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This manuscript describes and evaluates the FEEDNETICS model, a detailed mechanistic nutrient-based model that has been developed to be used as a data interpretation and decision-support tool by fish farmers, aquafeed producers, aquaculture consultants and researchers. The modelling framework comprises two main components: (i) fish model, that simulates at the individual level the fish growth, composition, and nutrient utilization, following basic physical principles and prior information on the organization and control of biochemical/metabolic processes; and (ii) farm model, that upscales all information to the population level. The model was calibrated and validated for five commercially relevant farmed fish species, i.e., gilthead seabream (Sparus aurata), European seabass (Dicentrarchus labrax), Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus mykiss), and Nile tilapia (Oreochromis niloticus), using data sets covering a wide range of rearing and feeding conditions. The results of the validation of the model for fish growth are consistent between species, presenting a mean absolute percentage error (MAPE) between 11.7 and 13.8%. Several uses cases are presented, illustrating how this tool can be used to complement experimental trial design and interpretation, and to evaluate nutritional and environmental effects at the farm level. FEEDNETICS provides a means of transforming data into useful information, thus contributing to more efficient fish farming.

The growth of the aquaculture industry requires more sustainable and circular economy-driven aquafeed formulas. Thus, the goal of the present study was to assess in farmed gilthead sea bream (Sparus aurata L.) how different combinations of novel and conventional fish feed ingredients supported proper animal performance in terms of growth and physiological biomarkers of blood/liver/head kidney. A 77-day feeding trial was conducted with three experimental diets (PAP, with terrestrial processed animal protein from animal by-products; NOPAP, without processed animal protein from terrestrial animal by-products; MIX, a combination of alternative ingredients of PAP and NOPAP diets) and a commercial-type formulation (CTRL), and their effects on growth performance and markers of endocrine growth regulation, lipid metabolism, antioxidant defense and inflammatory condition were assessed at circulatory and tissue level (liver, head kidney). Growth performance was similar among all dietary treatments. However, fish fed the PAP diet displayed a lower feed conversion and protein efficiency, with intermediate values in MIX-fed fish. Such gradual variation in growth performance was supported by different biomarker signatures that delineated a lower risk of oxidation and inflammatory condition in NOPAP fish, in concurrence with an enhanced hepatic lipogenesis that did not represent a risk of lipoid liver degeneration.

Land use allocation (LUA) is of prime importance for the development of urban sustainability and resilience. Since the process of planning and managing land use requires balancing different conflicting social, economic, and environmental factors, it has become a complex and significant issue in urban planning worldwide. LUA is usually regarded as a spatial multi-objective optimization (MOO) problem in previous studies. In this paper, we develop an MOO approach for tackling the LUA problem, in which maximum economy, minimum carbon emissions, maximum accessibility, maximum integration, and maximum compactness are formulated as optimal objectives. To solve the MOO problem, an improved non-dominated sorting genetic algorithm III (NSGA-III) is proposed in terms of mutation and crossover operations by preserving the constraints on the sizes for each land use type. The proposed approach was applied to KaMavota district, Maputo City, Mozambique, to generate a proper land use plan. The results showed that the improved NSGA-III yielded better performance than the standard NSGA-III. The optimal solutions produced by the MOO approach provide good trade-offs between the conflicting objectives. This research is beneficial for policymakers and city planners by providing alternative land use allocation plans for urban sustainability and resilience.

Proper emergency evacuation planning is a key to ensuring the safety and efficiency of resources allocation in disaster events. An efficient evacuation plan can save human lives and avoid other effects of disasters. To develop effective evacuation plans, this study proposed a multi-objective optimization model that assigns individuals to emergency shelters through safe evacuation routes during the available periods. The main objective of the proposed model is to minimize the total travel distance of individuals leaving evacuation zones to shelters, minimize the risk on evacuation routes and minimize the overload of shelters. The experimental results show that the Discrete Multi-Objective Cuckoo Search (DMOCS) has better and consistent performance as compared to the standard Multi-Objective Cuckoo Search (MOCS) in most cases in terms of execution time; however, the performance of MOCS is still within acceptable ranges. Metrics and measures such as hypervolume indicator, convergence evaluation and parameter tuning have been applied to evaluate the quality of Pareto front and the performance of the proposed algorithm. The results showed that the DMOCS has better performance than the standard MOCS.

