Search Results (15)

Background: Gastrointestinal (GI) involvement is the most frequent visceral complication of systemic sclerosis (SSc), affecting up to 90% of patients, yet it remains poorly understood compared to pulmonary or cutaneous manifestations. The aim of this review is to integrate current knowledge on the cellular mechanisms underlying GI disease in SSc and to identify research priorities. Methods: A narrative literature review was conducted through a systematic PubMed search up to September 2025, complemented by manual reference screening. Results: Histopathological and functional evidence consistently demonstrates that neuromuscular alterations, including degeneration of enteric neurons, loss of interstitial cells of Cajal, and smooth muscle atrophy, can precede fibrosis, challenging the traditional “fibrosis-first” paradigm. Fibroblast and myofibroblast activation are present in gastric and colonic samples, sustained by profibrotic mediators such as TGF-β, CTGF, and endothelin-1, although the cellular origins of these stromal cells remain uncertain. Additional pathogenic contributions include autonomic dysfunction, barrier dysfunction with dysbiosis, impaired vascular reserve of vessels perfusing the gut, and functional autoantibodies targeting interneural and neuromuscular function and communication. Compared with skin and lung, the GI tract displays less fibrosis and fewer inflammatory infiltrates, but immune-derived mediators and autoantibodies suggest distinct immunopathogenic pathways are activated. Conclusions: Collectively, these findings depict GI involvement in SSc as a multi-compartmental process integrating neural, epithelial, endothelial, stromal, and immune alterations. Addressing the lack of validated biomarkers, mechanistic models, and biomarker-stratified trials will be essential to move beyond symptomatic care and toward precision medicine approaches for SSc-related GI disease. Full article

Amphibian microbial communities are known to be shaped by host physiology and environmental factors, yet the relative roles of sexual dimorphism and tissue specialization remain poorly understood. Using 16S rRNA gene sequencing, we compared the gastrointestinal and integumentary microbiomes of a monomorphic Chinese frog population, Odorrana schmackeri, inhabiting identical montane streams. Our results showed distinct phylogenetic stratification between niches: Proteobacteria dominated both environmental microbiota and O. schmackeri gut and skin microbiotas but with differential sub-phylum specialization. The soil microbiota was dominated by unclassified_Vicinamibacteraceae, the water microbiota was Limnohabitans-dominated, the skin microbiota was dominated by Bordetella, and the gut microbiota was led by Acinetobacter. Alpha diversity analysis revealed significant tissue- and environmental-based divergences but no sexual differentiation, a pattern confirmed by beta diversity assessments showing stronger microbial community separation by tissue and environmental compartmentalization than by sex. Functional metagenomic prediction indicated convergent enrichment of metabolic pathways across host-associated and environmental communities. These results suggest that microbial community structure in O. schmackeri is principally governed by tissue-specific ecological selection pressures rather than host sexual characteristics. Our findings enhance understanding of microbiome assembly rules in vertebrate ectotherms and identify potential connections between microbiota in different ecological niches. Full article

Fusobacterium nucleatum is a Gram-negative anaerobe that occupies a central ecological niche in oral biofilms but has emerged as a trans-compartmental pathogen implicated in gastrointestinal and cardiovascular diseases. In inflammatory bowel diseases, Fusobacterium nucleatum adheres to the intestinal epithelium via adhesins such as FadA, disrupts tight junctions, and induces Toll-like receptor–mediated inflammatory cascades, amplifying epithelial permeability and sustaining mucosal inflammation. In colorectal cancer, Fusobacterium nucleatum promotes carcinogenesis through multiple mechanisms, including β-catenin activation, modulation of oncogenic microRNAs, and immune evasion via Fap2–TIGIT signaling, while also fostering a pro-inflammatory and immunosuppressive tumor microenvironment. Its enrichment correlates with advanced tumor stage, chemoresistance, and poor prognosis, underscoring its potential as a biomarker and therapeutic target. Beyond the gut, Fusobacterium nucleatum has been detected in atherosclerotic plaques and endocardial tissues, where it contributes to endothelial dysfunction, foam cell formation, oxidative stress, and plaque instability, thereby linking chronic oral infection with cardiovascular risk. Collectively, evidence suggests that Fusobacterium nucleatum acts as a pathophysiological connector across IBD, CRC, and CVD through conserved mechanisms of adhesion, immune modulation, and inflammation. Understanding these processes provides opportunities for innovative interventions, ranging from targeted antimicrobials and host-directed therapies to dietary and microbiome-based strategies, aimed at mitigating the systemic burden of this organism and improving clinical outcomes across multiple diseases. Full article

