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12 pages, 2753 KB  
Article
Insights into Ecological Features of Microbial Dark Matter Within the Symbiotic Community During Alexandrium pacificum Bloom: Co-Occurrence Interactions and Assembly Processes
by Yanlu Qiao, Shuo Wang, Lingzhe Wang, Shijie Li, Feng Wang, Bo Wang and Yuyang Liu
Coasts 2025, 5(3), 31; https://doi.org/10.3390/coasts5030031 - 2 Sep 2025
Abstract
The symbiotic microbiome constitutes a consortium that has been persistently domesticated by a specific algal species, fostering a close and enduring association with the host. The majority of microbial taxa remain uncharacterized. These unknown microbes, often referred to as “microbial dark matter (MDM)”, [...] Read more.
The symbiotic microbiome constitutes a consortium that has been persistently domesticated by a specific algal species, fostering a close and enduring association with the host. The majority of microbial taxa remain uncharacterized. These unknown microbes, often referred to as “microbial dark matter (MDM)”, have important ecological contributions. Given the challenges in discerning symbiotic microbes in natural environments, herein, ecological characteristics of MDM and known taxa within symbiotic communities were investigated in a simulated bloom process using Alexandrium pacificum without antibiotic treatment. Specifically, increased diversification was observed in MDM along the bloom process. Higher trophic interaction and less vulnerability of the molecular network were found in MDM taxa. The “bridge” role of MDM species was better than that of known taxa, as shown by higher betweenness centralization. Deterministic processes dominated in MDM taxa, which promote phylogenic diversity of such groups to some extent. The findings highlight that MDM taxa play an important role in sustaining community stability and functioning. This study broadens our understanding of the ecological contribution of MDM under disturbances from dinoflagellate blooms, providing essential theoretical insights and empirical data to inform the management of coastal toxic blooms. Full article
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32 pages, 2106 KB  
Review
Gut Microbiota-Derived Metabolites in Atherosclerosis: Pathways, Biomarkers, and Targets
by Alexandra-Kristine Tonch-Cerbu, Adrian-Gheorghe Boicean, Oana-Maria Stoia and Minodora Teodoru
Int. J. Mol. Sci. 2025, 26(17), 8488; https://doi.org/10.3390/ijms26178488 - 1 Sep 2025
Abstract
The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial [...] Read more.
The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut–heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research. Full article
(This article belongs to the Special Issue Cellular and Molecular Progression of Cardiovascular Diseases)
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15 pages, 2089 KB  
Protocol
A Protocol for Modeling Human Bone Inflammation: Co-Culture of Osteoblasts and Osteoclasts Exposed to Different Inflammatory Microenvironments
by Araceli Valverde and Afsar Raza Naqvi
Methods Protoc. 2025, 8(5), 97; https://doi.org/10.3390/mps8050097 (registering DOI) - 1 Sep 2025
Abstract
Bone remodeling relies on the coordinated activity of osteoblasts (OBs) and osteoclasts (OCs). Disruptions in OB-OC balance can lead to diseases such as periodontitis, a chronic microbial-induced inflammatory disease. To investigate how inflammation affects OB-OC interactions, we standardized an in vitro 2D indirect [...] Read more.
Bone remodeling relies on the coordinated activity of osteoblasts (OBs) and osteoclasts (OCs). Disruptions in OB-OC balance can lead to diseases such as periodontitis, a chronic microbial-induced inflammatory disease. To investigate how inflammation affects OB-OC interactions, we standardized an in vitro 2D indirect co-culture system using primary human OB and OC precursors from peripheral blood mononuclear cells in a transwell setup, which allows paracrine signaling and separate analysis of each cell type. When exposed to bacterial lipopolysaccharides (Aa LPS and E. coli LPS) and proinflammatory cytokines (IL-6 and TNF-α), we observed that inflammatory stimuli significantly increased OC differentiation, particularly TNF-α, while E. coli LPS specifically suppressed OB activity as observed by the expression of key markers and cellular staining. These results demonstrate that microbial and host-derived inflammatory factors can differentially modulate bone cell behavior. This approach offers a physiologically relevant and ethically advantageous alternative to animal models to screen dual-targeted bone therapies to restore perturbed metabolism. Full article
(This article belongs to the Section Molecular and Cellular Biology)
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26 pages, 1699 KB  
Review
Improving Biocontrol Potential of Antagonistic Yeasts Against Fungal Pathogen in Postharvest Fruits and Vegetables Through Application of Organic Enhancing Agents
by Gerefa Sefu Edo, Esa Abiso Godana, Guillaume Legrand Ngolong Ngea, Kaili Wang, Qiya Yang and Hongyin Zhang
Foods 2025, 14(17), 3075; https://doi.org/10.3390/foods14173075 - 31 Aug 2025
Viewed by 62
Abstract
Fruits and vegetables are essential for a healthy diet, providing vital nutrients and contributing to global food security. Fungal pathogens that interact with fruits and vegetables reduce their quality and shelf life and lead to economic losses and risks to human health through [...] Read more.
