Zinc and several physiologically relevant ligands of the aryl hydrocarbon receptor (AHR) are nutrients that promote intestinal barrier function. We have identified that AHR activation upregulates the expression of zinc importers in the intestinal epithelium to increase intracellular zinc concentrations, which leads to improved epithelial barrier function. Here, we investigated if an amino acid chelate of zinc, in cooperation with AHR activation, can improve the barrier function of a differentiated Caco-2 cell epithelium. Functional assays of the Caco-2 cell epithelium demonstrate that both ZnSO4 and a lysine and glutamic acid chelate of Zn, in combination with the physiological AHR agonist 6-formylindolo[3,2-b]carbazole (FICZ), increase expression of tight junction proteins at the mRNA and protein levels. FICZ increases uptake of zinc into the epithelium in the presence of ZnSO4 or the amino acid Zn chelate in the medium to equal extents. We conclude that the lysine and glutamic acid chelate of Zn is as efficacious as ZnSO4 in reducing permeability of the Caco-2 cell epithelium in the presence of FICZ. The results suggest that dietary supplementation with bioavailable forms of zinc together with nutritional AHR agonists may be beneficial in improving gut barrier function and help prevent inflammatory bowel disease (IBD).

Disruption of the physical barrier of intestinal epithelial cells is a hallmark of ulcerative colitis (UC). Deubiquitinating enzymes (DUBs), which modify the stability, localization, or activity of substrates by removing ubiquitin chains, have been involved in the development of UC. However, the biological role of DUBs in intestinal epithelial cells (IECs) has yet to be extensively investigated. In this work, we revealed that USP2 as the most differentially expressed DUB in the colon of mice with dextran sodium sulfate (DSS)-induced colitis and was downregulated mainly in the intestinal epithelium. Notably, the expression of USP2 was correlated with the levels of tight junction (TJ) proteins. Furthermore we showed that USP2 expression was reduced in the intestine of mice with acute colitis induced by DSS, as well as in IECs stimulated with LPS. Overexpression of USP2 restored the LPS-induced the reduction of TJPs. Mechanistically, USP2 attenuates the activation of NF-κB and the phosphorylation of the myosin light chain, possibly by reducing the K63-linked polyubiquitin chain on the tumour necrosis factor receptor-associated factor 6 (TRAF6). In vivo, colonic-specific overexpression of USP2 in mice ameliorated DSS-induced barrier damage. Together, our study proposed USP2 as a new deubiquitinating enzyme molecule involved in the course of UC regulating the function of IECs during the progression of UC.

Dysbiosis of intestinal microecology caused by sepsis plays a crucial role in the onset and progression of sepsis-induced acute lung injury (SALI). As a postbiotic type, inactivated probiotic bacteria can regulate the gut microbiome. Pasteurized bacteria are considered safer than live bacteria in immune dysregulation disorders. Weissella cibaria (W. cibaria) is considered a candidate probiotic with certain beneficial functions. However, whether inactivated W. cibaria can alleviate SALI and the underlying mechanisms remain unclear. This study aimed to investigate whether inactivated W. cibaria can regulate intestinal mucosal barrier function and gut microbiota, thereby improving SALI.

Following gavage of pasteurized W. cibaria in septic mice, lung tissue damage and inflammation levels were assessed. Circulating LPS levels and inflammatory cytokine concentrations in the blood were measured. Additionally, colonic tissue inflammation, intestinal mucosal barrier integrity, and alterations in the gut microbiota were evaluated.

Pasteurized W. cibaria increases survival rates in SALI mice and improves pathological damage and cell apoptosis in lung tissue. Pasteurized W. cibaria also reduces the lung inflammatory response in septic mice by lowering pro-inflammatory cytokine levels and increasing anti-inflammatory cytokine levels. Pasteurized W. cibaria appears to exert its effects by improving the intestinal mucosal barrier and reversing gut microbiota dysbiosis caused by sepsis. Specifically, pasteurized W. cibaria alleviates intestinal barrier damage and inflammation in SALI mice, enhancing the integrity of the intestinal mucosal barrier. Additionally, pasteurized W. cibaria increases the abundance of anti-inflammatory bacteria such as Muribaculaceae. Pasteurized W. cibaria also decreases the levels of LPS-producing bacteria, including Escherichia-Shigella and Helicobacter, leading to significant attenuation in metabolic endotoxemia, which in turn alleviates excessive lung inflammation in septic mice.

Pasteurized W. cibaria has the potential to act as a postbiotic agent, improving sepsis-induced gut microbiota dysbiosis and acute lung injury, and providing a novel strategy for treating SALI.

Diquat (DQ) is extensively utilized as a herbicide in farming, and its intake can result in serious systemic toxicity due to its induction of oxidative stress (OS) and disruption of intestinal homeostasis. The gastrointestinal tract is one of the first systems exposed to DQ, and damage to this system can influence the general health of the host. Our review summarizes the toxic effects of DQ on the intestinal barrier integrity, gut microbiome, and microbial metabolites (e.g., short-chain fatty acids [SCFAs], bile acids). By elucidating the mechanisms linking DQ-induced OS to gut dysbiosis, mitochondrial dysfunction, and inflammation, our work provides critical insights into novel therapeutic strategies, including probiotics, antioxidants (e.g., hydroxytyrosol, curcumin), and selenium nanoparticles. These findings address a pressing gap in understanding environmental toxin-related gut pathology and offer potential interventions to mitigate systemic oxidative damage.

