stool microbiota showed increased Bacteroidetes and decreased Proteobacteria abundances, along with an enrichment of beneficial taxa including Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila. Mucosal microbiota exhibited persistent dysbiosis, characterized by an increase in Proteobacteria and a reduced Firmicutes/Proteobacteria ratio. Notably, responders showed distinct compartment-specific microbial changes, with a decrease in Gammaproteobacteria in stool and an increase in Corynebacterium in tissue. Adalimumab induces divergent microbial changes in stool and mucosa. While stool microbiota trends toward eubiosis in responders, persistent mucosal dysbiosis may reflect asymptomatic inflammation. These findings underscore the importance of niche-specific microbiome profiling in UC and support its integration into personalized treatment monitoring. Full article
(This article belongs to the Section Microbiomes)
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21 pages, 8034 KiB  
Article
Decoding Forage-Driven Microbial–Metabolite Patterns: A Multi-Omics Comparison of Eight Tropical Silage Crops
by Xianjun Lai, Siqi Liu, Yandan Zhang, Haiyan Wang and Lang Yan
Fermentation 2025, 11(8), 480; https://doi.org/10.3390/fermentation11080480 - 20 Aug 2025
Abstract
Tropical forage crops vary widely in biochemical composition, resulting in inconsistent silage quality. Understanding how plant traits shape microbial and metabolic networks during ensiling is crucial for optimizing fermentation outcomes. Eight tropical forages—Sorghum bicolor (sweet sorghum), Sorghum × drummondii (sorghum–Sudangrass hybrid), Sorghum [...] Read more.
Tropical forage crops vary widely in biochemical composition, resulting in inconsistent silage quality. Understanding how plant traits shape microbial and metabolic networks during ensiling is crucial for optimizing fermentation outcomes. Eight tropical forages—Sorghum bicolor (sweet sorghum), Sorghum × drummondii (sorghum–Sudangrass hybrid), Sorghum sudanense (Sudangrass), Pennisetum giganteum (giant Napier grass), Pennisetum purpureum cv. Purple (purple elephant grass), Pennisetum sinese (king grass), Leymus chinensis (sheep grass), and Zea mexicana (Mexican teosinte)—were ensiled under uniform conditions. Fermentation quality, bacterial and fungal communities (16S rRNA and ITS sequencing), and metabolite profiles (untargeted liquid chromatography–mass spectrometry, LC-MS) were analyzed after 60 days. Sweet sorghum and giant Napier grass showed optimal fermentation, with high lactic acid levels (111.2 g/kg and 99.4 g/kg, respectively), low NH4+-N (2.4 g/kg and 3.1 g/kg), and dominant Lactiplantibacillus plantarum. In contrast, sheep grass and Mexican teosinte exhibited poor fermentation, with high NH4+-N (6.7 and 6.1 g/kg) and Clostridium dominance. Fungal communities were dominated by Kazachstania humilis (>95%), while spoilage-associated genera such as Cladosporium, Fusarium, and Termitomyces proliferated in poorly fermented silages. Metabolomic analysis identified 15,827 features, with >3000 significantly differential metabolites between silages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed divergence in flavonoid biosynthesis, lipid metabolism, and amino acid pathways. In the sweet sorghum vs. sheep grass comparison, oxidative stress markers ((±) 9-HODE, Agrimonolide) were elevated in sheep grass, while sweet sorghum accumulated antioxidants like Vitamin D3. Giant Napier grass exhibited higher levels of antimicrobial flavonoids (e.g., Apigenin) than king grass, despite both being dominated by lactic acid bacteria. Sorghum–Sudangrass hybrid silage showed enrichment of lignan and flavonoid derivatives, while Mexican teosinte accumulated hormone-like compounds (Gibberellin A53, Pterostilbene), suggesting microbial dysbiosis. These findings indicate that silage fermentation outcomes are primarily driven by forage-intrinsic traits. A “forage–microbiota–metabolite” framework was proposed to explain how plant-specific properties regulate microbial assembly and metabolic output. These insights can guide forage selection and development of precision inoculant for high-quality tropical silage. Full article
(This article belongs to the Section Industrial Fermentation)
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17 pages, 1768 KiB  
Article
Oral Administration of an Opuntia ficus-indica Fruit Extract Induces Changes in Gut Microbiota Composition: Relationship with Its Anti-Obesity and Anti-Steatotic Effects in Rats Fed a High-Fat High-Fructose Diet
by Iker Gómez-García, Irene Besné-Eseverri, Maria P. Portillo, Alfredo Fernández-Quintela, Ligia Esperanza Díaz, Jose I. Riezu-Boj, Fermín I. Milagro and Jenifer Trepiana
Foods 2025, 14(16), 2891; https://doi.org/10.3390/foods14162891 - 20 Aug 2025
Abstract
Diseases such as obesity and metabolic-dysfunction-associated fatty liver disease (MAFLD) are often associated with changes in gut microbiota composition. The present study aims to investigate the relationship between the potential preventive effects of an Opuntia ficus-indica var. colorada cactus pulp extract on obesity [...] Read more.
