Shrimp by-products are a promising source of bioactives. This study investigated the composition and the bioactivity of a preparation obtained in mild conditions via ethanol extraction from the cephalothorax of the Mediterranean red shrimp species Aristaeomorpha foliacea. The crude extract (CE) exhibited high levels of astaxanthin (AST) and polyphenols, which contributed to its notable antioxidant activity. Monounsaturated fatty acids dominated the lipid profile of CE (46%), reflecting a typical trait of deep-sea species, while polyunsaturated and saturated fatty acids accounted for 33% and 21%, respectively. Chemical fractionation yielded a hydrophobic fraction (HF; AST-enriched) and a polar fraction (PF; polyphenols-enriched). In hepatic (HuH7) and intestinal (HCT15) human cells, CE induced dose-dependent lipid droplet accumulation and protected against palmitic acid-induced lipotoxicity: it restored cell viability, reduced reactive oxygen species, prevented lipid peroxidation and induced modulation of antioxidant enzymes, including catalase, glutathione peroxidase, and superoxide dismutase. While the HF alone partially reproduced these effects, full antioxidant and cytoprotective activity required the synergistic contribution of both fractions. These findings support the potential application of shrimp waste-derived ethanol extracts as sustainable sources of functional ingredients for oxidative stress-related conditions.

Hormonal fluctuations throughout a woman’s life, from puberty to menopause, profoundly influence the composition of the vaginal and gut microbiota, with major implications for reproductive, metabolic, and psychological health. Recent findings indicate that lifestyle factors, such as diet, stress, sleep, and physical activity, modulate microbial communities and hormonal balance through an integrated microbiome–immune–endocrine axis. This review examines the evolution of the vaginal microbiota, the effects of hormonal changes on microbial balance, and evidence for probiotic and lifestyle-based interventions in conditions such as bacterial vaginosis, endometriosis, polycystic ovary syndrome, pregnancy complications, and menopausal disorders. Particular attention is given to the estrobolome, gut–brain communication, and metabolic regulators as mediators of systemic effects.

Lentils are highly nutritious, polyphenol-rich pulses with potential functional properties. Here, we investigated the anti-inflammatory effects of polyphenolic extracts obtained from green and red lentils (GLE and RLE) on murine bone marrow-derived dendritic cells (DCs) serving as sentinels of the immune system. GLE and RLE were analyzed for their total polyphenol content, polyphenolic profile and antioxidant activity. Our analysis revealed that both types of extracts had comparable total content of polyphenols and similar high antioxidant capacity. GLE was characterized by high levels of catechin and gallocatechin compared to RLE, while RLE showed higher levels of other polyphenolic compounds, such as kaempferol, myrtillin, rutin and rhoifolin, compared to GLE. The polyphenolic extracts were subsequently evaluated for their biological effects on immature DCs exposed to lipopolysaccharide (LPS) inflammatory stimulus. RLE induced a dose-dependent reduction in IL-1α, IL-1β and IL-6 levels similarly to quercetin, used as positive control. GLE also resulted in a dose-dependent reduction in IL-1β and IL-6 levels, however these effects were associated with marked cytotoxicity. Gene expression analysis revealed a significant reduction of IL-1α and IL-1β transcription occurring in LPS-stimulated DCs treated with 25mM QE of RLE, without inducing inflammatory activation in unstimulated cells. Our findings highlight that both GLE and RLE possess antioxidant properties, and that RLE exhibits more favorable anti-inflammatory activity associated with lower cytotoxicity. These results support the potential of red lentils as a source of bioactive compounds with immunomodulatory activities.