Fruits and vegetables are essential for a healthy diet, providing vital nutrients and contributing to global food security. Fungal pathogens that interact with fruits and vegetables reduce their quality and shelf life and lead to economic losses and risks to human health through the production of mycotoxins. Chemical fungicides, used to control postharvest pathogens, are posing serious environmental and health risks, driving interest in safer alternative strategies. Biocontrol methods using antagonistic microbes, such as yeasts, are eco-friendly, sustainable, and the most promising, but they often have limited efficacy and specificity in diverse produce. There is growing interest in the innovative enhancement of biocontrol strategies. The present review shows that inducing, enhancing, co-application, encapsulation, and post-application treatments are common enhancement techniques, while environmental, host, and pathogen characteristics, antagonistic microbial traits, and chemical inputs are the major gearing factors for the best application methods. These methods do not involve genetic modification, which is adequate to reduce the proliferation of GMOs (Genetically Modified Organisms) while optimizing antagonistic microbial performance by promoting growth, inducing host resistance, enhancing antifungal properties, improving adhesion, and boosting stress tolerance. Most enhancers fall under groups of nutritional additives, protective carriers, growth stimulants, and encapsulants. Integrating these enhancers and best methods promises reduced postharvest losses, supports sustainable agriculture, and addresses economic losses and food security challenges. This study highlights the role of organic and natural elicitors, their application methods, their mechanisms in improving BCAs (Biological Control Agents), and their overall efficiency. This review concisely compiles recent strategies, calling for further research to revolutionize fungal pathogen management, reduce food waste, and promote responsible farming practices. Full article
(This article belongs to the Special Issue Sustainable Agriculture for Food and Nutrition Security)
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35 pages, 16363 KB  
Review
Unlocking Polyphenol Efficacy: The Role of Gut Microbiota in Modulating Bioavailability and Health Effects
by Laura Mahdi, Annarita Graziani, Gyorgy Baffy, Emilie K. Mitten, Piero Portincasa and Mohamad Khalil
Nutrients 2025, 17(17), 2793; https://doi.org/10.3390/nu17172793 - 28 Aug 2025
Viewed by 507
Abstract
In humans, the bioactivity of polyphenols is highly dependent on dose intake and their interactions with the gastrointestinal tract and gut microbiota, which metabolize polyphenols into bioactive or inactive derivatives. Polyphenols are only partially absorbed in the small intestine, where enzymatic hydrolysis releases [...] Read more.
In humans, the bioactivity of polyphenols is highly dependent on dose intake and their interactions with the gastrointestinal tract and gut microbiota, which metabolize polyphenols into bioactive or inactive derivatives. Polyphenols are only partially absorbed in the small intestine, where enzymatic hydrolysis releases aglycone forms that may cross the gut barrier. A significant proportion of polyphenols escapes absorption and reaches the colon, where resident microbes convert them into simpler phenolic metabolites. Such molecules are often more bioavailable than the parent compounds and can enter systemic circulation, leading to distant effects. Although higher polyphenol consumption has been associated with preventive and therapeutic outcomes, even low intake or poor intestinal absorption may still confer benefits, as polyphenols in the colon can positively modulate gut microbiota composition and function, contributing to favorable shifts in the microbial metabolome. These interactions can influence host metabolic, immune, and neurological pathways, particularly through the gut–liver–brain axis. To provide a comprehensive understanding of these relationships, this review examines the dose-related activity of polyphenols, their microbiota-mediated biotransformation, their bioavailability, and the health effects of their metabolites, while also presenting a comparative overview of key studies in the field. We underscore the importance of integrating microbiome and polyphenol research to recapitulate and contextualize the health benefits of dietary polyphenols. Full article
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22 pages, 1751 KB  
Review
Exploring the Microbiome in Breast Cancer: The Role of Fusobacterium nucleatum as an Onco-Immune Modulator
by Alessandra D’Angelo, Anna Zenoniani, Martina Masci, Gitana Maria Aceto, Adriano Piattelli and Maria Cristina Curia
Microorganisms 2025, 13(9), 1995; https://doi.org/10.3390/microorganisms13091995 - 27 Aug 2025
Viewed by 352
Abstract
The breast microbiome remains stable throughout a woman’s life. The breast is not a sterile organ, and its microbiota exhibits a distinct composition compared to other body sites. The breast microbiome is a community characterized by an abundance of Proteobacteria and Firmicutes, [...] Read more.