The greater amberjack (Seriola dumerili), a key species in marine aquaculture, relies heavily on its intestine for nutrient absorption and immune function. However, the structural and functional specialization of its intestinal segments remains poorly understood. In this study, we divided the intestine of S. dumerili into foregut, midgut, and hindgut, and conducted a multi-omics analysis integrating histological staining (H&E/AB-PAS), digestive enzyme assays, transcriptome sequencing, and 16S rRNA microbiota profiling to characterize structural, functional, molecular, and microbial differences across intestinal segments. Histological examinations revealed that brush border microvillus length, muscle layer thickness, and folding height were significantly greater in the foregut and hindgut compared to the midgut, while mucus and goblet cell density was higher in the foregut and midgut. Digestive enzyme assays showed that lipase activity peaked in the foregut, α-amylase in the midgut, and protease in the midgut and hindgut. Alkaline phosphatase (AKP) and acid phosphatase (ACP) activities were highest in the foregut and midgut. Immune-related enzyme activities (SOD (Superoxide dismutase), GSH-Px (Glutathione peroxidase), T-AOC (Total Antioxidant Capacity)) were elevated and MDA levels were lower in the midgut, indicating its role as the primary immune site. Transcriptome analysis identified segment-specific expression of nutrient transporters, such as slc6a19b (hindgut, protein), apoa1b (foregut, lipid), and slc37a4 (midgut, carbohydrate). Microbiome analysis revealed Ruminococcus dominance in the foregut (lipid digestion) and Prevotella, Bifidobacterium, and Lactobacillus enrichment in the midgut (carbohydrate metabolism and immunity). These findings highlight functional zonation in S. dumerili: the foregut specializes in lipid digestion, the midgut in carbohydrate metabolism and immunity, and the hindgut in protein digestion. This study provides foundational insights for optimizing aquaculture practices and advancing research in nutrition, immunology, and disease modeling in S. dumerili.

According to the criteria established by the International League Against Epilepsy (ILAE), epilepsy is defined as a disorder characterized by at least two unprovoked seizures occurring more than 24 h apart. Its pathogenesis is closely related to various physiological and pathological factors. Advances in high-throughput metagenomic sequencing have increasingly highlighted the role of gut microbiota dysbiosis in epilepsy. Short-chain fatty acids (SCFAs), the major metabolites of the gut microbiota and key regulators of the gut-brain axis, support physiological homeostasis through multiple mechanisms. Recent studies have indicated that SCFAs not only regulate seizures by maintaining intestinal barrier integrity and modulating intestinal immune responses, but also affect the structure and function of the blood-brain barrier (BBB) and regulate neuroinflammation. This review, based on current literatures, explores the relationship between SCFAs and epilepsy, emphasizing how SCFAs affect epilepsy by modulating the intestinal barrier and BBB. In-depth studies on SCFAs may reveal their therapeutic potential and inform the development of gut microbiota-targeted epilepsy treatments.

Lacticaseibacillus paracasei has been regarded as a probiotic bacterium because of its role in anti-inflammatory properties and maintenance of intestinal barrier permeability. Here, we explored the anticolitic effects and mechanism of L. paracasei CCFM1222. The results showed that L. paracasei CCFM1222 supplementation could suppress the disease activity index (DAI) and colon length shortening in colitis mice, accompanied by a moderate increase in colonic tight junction proteins (ZO-1, occludin and claudin-1). L. paracasei CCFM1222 intervention significantly suppressed the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and significantly elevated the activities of antioxidant enzymes (including SOD, GSH-Px, and CAT) in the colon by regulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways in colitis mice. In addition, L. paracasei CCFM1222 significantly shifted the gut microbiota, including elevating the abundance of Catabacter, Ruminiclostridium 9, Alistipes, and Faecalibaculum, as well as reducing the abundance of Mucispirillum, Escherichia-Shigella, and Salmonella, which was associated with the improvement of colonic barrier damage. Overall, these results suggest that L. paracasei CCFM1222 is a good candidate for probiotic of improving colonic barrier damage and associated diseases.