Diseases such as obesity and metabolic-dysfunction-associated fatty liver disease (MAFLD) are often associated with changes in gut microbiota composition. The present study aims to investigate the relationship between the potential preventive effects of an Opuntia ficus-indica var. colorada cactus pulp extract on obesity and hepatic steatosis, and changes in gut microbiota composition, in a murine model fed a high-fat high-fructose diet. The low-dose extract was the most effective in reducing hepatic TG (−12.5%) and the weight of subcutaneous and visceral adipose tissue (−18.4% and 11.4%, respectively), while the high dose led to improved serum lipid profile (−74.2% in TG, −37.2% in total cholesterol, −50.5% in non-HDL cholesterol and +71.7% in HDL cholesterol). Opuntia extract supplementation did not prevent the dysbiosis in gut microbiota produced by the high-fat high-fructose diet. However, modifications in its composition, consistent with an increment in both Adlercreutzia muris and Cutibacterium acnes, and a reduction in Massiliimalia timonensis, were observed. It can be proposed that these changes may contribute to the extract effects against obesity and liver steatosis. Nevertheless, further research is required to establish a direct link between the anti-obesity and anti-steatotic effects and the functionality of the bacteria modified by the treatment. Full article
(This article belongs to the Special Issue Functional Foods, Gut Microbiota, and Health Benefits)
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23 pages, 10475 KiB  
Article
Flavonoids from Ficus pandurate var. angustifolia W.C. Cheng Restore Cognitive Impairment and Regulate the Gut Microbiota in Sleep-Deprived Mice
by Haochen Dai, Songmei Luo and Xin Zhang
Foods 2025, 14(16), 2888; https://doi.org/10.3390/foods14162888 - 20 Aug 2025
Abstract
Sleep deprivation (SD) induces cognitive impairment associated with gut microbiota dysbiosis, making it crucial to explore natural remedies targeting the microbiota–gut–brain axis. This study aims to investigate whether Ficus pandurata var. angustifolia W.C. Cheng (a traditional medicine–food plant rich in flavonoids) can mitigate [...] Read more.