Chronic colitis in patients with ulcerative colitis (UC) and Crohn’s disease (CD) predisposes patients to debilitating symptoms and an increased risk of colorectal cancer (CRC). Despite advances in biologics, only 30–40% of patients achieve sustained remission, underscoring the need for novel agents with complementary mechanisms of action and reduced toxicity. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist originally developed for type 2 diabetes, has demonstrated favorable metabolic and anti-inflammatory effects, suggesting potential utility in gastrointestinal disease. While GLP-1 receptor agonists have shown promise in acute colitis models and epidemiological studies indicate reduced CRC incidence among exposed individuals, the effects of dual agonists in chronic colitis-associated cancer (CAC) remain unknown. We evaluated Tirzepatide in the Winnie mouse, a model of spontaneous UC-like colitis and CAC. Weekly administration of Tirzepatide (30 nmol/kg, 8 weeks) markedly reduced colitis severity and tumor burden compared to vehicle controls. Treated mice exhibited improved weight stability independent of obesity, reflecting attenuation of inflammation and tumorigenesis rather than metabolic effects. Histologic analyses confirmed reduced inflammatory scores, preservation of crypt architecture, and fewer dysplastic lesions. At the molecular level, Tirzepatide suppressed transcription of colon cancer-associated genes (Axin2, Myc, Cdkn1a, Lgr5) and reduced pro-survival and proliferative signaling proteins (p-AKT, p-PFK2, Cyclin D1). Inflammatory cytokine transcripts (Il6, Il1β, Tnf) and stool lipocalin-2 levels were significantly decreased, corroborating broad anti-inflammatory activity. These findings align with reports of Tirzepatide suppressing tumor growth in patient-derived CRC xenografts, reinforcing a potential direct effect on epithelial oncogenic pathways rather than an indirect consequence of weight loss. Our results support Tirzepatide as a promising therapeutic candidate that bridges metabolic and immune pathways to mitigate colitis and CAC. Its dual receptor activity may synergize with existing therapies such as mesalamine or biologics, offering an advanced combination therapeutic approach to IBD management and cancer prevention. Future studies are warranted to define dosing strategies that dissociate metabolic from anti-inflammatory effects and to evaluate long-term outcomes in translational and clinical settings.

The intestinal microbiota has been implicated in neurological function through the gut–brain axis, and specific probiotic strains have been proposed to influence neuroactive pathways relevant to sleep. This randomized, double-blind, study enrolled 60 otherwise healthy adults reporting poor subjective sleep quality. Sixty participants (mean age 22.0 ± 3.0 years) were randomized to receive either a probiotic formulation (Lactobacillus rhamnosus HN001, L. rhamnosus SP1, L. acidophilus LA1, L. reuteri LR92; total daily dose 6×10⁹ CFU) or a matched non-bacterial comparator for six weeks, followed by three-week washout period. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) at baseline (T0), 3 weeks (T1), 6 weeks (T2), and after a 3-week washout (T3). Compared with the matched non-bacterial formulation, participants receiving the probiotic formulation showed a significant improvement in subjective sleep quality at T2 and T3, as assessed by between-group non-parametric analyses. PSQI scores in the probiotic group decreased from 19.2 ± 3.1 at baseline to 7.5 ± 3.9 at week 6, with improvements exceeding the minimal clinically important difference. Similar temporal patterns were observed for ISI scores. Benefits persisted through washout; however, the mechanisms underlying this persistence remain speculative. These findings suggest that supplementation with a targeted multi-strain Lactobacillus spp. formulation may provide additional benefits on perceived sleep quality when added to a matched non-bacterial formulation. Given the use of subjective sleep measures and the absence of microbiome or objective sleep assessments, further studies integrating polysomnography or actigraphy and microbiota profiling are required to confirm these results and clarify the underlying mechanisms.

The gut–brain axis represents a bidirectional communication pathway influencing mood through microbiota-related mechanisms. This randomized, double-blind, active-controlled pilot trial evaluated the effects of a multi-strain Lactobacillus spp. probiotic formulation added to an active control on depressive symptoms in adults with mild-to-moderate depressive symptoms. Sixty participants were randomly assigned to receive either a daily combination containing L. rhamnosus HN001, L. rhamnosus SP1, L. acidophilus LA1, and L. reuteri LR92 (3×10⁹ CFU total) plus L-theanine and Eschscholtzia californica (probiotic group) or an identical active control containing L-theanine and E. californica alone for six weeks. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and the Beck Depression Inventory-II at baseline, week 3, week 6, and after a three-week washout. Significant within-group reductions in depressive symptom scores were observed in the probiotic group, while changes in the active control group were smaller and not statistically significant. However, between-group comparisons did not reach statistical significance at any time point. These findings suggest that the probiotic-containing formulation was associated with improvements in depressive symptoms when administered on top of an active control. Due to the study design, effects cannot be attributed specifically to the probiotic component alone. Larger trials incorporating inert placebo controls and microbiome analyses are warranted.