The intestinal barrier serves as a boundary between the mucosal immune system in the lamina propria and the external environment of the intestinal lumen, which contains a diverse array of microorganisms and ingested environmental factors, including pathogens, food antigens, toxins, and other foreign substances. This barrier has a central role in regulating the controlled interaction between luminal factors and the intestinal immune system. Disruptions of intestinal epithelial cells, which serve as a physical barrier, or the antimicrobial peptides and mucins they produce, which act as a chemical barrier, can lead to a leaky gut. In this state, the intestinal wall is unable to efficiently separate the intestinal flora and luminal contents from the intestinal immune system. The subsequent activation of the immune system has an important role in the pathogenesis of inflammatory bowel disease, as well as in metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, and colorectal cancer. Dysregulated intestinal barrier integrity has also been described in patients with chronic inflammatory diseases outside the gastrointestinal tract, including rheumatoid arthritis and neurodegenerative disorders. Mechanistic studies of barrier dysfunction have revealed that the subsequent local activation and systemic circulation of activated immune cells and the cytokines they secrete, as well as extracellular vesicles, promote proinflammatory processes within and outside the gastrointestinal tract. In this Review, we summarise these findings and highlight several new therapeutic concepts currently being developed that attempt to control inflammatory processes via direct or indirect modulation of intestinal barrier function.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract caused by dysfunction of the immune system in genetically susceptible individuals. As current pharmacologic and surgical treatments remain suboptimal, increasing attention has been directed toward exosomes derived from mesenchymal stem/stromal cells (MSCs) as alternative therapeutic approaches. MSCs are multipotent stromal cells that can be isolated from various human tissues such as bone marrow, adipose, umbilical cord and periodontal ligament. Exosomes are cell-derived membrane-bound vesicles enclosing RNAs, proteins, growth factors, and cytokines. Previous studies indicate that the anti-inflammatory, immunomodulatory, and regenerative effects of MSCs are largely mediated by MSC-derived exosomes (MSC-Exos). Therefore, this review outlines current insights into the molecular mechanisms of MSC-Exos in IBD treatment to support the future development of MSC-Exos as a therapeutic strategy, thus providing novel observations into the clinical applications of MSC-Exos in IBD management.

Recently, there has been a gradual increase in the demand for chicken and eggs. The gut, as the vital place of nutrient digestion and absorption, is highly associated with the development of livestock and poultry and the quality of meat, eggs, and milk. Intestinal stem cells, as an important source of intestinal cell proliferation and renewal, exert a vital effect on repairing injured intestinal epithelial cells and keeping homeostasis. Intestinal stem cell-regulated intestinal epithelial balance is closely controlled and modulated by interlinked developmental loops that maintain cell proliferation and differentiation processes in balance. Some conservative signaling pathways, including the Wnt, Notch, hedgehog, and bone morphogenetic protein (BMP) loops, have been proved to modulate intestinal health in poultry. Meanwhile, studies have revealed the importance of the Hippo pathway in gastrointestinal tract physiology by regulating intestinal stem cells. Moreover, crosstalk between Hippo and other signaling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this review, we summarize studies on the role of the Hippo pathway in the intestine in these physiological processes and the underlying mechanisms responsible via interacting with these signaling pathways and discuss future research directions and potential therapeutic strategies targeting Hippo signaling in intestinal disease. A comprehensive understanding of how these signaling pathways regulate stem cell proliferation, differentiation, and self-renewal will help to understand the regulation of intestinal homeostasis. In addition, it has the capacity for creative ways to govern intestinal damage, enteritis, and associated disorders induced by different factors.

Efficient and stable animal models of celiac disease (CD) are crucial for CD research, dietary supplementation research, and new drug development. This study aimed to establish CD models by administering gliadin to parental and first-generation mice on a gluten-free diet using two intraperitoneal injection and a combination of sensitization by intraperitoneal injection and gavage. Various indicators, including clinical manifestations, characteristic indicators of CD, inflammatory factors, intestinal barriers, immune cells, and other related indicators, were used to compare different modeling methods. The results showed that all four methods induced varying degrees of CD symptoms in the mice. The analysis revealed that intraperitoneal injection in first-generation mice significantly increased specific IgG and total IgE antibody levels; markedly shortened intestinal villus and crypt hyperplasia in the jejunum; significantly increased pro-inflammatory cytokines IFN-γ, IL-17, IL-15, and TNF-α; and significantly decreased the anti-inflammatory cytokine IL-4. Additionally, immune cells in the spleen and intestinal lymph nodes were severely imbalanced. These results suggest that the intraperitoneal injection model in first-generation mice is more efficient, stable, and significant. This study provides a theoretical basis for the efficient construction of CD models.

Probiotics such as Lactobacillus and Bifidobacterium spp. have been shown to be critical for maintaining host homeostasis. In recent years, key compounds of postbiotics derived from probiotic metabolism and cellular secretion have been identified for their role in maintaining organ immunity and regulating intestinal inflammation. In particular, probiotic-derived extracellular vesicles (PEVs) can act as postbiotics, maintaining almost the same functional activity as probiotics. They also have strong biocompatibility and loading capacity to carry exogenous or parental active molecules to reach distal organs to play their roles. This provides a new direction for understanding the intrinsic microbiota-host communication mechanism. However, most current studies on PEVs are limited to their functional effects/benefits, and their specific physicochemical properties, composition, intrinsic mechanisms for maintaining host homeostasis, and possible threats remain to be explored. Here, we review and summarize the unique physicochemical properties of PEVs and their bioactivities and mechanisms in mediating microbiota-host communication, and elucidate the limitations of the current research on PEVs and their potential application as postbiotics.

