Search Results (36)

Overwinter Syndrome (OWS) affects grass carp (Ctenopharyngodon idellus) aquaculture in China, causing high mortality and economic losses under low temperatures. Failure of antibiotic therapies shows limits of the ‘low–temperature–pathogen’ model and shifts focus to mucosal barrier dysfunction and host–microbiome interactions in OWS. We compared healthy and diseased grass carp collected from the same pond using histopathology, transcriptomics, proteomics, and metagenomics. This integrated approach was used to characterize intestinal structure, microbial composition, and host molecular responses at both taxonomic and functional levels. Results revealed a three-layer barrier failure in OWS fish: the physical barrier was compromised, with structural damage and reduced mucosal index; microbial dysbiosis featured increased richness without changes in diversity or evenness, and expansion of the virobiota, notably uncultured Caudovirales phage; and mucosal immune dysregulation indicated loss of local immune balance. Multi-omics integration identified downregulation of lysosome-related and glycosphingolipid biosynthesis pathways at transcript and protein levels, with disrupted nucleotide metabolism. Overall gut microbial richness, rather than individual taxa abundance, correlated most strongly with host gene changes linked to immunity, metabolism, and epithelial integrity. Although biological replicates were limited by natural outbreak sampling, matched high-depth multi-omics datasets provide exploratory insights into OWS-associated intestinal dysfunction. In summary, OWS entails a cold-triggered breakdown of intestinal barrier integrity and immune homeostasis. This breakdown is driven by a global restructuring of the gut microbiome, which is marked by increased richness, viral expansion, and functional shifts, ultimately resulting in altered host–microbe crosstalk. This ecological perspective informs future mechanistic and applied studies for disease prevention. Full article

Background: Colorectal cancer (CRC) is a malignancy that ranks among the top three in terms of both global mortality and incidence. Although numerous studies have demonstrated that gut microbes are implicated in CRC pathogenesis, the precise mechanisms underlying host–microbiota metabolic crosstalk remain poorly understood. Objective: This study aims to identify and delineate key co-metabolites and their associated metabolic pathways that modulate the biomass of CRC-related gut bacteria within healthy individuals, through the construction of host–gut microbiota co-metabolic network models. We seek to elucidate the underlying mechanisms of metabolic interplay between the host and CRC-related gut microbiota, thereby offering novel perspectives on the microbial involvement in the initiation and progression of CRC. Methods: We coupled a colon tissue-specific host Genome-Scale Metabolic Model (GEM), which utilized transcriptomic data from healthy human colon tissues, with 12 CRC-associated pro-/anti-carcinogenic gut bacterial GEMs to construct a co-metabolic network. Through a comparative analysis of the network structure and systemic methods (including Flux Sampling and metabolic difference analysis), we simulated scenarios of constrained host co-metabolite supply. Finally, metabolic subsystem enrichment analysis was employed to elucidate the specific molecular mechanisms by which key co-metabolites affect microbial function. Results: The 17 key co-metabolites identified include chloride ions, zinc ions, and acetate. Among these, thirteen metabolites (e.g., ferric iron, succinate, and acetate) were confirmed by literature to be associated with CRC. All 17 key co-metabolites were found to significantly modulate the biomass of CRC-associated gut bacteria. These regulatory effects primarily influence microbial function through core pathways such as glycerophospholipid metabolism and folate metabolism. Conclusion: This research provides a systemic perspective for elucidating the mechanisms of host–gut microbiota metabolic interplay in CRC, thereby complementing the existing theoretical framework concerning microbial regulation by the host genetic background. Full article

