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Keywords = aging microbiome

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56 pages, 1035 KiB  
Review
Trace Elements—Role in Joint Function and Impact on Joint Diseases
by Łukasz Bryliński, Katarzyna Brylińska, Filip Woliński, Jolanta Sado, Miłosz Smyk, Olga Komar, Robert Karpiński, Marcin Prządka and Jacek Baj
Int. J. Mol. Sci. 2025, 26(15), 7493; https://doi.org/10.3390/ijms26157493 (registering DOI) - 2 Aug 2025
Abstract
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a [...] Read more.
Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article
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26 pages, 13311 KiB  
Article
A Spatiotemporal Atlas of the Gut Microbiota in Macaca mulatta brevicaudus: Implications for Health and Environment
by Jingli Yuan, Zewen Sun, Ruiping Sun, Jun Wang, Chengfeng Wu, Baozhen Liu, Xinyuan Zhao, Qiang Li, Jianguo Zhao and Keqi Cai
Biology 2025, 14(8), 980; https://doi.org/10.3390/biology14080980 (registering DOI) - 1 Aug 2025
Abstract
The gut microbiota of macaques, highly homologous to humans in biological characteristics and metabolic functions, serves as an ideal model for studying the mechanisms of human intestinal diseases and therapeutic approaches. A comprehensive characterization of the macaque gut microbiota provides unique insights into [...] Read more.
The gut microbiota of macaques, highly homologous to humans in biological characteristics and metabolic functions, serves as an ideal model for studying the mechanisms of human intestinal diseases and therapeutic approaches. A comprehensive characterization of the macaque gut microbiota provides unique insights into human health and disease. This study employs metagenomic sequencing to assess the gut microbiota of wild M. mulatta brevicaudus across various ages, sexes, and physiological states. The results revealed that the dominant bacterial species in various age groups included Segatella copri and Bifidobacterium adolescentis. The predominant bacterial species in various sexes included Alistipes senegalensis and Parabacteroides (specifically Parabacteroides merdae, Parabacteroides johnsonii, and Parabacteroides sp. CT06). The dominant species during lactation and non-lactation periods were identified as Alistipes indistinctus and Capnocytophaga haemolytica. Functional analysis revealed significant enrichment in pathways such as global and overview maps, carbohydrate metabolism and amino acid metabolism. This study enhances our understanding of how age, sex, and physiological states shape the gut microbiota in M. mulatta brevicaudus, offering a foundation for future research on (1) host–microbiome interactions in primate evolution, and (2) translational applications in human health, such as microbiome-based therapies for metabolic or immune-related disorders. Full article
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18 pages, 3360 KiB  
Article
Hydrogen Sulfide Has a Minor Impact on Human Gut Microbiota Across Age Groups
by Linshu Liu, Johanna M. S. Lemons, Jenni Firrman, Karley K. Mahalak, Venkateswari J. Chetty, Adrienne B. Narrowe, Stephanie Higgins, Ahmed M. Moustafa, Aurélien Baudot, Stef Deyaert and Pieter Van den Abbeele
Sci 2025, 7(3), 102; https://doi.org/10.3390/sci7030102 (registering DOI) - 1 Aug 2025
Abstract
Hydrogen sulfide (H2S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H2S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health [...] Read more.
Hydrogen sulfide (H2S) can be produced from the metabolism of foods containing sulfur in the gastrointestinal tract (GIT). At low doses, H2S regulates the gut microbial community and supports GIT health, but depending on dose, age, and individual health conditions, it may also contribute to inflammatory responses and gut barrier dysfunction. Controlling H2S production in the GIT is important for maintaining a healthy gut microbiome. However, research on this subject is limited due to the gaseous nature of the chemical and the difficulty of accessing the GIT in situ. In the present ex vivo experiment, we used a single-dose sodium sulfide preparation (SSP) as a H2S precursor to test the effect of H2S on the human gut microbiome across different age groups, including breastfed infants, toddlers, adults, and older adults. Metagenomic sequencing and metabolite measurements revealed that the development of the gut microbial community and the production of short-chain fatty-acids (SCFAs) were age-dependent; that the infant and the older adult groups were more sensitive to SSP exposure; that exogeneous SSP suppressed SCFA production across all age groups, except for butyrate in the older adult group, suggesting that H2S selectively favors specific gut microbial processes. Full article
(This article belongs to the Section Biology Research and Life Sciences)
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13 pages, 1191 KiB  
Article
Gut Microbiome Structural Dynamics in Japanese Quail Across Developmental Stages
by Daniela da Silva Gomes, Alexandre Lemos de Barros Moreira Filho, Wydemberg José de Araújo, Gustavo Felipe Correia Sales, Hemilly Marques da Silva, Thalis José de Oliveira, Antonio Venício de Sousa, Celso José Bruno de Oliveira and Patrícia Emília Naves Givisiez
Microbiol. Res. 2025, 16(8), 167; https://doi.org/10.3390/microbiolres16080167 - 1 Aug 2025
Abstract
The cecal microbiota is essential for intestinal health and performance. This study describes the succession patterns of the cecal microbiota in Japanese quail (Coturnix japonica) until 42 days of age. Sixty quails were raised using standard conditions and fed corn–soybean meal [...] Read more.