Chlorella vulgaris and Tetraselmis chuii are two microalgae species already marketed because of their richness in high-value and health-beneficial compounds. Previous studies have demonstrated the biological properties of compounds isolated from both microalgae, although data are not yet available on the impact that pre-treatment and gastrointestinal digestion could exert on these properties. The aim of the present study was to analyze the impact of the biomass pre-treatment (freeze/thaw cycles plus ultrasounds) and simulated gastrointestinal digestion in the bioaccessibility and in vitro antioxidant activity (ABTS, ORAC, Q-FRAP, Q-DPPH) of the released digests. The cell wall from microalgae were susceptible to the pre-treatment and the action of saliva and gastric enzymes, releasing bioactive peptides and phenolic compounds that contributed to the potent antioxidant activity of digests through their radical scavenging and iron reduction capacities. Our findings suggest the potential of these microalgae against oxidative stress-associated diseases at both, intestinal and systemic level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described., Approach and Results: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18])., Conclusions: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: The Gender-Equity Model for liver Allocation corrected by serum sodium (GEMA-Na) and the Model for End-stage Liver Disease 3.0 (MELD 3.0) could amend sex disparities for accessing liver transplantation (LT). We aimed to assess these inequities in Spain and to compare the performance of GEMA-Na and MELD 3.0., Methods: Nationwide cohort study including adult patients listed for a first elective LT (January 2016-December 2021). The primary outcome was mortality or delisting for sickness within the first 90 days. Independent predictors of the primary outcome were evaluated using multivariate Cox's regression with adjusted relative risks (RR) and 95% confidence intervals (95% CI). The discrimination of GEMA-Na and MELD 3.0was assessed using Harrell c-statistics (Hc)., Findings: The study included 6071 patients (4697 men and 1374 women). Mortality or delisting for clinical deterioration occurred in 286 patients at 90 days (4.7%). Women had reduced access to LT (83.7% vs. 85.9%; p = 0.037) and increased risk of mortality or delisting for sickness at 90 days (adjusted RR = 1.57 [95% CI 1.09-2.28]; p = 0.017). Female sex remained as an independent risk factor when using MELD or MELD-Na but lost its significance in the presence of GEMA-Na or MELD 3.0. Among patients included for reasons other than tumours (n = 3606; 59.4%), GEMA-Na had Hc = 0.753 (95% CI 0.715-0.792), which was higher than MELD 3.0 (Hc = 0.726 [95% CI 0.686-0.767; p = 0.001), showing both models adequate calibration., Interpretation: GEMA-Na and MELD 3.0 might correct sex disparities for accessing LT, but GEMA-Na provides more accurate predictions of waiting list outcomes and could be considered the standard of care for waiting list prioritization., Funding: Instituto de Salud Carlos III, Agencia Estatal de Investigación (Spain), and European Union., Competing Interests: MLR-P has received lecture fees from Chiesi and Advanz Pharma, outside the present work. RM-M has received lecture fees from Chiesi, outside the present work. JC has received lecture fees from Chiesi and Astellas, outside the present work. All other authors declare no competing interests., (© 2024 The Author(s).)

Biological therapies only benefit one-third of patients with Crohn's disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.