The breast microbiome remains stable throughout a woman’s life. The breast is not a sterile organ, and its microbiota exhibits a distinct composition compared to other body sites. The breast microbiome is a community characterized by an abundance of Proteobacteria and Firmicutes, which represent the result of host microbial adaptation to the fatty acid environment in the tissue. The breast microbiome demonstrates dynamic adaptability during lactation, responding to maternal physiological changes and infant interactions. This microbial plasticity modulates local immune responses, maintains epithelial integrity, and supports tissue homeostasis, thereby influencing both breast health and milk composition. Disruptions in this balance, the dysbiosis, are closely linked to inflammatory breast conditions such as mastitis. Risk factors for breast cancer (BC) include genetic mutations, late menopause, obesity, estrogen metabolism, and alterations in gut microbial diversity. Gut microbiota can increase estrogen bioavailability by deconjugating estrogen-glucuronide moieties. Perturbations of this set of bacterial genes and metabolites, called the estrobolome, increases circulating estrogens and the risk of BC. Fusobacterium nucleatum has recently been associated with BC. It moves from the oral cavity to other body sites hematogenously. This review deals with the characteristics of the breast microbiome, with a focus on F. nucleatum, highlighting its dual role in promoting tumor growth and modulating immune responses. F. nucleatum acts both on the Wnt/β-catenin pathway by positively regulating MYC expression and on apoptosis by inhibiting caspase 8. Furthermore, F. nucleatum binds to TIGIT and CEACAM1, inhibiting T-cell cytotoxic activity and protecting tumor cells from immune cell attack. F. nucleatum also inhibits T-cell function through the recruitment of myeloid suppressor cells (MDSCs). These cells express PD-L1, which further reduces T-cell activation. A deeper understanding of F. nucleatum biology and its interactions with host cells and co-existing symbiotic microbiota could aid in the development of personalized anticancer therapy. Full article
(This article belongs to the Section Microbiomes)
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14 pages, 2768 KB  
Article
Biosynthesis of the Siderophore Desferrioxamine E in Rouxiella badensis SER3 and Its Antagonistic Activity Against Fusarium brachygibbosum
by Luzmaria R. Morales-Cedeño, Sergio de los Santos Villalobos, Pedro D. Loeza-Lara, Debasis Mitra, Ajay Kumar, Ma. del Carmen Orozco-Mosqueda and Gustavo Santoyo
Appl. Microbiol. 2025, 5(3), 91; https://doi.org/10.3390/applmicrobiol5030091 - 26 Aug 2025
Viewed by 1067
Abstract
Iron is a limiting factor for plant and microbial growth because, in soil environments, it is predominantly present as oxyhydroxide minerals, rendering it unavailable to plants and microorganisms. Siderophores are chelating agents secreted to solubilize iron and facilitate its uptake. To understand the [...] Read more.