SAMP mice develop progressive Crohn’s disease (CD)-like ileitis without spontaneous colitis that worsens over time without chemical, genetic, or immunological manipulation. Even growing in an identical vivarium and fed with the same diet, SAMP mice reveal a distinct fecal microbiome, metabolome, and lipidome profile compared to AKR mice, their non-inflamed parental control strain. Differences are already present in 5-week-old mice, with a tendency to increase in 15-week-old mice. SAMP and AKR mice metabolome and lipidome profiles were substantially different, belonging to two clusters in line with the progression of intestinal disease. Similarly, the 16S analysis confirmed differences between 15-week-old AKR and SAMP mice. The protective role of dietary polyphenols has been documented in inflammatory bowel diseases (IBD); thus, we supplemented the chow diet with an anthocyanin-rich extract (RED) to evaluate disease reduction in SAMP mice and changes in fecal microbiota/metabolome. Our data reveal that 10-week supplementation with anthocyanin-rich extract ameliorated disease severity in SAMP mice despite limited fecal microbiota/metabolome differences.

Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors. In this report, we investigated the role of the gut microbiome using Winnie mice, an ulcerative colitis-like (UC-like) model with a missense mutation in the Muc2 gene. Upon rederivation from a conventional (CONV) to a specific pathogen-free (SPF) facility, Winnie mice developed severe colitis and, notably, spontaneous CAC that progressively worsened over time. In contrast, CONV Winnie mice showed only mild colitis but no tumorigenesis. By comparison, when re-derived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis and colon tumors, indicating an essential role for the gut microbiome in the development of CAC in these mice. Using shotgun metagenomics, metabolomics, and lipidomics, we identified a distinct proinflammatory microbial and metabolic signature that potentially drives the transition from colitis to CAC. Using either SPF Winnie or WT (Bl/6) donors, fecal microbiota transplantation (FMT) into GF Winnie recipients demonstrated that, while colitis developed regardless of the donor, only FM from SPF Winnie donors resulted in CAC in recipient mice. Our studies present a relevant model of CAC, providing strong evidence that the microbiome plays a key role in its pathogenesis, thus challenging the concept of colon cancer as a strictly nontransmissible disease.

Background/Objectives: Crohn’s disease (CD) is one of the most frequent causes of short bowel syndrome (SBS), a severe clinical condition with huge morbidity and social costs. SBS occurs when, following intestinal resections, the remaining small bowel in continuity is less than 200 cm in length. Intestinal failure (IF) can complicate SBS when intravenous nutritional or electrolyte supplementation is required to maintain dietary needs. The primary aim of this study was to identify clinical predictive factors of SBS in a cohort of outpatients with CD. Methods: We conducted a prospective, single-center, cohort study enrolling consecutive CD outpatients at a tertiary-level inflammatory bowel disease center. Detailed demographic and clinical features were collected. Significant factors associated with the onset of SBS in the univariate analysis were input into a multivariate logistic regression model to identify independent predictors of SBS. Results: In total, 232 CD patients (52.6% male, median age 49 years [IQR 37–60]) were included: 24.6% of them were smokers; extraintestinal manifestations (EIMs) were present in 21.6% of patients; and 67.7% of patients had at least one intestinal resection (27% of them with more than one surgical intervention). At enrollment, 96.1% of patients were on advanced therapies, and considering the course of the disease, 24.6% of patients were exposed to ≥3 different advanced therapies. A total of 18 patients had SBS and 9 had IF. In univariate analysis, the following variables were statistically associated with the risk of developing SBS: disease duration (p < 0.001), upper gastrointestinal disease localization (L4) (p < 0.001), penetrating behavior (p = 0.023), perianal disease (p = 0.036), length of first intestinal resection (p < 0.001), shorter time elapsing from CD diagnosis to start the first advanced therapy (p < 0.001), and treatment with advanced therapy after first intestinal resection (p < 0.001). In multivariate analysis, disease duration (OR 1.083, 95% C.I. 1.025–1.145, p = 0.005) and L4 (OR 20.079, 95% C.I. 2.473–163.06, p = 0.005) were independently associated with the development of SBS. Conversely, the number of different advanced therapies before the onset of SBS was independently associated with a reduced risk of developing SBS (OR 0.247, 95% C.I. 0.107–0.58, p = 0.001). Conclusions: Our data identifies several clinical features that could possibly predict the development of SBS in CD. Further studies with a larger sample size are needed to confirm our findings.