The gut microbiota has emerged as a critical immune–metabolic interface, orchestrating a complex network of interactions that extend well beyond digestion. This highly diverse community of bacteria, viruses, archaea, and eukaryotic microbes modulates host immunometabolism, metabolic reprogramming, and systemic inflammatory responses, thereby shaping human health and disease trajectories. Dysbiosis, or disruption of microbial homeostasis, has been implicated in inflammatory bowel disease, cardiometabolic disorders, neurodegeneration, dermatological conditions, and tumorigenesis. Through the biosynthesis of short-chain fatty acids (SCFAs), bile acid derivatives, tryptophan metabolites, and microbial-derived indoles, the gut microbiota regulates epigenetic programming, barrier integrity, and host–microbe cross-talk, thereby influencing disease onset and progression. In oncology, specific microbial taxa and oncomicrobiotics (cancer-modulating microbes) are increasingly recognized as key determinants of immune checkpoint inhibitor (ICI) responsiveness, chemotherapeutic efficacy, and resistance mechanisms. Microbiota-targeted strategies such as fecal microbiota transplantation (FMT), precision probiotics, prebiotics, synbiotics, and engineered microbial consortia are being explored to recalibrate microbial networks and enhance therapeutic outcomes. At the systems level, the integration of multi-omics platforms (metagenomics, transcriptomics, proteomics, and metabolomics) combined with network analysis and machine learning-based predictive modeling is advancing personalized medicine by linking microbial signatures to clinical phenotypes. Despite remarkable progress, challenges remain, including the standardization of microbiome therapeutics, longitudinal monitoring of host–microbe interactions, and the establishment of robust ethical and regulatory frameworks for clinical translation. Future directions should prioritize understanding the causal mechanisms of microbial metabolites in immunometabolic regulation, exploring microbial niche engineering, and developing precision microbiome editing technologies (CRISPR, synthetic biology). Full article

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

Lipopolysaccharide (LPS), the defining outer membrane component of Gram-negative bacteria, is a potent immunostimulant recognized by Toll-like receptor 4 (TLR4). While extensively studied for its roles in immune activation and barrier disruption, the potential function of LPS as a developmental cue remains largely unexplored. By leveraging Caenorhabditis elegans and its genetic and gnotobiotic advantages, we screened a panel of Escherichia coli LPS biosynthesis mutants. This screen revealed that the loss of outer core glycosylation in the ∆rfaG mutant causes significant developmental delay independent of bacterial metabolism. Animals exhibited developmental delay that was rescued by exogenous LPS or amino acid supplementation, implicating that LPS triggers nutrient-sensing signaling. Mechanistically, this developmental arrest was mediated by the host FOXO transcription factor DAF-16, which is the key effector of insulin/IGF-1 signaling (IIS). Our findings uncover an unprecedented role for microbial LPS as a critical regulator of host development, mediated through conserved host IIS pathways, fundamentally expanding our understanding of host–microbe crosstalk. Full article

As the world faces an escalating challenge of non-communicable diseases (NCDs), with phenotypes ranging from allergic chronic immuno-inflammatory diseases to neuropsychiatric disorders, it becomes evident that their seeds are sown during the early stages of life. Furthermore, within only a few decades, human obesity has reached epidemic proportions and now represents the most serious public health challenge of our time. Recent demonstrations that a growing number of these conditions are linked to aberrant gut microbiota composition and function have evoked active scientific interest in host-microbe crosstalk, characterizing and modulating the gut microbiota in at-risk circumstances. These efforts appear particularly justified during the most critical period of developmental plasticity when the child’s immune, metabolic, and microbiological constitutions lend themselves to long-term adjustment. Pregnancy and early infancy epitomize an ideal developmental juncture for preventive measures aiming to reduce the risk of NCDs; by promoting the health of pregnant and lactating women today, the health of the next generation(s) may be successfully improved. The perfect tools for this initiative derive from the earliest and most massive source of environmental exposures, namely the microbiome and nutrition, due to their fundamental interactions in the function of the host immune and metabolic maturation. Full article

Both microbe–microbe and host–microbe interactions can have effects beyond the local environment and influence immunological responses in remote organs such as the lungs. The crosstalk between the gut and the lungs, which is supported by complex connections and intricate pathways, is defined as the gut–lung axis. This review aimed to report on the potential role of the gut–lung gut–lung axis in the development and persistence of equine asthma. We summarized significant determinants in the development of asthma in horses and humans. The article discusses the gut–lung axis and proposes an integrative view of the relationship between gut microbiota and asthma. It also explores therapies for modulating the gut microbiota in horses with asthma. Improving our understanding of the horse gut–lung axis could lead to the development of techniques such as fecal microbiota transplants, probiotics, or prebiotics to manipulate the gut microbiota specifically for improving the management of asthma in horses. Full article

Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. Preclinical and clinical studies have documented intensive crosstalk between the gut microbiome, host organism, and immune system. According to the findings, polymorphic microbes might play diverse roles in tumorigenesis, cancer progression, and therapy response. Microbial imbalances and changes in the levels of bacterial metabolites and toxins promote cancer progression via EMT and angiogenesis. In contrast, a favorable microbial composition, together with microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), can attenuate the processes of tumor initiation, disease progression, and the formation of distant metastases. In this review, we highlight the role of the intratumoral and gut microbiomes in cancer cell invasion, migration, and metastatic ability and outline the potential options for microbiota modulation. As shown in murine models, probiotics inhibited tumor development, reduced tumor volume, and suppressed angiogenesis and metastasis. Moreover, modulation of an unfavorable microbiome might improve efficacy and reduce treatment-related toxicities, bringing clinical benefit to patients with metastatic cancer. Full article

The gut microbiota is a dynamic community of bacteria distributed in the gastroenteric tract and changes in response to diseases, diet, use of antibiotics and probiotics, hygiene status, and other environmental factors. Dysbiosis, a disruption of the normal crosstalk between the host and the microbes, is associated with obesity, diabetes, cancer, and cardiovascular diseases, is linked to a reduction of anti-inflammatory bacteria like Lactobacillus and Roseburia, and to an increase in the growth of proinflammatory species like Ruminococcus gnavus and Bacteroidetes. Some plants possess anticancer properties and various studies have reported that some of these are also able to modulate the gut microbiota. The aim of this work is to evaluate the crucial relationship between medical plants and gut microbiota and the consequences on the onset and progression of cancer. In vivo studies about hematological malignancies showed that beta-glucans tie to endogenous antibeta glucan antibodies and to iC3b, an opsonic fragment of the central complement protein C3, leading to phagocytosis of antibody-targeted neoplastic cells and potentiation of the cytotoxic activity of the innate immune system if administered together with monoclonal antibodies. In conclusion, this review suggests the potential use of medical plants to improve gut dysbiosis and assist in the treatment of cancer. Full article

The mammalian or mechanistic target of rapamycin (mTOR) integrates multiple intracellular and extracellular upstream signals involved in the regulation of anabolic and catabolic processes in cells and plays a key regulatory role in cell growth and metabolism. The activation of the mTOR signaling pathway has been reported to be associated with a wide range of human diseases. A growing number of in vivo and in vitro studies have demonstrated that gut microbes and their complex metabolites can regulate host metabolic and immune responses through the mTOR pathway and result in disorders of host physiological functions. In this review, we summarize the regulatory mechanisms of gut microbes and mTOR in different diseases and discuss the crosstalk between gut microbes and their metabolites and mTOR in disorders in the gastrointestinal tract, liver, heart, and other organs. We also discuss the promising application of multiple potential drugs that can adjust the gut microbiota and mTOR signaling pathways. Despite the limited findings between gut microbes and mTOR, elucidating their relationship may provide new clues for the prevention and treatment of various diseases. Full article

The cardiovascular and metabolic disorders, collectively known as cardiometabolic disease (CMD), are high morbidity and mortality pathologies associated with lower quality of life and increasing health-care costs. The influence of the gut microbiota (GM) in dictating the interpersonal variability in CMD susceptibility, progression and treatment response is beginning to be deciphered, as is the mutualistic relation established between the GM and diet. In particular, dietary factors emerge as pivotal determinants shaping the architecture and function of resident microorganisms in the human gut. In turn, intestinal microbes influence the absorption, metabolism, and storage of ingested nutrients, with potentially profound effects on host physiology. Herein, we present an updated overview on major effects of dietary components on the GM, highlighting the beneficial and detrimental consequences of diet–microbiota crosstalk in the setting of CMD. We also discuss the promises and challenges of integrating microbiome data in dietary planning aimed at restraining CMD onset and progression with a more personalized nutritional approach. Full article

