Search Results (823)

Per- and Polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals increasingly associated with adverse health outcomes. The gastrointestinal tract represents both a major route of exposure and a key target of PFAS toxicity. This review integrates updated evidence on how PFAS compromise intestinal homeostasis through interrelated structural, metabolic, and immunological mechanisms. PFAS disrupt epithelial integrity by down-regulating tight-junction proteins, inducing oxidative stress, and activating inflammasome signaling. Concurrently, metabolic reprogramming and PFAS-driven microbial dysbiosis contribute to barrier dysfunction and altered production of signal/metabolic molecules. These alterations may link environmental exposure to chronic intestinal inflammation and increase susceptibility to inflammatory bowel disease and related metabolic disorders. By synthesizing recent findings, key mechanistic gaps were highlighted also emphasizing the need for integrative experimental and translational studies to refine risk assessment in humans and develop preventive and therapeutic strategies. Full article

The gut–brain axis (GBA) interaction is important for human health and disease prevention. Organ chips are considered a solution for GBA research. Three-dimensional (3D) cultures and microfluidics engineered in an organ chip could improve the scientific knowledge in the GBA interactions field. In this study, a novel organ chip is developed, which achieves multicellular three-dimensional cultivation by utilizing a decellularized matrix. In addition, this paper reports the rapid prototyping process of the GBA microfluidic chip in polydimethylsiloxane (PDMS) using 3D printing interconnecting poly(ethylene/vinyl acetate) (PEVA) microchannel templates. In comparison to the static culture system of the transwell model, the intestinal epithelial barrier (IEB) and blood–brain barrier (BBB) models on our chip demonstrated superior barrier function and the efflux functionality of transporters under appropriate fluidic conditions. Additionally, it is observed that butyrate protected against BBB dysfunction induced by gut-derived lipopolysaccharide (LPS) via enhancing intestinal barrier function. These results demonstrate that this multicellular, three-dimensional cultivation integrated with a fluidic shear stress simulation chip offers a promising tool for gut–brain interaction study to predict therapy of intestinal and neurological disorders. Full article

Inflammatory bowel disease (IBD) involves chronic inflammation and disruption of the intestinal barrier, often accompanied by alterations in gut microbiota composition. This study examined the protective potential of a prebiotic mixture extract (PME) prepared from Vigna radiata (mung bean), Vigna angularis (red bean), and Foeniculum vulgare (fennel) using the HT-29 cell and colitis animal model. PME exhibited concentration-dependent antioxidant activity, with greater radical-scavenging capacity in the ABTS assay than in the DPPH assay. In LPS-stimulated HT-29 epithelial cells, PME reduced the mRNA expression of inflammation-associated genes (TNF-α, IL-1β, NF-κB) and upregulated tight junction markers (CLDN1 and OCLN), demonstrating its anti-inflammatory and supportive effects on the intestinal barrier. Vitexin, a C-glycosylated flavonoid, was detected in PME and is expected to mediate these protective effects. In a DSS-induced colitis mouse model, PME administration alleviated disease severity by increasing colon length, reducing serum levels of inflammatory cytokines and COX-2/PGE2, and restoring intestinal permeability. Furthermore, PME modulated the gut microbiota by enhancing beneficial bacteria such as Bifidobacterium and Faecalibaculum while suppressing inflammation-associated taxa, including Escherichia, Bacteroides, and Mucispirillum. These improvements collectively suggest that PME reinforces epithelial barrier integrity and promotes intestinal homeostasis through both anti-inflammatory and microbiota-regulating actions. Full article

Minthostachys verticillata (Griseb.) Epling, commonly known as peperina, is an aromatic species endemic to Argentina and traditionally used for gastrointestinal ailments. Despite its extensive folkloric use and inclusion in the Argentine Pharmacopoeia, its aqueous extract (the most commonly consumed preparation) has been described in terms of major phytochemical groups, and, currently, no studies have investigated its effects on key intestinal epithelial mechanisms. This plant is also employed in the production of beverages and herbal blends, and its massive consumption highlights the importance of its scientific study. Here, the aqueous extract of M. verticillata was characterized by liquid chromatography–tandem mass spectrometry, leading to the identification of fourteen polyphenolic compounds. In intestinal cell models, the extract displayed high IC₅₀ values, supporting its safety, and exhibited concentration-dependent bioactivity. In HT-29 cells, it modulated NF-κB activation induced by TNF-α and reduced LPS-stimulated IL-8 production. Pretreatment of Caco-2 monolayers prevented the decrease in transepithelial electrical resistance, increased FITC–dextran permeability, and nitric oxide production triggered by an inflammatory cocktail. Additionally, the extract inhibited HT-29 cell migration. These results demonstrate that M. verticillata aqueous extract exerts anti-inflammatory, barrier-protective, and anti-migratory effects in vitro, providing novel insights into how its polyphenolic composition may underlie these biological activities, supporting its traditional use and potential applications in intestinal health. Full article