Iron is a limiting factor for plant and microbial growth because, in soil environments, it is predominantly present as oxyhydroxide minerals, rendering it unavailable to plants and microorganisms. Siderophores are chelating agents secreted to solubilize iron and facilitate its uptake. To understand the evolutionary and ecological dynamics of microbial communities, as well as the evolution of pathogens within hosts, it is essential to study the genes shared between microorganisms for environmental adaptation and survival. In this study, we conducted microbiological assays to evaluate the effect of the siderophore produced by Rouxiella badensis strain SER3 on the mycelial growth of fungal pathogens such as Fusarium brachygibbosum 4BF. Using spectrophotometric techniques and bioinformatics tools, we identified desferrioxamine E (nocardamine) in the culture supernatant, and the corresponding biosynthetic gene cluster in the SER3 genome was confirmed through antiSMASH analysis and synteny comparisons. Gene expression analysis by RT-PCR showed differential expression of biosynthetic precursors when strain SER3 was grown alone or in interaction with fungal pathogen. Finally, scanning electron microscopy revealed structural damage to F. brachygibbosum hyphae during co-culture with strain SER3. These results suggest that the production of desferrioxamine E may act as a biocontrol mechanism employed by R. badensis SER3 against F. brachygibbosum. Full article
(This article belongs to the Topic New Challenges on Plant–Microbe Interactions)
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20 pages, 1286 KB  
Review
The Microbiome as a Driver of Insect Physiology, Behavior, and Control Strategies
by Hazem Al Darwish, Muqaddasa Tariq, Safiyah Salama, Tia Hart and Jennifer S. Sun
Appl. Microbiol. 2025, 5(3), 90; https://doi.org/10.3390/applmicrobiol5030090 - 26 Aug 2025
Viewed by 1068
Abstract
Insect pests impose major economic, agricultural, and public health burdens, damaging crops and transmitting pathogens such as dengue, malaria, and Zika. Conventional chemical control is increasingly ineffective due to insecticide resistance and environmental concerns, prompting a search for innovative strategies. The insect microbiome—comprising [...] Read more.
Insect pests impose major economic, agricultural, and public health burdens, damaging crops and transmitting pathogens such as dengue, malaria, and Zika. Conventional chemical control is increasingly ineffective due to insecticide resistance and environmental concerns, prompting a search for innovative strategies. The insect microbiome—comprising both obligate symbionts and environmentally acquired microbes—emerges as a key driver of host physiology and behavior. Microbes influence nutrient acquisition, immunity, reproduction, and chemosensory processing, often to promote their own transmission. By modulating olfactory and gustatory pathways, microbiota can alter host-seeking, mate choice, foraging, and oviposition patterns, reshaping ecological interactions and vector dynamics. These effects are shaped by microbial acquisition routes, habitat conditions, and anthropogenic pressures such as pesticide use, pollution, and climate change. Understanding these multi-directional interactions offers opportunities to design highly specific, microbe-based insect control strategies, from deploying microbial metabolites that disrupt host sensory systems to restoring beneficial symbionts in threatened pollinators. Integrating microbiome ecology with insect physiology and behavior not only deepens our understanding of host–microbe coevolution but also enables the development of sustainable, targeted alternatives to chemical insecticides. This review synthesizes current evidence linking microbiomes to insect biology and explores their potential as tools for pest and vector management. Full article
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19 pages, 17140 KB  
Article
Chinese Herbal Medicine Compound Microecological Agent (C-MEA) Improves Egg Production Performance in Caged Laying Ducks via Microbiota–Gut–Ovary Axis
by Yanfeng Lu, Lei Zhang, Rui Zhu, Xiujun Duan, Guobo Sun and Yuying Jiang
Vet. Sci. 2025, 12(9), 808; https://doi.org/10.3390/vetsci12090808 - 25 Aug 2025
Viewed by 333
Abstract
This study was conducted to investigate the effects of a Chinese herbal medicine compound microecological agent (C-MEA) on the egg production performance, ovarian follicle development, ovary transcriptome, and cecal microbiota of caged laying ducks. A total of 108 black Muscovy ducks (150 days [...] Read more.