Polyglutamine diseases are a group of neurodegenerative disorders caused by an abnormal expansion of CAG repeat tracts in the codifying regions of nine, otherwise unrelated, genes. While the protein products of these genes are suggested to play diverse cellular roles, the pathogenic mutant proteins bearing an expanded polyglutamine sequence share a tendency to self-assemble, aggregate and engage in abnormal molecular interactions. Understanding the shared paths that link polyglutamine protein expansion to the nervous system dysfunction and the degeneration that takes place in these disorders is instrumental to the identification of targets for therapeutic intervention. Among polyglutamine diseases, spinocerebellar ataxias (SCAs) share many common aspects, including the fact that they involve dysfunction of the cerebellum, resulting in ataxia. Our work aimed at exploring a putative new therapeutic target for the two forms of SCA with higher worldwide prevalence, SCA type 2 (SCA2) and type 3 (SCA3), which are caused by expanded forms of ataxin-2 (ATXN2) and ataxin-3 (ATXN3), respectively. The pathophysiology of polyglutamine diseases has been described to involve an inability to properly respond to cell stress. We evaluated the ability of GTPase-activating protein-binding protein 1 (G3BP1), an RNA-binding protein involved in RNA metabolism regulation and stress responses, to counteract SCA2 and SCA3 pathology, using both in vitro and in vivo disease models. Our results indicate that G3BP1 overexpression in cell models leads to a reduction of ATXN2 and ATXN3 aggregation, associated with a decrease in protein expression. This protective effect of G3BP1 against polyglutamine protein aggregation was reinforced by the fact that silencing G3bp1 in the mouse brain increases human expanded ATXN2 and ATXN3 aggregation. Moreover, a decrease of G3BP1 levels was detected in cells derived from patients with SCA2 and SCA3, suggesting that G3BP1 function is compromised in the context of these diseases. In lentiviral mouse models of SCA2 and SCA3, G3BP1 overexpression not only decreased protein aggregation but also contributed to the preservation of neuronal cells. Finally, in an SCA3 transgenic mouse model with a severe ataxic phenotype, G3BP1 lentiviral delivery to the cerebellum led to amelioration of several motor behavioural deficits. Overall, our results indicate that a decrease in G3BP1 levels may be a contributing factor to SCA2 and SCA3 pathophysiology, and that administration of this protein through viral vector-mediated delivery may constitute a putative approach to therapy for these diseases, and possibly other polyglutamine disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Inflammatory and oxidative processes are tightly regulated by innate and adaptive immune systems, which are involved in the pathology of a diversity of chronic diseases. Soybean peptides, such as lunasin, have emerged as one of the most hopeful food-derived peptides with a positive impact on health. The aim was to study the potential antioxidant and immunomodulatory activity of a lunasin-enriched soybean extract (LES). The protein profile of LES was characterized, and its behavior under simulated gastrointestinal digestion was evaluated. Besides its in vitro radical scavenging capacity, LES and lunasin's effects on cell viability, phagocytic capacity, oxidative stress, and inflammation-associated biomarkers were investigated in both RAW264.7 macrophages and lymphocytes EL4. Lunasin and other soluble peptides enriched after aqueous solvent extraction partially resisted the action of digestive enzymes, being potentially responsible for the beneficial effects of LES. This extract scavenged radicals, reduced reactive oxygen species (ROS) and exerted immunostimulatory effects, increasing nitric oxide (NO) production, phagocytic activity, and cytokine release in macrophages. Lunasin and LES also exerted dose-dependent immunomodulatory effects on EL4 cell proliferation and cytokine production. The modulatory effects of soybean peptides on both immune cell models suggest their potential protective role against oxidative stress, inflammation, and immune response-associated disorders.

The estimated increase in world population will lead to a deterioration in global food security, aggravated in developing countries by hidden hunger resulting from protein deficiency. To reduce or avoid this crisis, a dietary shift towards the consumption of sustainable, nutrient-rich, and calorically efficient food products has been recommended by the FAO and WHO. Plant proteins derived from grains and seeds provide nutritionally balanced diets, improve health status, reduce poverty, enhance food security, and contain several functional compounds. In this review, the current evidence on the nutritional and functional properties of underutilized grains is summarized, focusing on their incorporation into functional foods and the role of their proteins as novel source of bioactive peptides with health benefits.