Diquat is a widely used bipyridyl herbicide that is extensively applied in agricultural production and water management due to its high efficacy in weed control. However, its environmental persistence and the toxic effects it induces have raised widespread concern. Studies show that Diquat primarily enters the body through the digestive tract, leading to poisoning. The core mechanism of its toxicity involves reactive oxygen species (ROS)-induced oxidative stress, which not only directly damages the intestinal barrier function but also exacerbates inflammation and systemic toxicity by disrupting the balance of the gut microbiota and the normal production of metabolic products. This review systematically summarizes the physicochemical properties of Diquat, with a focus on analyzing the mechanisms by which it damages the gut tissue structure, barrier function, and microbiota after digestive tract exposure. The aim is to provide theoretical support for a deeper understanding of Diquat's toxic mechanisms and its digestive tract-centered toxic characteristics, laying a scientific foundation for the development of effective interventions and protective strategies against its toxicity.

Resistant starch (RS) is a novel type of prebiotic that exerts positive effects on lipid metabolism and intestinal flora. In this study, we investigated the effects of dietary RS on lipid metabolism and the intestinal barrier in largemouth bass (Micropterus salmoides). The experimental fish were fed either a control diet (C), a high-fat diet (H), or H diets supplemented with 0.5 %, 1.5 %, and 3 % RS (HRS0.5, HRS1.5, and HRS3.0). Dietary supplementation with 1.5 % and 3.0 % RS increased the final weight and feed utilization. Moreover, the hepatic crude protein content and the expression of genes related to lipid lipolysis were significantly higher in the HRS1.5 group compared to the H group, whereas hepatic crude lipid content and the expression of genes related to lipid synthesis were considerably lower in the HRS1.5 and HRS3.0 groups than in the H group. Additionally, hepatocyte vacuolation was alleviated in the HRS1.5 and HRS3.0 groups, and the number of liver lipid droplets was significantly decreased. Dietary supplementation with 1.5 % and 3.0 % RS downregulated the expression of pro-inflammatory factors while upregulating the expression of anti-inflammatory factors. Furthermore, analysis of gut microbiota composition revealed that RS supplementation increased the population of beneficial bacteria and short-chain fatty acid (SCFA) contents, decreased the abundance of pathogenic bacteria, and enhanced the diversity and richness of the intestinal flora. Non-targeted metabolomics analysis indicated that the levels of L-arginine and betaine were significantly higher in the HRS1.5 group, while levels of L-methionine and taurocholic acid were notably elevated in the HRS3.0 group. In conclusion, dietary supplementation with 1.5-3.0 % RS improved the balance of intestinal flora, promoted the growth of beneficial bacteria, adjusted the metabolites profile, and increased the SCFA levels. These results suggest that dietary supplementation with 1.5-3.0 % RS can restore the intestinal protective barrier, reduce hepatic lipid accumulation, and regulate lipid metabolism in largemouth bass.

The intestinal barrier function (IBF) is essential for intestinal homeostasis. Its alterations have been linked to intestinal and systemic disease. Regulation of intestinal permeability is key in the maintenance of the IBF, in which the intestinal epithelium and tight junctions, the mucus layer, sIgA, and antimicrobial peptides are important factors. This review addresses the concept of IBF, focusing on permeability, and summarizes state-of-the-art information on how starvation and macronutrients regulate it. Novel mechanisms regulate intestinal permeability, like its induction by the normal process of nutrient absorption, the contribution of starvation-induced autophagy, or the stimulation of sIgA production by high-protein diets in a T-cell-independent fashion. In addition, observations evidence that starvation and protein restriction increase intestinal permeability, compromising mucin, antimicrobial peptides, and/or intestinal sIgA production. Regarding specific macronutrients, substantial evidence indicates that casein (compared to other protein sources), specific protein-derived peptides and glutamine reinforce IBF. Dietary carbohydrates regulate intestinal permeability in a structure- and composition-dependent fashion; fructose, glucose, and sucrose increase it, while nondigestible oligosaccharides (NDOs) decrease it. Among NDOs, human milk oligosaccharides (HMOs) stand as a promising tool. NODs effects are mediated by intestinal microbiota modulation, production of short-chain fatty acids, and direct interactions with intestinal cells. Finally, evidence supports avoiding high-fat diets for their detrimental effects on IBF. Most studies have been carried out in vitro or in animal models. More information is needed from clinical studies to substantiate beneficial effects and the use of macronutrients in the treatment and prevention of IBF-related diseases.

Apigenin was previously identified as a potent hypouricemic agent by comparative metabolomics and in silico analysis. Bioavailability (absorption, distribution, metabolism, and excretion) is the major concern for bioefficacy of phytochemicals administered orally. Therefore, the objective of this study was to establish an enterohepatic microenvironment biomimetic model comprised of intestine epithelial cells and liver cells to evaluate the bioavailability and hypouricemic bioactivity of apigenin. The results indicated that cumulative 26 % of the supplemented apigenin was absorbed by intestinal epithelium over 240 min. With a maximum 24 % (1.37 μg/mL) of the absorbed apigenin, in its parent form, was distributed to the basolateral extra-enterohepatic compartment. Extensive phase I and phase II metabolism occurred in both enterocytes and hepatocytes. Ten and eighteen metabolites were detected in apical and basolateral medium representing intestinal excretion and systemic distribution, respectively. Apigenin-7-sulfate was the predominant metabolite released in intestinal lumen, while apigenin sulfation, acetylation, and taurine-conjugated products were the major metabolites likely distributed systemically. Importantly, apigenin supplementation significantly lowered uric acid level in the basolateral compartment, which demonstrated its hypouricemic bioactivity after the absorption through intestinal epithelium and supported its potential as a nutraceutical for hyperuricemia prevention. This in vitro enterohepatic model provides a valuable tool for rapidly assessing the bioavailability and bioactivity of dietary components.