This review first provides an overview of the functional diversity of Orthoptera-associated microbiota and the services they provide to their hosts. However, data are widely scattered across the different families studied, making it difficult to establish whether a core microbiota is present. The abundance of some genera (Pantoea, Enterococcus, Enterobacter, Acinetobacter) is associated with the degradation of cellulose compounds, although their clear contribution remains to be determined. In addition, P. agglomerans may play a role in the production of aggregation pheromones in the desert locust. In terms of gut compartmentalisation, the diversity of the bacterial community in the foregut appears to be highly variable between individuals and species, whereas it is more uniform in other parts of the gut. Metabolic pathways of the gut microbiota revealed differences in amino acid metabolism between the midgut and hindgut. Bacteria in the midgut are associated with amino acid synthesis and anaerobic metabolism, whereas pathways in the hindgut may be involved in amino acid catabolism and ace-tyl-CoA-mediated processes. Further research is needed to better understand these different components of the bacterial community in digestive processes, and to identify bacterial species of particular interest in explaining species’ lifestyles or for bioconversion. Full article

Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn’s Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before ($t_0$), after 24 weeks of ($t_1)$ and after 52 weeks of ($t_{2 }$) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at $t_0$, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia, albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model’s satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions. Full article

The intestinal epithelium constitutes a selectively permeable barrier between the internal and external environment that allows the absorption of nutrients, electrolytes, and water, as well as an effective defense against intraluminal bacteria, toxins, and potentially antigenic material. Experimental evidence suggest that intestinal inflammation is critically dependent on an imbalance of homeostasis between the gut microbiota and the mucosal immune system. In this context, mast cells play a crucial role. The intake of specific probiotic strains can prevent the development of gut inflammatory markers and activation of the immune system. Here, the effect of a probiotic formulation containing L. rhamnosus LR 32, B. lactis BL04, and B. longum BB 536 on intestinal epithelial cells and mast cells was investigated. To mimic the natural host compartmentalization, Transwell co-culture models were set up. Co-cultures of intestinal epithelial cells interfaced with the human mast cell line HMC-1.2 in the basolateral chamber were challenged with lipopolysaccharide (LPS), and then treated with probiotics. In the HT29/HMC-1.2 co-culture, the probiotic formulation was able to counteract the LPS-induced release of interleukin 6 from HMC-1.2, and was effective in preserving the epithelial barrier integrity in the HT29/Caco-2/ HMC-1.2 co-culture. The results suggest the potential therapeutic effect of the probiotic formulation. Full article

Antifibrotic therapies for the treatment of liver fibrosis represent an unconquered area of drug development. The significant involvement of the gut microbiota as a driving force in a multitude of liver disease, be it pathogenesis or fibrotic progression, suggest that targeting the gut–liver axis, relevant signaling pathways, and/or manipulation of the gut’s commensal microbial composition and its metabolites may offer opportunities for biomarker discovery, novel therapies and personalized medicine development. Here, we review potential links between bacterial translocation and deficits of host-microbiome compartmentalization and liver fibrosis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies, translated from our current knowledge of the gut–liver axis, targeted at restoring intestinal eubiosis, ameliorating hepatic fibrosis and rising portal hypertension that characterize and define the course of decompensated cirrhosis. Full article