Myotonic dystrophy type 1 (DM1) exhibits highly heterogeneous clinical manifestations caused by an unstable CTG repeat expansion reaching up to 4000 CTG. The clinical variability depends on CTG repeat number, CNG repeat interruptions, and somatic mosaicism. Currently, none of these factors are simultaneously and accurately determined due to the limitations of gold standard methods used in clinical and research laboratories. An amplicon method for targeting the DMPK locus using single-molecule real-time sequencing was recently developed to accurately analyze expanded alleles. However, amplicon-based sequencing still depends on PCR, and the inherent bias toward preferential amplification of smaller repeats can be problematic in DM1. Thus, an amplification-free long-read sequencing method was developed by using CRISPR/Cas9 technology in DM1. This method was used to sequence the DMPK locus in patients with CTG repeat expansion ranging from 130 to >1000 CTG. We showed that elimination of PCR amplification improves the accuracy of measurement of inherited repeat number and somatic repeat variations, two key factors in DM1 severity and age at onset. For the first time, an expansion composed of >85% CCG repeats was identified by using this innovative method in a DM1 family with an atypical clinical profile. No-amplification targeted sequencing represents a promising method that can overcome research and diagnosis shortcomings, with translational implications for clinical and genetic counseling in DM1., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.

Long-term humoral immunity and its protective role in liver transplantation (LT) patients have not been elucidated. We performed a prospective multicenter study to assess the persistence of immunoglobulin G (IgG) antibodies in LT recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 LT recipients were matched with 65 nontransplanted patients by a propensity score including variables with recognized impact on COVID-19. LT recipients showed a lower prevalence of anti-nucleocapsid (27.7% versus 49.2%; P = 0.02) and anti-spike IgG antibodies (88.2% versus 100.0%; P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplantation patients 1 year after COVID-19 (median, 0.49 [interquartile range, 0.15-1.40] versus 1.36 [interquartile range, 0.53-2.91]; P < 0.001). Vaccinated LT recipients showed higher antibody levels compared with unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in nontransplanted individuals (P = 0.70). In LT patients, a longer interval since transplantation (odds ratio, 1.10; 95% confidence interval, 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies 1 year after infection. In conclusion, compared with nontransplanted patients, LT recipients show a lower long-term persistence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, SARS-CoV-2 vaccination after COVID-19 in LT patients achieves a significant increase in antibody levels, comparable to that of nontransplanted patients., (© 2021 by the American Association for the Study of Liver Diseases.)

Abstract: Congenital facial palsy is a rare condition, usually related to a traumatic event during birth or as a feature of a syndrome. In this report, two cases of infants with peripheral facial palsy since birth are described, in which magnetic resonance imaging demonstrated unilateral aplasia of the facial nerve. There are only a few cases with similar findings described in the literature. A multidisciplinary approach is recommended to provide the best care. Although no reinnervation of the facial muscles is likely to occur, rehabilitative therapies may be valuable as complementary treatments., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Among the trinucleotide repeat disorders, myotonic dystrophy type 1 (DM1) is one of the most complex neuromuscular diseases caused by an unstable CTG repeat expansion in the DMPK gene. DM1 patients exhibit high variability in the dynamics of CTG repeat instability and in the manifestations and progression of the disease. The largest expanded alleles are generally associated with the earliest and most severe clinical form. However, CTG repeat length alone is not sufficient to predict disease severity and progression, suggesting the involvement of other factors. Several data support the role of epigenetic alterations in clinical and genetic variability. By highlighting epigenetic alterations in DM1, this review provides a new avenue on how these changes can serve as biomarkers to predict clinical features and the mutation behavior.