Sleep deprivation (SD) induces cognitive impairment associated with gut microbiota dysbiosis, making it crucial to explore natural remedies targeting the microbiota–gut–brain axis. This study aims to investigate whether Ficus pandurata var. angustifolia W.C. Cheng (a traditional medicine–food plant rich in flavonoids) can mitigate cognitive impairment caused by SD by modulating the gut microbiota. The sleep-deprived mouse model was established using the multiple platform water environment method. This study investigated the effects of F. pandurata var. angustifolia flavonoids (FCFs) via behavioral tests, 16S rRNA sequencing, and biochemical analyses to assess cognitive function, gut microbiota, and related pathways. FCF alleviated SD-induced cognitive deficits, reversed gut microbiota dysbiosis (increased beneficial bacteria like Lactobacillus, reduced harmful ones like Desulfovibrio), promoted short-chain fatty acids production, improved colonic histopathology and intestinal barrier function, reduced serum lipopolysaccharide, inhibited glial cell activation and TLR4/NF-κB signaling, and regulated neurotransmitters. In conclusion, FCF ameliorates SD-induced cognitive impairment through regulating gut microbiota, enhancing intestinal barrier, and suppressing neuroinflammation via the microbiota–gut–brain axis, providing a theoretical basis for its application. Full article
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26 pages, 2284 KiB  
Article
Blood Microbiome Analysis Reveals Biomarkers of Treatment Response in Drug-Naïve Patients with First-Episode Psychosis: A Pilot Study
by Marianthi Logotheti, Thomas Gkekas, Panagiotis C. Agioutantis, Alex Hatzimanolis, Stefania Foteli, Diomi Mamma, Nikolaos C. Stefanis, Fragiskos N. Kolisis and Heleni Loutrari
Microorganisms 2025, 13(8), 1935; https://doi.org/10.3390/microorganisms13081935 - 19 Aug 2025
Abstract
Patients with First-Episode Psychosis (FEP) exhibit variable responses to antipsychotic treatment. Emerging evidence suggests that disease-related dysbiosis of gut and oropharyngeal microbiota may lead to the abnormal translocation of microorganisms via the bloodstream. This study aims to explore the blood microbiome to identify [...] Read more.
Patients with First-Episode Psychosis (FEP) exhibit variable responses to antipsychotic treatment. Emerging evidence suggests that disease-related dysbiosis of gut and oropharyngeal microbiota may lead to the abnormal translocation of microorganisms via the bloodstream. This study aims to explore the blood microbiome to identify candidate biomarkers associated with treatment outcomes in FEP. To address this, blood samples were collected from twenty drug-naïve individuals with FEP, both before and after four weeks of antipsychotic medication. DNA extracted from these samples underwent 16S rRNA gene sequencing and comprehensive bioinformatics analysis. Clinical assessments were based on the Positive and Negative Syndrome Scale and standard remission criteria. Peripheral cytokines (IL1β, TNF-α, IL10) were quantified by immunoassays. Baseline comparisons showed a significantly greater microbiome alpha diversity in remitters, along with differential prevalence in five taxa and 217 metabolic pathways. Post-treatment assessments uncovered a significantly distinct impact of antipsychotics on blood bacterial composition between remission groups, while initial differences on metabolic profiles persisted. Additionally, strong correlations were observed, linking specific taxa abundances to cytokine levels. Conclusively, this pilot study suggests that blood microbiome profiling could provide novel biomarkers for predicting therapeutic response in early psychosis, paving the way for precision medicine interventions. Full article
(This article belongs to the Special Issue Advances in Human Microbiomes)
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21 pages, 2248 KiB  
Review
Ultra-Processed Foods, Gut Microbiota, and Inflammatory Bowel Disease: A Critical Review of Emerging Evidence
by Amanda Luísa Spiller, Beatriz Gabriela da Costa, Ryan Nunes Yoshio Yoshihara, Enya Julia Zucari Nogueira, Natalia Salvador Castelhano, Andrey Santos, Maiara Brusco De Freitas, Daniéla Oliveira Magro and Ligia Yukie Sassaki
Nutrients 2025, 17(16), 2677; https://doi.org/10.3390/nu17162677 - 19 Aug 2025
Abstract
Background/Aims: Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions marked by dysregulated inflammation in the gastrointestinal tract. Although the pathophysiology of IBD remains incompletely understood, it involves complex interactions between genetic predisposition and environmental triggers, such [...] Read more.