This study was conducted to investigate the effects of a Chinese herbal medicine compound microecological agent (C-MEA) on the egg production performance, ovarian follicle development, ovary transcriptome, and cecal microbiota of caged laying ducks. A total of 108 black Muscovy ducks (150 days old) were randomly divided into three groups for 30 days in a formal feeding trial. Compared with the control basic diet (Group C) and 16 g/kg C-MEA dosage (Group B), the 8 g/kg C-MEA dosage (Group A) increased egg production (average laying rate 69.35%) and follicle development (5~7 Fs, 6~7 LYFs, 11~13 SYFs) mass (p < 0.05). According to RNA-Seq, the ovaries’ transcriptome among different dietary groups enriched six key pathways, including neuroactive ligand–receptor interaction, the PPAR signaling pathway, ECM–receptor interaction, focal adhesion, the adherens junction, and the FoxO signaling pathway, as well as 46 candidate key genes. According to 16S-Seq, the microbial diversity was significantly increased in Group A, and the genus abundances of Sphaerochaeta and UCG-004 were significantly changed among different dietary groups (p < 0.05). Supplementation with C-MEA may optimize the cecal microflora and the interactions between the intestinal microflora and the host. The results from combining RNA-Seq and 16S-Seq demonstrated that the relationship between Sphaerochaeta and the hub gene cluster (F2, KNG1, C5, PLG, F2RL1, FABP1, and GCG) is the most prominent. In conclusion, the egg performance of caged laying ducks can be modulated through the microbiota–gut–ovary axis. Our findings provide new insights for improving gut health and reproductive performance of caged laying ducks. Full article
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17 pages, 4342 KB  
Article
Metagenomic Signatures of Colorectal Cancer in the Jordanian Population: A Regional Case-Control Analysis Using 16S rRNA Profiling
by Lo’ai Alanagreh, Minas A. Mustafa, Mohammad Borhan Al-Zghoul, Muhannad I. Massadeh, Osamah Batiha, Maher Sughayer, Rashed Taiseer Almashakbeh, Haya Bader Abu Suilike, Faten S. Tout and Foad Alzoughool
Microorganisms 2025, 13(8), 1963; https://doi.org/10.3390/microorganisms13081963 - 21 Aug 2025
Viewed by 877
Abstract
The gut microbiota plays a pivotal role in developing colorectal cancer (CRC) through interactions with host immunity, metabolism, and inflammation. However, microbiome-based studies remain scarce in Middle Eastern populations, limiting regional insights into microbial signatures associated with CRC. This study aimed to characterize [...] Read more.
The gut microbiota plays a pivotal role in developing colorectal cancer (CRC) through interactions with host immunity, metabolism, and inflammation. However, microbiome-based studies remain scarce in Middle Eastern populations, limiting regional insights into microbial signatures associated with CRC. This study aimed to characterize the gut microbiota profiles of Jordanian CRC patients using 16S rRNA gene sequencing and compare them to those of healthy controls from the GutFeeling KnowledgeBase (GutFeelingKB). Stool samples from 50 CRC patients were analyzed using Illumina iSeq targeting the V3–V4 region. Taxonomic profiling was conducted with a standardized 16S metagenomics pipeline and compared with GutFeelingKB reference data. CRC samples were enriched in Streptococcus, Enterococcus, Klebsiella, Escherichia, Citrobacter, Veillonella, Megamonas, and Eggerthella, while beneficial butyrate-producing genera such as Roseburia, Ruminococcus, Akkermansia, Faecalibacterium, and Bacteroides were significantly depleted. The absence of Fusobacterium nucleatum and Bacteroides fragilis—commonly seen in global studies—suggests region-specific microbial patterns. This study is the first metagenomic study profiling CRC-associated microbiota in Jordan. The findings reveal a dysbiotic microbial signature that reflects both global changes associated with CRC and local ecological influences. This research emphasizes the importance of population-specific microbiome studies and highlights the need to include appropriately matched controls in future investigations. Full article
(This article belongs to the Section Gut Microbiota)
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56 pages, 4337 KB  
Review
Glycomics in Human Diseases and Its Emerging Role in Biomarker Discovery
by Sherifdeen Onigbinde, Moyinoluwa Adeniyi, Oluwatosin Daramola, Favour Chukwubueze, Md Mostofa Al Amin Bhuiyan, Judith Nwaiwu, Tuli Bhattacharjee and Yehia Mechref
Biomedicines 2025, 13(8), 2034; https://doi.org/10.3390/biomedicines13082034 - 21 Aug 2025
Viewed by 638
Abstract
Glycosylation, the enzymatic addition of glycans to proteins and lipids, is a critical post-translational modification that influences protein folding, stability, trafficking, immune modulation, and cell signaling. The vast structural diversity of glycans arising from differences in monosaccharide composition, branching, and terminal modifications such [...] Read more.