Doxorubicin (DXR) is a widely used chemotherapy drug that can induce severe intestinal mucositis. Although the influence of gut bacteria on DXR-induced damage has been documented, the role of eukaryotic commensals remains unexplored. We discovered Tritrichomonas muris (Tmu) in one of our mouse colonies exhibiting abnormal tuft cell hyperplasia, prompting an investigation into its impact on DXR-induced intestinal injury. Mice from Tmu-colonized and Tmu-excluded facilities were injected with DXR. Tissue morphology and gene expression were evaluated at acute injury (6 h) and regenerative (72 h and 120 h) phases. Changes to crypt and villus morphology were more subtle than previously reported and region-specific, with significantly shorter jejunal villi in Tmu+ mice at 72 h post-DXR compared with Tmu- controls. Most notably, we observed elevated rates of DXR-induced apoptosis, measured by cleaved caspase 3 (CC3) staining, in Tmu+ intestinal crypts at 6 h post-DXR. Tmu+ mice also exhibited reduced expression of active intestinal stem cell (aISC) marker Lgr5 and facultative ISC (fISC) marker Ly6a at 6 h post-DXR compared with Tmu- controls. Tmu, but not DXR, was associated with increased inflammation and expression of type 2 cytokines IL-5 and IL-13. Tmu+ mice also exhibited a decreased fecal abundance of Lactobacillus, which promotes gut barrier integrity, and reduced claudin expression, indicating potential barrier dysfunction that could explain the increase in DXR-induced apoptosis. These findings highlight the significant influence of commensal microbiota, particularly eukaryotic organisms like Tmu, on intestinal biology and response to chemotherapy, underscoring the complexity of gut microbiota interactions in drug-induced mucositis.NEW & NOTEWORTHY Our study found that the eukaryotic commensal Tritrichomonas muris (Tmu) significantly increases DXR-induced intestinal apoptosis in mice. Tmu also reduces Lgr5 expression post-DXR injury and elevates inflammation and type 2 cytokine expression in the absence of injury. 16S sequencing identifies decreased abundance of protective Lactobacillus in Tmu colonized mice, as well as decreased expression of barrier-forming claudins, which may explain increased apoptosis. These findings emphasize the complex role of microbiota in drug-induced intestinal damage.

The mucosal barrier serves as a crucial defense against external pathogens and allergens, being widely distributed across the respiratory, gastrointestinal, urogenital tracts, and oral cavity. Its disruption can lead to various diseases, including inflammatory bowel disease, asthma, urinary tract infections, and oral inflammation. Current mainstream treatments for mucosa-associated diseases primarily involve glucocorticoids and immunosuppressants, but their long-term use may cause adverse effects. Therefore, the development of safer and more effective therapeutic strategies has become a focus of research. Natural products, with their multi-target and multi-system regulatory advantages, offer a promising avenue for the treatment of mucosal diseases. This review summarizes the potential applications of natural products in diseases of mucosal barrier dysfunction through mechanisms such as immune modulation, inflammation inhibition, tight junction protein restoration, and gut microbiota regulation, with the aim of providing insights for the exploration of novel therapeutic strategies.

Bile acids and their corresponding intestinal epithelial receptors, the farnesoid X receptor (FXR), the G protein-coupled bile acid receptor (TGR5), play crucial roles in the physiological and pathological processes of intestinal epithelial cells. These acids and receptors are involved in the regulation of intestinal absorption, signal transduction, cellular proliferation and repair, cellular senescence, energy metabolism, and the modulation of gut microbiota. A comprehensive literature search was conducted using PubMed, employing keywords such as bile acid, bile acid receptor, FXR (nr1h4), TGR5 (gpbar1), intestinal epithelial cells, proliferation, differentiation, senescence, energy metabolism, gut microbiota, inflammatory bowel disease (IBD), colorectal cancer (CRC), and irritable bowel syndrome (IBS), with a focus on publications available in English. This review examines the diverse effects of bile acid signaling and bile receptor pathways on the proliferation, differentiation, senescence, and energy metabolism of intestinal epithelial cells. Additionally, it explores the interactions between bile acids, their receptors, and the microbiota, as well as the implications of these interactions for host health, particularly in relation to prevalent intestinal diseases. Finally, the review highlights the importance of developing highly specific ligands for FXR and TGR5 receptors in the context of metabolic and intestinal disorders.