Colorectal cancer (CRC) is one of the most common and fatal malignant tumors globally, and its development is increasingly related to the gut microbiota. Despite its effect on CRC having been extensively researched, the intestinal mucus barrier, which forms a fundamental link between the host tissues and gut microbes, is seldom discussed. A double-layered barrier, mainly formed by MUC2 mucin, isolates the outside world from epithelial cells to maintain intestinal homeostasis. Furthermore, it is subjected to a dynamic impact of microbial activity. Now, increasing evidence shows that mucus barrier disruption driven by certain gut microbes is an early event in the development of CRC. This review first introduces the structure and function of the colonic mucus barrier and then discusses how gut microbiota in different areas promote the development of CRC by disrupting the mucus layer. Finally, we examine translational opportunities for exploiting microbiota–mucus barrier interactions in CRC therapy. Full article

Goose astrovirus 2 (GAstV-2) infection leads to visceral gout and swollen kidneys in goslings, causing a 5–50% mortality rate and significant economic losses for goose flocks. While most studies on the virus’s pathological damage have focused on the kidneys, few reports have examined the effects of this fecal-oral pathogen on the digestive system. This study investigated GAstV-2 localization, cellular targets, and its impact on intestinal structure and homeostasis in orally infected goslings. Twenty 1-day-old goslings were randomly assigned to the infected and control groups. Clinical signs, organ lesions, viral distribution, histopathology, and alterations in intestinal cell populations, cytokine expression, and signaling pathways were assessed at 7 days post-infection. GAstV-2 was detected in the duodenum, jejunum, ileum, cecum, and rectum, with the highest viral load in duodenal crypt cells. Infection induced crypt cell necrosis, reduced villus height, decreased villus-to-crypt ratio, and lowered numbers of goblet cells and Lgr5+ intestinal stem cells. In contrast, Paneth cell abundance, Bmi1+ stem cells, and tight junction-related gene expression increased. Inhibition of stem cell differentiation into goblet cells was observed, mediated by modulation of the Notch signaling pathway. Proinflammatory cytokines, including IL-1β, IL-6, IL-8, IL-22, and TNF-α, were markedly upregulated, indicating a strong inflammatory response. These results demonstrate that GAstV-2 preferentially targets duodenal crypt cells, disrupts epithelial renewal, and impairs mucosal barrier function, while triggering compensatory regenerative and immune mechanisms. This study provides new insights into the intestinal pathogenesis of GAstV-2 and identifies potential targets for interventions to mitigate intestinal injury and economic losses in gosling production. Full article

Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk and play crucial roles in shaping the gut microbiome and promoting infant health. Although their functions during infancy are well established, emerging evidence suggests that HMOs exert region-specific effects throughout the gastrointestinal tract, extending their benefits beyond early life. This review summarizes current findings on HMO activity in the oral cavity, stomach, small intestine, and large intestine, focusing on their microbiota-modulating, barrier-enhancing, and immunoregulatory effects. In the oral cavity, HMOs inhibit pathogen adhesion and biofilm formation, maintaining oral homeostasis. In the stomach, fucosylated and sialylated HMOs act as soluble decoy receptors, preventing Helicobacter pylori infection. In the small intestine, HMOs strengthen epithelial integrity, regulate inflammation, and promote nutrient absorption. In the large intestine, they serve as selective prebiotics for beneficial microbes, enhancing short-chain fatty acid production and improving barrier function. Although preclinical and clinical studies demonstrate their safety and efficacy, further research is required to elucidate their mechanisms in adults. Overall, HMOs represent multifunctional bioactive glycans with promising applications for gastrointestinal health across all ages. Full article