Redox status is a key determinant in the fate of β-cell. These cells are not primarily detoxifying and thus do not possess extensive antioxidant defense machinery. However, they show a wide range of redox regulating proteins, such as peroxiredoxins, thioredoxins or thioredoxin reductases, etc., being functionally compartmentalized within the cells. They keep fragile redox homeostasis and serve as messengers and amplifiers of redox signaling. β-cells require proper redox signaling already in cell ontogenesis during the development of mature β-cells from their progenitors. We bring details about redox-regulated signaling pathways and transcription factors being essential for proper differentiation and maturation of functional β-cells and their proliferation and insulin expression/maturation. We briefly highlight the targets of redox signaling in the insulin secretory pathway and focus more on possible targets of extracellular redox signaling through secreted thioredoxin1 and thioredoxin reductase1. Tuned redox homeostasis can switch upon chronic pathological insults towards the dysfunction of β-cells and to glucose intolerance. These are characteristics of type 2 diabetes, which is often linked to chronic nutritional overload being nowadays a pandemic feature of lifestyle. Overcharged β-cell metabolism causes pressure on proteostasis in the endoplasmic reticulum, mainly due to increased demand on insulin synthesis, which establishes unfolded protein response and insulin misfolding along with excessive hydrogen peroxide production. This together with redox dysbalance in cytoplasm and mitochondria due to enhanced nutritional pressure impact β-cell redox homeostasis and establish prooxidative metabolism. This can further affect β-cell communication in pancreatic islets through gap junctions. In parallel, peripheral tissues losing insulin sensitivity and overall impairment of glucose tolerance and gut microbiota establish local proinflammatory signaling and later systemic metainflammation, i.e., low chronic inflammation prooxidative properties, which target β-cells leading to their dedifferentiation, dysfunction and eventually cell death. Full article

Background: Starting late 2019, a novel coronavirus spread from the capital of the Hubei province in China to the rest of the country, then to most of the world. To anticipate future trends in the development of the pandemic, we explore here, based on public records of infected persons, how variation in the virus tropism could end up in different patterns, warranting a specific strategy to handle the epidemic. Methods: We use a compartmental model to describe the evolution of an individual through several possible states: susceptible, infected, alternative infection, detected, and removed. We fit the parameters of the model to the existing data, taking into account significant quarantine changes where necessary. Results: The model indicates that Wuhan quarantine measures were effective, but that alternative virus forms and a second propagation route are compatible with available data. For the Hong Kong, Singapore, and Shenzhen regions, the secondary route does not seem to be active. Conclusions: Hypotheses of an alternative infection tropism (the gut tropism) and a secondary propagation route are discussed using a model fitted by the available data. Corresponding prevention measures that take into account both routes should be implemented to the benefit of epidemic control. Full article

This paper presents an educational mobile assistant application for type 1 diabetes patients. The proposed application is based on four mathematical models that describe the glucose-insulin-glucagon dynamics using a compartmental model, with additional equations to reproduce aerobic exercise, gastric glucose absorption by the gut, and subcutaneous insulin absorption. The medical assistant was implemented in Java and deployed and validated on several smartphones with Android OS. Multiple daily doses can be simulated to perform intensive insulin therapy. As a result, the proposed application shows the influence of exercise periods, food intakes, and insulin treatments on the glucose concentrations. Four parameter variations are studied, and their corresponding glucose concentration plots are obtained, which show agreement with simulators of the state of the art. The developed application is focused on type-1 diabetes, but this can be extended to consider type-2 diabetes by modifying the current mathematical models. Full article