Background/Aims: Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions marked by dysregulated inflammation in the gastrointestinal tract. Although the pathophysiology of IBD remains incompletely understood, it involves complex interactions between genetic predisposition and environmental triggers, such as gut microbiota imbalances and immune dysfunction, leading to chronic inflammation and mucosal injury. IBD affects approximately 7 million individuals globally, with prevalence increasing in Europe, North America, and Oceania. This rise parallels the growing consumption of ultra-processed foods (UPFs), which are typically rich in sugars, fats, and additives but low in fiber, vitamins, and other essential nutrients. These associations, this review critically examines the influence of UPF consumption on gut microbiota composition and function and its potential link to IBD. Methods: A bibliographic search was conducted in the SciELO, PubMed, and Cochrane databases. Results and Conclusions: High UPF consumption is associated with intestinal dysbiosis, marked by reduced microbial diversity, decreased short-chain fatty acid production, impaired barrier integrity, and mucus layer disruption. These alterations may promote immune-mediated diseases, including IBD, where dysbiosis is often characterized by an overgrowth of pathogenic bacteria such as Clostridium and Enterococcus, ultimately triggering inflammatory responses in the host. Full article
(This article belongs to the Special Issue Diet, Gut Health, and Clinical Nutrition)
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25 pages, 1806 KiB  
Review
Beyond the Skin: Exploring the Gut–Skin Axis in Chronic Spontaneous Urticaria and Other Inflammatory Skin Diseases
by Laura Haidar, Camelia Felicia Bănărescu, Cristina Uța, Elena-Larisa Zimbru, Răzvan-Ionuț Zimbru, Alexandru Tîrziu, Raul Pătrașcu, Alina-Florina Șerb, Marius Georgescu, Daciana Nistor and Carmen Panaitescu
Biomedicines 2025, 13(8), 2014; https://doi.org/10.3390/biomedicines13082014 - 19 Aug 2025
Abstract
Emerging evidence suggests a critical role of the gut microbiome in modulating systemic immune responses, with increasing relevance in dermatological diseases. Chronic spontaneous urticaria (CSU), traditionally viewed as an isolated cutaneous disorder, is now recognized as a systemic immune condition involving complex interactions [...] Read more.
Emerging evidence suggests a critical role of the gut microbiome in modulating systemic immune responses, with increasing relevance in dermatological diseases. Chronic spontaneous urticaria (CSU), traditionally viewed as an isolated cutaneous disorder, is now recognized as a systemic immune condition involving complex interactions between innate and adaptive immunity, mast cell dysregulation, and non-IgE-mediated pathways. This review explores the gut–skin axis as a unifying concept linking intestinal dysbiosis to inflammatory skin diseases, including atopic dermatitis, psoriasis, rosacea, and acne. Special emphasis is placed on CSU, where altered gut microbial composition, characterized by reduced diversity, depletion of short-chain fatty acid-producing bacteria, and expansion of Proteobacteria, may contribute to increased intestinal permeability, systemic immune activation via toll-like receptors, and heightened mast cell sensitivity. We discuss findings from animal models demonstrating that gut microbiota modulation can attenuate mast cell hyperreactivity and reduce urticarial symptoms. In parallel, we examine clinical evidence supporting the potential role of probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation as adjunctive strategies in CSU management. Despite promising findings, challenges remain in translating microbiome research into effective therapies due to interindividual variability, the complexity of host–microbiome interactions, and a lack of standardized protocols. Future research should focus on identifying predictive microbial patterns and developing personalized microbiome-targeted interventions. Understanding the bidirectional gut–skin relationship may open new therapeutic avenues beyond symptomatic treatment, positioning the microbiome as a novel target in CSU and related inflammatory dermatoses. Full article
(This article belongs to the Special Issue Urticaria: New Insights into Pathogenesis, Diagnosis and Therapy)
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26 pages, 857 KiB  
Review
The Infant Oral Microbiome: Developmental Dynamics, Modulating Factors, and Implications for Oral and Systemic Health
by Paula Olate, Ailín Martínez, Eulàlia Sans-Serramitjana, Matías Cortés, Rommy Díaz, Genisley Hernández, Erwin A. Paz, Néstor Sepúlveda and John Quiñones
Int. J. Mol. Sci. 2025, 26(16), 7983; https://doi.org/10.3390/ijms26167983 - 19 Aug 2025
Abstract
The infant oral microbiome is a complex and dynamic microbial community that undergoes various transformations during human development. From birth, these microorganisms are modulated by factors such as birth type, nutrition, oral hygiene, hormonal changes, and environmental and socioeconomic conditions. These elements interact [...] Read more.