Heat stress (HS) significantly threatens the sustainability of the rabbit industry, primarily by inducing oxidative damage to the intestine, which compromises both the health and productivity of rabbits. Chlorogenic acid (CGA) belongs to a major class of natural polyphenols and possesses significant antioxidant properties. This study aimed to elucidate the protective effects and underlying mechanisms of CGA against HS-induced intestinal damage in rabbits. In vivo, compared with the HS group, CGA significantly elevated serum CAT and SOD activities (p < 0.05), as well as reduced serum MDA and jejunal HSP70 levels (p < 0.05) in HS-challenged rabbits. In addition, CGA reversed HS-induced downregulation of antioxidant genes (HO-1, SOD1) and upregulation of apoptosis-related genes (Bax, caspase-3) (p < 0.05). In vitro, CGA significantly suppressed HS-induced intestinal epithelial cell apoptosis, ROS overproduction, and tight junction protein (occludin, ZO-1) downregulation (p < 0.05) by activating Nrf2 signaling. Specific inhibition of Nrf2 significantly abolished CGA’s protective effects. These results strongly suggest that CGA alleviates HS-induced intestinal oxidative damage and maintains barrier integrity via Nrf2 signaling. This finding offers a safe nutritional intervention to enhance HS resistance and growth performance in rabbits, addressing a key constraint to the sustainability of the rabbit industry amid global warming. Full article

Inflammatory bowel disease is characterised by chronic mucosal inflammation, oxidative stress, and impaired epithelial barrier function. Current therapies primarily suppress inflammation but do not effectively restore epithelial integrity. In this study, we established in vitro cell cultures of Vitis labrusca var. Isabella to obtain juices that were chemically characterised and assessed for antioxidant and anti-inflammatory activities in human intestinal epithelial cell lines (i.e., Caco-2). Chemical analysis revealed variable levels of stilbenoids, including trans-resveratrol and resveratrol diglucosides depending on culture conditions. The suspension-derived juice grown in darkness (SVMD) significantly reduced lipopolysaccharide-induced IL-1β and TNF-α release and mitigated oxidative stress in Caco-2 cells by lowering levels of intracellular reactive oxygen species. In Caco-2 monolayers infected with Salmonella enterica, SVMD preserved transepithelial electrical resistance, indicating protection of epithelial barrier integrity, without exerting direct antibacterial effects. These findings demonstrate that V. labrusca cell-culture juices exert potent antioxidant and anti-inflammatory actions and promote epithelial protection through modulation of redox balance. Overall, this study highlights the potential of sustainable cell-culture-derived materials as promising natural products for supporting intestinal homeostasis and managing gut inflammatory disorders. Full article

The exopolysaccharides (EPS) from the mycelial fermentation of Cordyceps sinensis Cs-HK1, especially the low-molecular weight, protein-rich exopolysaccharide fractions (EPS-LM), have previously exhibited significant antioxidant activity. This study further investigated the antioxidant and protective effects of EPS-LM on intestinal epithelial barrier integrity in Caco-2 monolayers challenged with hydrogen peroxide (H₂O₂, 550 μM). EPS-LM contained two major molecular-weight fractions, 25 kDa and 1.7 kDa, with 19.3% total carbohydrate and 28.7% protein content (w/w). Treatment of the cells with EPS-LM (50–200 μg/mL) showed concentration-dependent protective effects against ROS-induced losses of cell viability and epithelial barrier integrity. EPS-LM treatment enhanced the activities of major antioxidant enzymes (SOD, GSH-Px, and CAT) and modulated NRF2 and its downstream target NQO1, consistent with alleviated oxidative stress. It also improved several indicators of intestinal barrier function, including increased transepithelial electrical resistance and upregulation of tight junction proteins (Occludin, ZO-1, and Claudin-1). These results provide new experimental evidence and theoretical basis for the nutraceutical potential of EPS-LM to mitigate oxidative stress and preserve intestinal epithelial barrier integrity. Full article