The intestine is an important immune organ of aquatic animals and it plays an essential role in maintaining body health and anti-oxidative stress. To investigate the toxic effects of deltamethrin in intestinal tissue of Chinese mitten crabs (Eriocheir sinensis), 120 healthy crabs were randomly divided into two experimental groups (blank control group and deltamethrin-treated group), with three replicates in each group. After being treated with deltamethrin for 24 h, 48 h, 72 h, and 96 h, intestinal tissues were collected aseptically to assess the effects of deltamethrin on oxidative stress, immunity, apoptosis-related genes, and the structure of microflora in intestinal tissues. Additionally, correlations between gut microbiota composition and intestinal tissue damage-associated genes were analyzed. The results demonstrated that prolonged exposure to deltamethrin induced oxidative stress damage in intestinal tissue. Compared with the blank control group, the expression of autophagy-related genes B-cell lymphoma/Leukemia-2 (bcl-2), c-Jun N-terminal kinase (jnk), Microtuble-associated protein light chain 3 (lc3c), Cysteine-dependent Aspartate-specific Protease 8 (caspase 8), BECN1(beclin1), oxidative stress damage-related genes MAS1 proto-oncogene (mas), Glutathione Peroxidase (gpx), kelch-like ECH-associated protein 1 (keap1), Sequestosome 1 (p62), Interleukin-6 (il-6), and immune-related genes Lipopolysaccharide-induced TNF-alpha Factor (litaf), Heat shock protein 90 (hsp90) and prophenoloxidase (propo) in the deltamethrin treatment group were significantly up-regulated at 96 h (p < 0.05 or p < 0.01). Additionally, 16S rRNA sequencing showed that the diversity of intestinal flora in the deltamethrin-treated group was significantly higher compared with the blank control group (p < 0.01). Analysis of the differences in the composition of intestinal flora at the genus level showed that the relative abundance of Candidatus Bacilloplasma in the deltamethrin treatment group was significantly lower than that in the blank control group (p < 0.01). In contrast, the relative abundances of Flavobacterium, Lachnospiraceae_NK4A136_group, Acinetobacter, Chryseobacterium, Lacihabitans, Taibaiella, Hydrogenophaga, Acidovorax, and Undibacterium were significantly higher than those in the blank control group (p < 0.05 or p < 0.01). Pearson correlation analysis revealed that Malaciobacter, Shewanella, and Prevotella exhibited significant positive correlations with gene indicators (jnk, gpx, lc3c, litaf, hsp90), while Dysgonomonas, Vibrio, and Flavobacterium demonstrated significant negative correlations with multiple gene indicators (caspase 8, p62, il-16, keap1, jnk, etc). These results demonstrate that deltamethrin significantly impacts the gut microbiota, immune function, and antioxidant capacity of E. sinensis. The changes in gut microbiota have correlations with the biomarkers of intestinal tissue injury genes, indicating that gut microbiota plays a crucial role in deltamethrin-induced intestinal tissue damage. These insights contribute to a better understanding of the ecological risks associated with deltamethrin exposure in aquatic organisms.

Objectives: This study investigated the effects of 2-week ingestion of hemp fiber (high and low doses) versus placebo bars on gut permeability and plasma metabolite shifts during recovery from 2.25 h intensive cycling. Hemp hull powder is a rich source of two bioactive compounds, N-trans-caffeoyl tyramine (NCT) and N-trans-feruloyl tyramine (NFT), with potential gut health benefits. Methods: The study participants included 23 male and female cyclists. A three-arm randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and 2-week washout periods. Supplement bars provided 20, 5, or 0 g/d of hemp hull powder. Participants engaged in an intensive 2.25 h cycling bout at the end of each of the three supplementation periods. Five blood samples were collected before and after supplementation (overnight fasted state), and at 0 h-, 1.5 h-, and 3 h-post-exercise. Five-hour urine samples were collected pre-supplementation and post-2.25 h cycling after ingesting a sugar solution containing 5 g of lactulose, 100 mg of 13C mannitol, and 1.9 g of mannitol in 450 mL of water. An increase in the post-exercise lactulose/13C mannitol ratio (L:13CM) was used as the primary indicator of altered gut permeability. Other outcome measures included muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. Results: No trial differences were found for L:13CM, cortisol, blood cell counts, and muscle damage biomarkers. Orthogonal partial least-squares discriminant analysis (OPLSDA) showed distinct trial differences when comparing high- and low-dose hemp fiber compared to placebo supplementation (R2Y = 0.987 and 0.995, respectively). Variable Importance in Projection (VIP) scores identified several relevant metabolites, including 3-hydroxy-4-methoxybenzoic acid (VIP = 1.9), serotonin (VIP = 1.5), 5-hydroxytryptophan (VIP = 1.4), and 4-methoxycinnamic acid (VIP = 1.4). Mummichog analysis showed significant effects of hemp fiber intake on multiple metabolic pathways, including alpha-linolenic acid, porphyrin, sphingolipid, arginine and proline, tryptophan, and primary bile acid metabolism. Conclusions: Hemp fiber intake during a 2-week supplementation period did not have a significant effect on post-exercise gut permeability in cyclists (2.25 h cycling bout) using urine sugar data. On the contrary, untargeted metabolomics showed that the combination of consuming nutrient-rich hemp fiber bars and exercising for 135 min increased levels of beneficial metabolites, including those derived from the gut in healthy cyclists.