The infant oral microbiome is a complex and dynamic microbial community that undergoes various transformations during human development. From birth, these microorganisms are modulated by factors such as birth type, nutrition, oral hygiene, hormonal changes, and environmental and socioeconomic conditions. These elements interact continuously, shaping the diversity and stability of the oral microbiome and consequently influencing the oral and general health of individuals. The main objective of this study was to review the literature on the evolution of the oral microbiome at different stages of growth, with special emphasis on the maintenance of dental homeostasis and prevention of pathologies such as caries and periodontitis. A bibliographic review of scientific databases was conducted, focusing on the last decade. In general, oral microbiome dysbiosis increases the risk of oral diseases and systemic conditions. Diet, parental practices, and horizontal transmission of bacteria from caregivers have been shown to modulate and influence the composition and functioning of the infant oral microbiome. Despite these advances, gaps remain in our understanding of the impact of the pediatric oral microbiome on long-term comprehensive health. Therefore, longitudinal research is needed to understand the development of the oral microbiome and its potential role in early prediction, prevention, and treatment of oral and systemic diseases. Full article
(This article belongs to the Topic Oral Health Management and Disease Treatment)
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13 pages, 293 KiB  
Review
Year in Review: Advances in Research in Gout Pathophysiology in 2024
by Rocio Paz Gonzalez and Monica Guma
Gout Urate Cryst. Depos. Dis. 2025, 3(3), 15; https://doi.org/10.3390/gucdd3030015 - 18 Aug 2025
Abstract
This review provides an overview of the most significant developments in gout pathophysiology research published in 2024. Thirteen studies were selected based on originality, scientific rigor, and potential clinical impact and grouped into four major categories: inflammation and pain mechanisms (LRRC8 anion channels, [...] Read more.
This review provides an overview of the most significant developments in gout pathophysiology research published in 2024. Thirteen studies were selected based on originality, scientific rigor, and potential clinical impact and grouped into four major categories: inflammation and pain mechanisms (LRRC8 anion channels, CXCL5-CXCR2 axis, CD38 and NAD+ metabolism, PLK1 and NLRP3 inflammasome localization, and IFN1 suppression), biomarkers and proteomics (scRNA-seq reveals monocyte and T-cell flare signatures, and Olink serum profiling reveals a proinflammatory signature in hyperuricemia and also identifies TNFSF14 as a novel flare biomarker, while a multi-omics integrative study implicates TRIM46 as a key causal gene), gut virome, and novel therapies (vagus nerve stimulation, biomimetic nanosystem, and restoration of Urate Oxidase (Uox) function). The studies selected focused primarily on work on subjects other than on hyperuricemia. The findings collectively expand our understanding of gout’s complex pathophysiology and highlight potential strategies for diagnosis, management, and innovative treatments. Full article
18 pages, 969 KiB  
Review
Obesity-Mediated Inflammation and Its Influence on Inflammatory Bowel Disease: Pathophysiology, Clinical Impact, and Therapeutic Implications
by Diego Casas-Deza, Santiago García-López, Vanesa Bernal-Monterde, Cristina Polo-Cuadro, Carmen Yagüe-Caballero and José M. Arbones-Mainar
Biomolecules 2025, 15(8), 1185; https://doi.org/10.3390/biom15081185 - 18 Aug 2025
Abstract
Obesity and inflammatory bowel disease (IBD) are two chronic conditions whose prevalence continues to rise globally. Emerging evidence suggests a bidirectional interplay between them, mediated by shared pathophysiological pathways. This narrative review explores the mechanisms Ilinking obesity to IBD development and progression, focusing [...] Read more.