Recent trends show a continuous worldwide rise in the incidence of ulcerative colitis (UC), leading to increased interest in its etiology and pathogenesis, which is currently unknown. To gain a better mechanistic understanding of this disease, many mouse models have been developed over the last several years, with variations of dextran sodium sulfate administration representing the most widely employed. The Winnie mouse strain was created through elicited random mutations in Muc2, resulting in a progressive, chronic intestinal inflammation localized to the colon that worsens over time. Moreover, Winnie mice display immunologic and microbiota features that are similar to those that can be found in UC patients. Phenotypically, the presence, albeit rare, of rectal prolapse and other complications impacting quality of life can be observed in Winnie mice, as well as extraintestinal manifestations that are often associated with UC. While Winnie mice are currently less studied compared to other more established models of colitis, much has been discovered in the initial years of its use as a UC-like model. In summary, the use of Winnie mice adds to the growing armamentarium that is required to develop precision-based medicine for its future application in treating complex multifactorial diseases, such as UC.

Dysbiosis, characterized by a microbial imbalance, particularly within the gut microbiota, has emerged as a significant health concern linked to various diseases. This study analyzed 8097 patent documents from The Lens database (2005–2024) to examine global innovation trends in dysbiosis management. The patent filings showed exponential growth, peaking at 1222 documents in 2022, with the United States leading in publications (4361 documents). The analysis revealed three primary innovation clusters: bacterial-based therapeutics (44.8% of patents), specific therapeutic applications (27.6%), and diagnostic methods (15.9%). The disease associations predominantly included inflammatory conditions, infections, and cancer. The patent classifications highlighted a significant focus on probiotic development and microbiota modulation. The surge in patent activity since 2014 correlates with advances in DNA sequencing technology and the growing recognition of dysbiosis’s role in human health. This analysis provides valuable insights into the evolving landscape of microbiome therapeutics and future directions for dysbiosis management.

Nowadays, inflammatory bowel disease(IBD)-patient therapies are mainly based on corticosteroid, thiopurine, and immunomodulator treatments. Patients with active disease, that do not respond to corticosteroid and/or thiopurine treatment, can switch to the usage of the chimeric monoclonal antibody infliximab(IFX). However, to date, no treatment appeared to be conclusive in lowering the incidence of IBD relapses. With the aim to increase the effectiveness of IFX treatment, we combined it with an adjuvant purple corn supplementation enriched in anthocyanins. IBD-patients were enrolled before they underwent to the IFX-infusion, and they were allocated in 2 different study arms. Patients in the intervention-arm followed a dietary supplementation with purple corn water-soluble extract, whereas control patients had a daily consumption of red fruit tea. 16S rDNA gene-sequencing and high-resolution mass-spectrometry metabo-lipidomics analyses were conducted on stool and sera samples, respectively. As a result, the experimental intervention mainly affected the serum metabolome of IBD-patients by decreasing the concentration of specific lipids. Focusing on IBD patient annotated taxa, a significant decrease in Lactobacillus and Bifidobacterium relative abundances was found. As far as it concerns the ulcerative colitis patient subset, the experimental intervention led to a decrease in Alistipes and Erysipelotrichaceae UCG-003 genus abundances and a concomitant Parabacteroides increase. On the contrary, after treatment, Crohn's disease patients did not exhibit metataxonomics differences at the genus level. At the end of the treatment that led to a reshaped microbiota community, the gathered data paves the way for the usage of a specifically designed probiotic supplementation as a valuable strategy for IBD-patients under IFX infusion.