The cecal microbiota is essential for intestinal health and performance. This study describes the succession patterns of the cecal microbiota in Japanese quail (Coturnix japonica) until 42 days of age. Sixty quails were raised using standard conditions and fed corn–soybean meal diets. Cecal contents were sampled from five birds weekly from 7 to 42 days of age and submitted to Illumina 16S rRNA sequencing for metabarcoding analysis. Diversity and functional prediction were carried out with QIIME2, PICRUSt2, STAMP and MicrobiomeAnalyst 2.0. Firmicutes increased from 50% at 7 days to more than 80% at 42 days, whereas Bacteroidota decreased from 45% to 12% in the same period. Alpha diversity progressively increased with age, indicating a richer and more balanced microbiota at later ages. Genera such as Bacteroides were predominant in the beginning and later were replaced by Lachnospiraceae, Ruminococcus and Faecalibacterium. These developmental taxonomic features aligned with significant shifts in ten metabolic pathways identified by prediction, revealing a transition from biosynthetic functions to complex carbohydrate metabolism and cell wall biosynthesis. The first seven days are considered a critical window for probiotics intervention, which may favor the establishment of a microbiota that is more stable and beneficial to quail performance. Full article
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10 pages, 478 KiB  
Review
Chewing Matters: Masticatory Function, Oral Microbiota, and Gut Health in the Nutritional Management of Aging
by Monia Lettieri, Alessio Rosa, Fabrizio Spataro, Giovanni Capria, Paolo Barnaba, Marco Gargari and Mirko Martelli
Nutrients 2025, 17(15), 2507; https://doi.org/10.3390/nu17152507 - 30 Jul 2025
Viewed by 188
Abstract
Aging is a multifactorial process that affects various physiological functions, including masticatory performance, which is crucial for oral health and nutritional well-being. Impaired masticatory function, often due to factors such as tooth loss, reduced salivation, or muscle atrophy, can lead to significant nutritional [...] Read more.
Aging is a multifactorial process that affects various physiological functions, including masticatory performance, which is crucial for oral health and nutritional well-being. Impaired masticatory function, often due to factors such as tooth loss, reduced salivation, or muscle atrophy, can lead to significant nutritional challenges and compromise the overall health of elderly individuals. Recent research has illuminated the interconnectedness of masticatory function, oral microbiota, and gut health, suggesting that altered chewing ability may disrupt oral microbial communities, which in turn affect gastrointestinal health and systemic inflammation. This commentary review provides a comprehensive analysis of the role of masticatory function in aging, exploring its impact on the oral microbiota, gut health, and broader nutritional status. We discuss the potential consequences of impaired mastication, including malnutrition, dysbiosis, and gastrointestinal disorders, and explore possible strategies for improving masticatory function and maintaining a healthy gut microbiome through interventions like dietary modifications, oral care, and rehabilitation. We aim to underscore the importance of integrating masticatory function management into the broader context of aging-related healthcare, promoting holistic, multidisciplinary approaches to support nutritional needs and quality of life in older adults. Full article
(This article belongs to the Special Issue Exploring the Lifespan Dynamics of Oral–Gut Microbiota Interactions)
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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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33 pages, 1137 KiB  
Review
Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan
by Deasy Fetarayani, Mega Kahdina, Alief Waitupu, Laras Pratiwi, Mukti Citra Ningtyas, Galih Januar Adytia and Henry Sutanto
Med. Sci. 2025, 13(3), 100; https://doi.org/10.3390/medsci13030100 - 28 Jul 2025
Viewed by 422
Abstract
Aging is associated with complex immune dysfunction that contributes to the onset and progression of the “geriatric giants”, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell [...] Read more.