Glycosylation, the enzymatic addition of glycans to proteins and lipids, is a critical post-translational modification that influences protein folding, stability, trafficking, immune modulation, and cell signaling. The vast structural diversity of glycans arising from differences in monosaccharide composition, branching, and terminal modifications such as sialylation, fucosylation, and sulfation underpins their functional specificity and regulatory capacity. This review provides a comprehensive overview of glycan biosynthesis, with a focus on N-glycans, O-glycans, glycosaminoglycans (GAGs), and glycolipids. It explores their essential roles in maintaining cellular homeostasis, development, and immune surveillance. In health, glycans mediate cell–cell communication, protein interactions, and immune responses. In disease, however, aberrant glycosylation is increasingly recognized as a hallmark of numerous pathological conditions, including cancer, neurodegenerative disorders, autoimmune diseases, and a wide range of infectious diseases. Glycomic alterations contribute to tumor progression, immune evasion, therapy resistance, neuroinflammation, and synaptic dysfunction. Tumor-associated carbohydrate antigens (TACAs) and disease-specific glycoforms present novel opportunities for biomarker discovery and therapeutic targeting. Moreover, glycan-mediated host–pathogen interactions are central to microbial adhesion, immune escape, and virulence. This review highlights current advances in glycomics technologies, including mass spectrometry, lectin microarrays, and glycoengineering, which have enabled the high-resolution profiling of the glycome. It also highlights the emerging potential of single-cell glycomics and multi-omics integration in precision medicine. Understanding glycome and its dynamic regulation is essential for uncovering the molecular mechanisms of disease and translating glycomic insights into innovative diagnostic and therapeutic strategies. Full article
(This article belongs to the Special Issue Role of Glycomics in Health and Diseases)
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51 pages, 4873 KB  
Review
Type 2 Diabetes and the Multifaceted Gut-X Axes
by Hezixian Guo, Liyi Pan, Qiuyi Wu, Linhao Wang, Zongjian Huang, Jie Wang, Li Wang, Xiang Fang, Sashuang Dong, Yanhua Zhu and Zhenlin Liao
Nutrients 2025, 17(16), 2708; https://doi.org/10.3390/nu17162708 - 21 Aug 2025
Viewed by 1052
Abstract
Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic [...] Read more.
Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic organs. The gut hosts trillions of microbes and enteroendocrine cells that influence inflammation, energy homeostasis, and hormone regulation. Disruptions in gut homeostasis (dysbiosis and increased permeability) have been linked to obesity, insulin resistance, and β-cell dysfunction, suggesting multifaceted “Gut-X axes” contribute to T2D development. We aimed to comprehensively review the evidence for gut-mediated crosstalk with the pancreas, endocrine system, liver, and kidneys in T2D. Key molecular mechanisms (incretins, bile acids, short-chain fatty acids, endotoxins, etc.) were examined to construct an integrated model of how gut-derived signals modulate metabolic and inflammatory pathways across organs. We also discuss clinical implications of targeting Gut-X axes and identify knowledge gaps and future research directions. A literature search (2015–2025) was conducted in PubMed, Scopus, and Web of Science, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews). Over 150 high-impact publications (original research and review articles from Nature, Cell, Gut, Diabetologia, Lancet Diabetes & Endocrinology, etc.) were screened. Data on gut microbiota, enteroendocrine hormones, inflammatory mediators, and organ-specific outcomes in T2D were extracted. The GRADE framework was used informally to prioritize high-quality evidence (e.g., human trials and meta-analyses) in formulating conclusions. T2D involves perturbations in multiple Gut-X axes. This review first outlines gut homeostasis and T2D pathogenesis, then dissects each axis: (1) Gut–Pancreas Axis: how incretin hormones (GLP-1 and GIP) and microbial metabolites affect insulin/glucagon secretion and β-cell health; (2) Gut–Endocrine Axis: enteroendocrine signals (e.g., PYY and ghrelin) and neural pathways that link the gut with appetite regulation, adipose tissue, and systemic metabolism; (3) Gut–Liver Axis: the role of microbiota-modified bile acids (FXR/TGR5 pathways) and bacterial endotoxins in non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; (4) Gut–Kidney Axis: how gut-derived toxins and nutrient handling intersect with diabetic kidney disease and how incretin-based and SGLT2 inhibitor therapies leverage gut–kidney communication. Shared mechanisms (microbial SCFAs improving insulin sensitivity, LPS driving inflammation via TLR4, and aryl hydrocarbon receptor ligands modulating immunity) are synthesized into a unified model. An integrated understanding of Gut-X axes reveals new opportunities for treating and preventing T2D. Modulating the gut microbiome and its metabolites (through diet, pharmaceuticals, or microbiota therapies) can improve glycemic control and ameliorate complications by simultaneously influencing pancreatic islet function, hepatic metabolism, and systemic inflammation. However, translating these insights into clinical practice requires addressing gaps with robust human studies. This review provides a state-of-the-art synthesis for researchers and clinicians, underlining the gut as a nexus for multi-organ metabolic regulation in T2D and a fertile target for next-generation therapies. Full article
(This article belongs to the Special Issue Dietary Regulation of Glucose and Lipid Metabolism in Diabetes)
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17 pages, 2145 KB  
Article
Dietary Iron Intake Impacts the Microbial Composition of the Murine Intestinal and Lung Microbiome
by Ama-Tawiah Essilfie, Alison Smith, Rebecca Watts, Pramila Maniam, Iain L. Lamont, David M. Frazer, Gregory J. Anderson and David W. Reid
Nutrients 2025, 17(16), 2696; https://doi.org/10.3390/nu17162696 - 20 Aug 2025
Viewed by 483
Abstract
Background: Iron is an essential nutrient for many bacterial pathogens and normal cellular function and homeostasis of their hosts. Studies suggest that iron deficiency or overload may contribute to the pathogenesis of several chronic conditions and modify host–microbial interactions. In this study, we [...] Read more.
Background: Iron is an essential nutrient for many bacterial pathogens and normal cellular function and homeostasis of their hosts. Studies suggest that iron deficiency or overload may contribute to the pathogenesis of several chronic conditions and modify host–microbial interactions. In this study, we assessed the impact of varying dietary iron intakes on the microbiota of the intestinal tract and lungs of wild-type mice. Methods: Male C57BL/6J mice were fed either a standard pellet chow (high iron diet), a ferrous ammonium sulfate (FeAS)-supplemented diet or an iron-deficient diet for four weeks. Tissue from the lung, duodenum and colon was collected, and 16S rRNA gene fragments were pyrosequenced. Results: Total serum iron levels were negatively associated with richness of the lung microbiome (p = 0.035). In the murine lungs, there was no association between the iron diet and the overall lung microbiota community composition, but Bacteroides spp. were significantly enriched in the lungs of mice fed the FeAS diet (LDA score > 4, p < 0.05). The community composition of the intestinal microbiota changed significantly depending on the iron diet, with increased richness in the low-iron compared to the iron-supplemented groups (p = 0.053). In the duodenum, Prevotella spp. were reduced (Mean = 7.869, SEM = 3.464, p < 0.05), and Desulfovibrio species increased (Mean = 5.343, SEM = 1.362, p < 0.001) in iron-supplemented groups compared to the low-iron-diet group. In the colon, Bifidobacterium and Bacteroides species were reduced (Mean = 7.175, SEM = 2.246, p < 0.01 and Mean = 6.967, SEM = 1.834, p < 0.01 respectively), and Pseudomonas increased (Mean = 24.03, SEM = 8.919, p < 0.05) in mice on higher-iron diets compared to the low-iron diet. Discussion: This study demonstrates that dietary iron intake significantly impacts the intestinal microbiota and has a small, yet significant, effect on the lung microbiome in C57BL/6J mice. Whilst dietary iron content per se did not significantly modulate the composition of the lung microbiota, serum iron levels had subtle impacts on the community composition of the lung microbiota. Full article
(This article belongs to the Special Issue Mineral Nutrition on Human Health and Disease)
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19 pages, 3354 KB  
Article
Microbial Assembly and Stress-Tolerance Mechanisms in Salt-Adapted Plants Along the Shore of a Salt Lake: Implications for Saline–Alkaline Soil Remediation
by Xiaodong Wang, Liu Xu, Xinyu Qi, Jianrong Huang, Mingxian Han, Chuanxu Wang, Xin Li and Hongchen Jiang
Microorganisms 2025, 13(8), 1942; https://doi.org/10.3390/microorganisms13081942 - 20 Aug 2025
Viewed by 506
Abstract
Investigating the microbial community structure and stress-tolerance mechanisms in the rhizospheres of salt-adapted plants along saline lakes is critical for understanding plant–microbe interactions in extreme environments and developing effective strategies for saline–alkaline soil remediation. This study explored the rhizosphere microbiomes of four salt-adapted [...] Read more.