Ultra-processed food (UPF) consumption has been linked to adverse metabolic outcomes, potentially mediated by alterations in gut microbiota and metabolite production.

This study aims to explore the cross-sectional and longitudinal associations between NOVA-classified UPF consumption, fecal microbiota, and fecal metabolome in a population of Mediterranean older adults at high cardiovascular risk.

A total of 385 individuals, aged between 55 and 75 years, were included in the study. Dietary and lifestyle information, anthropometric measurements, and stool samples were collected at baseline and after 1-year follow-up. Fecal microbiota and metabolome were assessed using 16 S rRNA sequencing and liquid chromatography-tandem mass spectrometry, respectively.

At baseline, higher UPF consumption was associated with lower abundance of Ruminococcaceae incertae sedis (β = - 0.275, P = 0.047) and lower concentrations of the metabolites propionylcarnitine (β = - 0.0003, P = 0.013) and pipecolic acid (β = - 0.0003, P = 0.040) in feces. Longitudinally, increased UPF consumption was linked to reduced abundance of Parabacteroides spp. after a 1-year follow-up (β = - 0.278, P = 0.002).

High UPF consumption was associated with less favorable gut microbiota and metabolite profiles, suggesting a possible link to reduced short-chain fatty acid (SCFA) production, altered mitochondrial energy metabolism, and impaired amino acid metabolism. These findings support the reduction of UPF consumption and the promotion of dietary patterns rich in fiber for better gut health. Further research is needed to confirm these associations and clarify the underlying mechanisms.

ISRCTN89898870 ( https://doi.org/10.1186/ISRCTN89898870 ).

Peptides represent a rapidly expanding class of drugs with broad therapeutic potential. However, due to their large molecular weight and susceptibility to degradation in the gastrointestinal tract, most peptide drugs are administered via subcutaneous injections. Despite extensive research, a painless broad delivery platform for these drugs is still lacking. Recently, an octopus-inspired buccal patch has shown promise in addressing this challenge by leveraging a synergistic combination of mechanical stretching and permeation enhancers. In this study, the patch and the loaded formulation were optimized to improve ease of use, scalability, and efficacy. Through assessments of mechanical properties, finite element simulations, and ex vivo experiments, we evaluated the effects of patch design and material, as well as the drug matrix composition and the formulation preparation methods on the delivery performance. A patch with a > 9-fold larger effective surface area, produced via mold casting of medical-grade silicone (shore hardness 50) and loaded with a lyophilized drug matrix, emerged as the most promising system. In beagle dogs, 30-min application of this patch resulted in a 14.6 % bioavailability for teriparatide (4118 g mol-1), while bioavailability of semaglutide (4114 g mol-1) was 9.6 times higher than that of the commercial tablet. This work showcases how systematic optimization of this technology can improve and simplify the buccal administration of macromolecular drugs, facilitating the clinical translation of this non-invasive dosage form.

Maintaining intestinal health is crucial for the overall well-being and productivity of livestock, as it impacts nutrient absorption, immune function, and disease resistance. Oxidative stress and inflammation are key threats to intestinal integrity. This study explored the antioxidant, anti-inflammatory, and barrier-strengthening properties of a fermented plant macerate (FPM) derived from 45 local herbs, using a specifically developed fermentation process utilizing the plants' inherent microbiota to enhance bioactivity and sustainability.

In vitro experiments with IPEC-J2 cells showed that FPM significantly reduced intracellular reactive oxygen species (ROS) levels, improved barrier integrity, and enhanced cell migration under stress. Similar antioxidant effects were observed in THP-1 macrophages, where FPM reduced ROS production and modulated inflammatory responses by decreasing pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α), monokine induced by gamma interferon (MIG), interferon-inducible T cell alpha chemoattractant (I-TAC), macrophage inflammatory proteins (MIP)-1α and -1β] and increasing anti-inflammatory interleukin (IL)-10 levels. Mechanistic studies with HEK-Blue reporter cell lines revealed that FPM inhibited nuclear factor kappa B (NF-κB) activation via a toll-like receptor (TLR)4-independent pathway. In vivo, FPM significantly reduced ROS levels in Drosophila melanogaster and improved activity and LT50 values in Caenorhabditis elegans under oxidative stress, although it did not affect intestinal barrier integrity in these models.

The findings indicate that FPM shows promising application as a functional feed supplement for improving intestinal health in livestock by mitigating oxidative stress and inflammation. Further studies, including livestock feeding trials, are recommended to validate these results.