Most probiotics require separate administration from antibiotics due to sensitivity issues. Clostridium butyricum, however, exhibits intrinsic resistance, making it a promising candidate for combined therapy against diarrhea. In this study, a diarrhea model was established in mice induced by Escherichia coli, followed by treatment with azithromycin (AZM), C. butyricum (RH₂), or their combination (COM) to assess therapeutic efficacy. The results demonstrated that mice in RH₂ and COM groups achieved full body weight recovery and significant alleviation of diarrhea, accompanied by normalized fecal E. coli loads, preserved tissue integrity, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and elevated anti-inflammatory IL-10. In contrast, AZM treatment led to sex-specific disparities in weight recovery and E. coli loads, and both sexes experienced relapse-prone diarrhea. Furthermore, the AZM group displayed shortened colons, sustained inflammatory infiltration, epithelial damage, and elevated IL-1β and male-specific IL-6. Gut microbiota analysis revealed that the COM group retained beneficial genera (e.g., Parabacteroides, Blautia) from the AZM group while uniquely enriching Lachnospiraceae taxa (e.g., NK4A136_group, FCS020_group). Untargeted metabolomics demonstrated the COM group activated GABA/arginine pathways, enhancing anti-inflammatory and barrier functions, whereas azithromycin disrupted butyrate synthesis and steroid metabolism. These findings highlight the advantage of combining C. butyricum with azithromycin for intestinal protection. Full article

Oxidative stress is believed to deteriorate production performance and cause substantial economic losses in commercial poultry farming. Resveratrol (RES) is a polyphenolic antioxidant that can improve intestinal barrier function and regulate gut microbiota composition. This study aimed to evaluate whether short-term (14 days) dietary resveratrol (1000–3000 mg/kg) mitigates dexamethasone (DEX)-induced oxidative stress and performance loss in yellow-feathered broilers. Two hundred and forty 52-day-old birds were assigned to five treatments (n = 8 pens × 6). Control (CON) and DEX groups received the basal diet; DR1, DR2 and DR3 were provided with the basal diet plus 1000, 2000 or 3000 mg/kg RES. During days 1–5, the DEX and RES (DR1, DR2 and DR3) groups were intraperitoneally injected with 5 mg/kg BW DEX; CON birds received saline. DEX significantly reduced average daily gain (ADG) and raised feed conversion ratio (FCR) (p < 0.05) without altering feed intake. RES at 1000–2000 mg/kg improved ADG, reduced FCR and lowered serum corticosterone and blood urea nitrogen while increasing albumin (p < 0.05). DEX elevated malondialdehyde (MDA) in liver and thigh muscle, suppressed liver catalase (CAT) activity, and suppressed thigh muscle superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and CAT activities. In serum, only SOD activity decreased. RES partially alleviated the abnormal changes in these antioxidant indices. Intestinally, DEX increased MDA, shortened villi and reduced the villus-to-crypt ratio, whereas RES partially reinstated ileal morphology, decreased MDA dose-dependently and linearly enhanced duodenal SOD activity (p < 0.05). DEX downregulated Occludin mRNA; RES upregulated Occludin and elevated ileal GPX2, SOD, CAT and PPAR-γ transcripts with a quadratic response to RES dose, while lowering duodenal CAT mRNA. Overall, short-term RES supplementation—particularly at 1000–2000 mg/kg—improves growth performance, meat quality and intestinal health of yellow-feathered broilers under DEX-induced oxidative stress by enhancing systemic and intestinal antioxidant capacity and reinforcing epithelial barrier integrity. Full article

Anti-TNF-α therapy is widely used for inflammatory bowel disease (IBD), but response rates vary, and long-term efficacy declines in many patients. Given the limitations of existing treatments, novel therapeutic strategies are needed. This study investigates whether Lactobacillus murinus (L. murinus) attenuates tumor necrosis factor alpha (TNF-α)-induced pro-inflammatory responses in a human intestinal epithelial cell model of colitis by modulating the aryl hydrocarbon receptor (AHR). An in vitro model was established using Caco-2 cell monolayers treated with TNF-α to simulate intestinal inflammation. Cells were pre-treated with L. murinus or known AHR ligands, and the effects on AHR activation, barrier integrity, and inflammatory response were assessed via transepithelial electrical resistance (TEER) and IL-8 quantifications. As CYP1A1 is a well-established transcriptional target of AHR, its mRNA expression was used as a surrogate marker of AHR modulation in this model. TNF-α stimulation significantly disrupted epithelial barrier integrity and increased IL-8 secretion in a dose-dependent manner. L. murinus pre-treatment enhanced CYP1A1 expression and was associated with reduced TNF-α-induced barrier disruption and IL-8 secretion. Notably, the beneficial effects of L. murinus on epithelial integrity were not replicated by synthetic AHR ligands, suggesting ligand-selective differences in AHR related responses. These findings suggest that AHR-associated signaling induced by L. murinus may contribute to mitigation of TNF-α-induced epithelial barrier dysfunction and inflammation. This study identifies a potential probiotic-associated mechanism that warrants further investigation, including studies designed to establish a causal role of AHR dependency in the observed effects. In addition, future studies are needed to identify the specific L. murinus metabolites responsible for inducing CYP1A1 expression and activating the AHR pathway. Full article