Obesity and inflammatory bowel disease (IBD) are two chronic conditions whose prevalence continues to rise globally. Emerging evidence suggests a bidirectional interplay between them, mediated by shared pathophysiological pathways. This narrative review explores the mechanisms Ilinking obesity to IBD development and progression, focusing on the role of adipose tissue dysfunction. Both diseases exhibit intestinal dysbiosis, low-grade systemic inflammation, and impaired epithelial barrier integrity, contributing to immune activation. Visceral adiposity, particularly mesenteric fat, acts as an immunometabolic organ producing cytokines and adipokines that may exacerbate intestinal inflammation. In Crohn’s disease, mesenteric fat expansion, or “creeping fat”, is associated with transmural inflammation, fibrosis, and luminal narrowing. Epidemiological data on obesity as a risk factor for IBD remain inconsistent due to methodological heterogeneity and confounders. Similarly, the impact of obesity on IBD outcomes, including disease activity, phenotype, and the need for surgery, is debated. While mesenteric surgical approaches like Kono-S anastomosis showed initial promise in reducing recurrence, recent randomized trials offer conflicting results. Finally, metabolic drugs such as statins, metformin, and GLP-1 receptor agonists have demonstrated anti-inflammatory properties with potential utility in IBD management. Prospective studies are warranted to elucidate the clinical significance of obesity and metabolic dysfunction in IBD and evaluate targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Metabolic Inflammation and Insulin Resistance in Obesity)
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18 pages, 1078 KiB  
Review
The Obesity–Periodontitis Axis: Microbial Mechanisms and Clinical Implications
by Evelyn Lins Araújo, Lorena Abreu Fernandes, Tamires Szeremeske Miranda and Sabri Saeed Sanabani
Oral 2025, 5(3), 61; https://doi.org/10.3390/oral5030061 - 18 Aug 2025
Abstract
Background: Obesity and periodontitis are two chronic inflammatory diseases with a bidirectional relationship possibly mediated by microbial and immunologic signaling pathways. This narrative review aims to investigate how microbial dysbiosis and inflammation link these diseases, focusing on the interactions between the oral and [...] Read more.
Background: Obesity and periodontitis are two chronic inflammatory diseases with a bidirectional relationship possibly mediated by microbial and immunologic signaling pathways. This narrative review aims to investigate how microbial dysbiosis and inflammation link these diseases, focusing on the interactions between the oral and gut microbiomes. Materials and methods: Peer-reviewed studies (2015–2024) from PubMed, MEDLINE, Ovid and Google Scholar were selected for their relevance to microbial dysbiosis and inflammation, prioritizing clear methodology. Non-peer-reviewed sources or studies lacking microbial/inflammatory data were excluded. Conflicting results and methodological differences, including sampling and study design, were assessed qualitatively on the basis of coherence and methodological rigor. Results: Obesity has been shown to significantly alter the composition of the oral microbiome, characterized by reduced diversity and an increased Firmicutes/Bacteroidetes ratio. At the same time, periodontal pathogens such as Porphyromonas gingivalis can invade the gut, impair barrier function and promote systemic inflammation. Both diseases share common inflammatory pathways involving adipokines and immune-system dysregulation, creating a feedback loop that exacerbates disease progression in both conditions. Obesity also appears to impair the effectiveness of conventional periodontal treatments. Conclusions: The microbial axis between the oral cavity and the gut represents a central pathway in the complex interactions between obesity and periodontitis. This relationship involves microbial dysbiosis, bacterial translocation and shared inflammatory mechanisms that collectively contribute to disease progression. Clinical relevance: A better understanding of the relationship between obesity and periodontitis supports the development of customized treatment strategies for obese patients with periodontal disease. Future research should focus on developing targeted interventions that address both conditions simultaneously to improve patient outcomes and develop more effective prevention and treatment strategies. Full article
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20 pages, 598 KiB  
Review
Oral Microbiome as a Biomarker and Therapeutic Target in Head and Neck Cancer: Current Insights and Future Directions
by Saad Ahmad, Dasantha Jayamanne, Sarah Bergamin, Anna Lawless, Alexander Guminski, Adrian Lee, Alexander Yuile, Helen Wheeler, Thomas Eade, Michael Back, Mark Molloy and Byeongsang Oh
Cancers 2025, 17(16), 2667; https://doi.org/10.3390/cancers17162667 - 15 Aug 2025
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Abstract
Background/Objectives: The oral microbiome has been implicated in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). This review examines the association between specific oral bacterial taxa and HNSCC. Methods: A systematic review was conducted following the Preferred Reporting Items [...] Read more.