Aging is associated with complex immune dysfunction that contributes to the onset and progression of the “geriatric giants”, including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation—or “inflammaging”—amplifies systemic decline. Key molecular pathways such as NF-κB, mTOR, and the NLRP3 inflammasome mediate immune aging, interacting with oxidative stress, mitochondrial dysfunction, and epigenetic modifications. These processes not only impair infection control and vaccine responsiveness but also promote tissue degeneration and multimorbidity. This review explores emerging interventions—ranging from senolytics and immunonutrition to microbiome-targeted therapies and exercise—that may restore immune homeostasis and extend healthspan. Despite advances, challenges remain in translating immunological insights into clinical strategies tailored to older adults. Standardization in microbiome trials and safety optimization in senolytic therapies are critical next steps. Integrating geroscience into clinical care could help to mitigate the burden of aging-related diseases by targeting fundamental drivers of immune dysfunction. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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25 pages, 3631 KiB  
Article
Prebiotic Xylo-Oligosaccharides Modulate the Gut Microbiome to Improve Innate Immunity and Gut Barrier Function and Enhance Performance in Piglets Experiencing Post-Weaning Diarrhoea
by James S. Stanley, Stephen C. Mansbridge, Michael R. Bedford, Ian F. Connerton and Kenneth H. Mellits
Microorganisms 2025, 13(8), 1760; https://doi.org/10.3390/microorganisms13081760 - 28 Jul 2025
Viewed by 321
Abstract
During commercial pig production, weaning is a major stressor that disrupts the gut microbiome, compromises intestinal barrier integrity, and increases the susceptibility of piglets to pathogens. This often results in post-weaning diarrhoea (PWD), leading to growth retardation, morbidity, and economic loss. This study [...] Read more.
During commercial pig production, weaning is a major stressor that disrupts the gut microbiome, compromises intestinal barrier integrity, and increases the susceptibility of piglets to pathogens. This often results in post-weaning diarrhoea (PWD), leading to growth retardation, morbidity, and economic loss. This study investigated the effects of dietary xylo-oligosaccharide (XOS) supplementation on the growth performance and gut health of 216 piglets with naturally occurring PWD. Piglets received either 0 (CON), 50 (XOS-50), or 500 (XOS-500) mg XOS/kg feed from weaning at 28 days of age (d1) for 54 days. XOS-500 significantly improved body weight at d22 and d54, but had no effect on average daily gain, daily feed intake (DFI), or feed conversion ratio. The intestinal microbiota alpha-diversity was unaffected by XOS, though jejunal beta diversity differed between CON and XOS-500 groups at d22. Jejunal Chao richness correlated positively with d54 body weight, while ileal Chao richness correlated negatively with DFI. Salmonella was present in all diet groups but did not differ in abundance; however, the levels were negatively correlated with alpha diversity. XOSs increased Lactobacillus (d22, d54) and Clostridium_XI (d22), while reducing Veillonellaceae spp. (d22). XOSs reduced jejunal goblet cell (GC) density at d22 but increased duodenal and jejunal GCs and reduced duodenal crypt depth at d54. XOSs upregulated the genes for the tight junction proteins CLDN2, CLDN3, ALPI, and ZO-1, while downregulating the cytokine IL-8. These findings highlight XOSs’ potential to improve growth and gut health in weaning piglets with naturally occurring PWD, to maintain productivity and enhance welfare. Full article
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19 pages, 4491 KiB  
Article
Temporal Dynamics of Fecal Microbiome and Short-Chain Fatty Acids in Sows from Early Pregnancy to Weaning
by Sui Liufu, Xin Xu, Qun Lan, Bohe Chen, Kaiming Wang, Lanlin Xiao, Wenwu Chen, Wu Wen, Caihong Liu, Lei Yi, Jingwen Liu, Xianchuang Fu and Haiming Ma
Animals 2025, 15(15), 2209; https://doi.org/10.3390/ani15152209 - 27 Jul 2025
Viewed by 238
Abstract
Although age-related changes in the gut microbiome of pigs have been extensively studied, the dynamic patterns of fecal microbiota and SCFAs during the gestation-to-weaning period in sows remain poorly characterized. We aim to characterize the changes in fecal microbiota and SCFAs from pregnancy [...] Read more.