Listeria monocytogenes (L. monocytogenes) is a major foodborne pathogen which can invade intestinal epithelial cells and cause severe systemic infection. Probiotics, as well as their surface layer proteins, hold broad promise for enhancing intestinal barrier function and defending against pathogenic invasion. In the present study, the antagonistic effects of surface layer protein ornithine carbamoyltransferase (OTC) from Enterococcus faecium (E. faecium) WEFA23 against L. monocytogenes were systematically evaluated in vitro in human intestinal epithelial Caco-2 cells, including assessments of anti-adhesion and anti-invasion capacity, inflammatory cytokine responses, intestinal barrier integrity, and transcriptomic changes, by comparing the effects of wild-type E. faecium WEFA23 and a previously constructed E. faecium WEFA23 otc gene knockout strain (E. faecium WEFA23 otc^−/−). The results demonstrated that E. faecium WEFA23 achieved significant stronger anti-adhesion and anti-invasion capacity of L. monocytogenes (p < 0.05) in the presence of OTC, potentially through increasing tight junction protein expression, regulating inflammatory cytokines, and modulating the virulence factors of the pathogen. To elucidate the potential mechanism of the inhibitory effect of OTC protein, RNA-seq was performed. The results revealed that the significantly regulated core differentially expressed genes (DEGs), including ADCY2, OARI3, CCL5, and CXCL9, were found to be involved in γ-aminobutyric acid (GABA)-ergic synapse, calcium, and toll-like receptor signaling pathways. These findings demonstrated that OTC is involved in blocking Listeria invasion and revealed the function of the OTC from E. faecium WEFA23 in antimicrobial and intestinal mucosal defense, providing a conceptual foundation for the development of new probiotic intervention strategies in anti-infection. Full article

Micro- and nanoplastics (MNPs) are increasingly recognized as emerging intestinal toxicants. This scoping review maps and integrates evidence from 56 studies (47 primary and 11 review articles, 2000–mid-2025) on how nanoplastics, particularly ≤100 nm polystyrene, disrupt gut homeostasis. The evidence consistently supports a three-stage mechanistic cascade: 1. Oxidative-stress initiation—Nanoplastics generate reactive oxygen species (ROS) and suppress antioxidant defenses, producing redox imbalance in intestinal tissue and commensal bacteria. 2. Barrier dysfunction—Resulting oxidative injury reduces tight-junction proteins, depletes mucus-secreting goblet cells, and activates inflammatory signaling (NF-κB, TLR4). 3. Microbiome reconfiguration—The altered intestinal microenvironment favors Gram-negative expansion and depletion of Gram-positive commensals, observed as decreases in the Firmicutes/Bacteroidetes (F/B) and Gram+/Gram− ratios. High-dose nanoplastic exposures reproducibly induced these effects in mice and zebrafish, whereas environmentally realistic, low-dose PET fragments produced minimal dysbiosis. Functionally important taxa—short-chain-fatty-acid producers (Faecalibacterium, Roseburia) and mucin degraders (Akkermansia muciniphila)—were consistently reduced, linking microbial shifts to epithelial injury and inflammatory tone. Together, these findings define an oxidative–barrier–microbiome axis as the dominant pathway of nanoplastic-induced intestinal disruption. Future work should emphasize environmentally relevant exposures, multi-omics functional endpoints, and mechanistic models that integrate oxidative stress, epithelial pathology, and microbiome ecology to guide realistic human-health risk assessment. Full article