Purpose This retrospective study aims to analyze the clinical and functional results obtained over a seven-year period of performing reverse total shoulder arthroplasty (RTSA) and the subsequent postoperative rehabilitation protocol. Methods We analyzed data from 80 patients who were evaluated at a preoperative, as well as monthly postoperative outpatient consultation, until the discharge from the rehabilitation program, using Constant Score (CS). Results A comparison of preoperative and postoperative (after rehabilitation protocol) results revealed an improved functional score of absolute CS (20.8 increase), normal relative CS (29.1 increase), and individual relative CS (31.7 increase) with statistical significance (p<0.05). From the analysis of CS subscores, there was a positive evolution of the pain subscore, as well as flexion, abduction, and external rotation combined with abduction range of motion (ROM). Contrarily, there was a negative evolution of the combined internal rotation, extension, and adduction ROM, as well as deltoid muscle strength. No statistically significant correlations were found between age and postoperative CS, as well as between the time interval from surgery to the beginning of outpatient rehabilitation and CS evolution. Conclusion Our study demonstrates that RTSA is an effective therapeutic option that, if combined with a well-structured rehabilitation program, can improve pain, mobility, and upper limb functionality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Pereira et al.)

Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disease caused by an abnormal CTG repeat expansion in the 3'UTR region of the DMPK gene. In patients, the CTG repeat size varies from fifty to thousands CTG and usually increases across generations (intergenerational instability) and over time in tissues (somatic instability). Larger expansions are associated with more severe symptoms and a decreasing age of onset. Thus, the larger expansions are often associated with the most severe clinical form of DM1 (congenital form). Our PhD project is to identify new genetic and chemical factors reducing the number of repeats and to better understand the mechanisms underlying instability. To this end, genetic and pharmacological screenings are carried out in a HEK293 cell model allowing the rapid detection of expansions (increase in CTG repeat number) and contractions (decrease in CTG repeat number). The effects of different genes and chemical factors, selected during the screening, on the dynamics of the CTG repeat instability will be studied in a DM1 cell model. The results of our work will provide a better understanding of the mechanisms behind contractions. In addition, the identification of new pharmacological compounds promoting CTG contractions and thus reducing or even reversing the progression of disease will offer new therapeutic prospects for DM1 but also for other triplet repeat diseases., (© 2021 médecine/sciences – Inserm.)

Most textbook definitions recognize only animals as having nervous systems. However, for the past couple decades, botanists have been meticulously studying long-distance signaling systems in plants, and some researchers have stated that plants have a simple nervous system. Thus, an academic conflict has emerged between those who defend and those who deny the existence of a nervous system in plants. This article analyses that debate, and we propose an alternative to answering yes or no: broadening the definition of a nervous system to include plants. We claim that a definition broader than the current one, which is based only on a phylogenetic viewpoint, would be helpful in obtaining a deeper understanding of how evolution has driven the features of signal generation, transmission and processing in multicellular beings. Also, we propose two possible definitions and exemplify how broader a definition allows for new viewpoints on the evolution of plants, animals and the nervous system.

The gastrointestinal tract is optimized to efficiently absorb nutrients and provide a competent barrier against a variety of lumen environmental compounds. Different regulatory mechanisms jointly collaborate to maintain intestinal homeostasis, but alterations in these mechanisms lead to a dysfunctional gastrointestinal barrier and are associated to several inflammatory conditions usually found in chronic pathologies such as inflammatory bowel disease (IBD). The gastrointestinal mucus, mostly composed of mucin glycoproteins, covers the epithelium and plays an essential role in digestive and barrier functions. However, its regulation is very dynamic and is still poorly understood. This review presents some aspects concerning the role of mucus in gut health and its alterations in IBD. In addition, the impact of gut microbiota and dietary compounds as environmental factors modulating the mucus layer is addressed. To date, studies have evidenced the impact of the three-way interplay between the microbiome, diet and the mucus layer on the gut barrier, host immune system and IBD. This review emphasizes the need to address current limitations on this topic, especially regarding the design of robust human trials and highlights the potential interest of improving our understanding of the regulation of the intestinal mucus barrier in IBD.