The innate immune response is highly dependent on the action of macrophages. They are abundant in the intestine subepithelial lamina propria of the mucosa, where they deploy multiple tasks and play a critical role. The balance between the gut microbiota and M2 macrophages is critical for gut health and homeostasis. Gut microbiota has the power to change macrophage phenotype and replenish the resident macrophage niche during and post infection. As far as the extracellular enteric parasitic infections invasive amebic colitis and giardiasis are concerned, a change of macrophages phenotype to a pro-inflammatory state is dependent on direct contact of the protozoan parasites with host cells. Macrophages induce strong pro-inflammatory response by inflammasome activation and secretion of interleukin IL-1β. Inflammasomes play a key role in the response to cellular stress and microbe attacks. The balance between gut mucosal homeostasis and infection is dependent on the crosstalk between microbiota and resident macrophages. Parasitic infections involve NLRP1 and NLRP3 inflammasome activation. For Entamoeba histolytica and Giardia duodenalis infections, inflammasome NLRP3 activation is crucial to promote the host defenses. More studies are needed to further elucidate possible therapeutic and protective strategies against these protozoan enteric parasites’ invasive infections in humans. Full article

Adult stem cells lie at the crossroads of tissue repair, inflammation, and malignancy. Intestinal microbiota and microbe–host interactions are pivotal to maintaining gut homeostasis and response to injury, and participate in colorectal carcinogenesis. Yet, limited knowledge is available on whether and how bacteria directly crosstalk with intestinal stem cells (ISC), particularly cancerous stem-like cells (CR-CSC), as engines for colorectal cancer initiation, maintenance, and metastatic dissemination. Among several bacterial species alleged to initiate or promote colorectal cancer (CRC), the pathobiont Fusobacterium Nucleatum has recently drawn significant attention for its epidemiologic association and mechanistic linkage with the disease. We will therefore focus on current evidence for an F. nucleatum-CRCSC axis in tumor development, highlighting the commonalities and differences between F. nucleatum-associated colorectal carcinogenesis and gastric cancer driven by Helicobacter Pylori. We will explore the diverse facets of the bacteria–CSC interaction, analyzing the signals and pathways whereby bacteria either confer “stemness” properties to tumor cells or primarily target stem-like elements within the heterogeneous tumor cell populations. We will also discuss the extent to which CR-CSC cells are competent for innate immune responses and participate in establishing a tumor-promoting microenvironment. Finally, by capitalizing on the expanding knowledge of how the microbiota and ISC crosstalk in intestinal homeostasis and response to injury, we will speculate on the possibility that CRC arises as an aberrant repair response promoted by pathogenic bacteria upon direct stimulation of intestinal stem cells. Full article

Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ. With the development of non-culture-dependent techniques, the presence of low-biomass microbiomes in the lungs has been identified. The species of the lung microbiome are similar to those of the oral microbiome, suggesting that the microbiome is derived passively within the lungs from the oral cavity via micro-aspiration. Elimination, immigration, and relative growth within its communities all contribute to the composition of the lung microbiome. The lung microbiome is reportedly altered in many lung diseases that have not traditionally been considered infectious or microbial, and potential pathways of microbe–host crosstalk are emerging. Recent studies have shown that the lung microbiome also plays an important role in brain autoimmunity. There is a close relationship between the lungs and the brain, which can be called the lung–brain axis. However, the problem now is that it is not well understood how the lung microbiota plays a role in the disease—specifically, whether there is a causal connection between disease and the lung microbiome. The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses. However, fungi and viruses have not been fully studied compared to bacteria in the lungs. In this review, we mainly discuss the role of the lung microbiome in chronic lung diseases and, in particular, we summarize the recent progress of the lung microbiome in multiple sclerosis, as well as the lung–brain axis. Full article

Immune cells and commensal microbes in the human intestine constantly communicate with and react to each other in a stable environment in order to maintain healthy immune activities. Immune system-microbiota cross-talk relies on a complex network of pathways that sustain the balance between immune tolerance and immunogenicity. Probiotic bacteria can interact and stimulate intestinal immune cells and commensal microflora to modulate specific immune functions and immune homeostasis. Growing evidence shows that probiotic bacteria present important health-promoting and immunomodulatory properties. Thus, the use of probiotics might represent a promising approach for improving immune system activities. So far, few studies have been reported on the beneficial immune modulatory effect of probiotics. However, many others, which are mainly focused on their metabolic/nutritional properties, have been published. Therefore, the mechanisms behind the interaction between host immune cells and probiotics have only been partially described. The present review aims to collect and summarize the most recent scientific results and the resulting implications of how probiotic bacteria and immune cells interact to improve immune functions. Hence, a description of the currently known immunomodulatory mechanisms of probiotic bacteria in improving the host immune system is provided. Full article