Although age-related changes in the gut microbiome of pigs have been extensively studied, the dynamic patterns of fecal microbiota and SCFAs during the gestation-to-weaning period in sows remain poorly characterized. We aim to characterize the changes in fecal microbiota and SCFAs from pregnancy to weaning, and to investigate their associations with maternal weight gain during gestation. We systematically collected 100 fecal samples at four time points (day 30 of pregnancy (T1), 1–2 days before delivery (T2), day 10 after delivery (T3), and day 21 of weaning stage (T3)), and measured the body weight of sows at T1 (132 kg ± 10.8) and T2 (205 kg ± 12.1). The primary nutrient components of the diets during the gestation and lactation periods are summarized. All fecal samples were subjected to 16S rRNA gene sequencing. We found that a high proportion of crude fiber (bran) is a key feature of the gestation diet, which may affect enterotype shifts and gut microbial composition. Sows fed a high-fiber diet showed significant enrichment of gut microbiota, including genera such as Prevotellaceae_UCG-003, Prevotellaceae_NK3B31_group, and Prevotella_9 during the gestational period (LDA score > 2). Moreover, Eubacterium_coprostanoligenes_group (average relative abundance: 5.5%) and Lachnospiraceae_NK4A136_group (average relative abundance: 2.5%) were the dominant bacteria during the lactation stage. Fecal propionate and butyrate levels were lowest in late gestation, and propionate negatively and acetate positively correlated with body weight change (p < 0.05). Additionally, certain Prevotella taxa were associated with arachidonic acid metabolism and acetate production (p < 0.05). Our study identified key microbial communities across four stages from gestation to weaning and revealed that dietary patterns can shape the sow gut microbiota. Furthermore, we observed significant correlations between SCFAs and body weight change during pregnancy. These findings provide a scientific basis and theoretical support for future strategies aimed at modulating gut microbiota and targeting SCFAs to improve maternal health and productivity throughout the gestation-to-weaning period. Full article
(This article belongs to the Section Pigs)
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28 pages, 1210 KiB  
Review
Metformin Beyond Diabetes: A Precision Gerotherapeutic and Immunometabolic Adjuvant for Aging and Cancer
by Abdul Rehman, Shakta Mani Satyam, Mohamed El-Tanani, Sainath Prabhakar, Rashmi Kumari, Prakashchandra Shetty, Sara S. N. Mohammed, Zaina Nafees and Basma Alomar
Cancers 2025, 17(15), 2466; https://doi.org/10.3390/cancers17152466 - 25 Jul 2025
Viewed by 237
Abstract
Metformin, a long-established antidiabetic agent, is undergoing a renaissance as a prototype gerotherapeutic and immunometabolic oncology adjuvant. Mechanistic advances reveal that metformin modulates an integrated network of metabolic, immunological, microbiome-mediated, and epigenetic pathways that impact the hallmarks of aging and cancer biology. Clinical [...] Read more.
Metformin, a long-established antidiabetic agent, is undergoing a renaissance as a prototype gerotherapeutic and immunometabolic oncology adjuvant. Mechanistic advances reveal that metformin modulates an integrated network of metabolic, immunological, microbiome-mediated, and epigenetic pathways that impact the hallmarks of aging and cancer biology. Clinical data now demonstrate its ability to reduce cancer incidence, enhance immunotherapy outcomes, delay multimorbidity, and reverse biological age markers. Landmark trials such as UKPDS, CAMERA, and the ongoing TAME study illustrate its broad clinical impact on metabolic health, cardiovascular risk, and age-related disease trajectories. In oncology, trials such as MA.32 and METTEN evaluate its influence on progression-free survival and tumor response, highlighting its evolving role in cancer therapy. This review critically synthesizes the molecular underpinnings of metformin’s polypharmacology, examines results from pivotal clinical trials, and compares its effectiveness with emerging gerotherapeutics and senolytics. We explore future directions, including optimized dosing, biomarker-driven personalization, rational combination therapies, and regulatory pathways, to expand indications for aging and oncology. Metformin stands poised to play a pivotal role in precision strategies that target the shared roots of aging and cancer, offering scalable global benefits across health systems. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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26 pages, 764 KiB  
Review
The Role of Oxidative Stress in Skin Disorders Associated with Alcohol Dependency and Antioxidant Therapies
by Joanna Wróblewska, Anna Długosz, Damian Czarnecki, Wioletta Tomaszewicz, Błażej Błaszak, Joanna Szulc and Weronika Wróblewska
Molecules 2025, 30(15), 3111; https://doi.org/10.3390/molecules30153111 - 25 Jul 2025
Viewed by 390
Abstract
Alcohol dependency is a complex and chronic condition that negatively impacts multiple organ systems, including the skin. A key pathological factor in this process is oxidative stress, leading to progressive cellular damage, chronic inflammation, and accelerated cutaneous aging. Alcohol metabolism generates reactive oxygen [...] Read more.