Abstract IL-33 is a pleiotropic cytokine known to possess dichotomous roles during gut health and disease. We previously described that IL-33 promotes epithelial restitution/repair in otherwise healthy (C57BL/6) mice that have been challenged with dextran sodium sulphate (DSS) to induce acute colitis, with the end result of efficient resolution of inflammation. However, in SAMP1/YitFc (SAMP) mice that spontaneously develop Crohn’s disease (CD)-like ileitis, elevated IL-33 levels persist as disease progresses, perpetuating chronic gut inflammation and severe fibrosis. While IL-33 has been implicated in the development of inflammation-associated fibrosis, the precise mechanism(s) by which this occurs remains unclear. The aim of this study was to determine IL-33-dependent events leading to intestinal fibrosis in ileitis-prone SAMP mice. Our results show IHC co-localization of IL-33 with fibrotic lesions, specifically in cells morphologically-consistent with both macrophages and subepithelial myofibroblasts (SEMFs). Bulk RNA-Seq analysis of the human SEMF cell line, CCD-18Co, stimulated +/- IL-33 identifies one of the highest-expressing transcripts as SERPINE1, encoding for plasminogen activator inhibitor-1 (PAI-1), which has previously been reported as highly-enriched in IBD patients with active disease that do not respond to anti-TNF therapy. Analysis of publicly-available scRNA-Seq data confirms the increased expression of SERPINE1 in IBD patients that localizes to mesenchymal cell populations. Of note, robust upregulation of SERPINE1 is detected in activated fibroblasts from involved vs. non-involved areas of CD patients. Furthermore, spatial transcriptomics of SAMP ilea reveal a progressive and concomitant increase in both Il33 and Serpine1, with strong clusterization compared to healthy AKR controls, particularly during later time points when fibrosis is evident. Currently, results are pending on the treatment of SAMP mice with the PAI-1 inhibitor, MDI-2268, to determine its direct effect(s) on the development of inflammation-associated intestinal fibrosis. Taken together, these findings suggest IL-33-dependent regulation of Serpine1/PAI-1 that promotes intestinal fibrosis, commonly observed in CD patients, and may provide a novel target to treat IBD patients with fibrostenoic disease.

The contribution of nutritional factors to disease development has been demonstrated for several chronic conditions including obesity, type 2 diabetes, metabolic syndrome, and about 30 percent of cancers. Nutrients include macronutrients and micronutrients, which are required in large and trace quantities, respectively. Macronutrients, which include protein, carbohydrates, and lipids, are mainly involved in energy production and biomolecule synthesis; micronutrients include vitamins and minerals, which are mainly involved in immune functions, enzymatic reactions, blood clotting, and gene transcription. Among the numerous micronutrients potentially involved in disease development, the present review will focus on iron and its relation to tumor development. Recent advances in the understanding of iron-related proteins accumulating in the tumor microenvironment shed light on the pivotal role of iron availability in sustaining pathological tumor hallmarks, including cell cycle regulation, angiogenesis, and metastasis.