Investigating the microbial community structure and stress-tolerance mechanisms in the rhizospheres of salt-adapted plants along saline lakes is critical for understanding plant–microbe interactions in extreme environments and developing effective strategies for saline–alkaline soil remediation. This study explored the rhizosphere microbiomes of four salt-adapted species (Suaeda glauca, Artemisia carvifolia, Chloris virgata, and Limonium bicolor) from the Yuncheng Salt Lake region in China using high-throughput sequencing. Cultivable salt-tolerant plant growth-promoting rhizobacteria (PGPR) were isolated and characterized to identify functional genes related to stress resistance. Results revealed that plant identity and soil physicochemical properties jointly shaped the microbial community composition, with total organic carbon being a dominant driver explaining 17.6% of the variation. Cyanobacteria dominated low-salinity environments, while Firmicutes thrived in high-salinity niches. Isolated PGPR strains exhibited tolerance up to 15% salinity and harbored genes associated with heat (htpX), osmotic stress (otsA), oxidative stress (katE), and UV radiation (uvrA). Notably, Peribacillus and Isoptericola strains demonstrated broad functional versatility and robust halotolerance. Our findings highlight that TOC (total organic carbon) plays a pivotal role in microbial assembly under extreme salinity, surpassing host genetic influences. The identified PGPR strains, with their stress-resistance traits and functional gene repertoires, hold significant promise for biotechnological applications in saline–alkaline soil remediation and sustainable agriculture. Full article
(This article belongs to the Section Plant Microbe Interactions)
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Review
Exploring the Molluscan Microbiome: Diversity, Function, and Ecological Implications
by Tsireledzo Goodwill Makwarela, Nimmi Seoraj-Pillai and Tshifhiwa Constance Nangammbi
Biology 2025, 14(8), 1086; https://doi.org/10.3390/biology14081086 - 20 Aug 2025
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Abstract
Mollusks are among the most ecologically and economically significant invertebrates; yet, their associated microbiomes remain understudied relative to those of other metazoans. This scoping review synthesizes the current literature on the diversity, composition, functional roles, and ecological implications of molluscan microbiomes, with an [...] Read more.
Mollusks are among the most ecologically and economically significant invertebrates; yet, their associated microbiomes remain understudied relative to those of other metazoans. This scoping review synthesizes the current literature on the diversity, composition, functional roles, and ecological implications of molluscan microbiomes, with an emphasis on three major groups: gastropods, bivalves, and cephalopods. Drawing on studies from terrestrial, freshwater, and marine systems, we identified the dominant bacterial phyla, including Proteobacteria, Bacteroidetes, and Firmicutes, and explored how microbiota vary across different habitats, diets, tissue types, and host taxonomies. We examined the contribution of molluscan microbiomes to host functions, including digestion, immune modulation, stress responses, and nutrient cycling. Particular attention was given to the role of microbiota in shell formation, pollutant degradation, and adaptation to environmental stressors. The review also evaluated microbial interactions at different developmental stages and under aquaculture conditions. Factors influencing microbiome assembly, such as the host’s genetics, life history traits, and environmental exposure, were mapped using conceptual and graphical tools. Applications of molluscan microbiome research in aquaculture, conservation biology, and environmental biomonitoring are highlighted. However, inconsistencies in the sampling methods, taxonomic focus, and functional annotations limit the generalizability across taxa. We identify key knowledge gaps and propose future directions, including the use of meta-omics, standardized protocols, and experimental validation to deepen insights. By synthesizing emerging findings, this review contributes to a growing framework for understanding mollusk–microbiome interactions and their relevance to host fitness and ecosystem health. It further establishes the importance of mollusks as model systems for advancing microbiome science. Full article
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