Background/Objectives: The oral microbiome has been implicated in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). This review examines the association between specific oral bacterial taxa and HNSCC. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to examine the relationship between the oral microbiome and HNSCC. A comprehensive literature search was conducted in databases including EMBASE, Cochrane Library, Web of Science, Medline, and PubMed. Results: Following the screening of 284 articles, 21 studies met the inclusion criteria, comprising 1023 HNSCC patients (male: n = 806, 79%; female: n = 217, 21%) and 837 healthy controls (male: n = 622, 74%; female: n = 215, 25.7%). Although findings on alpha diversity were inconsistent, a significant difference in beta diversity was consistently reported between HNSCC patients and healthy controls. HNSCC patients exhibited higher relative abundances of Firmicutes and Synergistetes at the phylum level; Fusobacterium, Prevotella, Porphyromonas, Parvimonas, and Peptostreptococcus at the genus level; and Fusobacterium nucleatum, Prevotella intermedia, Lactobacillus spp., and Porphyromonas gingivalis at the species level. In contrast, healthy controls showed higher abundances of Proteobacteria and Actinobacteria at the phylum level; Streptococcus, Actinomyces, Corynebacterium, Rothia, and Veillonella at the genus level; and Haemophilus influenzae, Rothia mucilaginosa, and Streptococcus mitis at the species level in most studies. Conclusions: The findings indicate distinct alterations in oral microbiome diversity and composition among HNSCC patients, highlighting the role of microbial dysbiosis in cancer progression. Standardized protocols for oral sample collection and microbiota analysis are essential to facilitate more robust, comparable, and clinically meaningful research outcomes. Full article
(This article belongs to the Special Issue Gut Microbiome, Diet and Cancer Risk)
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40 pages, 1275 KiB  
Review
Do Long COVID and COVID Vaccine Side Effects Share Pathophysiological Picture and Biochemical Pathways?
by Jean-François Lesgards, Dominique Cerdan and Christian Perronne
Int. J. Mol. Sci. 2025, 26(16), 7879; https://doi.org/10.3390/ijms26167879 - 15 Aug 2025
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Abstract
COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these [...] Read more.
COVID affects around 400 million individuals today with a strong economic impact on the global economy. The list of long COVID symptoms is extremely broad because it is derived from neurological, cardiovascular, respiratory, immune, and renal dysfunctions and damages. We review here these pathophysiological manifestations and the predictors of this multi-organ pathology like the persistence of the virus, altered endothelial function, unrepaired tissue damage, immune dysregulation, and gut dysbiosis. We also discuss the similarities between long COVID and vaccine side effects together with possible common immuno-inflammatory pathways. Since the spike protein is present in SARS-CoV-2 (and its variants) but also produced by the COVID vaccines, its toxicity may also apply to all mRNA or adenoviral DNA vaccines as they are based on the production of a very similar spike protein to the virus. After COVID infection or vaccination, the spike protein can last for months in the body and may interact with ACE2 receptors and mannan-binding lectin (MBL)/mannan-binding lectin serine protease 2 (MASP-2), which are present almost everywhere in the organism. As a result, the spike protein may be able to trigger inflammation in a lot of organs and systems similar to COVID infection. We suggest that three immuno-inflammatory pathways are particularly key and responsible for long COVID and COVID vaccine side effects, as it has been shown for COVID, which may explain in large part their strong similarities: the renin–angiotensin–aldosterone system (RAAS), the kininogen–kinin–kallikrein system (KKS), and the lectin complement pathway. We propose that therapeutic studies should focus on these pathways to propose better cures for both long COVID as well as for COVID vaccine side effects. Full article
(This article belongs to the Special Issue Molecular Research and Insights into COVID-19: Third Edition)
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15 pages, 3220 KiB  
Article
Intrathecal Anti-Akkermansia muciniphila IgG Responses in Multiple Sclerosis Patients Linked to CSF Immune Cells and Disease Activity
by Carolina Cruciani, Camille Mathé, Marco Puthenparampil, Paula Tomas-Ojer, Maria José Docampo, Roland Opfer, Ilijas Jelcic, Arnaud B. Nicot, David-Axel Laplaud, Roland Martin, Mireia Sospedra and Laureline Berthelot
J. Clin. Med. 2025, 14(16), 5771; https://doi.org/10.3390/jcm14165771 - 15 Aug 2025
Viewed by 183
Abstract
Background/Objectives: Gut microbial dysbiosis, leaky gut, and increased transepithelial translocation of commensal bacteria have been documented in multiple sclerosis (MS). Intrathecal IgGs specific for Akkermansia muciniphila, a gut bacterium, are increased in patients with MS and associated with clinical disability. Our [...] Read more.