Type IV collagen is proposed to be a key molecule in the evolvement of multicellular animals by forming the architectural unit basement membrane, a specialized form of the extracellular matrix. Functions of the basement membrane include guiding organ regeneration, tissue repair, modulation of cell differentiation, apical–basal polarity identification, cell migration and adhesion, regulation of growth factor signaling gradients, maintenance of tissue architecture and compartmentalization. Type IV collagenopathy is a devastating systemic disease affecting the circulatory, renal and visual systems and the skeletal muscles. It is observed in patients carrying mutations in the COL4A1 gene, which codes for the ubiquitous basement membrane component. Col4a1 mouse mutants display the human symptoms of type IV collagenopathy. We chose the Drosophila melanogaster model as we recorded dominant, temperature-sensitive mutations in the cognate col4a1 gene of the fruit fly and demonstrated phenotypic elements which have not yet been explored in humans or in mouse models. In this paper we show a transition of the Z-discs, normally bordering each sarcomere, to the level of M-discs significantly penetrant in the mutants, uneven distribution of fused mitochondria in the Malpighian tubules of the excretory organ and a loss of sarcomere structure in the visceral muscles in the gut of mutants. Our observations demonstrate the systemic nature of the col4a1 mutations in the fruit fly. However, these traits are elements of the type IV collagen-associated pathology and may provide insights into approaches that can alleviate symptoms of the disease. Full article

The sea urchin Strongylocentrotus purpuratus (order Camarodonta, family Strongylocentrotidae) can be found dominating low intertidal pool biomass on the southern coast of Oregon, USA. In this case study, three adult sea urchins were collected from their shared intertidal pool, and the bacteriome of their pharynx, gut tissue, and gut digesta, including their tide pool water and algae, was determined using targeted high-throughput sequencing (HTS) of the 16S rRNA genes and bioinformatics tools. Overall, the gut tissue demonstrated Arcobacter and Sulfurimonas (Epsilonproteobacteria) to be abundant, whereas the gut digesta was dominated by Psychromonas (Gammaproteobacteria), Propionigenium (Fusobacteria), and Flavobacteriales (Bacteroidetes). Alpha and beta diversity analyses indicated low species richness and distinct microbial communities comprising the gut tissue and digesta, while the pharynx tissue had higher richness, more closely resembling the water microbiota. Predicted functional profiles showed Kyoto Encyclopedia of Genes and Genomes (KEGG) Level-2 categories of energy metabolism, membrane transport, cell motility, and signal transduction in the gut tissue, and the gut digesta represented amino acid, carbohydrate, vitamin and cofactor metabolisms, and replication and repair. Co-occurrence network analysis showed the potential relationships and key taxa, such as the highly abundant Arcobacter and Propionigenium, influencing population patterns and taxonomic organization between the gut tissue and digesta. These results demonstrate a trend of microbial community integration, allocation, predicted metabolic roles, and taxonomic co-occurrence patterns in the S. purpuratus gut ecosystem. Full article

Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen responsible for human diseases ranging from diarrhoea to life-threatening complications. Survival of the pathogen and modulation of virulence gene expression along the human gastrointestinal tract (GIT) are key features in bacterial pathogenesis, but remain poorly described, due to a paucity of relevant model systems. This review will provide an overview of the in vitro and in vivo studies investigating the effect of abiotic (e.g., gastric acid, bile, low oxygen concentration or fluid shear) and biotic (e.g., gut microbiota, short chain fatty acids or host hormones) parameters of the human gut on EHEC survival and/or virulence (especially in relation with motility, adhesion and toxin production). Despite their relevance, these studies display important limitations considering the complexity of the human digestive environment. These include the evaluation of only one single digestive parameter at a time, lack of dynamic flux and compartmentalization, and the absence of a complex human gut microbiota. In a last part of the review, we will discuss how dynamic multi-compartmental in vitro models of the human gut represent a novel platform for elucidating spatial and temporal modulation of EHEC survival and virulence along the GIT, and provide new insights into EHEC pathogenesis. Full article

Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT) of teleosts are the gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), the gill-associated lymphoid tissue (GIALT) and the recently discovered nasopharynx-associated lymphoid tissue (NALT). Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT⁺ B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture. Full article

Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21⁺ follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response. Full article