Green synthesis from plant waste involves the generation of functional nanoparticles (NPs), offering significant potential for a wide range of applications. Numerous studies have focused on the use of plant extracts to produce AuNPs suitable for various applications in the medical field, particularly in photothermal therapy and cancer therapy, owing to their plasmonic properties. Moreover, NP-mediated immunostimulation and immunosuppression is an intriguing field of research, focusing on how manipulation of NP physicochemical properties can influence their inter-action with immune cells and immune modulation. However, to date, few investigations have been conducted on the modulation of the inflammatory response mediated by green-synthesized nanostructures. To this aim, we synthesized AuNPs using extracts of Laurus nobilis, which exhibit high crystallinity and are inherently coated by a dense network of polyphenols, thus maintaining stability on their surface through the green synthesis approach. Then, in order to explore how these green-synthesized nanostructures can enhance or suppress the inflammatory cellular responses, we investigated the response of free polyphenols and AuNPs@polyphenols in murine bone marrow derived dendritic cells (BMDCs), by means of morphomechanical analysis and biochemical assays. Our findings demonstrated that DCs exposed to both free polyphenol extract and AuNPs@polyphenols were able to inhibit the secretion of crucial inflammatory mediators in response to lipopolysaccharide (LPS) administration. Therefore, polyphenols immobilized on Au surface were more effective in the inflammation suppression. These evidence paving the way for a powerful strategy to develop edible anti-inflammatory adjuvants, overcoming the limitations associated with the use of free polyphenols in clinical practice.

The colonic epithelium is the most rapidly renewing tissue in the body and is organized into a single cell layer of invaginations called crypts. Crypt renewal occurs through Lgr5+ gut stem cells situated at the crypt base, which divide, produce daughter cells that proliferate, migrate, differentiate into all the cells required for normal gut function (eg. Goblet cells, enterocytes), and are finally shed into the crypt lumen. In health this rapid renewal helps maintain barrier function next to the hostile gut luminal environment that contains microbes and food. In parallel, the peri-cryptal lamina propria hosts the largest monocyte-derived macrophage population in the human body. Different macrophage phenotypes have been associated with intestinal health/intact barrier function, namely M2 compared to M1 macrophages that indicate inflammation/compromised barrier function. However, the direct effect of different macrophage subtypes have on colonic crypt renewal is not well understood. In this study we have utilized a reductionist 3D in vitro co-culture model to determine the regulatory capacity of M1 and M2 macrophages on colonic crypt renewal. We show that colonic crypt proliferation is increased in the presence of M1 or M2 macrophages, while we further demonstrate that a decrease in goblet and tuft cell expression as well as an increase in Lgr5+ stem cell numbers is only achieved through M1-crypt crosstalk in a contact dependent manner.

In type 2 Diabetes, β-cell failure is caused by loss of cell mass, mostly by apoptosis, but also by simple dysfunction (dedifferentiation, decline of glucose-stimulated insulin secretion). Apoptosis and dysfunction are caused, at least in part, by glucotoxicity, in which increased flux of glucose in the hexosamine biosynthetic pathway plays a role. In this study, we sought to clarify whether increased hexosamine biosynthetic pathway flux affects another important aspect of β-cell physiology, that is β-cell–β-cell homotypic interactions. We used INS-1E cells and murine islets. The expression and cellular distribution of E-cadherin and β-catenin was evaluated by immunofluorescence, immunohistochemistry and western blot. Cell–cell adhesion was examined by the hanging-drop aggregation assay, islet architecture by isolation and microscopic observation. E-cadherin expression was not changed by increased hexosamine biosynthetic pathway flux, however, there was a decrease of cell surface, and an increase in intracellular E-cadherin. Moreover, intracellular E-cadherin delocalized, at least in part, from the Golgi complex to the endoplasmic reticulum. Beta-catenin was found to parallel the E-cadherin redistribution, showing a dislocation from the plasmamembrane to the cytosol. These changes had as a phenotypic consequence a decreased ability of INS-1E to aggregate. Finally, in ex vivo experiments, glucosamine was able to alter islet structure and to decrease surface abundandance of E-cadherin and β-catenin. Increased hexosamine biosynthetic pathway flux alters E-cadherin cellular localization both in INS-1E cells and murine islets and affects cell–cell adhesion and islet morphology. These changes are likely caused by alterations of E-cadherin function, highlighting a new potential target to counteract the consequences of glucotoxicity on β-cells.