Background/Objectives: Gut microbial dysbiosis, leaky gut, and increased transepithelial translocation of commensal bacteria have been documented in multiple sclerosis (MS). Intrathecal IgGs specific for Akkermansia muciniphila, a gut bacterium, are increased in patients with MS and associated with clinical disability. Our objective here was to explore the putative involvement of intrathecal anti-A. muciniphila IgG in MS pathogenesis by characterizing patients with different anti-A. muciniphila IgG indices. Methods: Serum and intrathecal IgG specific for A. muciniphila and other gut bacteria, as well as routine cerebrospinal fluid (CSF) parameters, were measured in 61 patients with MS. Examination of these patients included immunophenotyping of CSF-infiltrating and paired circulating lymphocytes, intrathecal markers of neurodegeneration and inflammation, and a detailed characterization of demographic, clinical, and magnetic resonance imaging (MRI) features. Results: Plasma blasts (p < 0.01), B cells (p < 0.01), and Th2 cells (p < 0.01), which might be involved in antibody production, were increased in the CSF of these patients, as well as blood pro-inflammatory Th17 cells (p < 0.05). Anti-A. muciniphila IgG indices were negatively associated with blood-brain barrier (BBB) permeability and circulating monocytes (p < 0.001), and positively with brain lesion load (p < 0.01). Conclusions: The differences between patients with low and high anti-A. muciniphila IgG indexes regarding BBB permeability, CSF cell infiltrates, and pro-inflammatory peripheral immune cells, as well as imaging features, support a role of anti-A. muciniphila immune response in MS pathogenesis. Full article
(This article belongs to the Section Immunology)
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Review
A Comprehensive Review of Antibiotic Resistance in the Oral Microbiota: Mechanisms, Drivers, and Emerging Therapeutic Strategies
by Ena Kulis, Ivan Cvitkovic, Nikola Pavlovic, Marko Kumric, Doris Rusic and Josko Bozic
Antibiotics 2025, 14(8), 828; https://doi.org/10.3390/antibiotics14080828 - 15 Aug 2025
Viewed by 364
Abstract
Recent advances in microbiome research have highlighted the oral cavity as a complex and dynamic ecosystem, home to over 700 microbial species that play critical roles in both oral and systemic health. The oral microbiota not only maintains local tissue homeostasis but also [...] Read more.
Recent advances in microbiome research have highlighted the oral cavity as a complex and dynamic ecosystem, home to over 700 microbial species that play critical roles in both oral and systemic health. The oral microbiota not only maintains local tissue homeostasis but also serves as a reservoir for antimicrobial resistance (AMR) genes, contributing to the global spread of resistance. Frequent and sometimes inappropriate antibiotic use in dental practice, along with exposure to antiseptics and biocides, drives the emergence and horizontal transfer of resistance determinants within oral biofilms. This review synthesizes current knowledge on the molecular mechanisms and ecological drivers of AMR in the oral microbiome, emphasizing the clinical implications of dysbiosis and drug-resistant infections. The authors advocate for the development of dental clinical guidelines tailored to the unique characteristics of the oral microbiota, focusing on personalized therapy through molecular diagnostics, standardized AMR risk assessment, and the integration of non-antibiotic strategies such as probiotics and photodynamic therapy. Continuous education in antimicrobial stewardship and the implementation of oral-specific AMR surveillance is also highlighted as an essential component of effective resistance management. To support rational prescribing, a dedicated mobile application has been developed, leveraging microbiota data and resistance profiles to guide evidence-based, targeted therapy and reduce unnecessary antibiotic use. Collectively, these strategies aim to preserve antibiotic efficacy, ensure patient safety, and promote sustainable infection management in the dental field. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Oral Diseases)
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