Alcohol dependency is a complex and chronic condition that negatively impacts multiple organ systems, including the skin. A key pathological factor in this process is oxidative stress, leading to progressive cellular damage, chronic inflammation, and accelerated cutaneous aging. Alcohol metabolism generates reactive oxygen species (ROS), which overwhelm endogenous antioxidant defenses and contribute to a range of skin alterations, including nonspecific changes such as xerosis, erythema, and wrinkle formation, as well as inflammatory and neoplastic skin disorders. Additionally, alcohol-induced alterations of the skin microbiome may further exacerbate skin barrier dysfunction and inflammatory responses. This review explores the biochemical mechanisms and skin microbiome alterations linking alcohol-induced oxidative stress to skin damage and disease. Furthermore, it evaluates the therapeutic potential of antioxidant-based interventions, both natural and synthetic. Antioxidants may offer protective and regenerative effects by scavenging free radicals, modulating inflammatory responses, and enhancing skin barrier function. The paper aims to provide a comprehensive overview of the molecular and microbial interplay between alcohol, oxidative stress, and skin health, while identifying future directions for targeted antioxidant therapy in individuals with alcohol dependency. Full article
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27 pages, 4050 KiB  
Article
The Gut Mycobiome and Nutritional Status in Paediatric Phenylketonuria: A Cross-Sectional Pilot Study
by Malgorzata Ostrowska, Elwira Komoń-Janczara, Bozena Mikoluc, Katarzyna Iłowiecka, Justyna Jarczak, Justyna Zagórska, Paulina Zambrzycka, Silvia Turroni and Hubert Szczerba
Nutrients 2025, 17(15), 2405; https://doi.org/10.3390/nu17152405 - 23 Jul 2025
Viewed by 218
Abstract
Background: Phenylketonuria (PKU) is a metabolic disorder managed through a strict, lifelong low-phenylalanine diet, which may influence gut microbiome dynamics. While gut bacterial alterations in PKU are increasingly investigated, the fungal community (mycobiome) remains largely unexplored. This study compared gut mycobiome composition and [...] Read more.
Background: Phenylketonuria (PKU) is a metabolic disorder managed through a strict, lifelong low-phenylalanine diet, which may influence gut microbiome dynamics. While gut bacterial alterations in PKU are increasingly investigated, the fungal community (mycobiome) remains largely unexplored. This study compared gut mycobiome composition and dietary profiles of paediatric PKU patients and healthy controls, stratified by age (<10 and 10–18 years). Methods: Stool samples from 20 children (10 PKU, 10 controls) were analysed using ITS1/ITS2 amplicon sequencing. Nutritional status was assessed using Body Mass Index percentiles (Polish standards), and nutrient intake was evaluated from three-day dietary records compared to national reference values. Correlations between fungal taxa and dietary factors were explored. Results: Although alpha diversity did not differ significantly, beta diversity and LEfSe analyses revealed distinct fungal profiles between PKU patients and controls, indicating a trend toward group separation (PERMANOVA: F = 1.54646, p = 0.09; ANOVA: p = 0.0609). PKU patients showed increased Eurotiales (p = 0.029), Aspergillaceae (p = 0.029), and Penicillium (p = 0.11) and decreased Physalacriaceae (0% vs. 5.84% in controls) and Malassezia (p = 0.13). Spearman’s analysis showed significant correlations between Geotrichum and intake of protein (ρ = 0.55, p = 0.0127) and phenylalanine (ρ = 0.70, p = 0.0005). Conclusions: Dietary treatment in PKU is associated with age-dependent shifts in the gut mycobiome, notably increasing the abundance of taxa such as Eurotiales, Aspergillaceae, and Penicillium, involved in carbohydrate/lipid metabolism and mucosal inflammation. These findings highlight the potential of gut fungi as nutritional and clinical biomarkers in PKU. Full article
(This article belongs to the Special Issue Nutrients: 15th Anniversary)
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13 pages, 1791 KiB  
Article
Hydrogen Gas Inhalation Improved Intestinal Microbiota in Ulcerative Colitis: A Randomised Double-Blind Placebo-Controlled Trial
by Takafumi Maruyama, Dai Ishikawa, Rina Kurokawa, Hiroaki Masuoka, Kei Nomura, Mayuko Haraikawa, Masayuki Orikasa, Rina Odakura, Masao Koma, Masashi Omori, Hirotaka Ishino, Kentaro Ito, Tomoyoshi Shibuya, Wataru Suda and Akihito Nagahara
Biomedicines 2025, 13(8), 1799; https://doi.org/10.3390/biomedicines13081799 - 23 Jul 2025
Viewed by 276
Abstract
Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of [...] Read more.
Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events. Full article
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16 pages, 1317 KiB  
Systematic Review
Association Between Oral Dysbiosis and Depression: A Systematic Review
by Paula García-Rios, Miguel R. Pecci-Lloret, María Pilar Pecci-Lloret, Laura Murcia-Flores and Nuria Pérez-Guzmán
J. Clin. Med. 2025, 14(14), 5162; https://doi.org/10.3390/jcm14145162 - 21 Jul 2025
Viewed by 295
Abstract
Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient’s functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various [...] Read more.
Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient’s functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various studies are exploring a possible association between oral dysbiosis and depression—an increasingly relevant topic, as confirmation of such a relationship could position the oral microbiota as a potential etiological or diagnostic factor for depression, given its accessibility and ease of analysis. Aim: To present a qualitative synthesis of studies addressing how oral dysbiosis influences the onset of depression, as well as the importance of controlling this alteration of the oral microbiota to aid in the prevention of the disease. Materials and Methods: The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) outline the procedures to be followed for conducting this systematic review. The article search was carried out on 22 May 2025, across the PubMed, Scopus, Scielo, and The Cochrane Library databases, using terms related to “depression” and “oral dysbiosis”. Studies published within the last 10 years that addressed the potential association between oral dysbiosis, and depression were included. Furthermore, the quality of the studies was assessed using various tools depending on their design: the Newcastle–Ottawa Scale (NOS) was applied to case-control and cohort studies; the Joanna Briggs Institute (JBI) critical appraisal checklist was used for cross-sectional studies; and experimental studies were evaluated using SYRCLE’s Risk of Bias Tool. Results: A total of eleven studies were included in this systematic review. The findings suggest the presence of alterations in the oral microbiota of patients with depression, particularly in terms of composition, structure, and diversity. A reduction in alpha diversity—an indicator of local microbial balance—was observed, along with an increase in beta diversity, indicating greater inter-individual variability, which may be associated with inflammatory processes or immunological dysfunctions. Some studies reported differing results, which may be attributable to methodological variability regarding study design, or the populations sampled. Conclusions: This systematic review suggests that the oral microbiome could be considered a diagnostic biomarker and therapeutic target for depression, as the analyzed studies demonstrate a significant association between oral microbiome dysbiosis and this mental disorder. However, the methodological heterogeneity among the studies highlights the need for further research to confirm this potential relationship. Full article
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14 pages, 869 KiB  
Article
Subgingival Microbiome Profiles in Bulgarian Children Aged 10–14 with Gingival Inflammation and Healthy Periodontium: A Targeted PCR Study
by Hristina Tankova and Nadezhda Mitova
Microorganisms 2025, 13(7), 1656; https://doi.org/10.3390/microorganisms13071656 - 14 Jul 2025
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Abstract
The subgingival microbiome is a critical component of the oral microbiota and plays a central role in pediatric periodontology. This study investigated differences in periodontopathogen profiles in children with gingival inflammation compared to healthy controls using real-time PCR, with a focus on the [...] Read more.
The subgingival microbiome is a critical component of the oral microbiota and plays a central role in pediatric periodontology. This study investigated differences in periodontopathogen profiles in children with gingival inflammation compared to healthy controls using real-time PCR, with a focus on the microbial complexes defined by Socransky. A total of 73 children (ages 10–14) underwent comprehensive periodontal assessment, including assessments of general health status, the O’Leary hygiene index (HI), gingival condition, and the papillary bleeding index (PBI). Subgingival plaque samples were analyzed using real-time PCR to identify key bacterial species associated with gingival health and disease. Highly pathogenic periodontopathogens such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Eubacterium nodatum were absent in healthy subjects. In contrast, Tannerella forsythia was significantly more frequently detected in children with gingival inflammation (p < 0.05). The most abundant species in the inflammation group were Prevotella intermedia and Capnocytophaga gingivalis. Children with gingival inflammation exhibit a distinct subgingival microbiome profile characterized by an increased presence of specific periodontopathogens, including a higher prevalence of red complex species as defined by Socransky. However, the cross-sectional nature of this study limits the ability to establish causal relationships. Full article
(This article belongs to the Section Medical Microbiology)
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