Heart failure with preserved ejection fraction (HFpEF) represents a significant and growing clinical challenge. Initially, for an extended period, HFpEF was simply considered as a subset of heart failure, manifesting as haemodynamic disorders such as hypertension, myocardial hypertrophy, and diastolic dysfunction. However, the rising prevalence of obesity and diabetes has reshaped the HFpEF phenotype, with nearly 45% of cases coexisting with diabetes. Currently, it is recognized as a multi-system disorder that involves the heart, liver, kidneys, skeletal muscle, adipose tissue, along with immune and inflammatory signaling pathways. In this review, we summarize the landscape of metabolic rewiring and the crosstalk between the heart and other organs/systems (e.g., adipose, gut, liver and hematopoiesis system) in diabetic HFpEF for the first instance. A diverse array of metabolites and cytokines play pivotal roles in this intricate crosstalk process, with metabolic rewiring, chronic inflammatory responses, immune dysregulation, endothelial dysfunction, and myocardial fibrosis identified as the central mechanisms at the heart of this complex interplay. The liver-heart axis links nonalcoholic steatohepatitis and HFpEF through shared lipid accumulation, inflammation, and fibrosis pathways, while the gut-heart axis involves dysbiosis-driven metabolites (e.g., trimethylamine N-oxide, indole-3-propionic acid and short-chain fatty acids) impacting cardiac function and inflammation. Adipose-heart crosstalk highlights epicardial adipose tissue as a source of local inflammation and mechanical stress, whereas the hematopoietic system contributes via immune cell activation and cytokine release. We contend that, based on the viewpoints expounded in this review, breaking this inter-organ/system vicious cycle is the linchpin of treating diabetic HFpEF.

Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is frequently complicated by extraintestinal manifestations such as functional hyposplenism. Increasing evidence highlights its pathogenesis as a multifactorial interplay of gut dysbiosis, intestinal barrier dysfunction, and dysregulated immune responses. While probiotics, particularly Lactobacillus spp., have emerged as potential therapeutics for IBD, restoring intestinal homeostasis, their systemic immunomodulatory effects remain underexplored. Here, we investigated the protective role of Lactobacillus johnsonii N5 in DSS-induced colitis, focusing on inflammation inhibition and splenic T cell regulation. Pretreatment with L. johnsonii N5 significantly attenuated colitis severity, as evidenced by preserved body weight, reduced disease activity index, and prevention of colon shortening. N5 suppressed colonic pro-inflammatory factors such as TNF-α, Il-1b, Il-6, and CXCL1, while elevating anti-inflammatory IL-10 at both mRNA and protein levels. Transcriptomic analysis of the spleen revealed that N5 mediated the downregulation of inflammatory pathways, including the IL-17 and TNF signaling pathways, as well as the HIF-1 signaling pathway, and modulated the metabolic pathway of oxidative phosphorylation. Flow cytometry analysis demonstrated that N5 rebalanced splenic Treg/Th17 responses by expanding the Treg population and reducing the production of IL-17A in Th17 cells. Notably, Th17-associated IL-17A positively correlated with intestinal pro-inflammatory mediators, emphasizing the role of Th17 cells in driving colitis. In contrast, splenic Treg abundance positively correlated with colonic IL-10 levels, suggesting a link between systemic immune regulation and intestinal anti-inflammatory responses. Our study underscores the therapeutic potential of targeting gut-immune crosstalk through probiotics, thereby offering valuable insights for developing live bacterial-based interventions for IBD and other inflammatory disorders.

Polyethylene terephthalate microplastics (PET-MPs) have been detected in the environment and human metabolites or tissues; however, their potential effects on humans under actual exposure doses remain unclear. Herein, male adult mice were exposed to 10 µm PET-MPs at concentrations of 10, 50, and 250 mg/kg per body weight consecutively for 28 days. Changes in blood biochemistry, inflammatory factors, colonic histopathology, colonic mucus gene mRNA levels, and the gut microflora were monitored to study PET-MPs toxicity. The results showed that PET-MPs exposure increased relative serum alanine aminotransferase (ALT) and glucose (GLU) levels in 50 mg/kg bw PET-MPs exposure group, and altered relative levels of inflammatory factors, thereby inducing the inflammatory response. Moreover, PET-MPs exposure increased mRNA expression levels of colonic mucus secretion related and barrier function related genes, indicating intestinal mucus secretion and barrier integrity dysfunction, which was consistent with the results of histopathological results. In addition, gut microbiota analysis revealed that the diversity and community composition were altered after PET-MPs exposure, suggesting a metabolic disorder. Therefore, our results demonstrated that exposure to PET-MPs led to intestinal injury and changes in the gut microbiome composition in mice. Overall, the study findings provided basic data about the health risks of PET-MPs to humans, highlighting that MPs-induced toxicity warrants more concern in the future.

Biosynthesis-a process utilizing biological systems to synthesize chemical compounds-has emerged as a revolutionary solution to 21st-century challenges due to its environmental sustainability, scalability, and high stereoselectivity and regioselectivity. Recent advancements in artificial intelligence (AI) are accelerating biosynthesis by enabling intelligent design, construction, and optimization of enzymatic reactions and biological systems. We first introduce the molecular retrosynthesis route planning in biochemical pathway design, including single-step retrosynthesis algorithms and AI-based chemical retrosynthesis route design tools. We highlight the advantages and challenges of large language models in addressing the sparsity of chemical data. Furthermore, we review enzyme discovery methods based on sequence and structure alignment techniques. Breakthroughs in AI-based structural prediction methods are expected to significantly improve the accuracy of enzyme discovery. We also summarize methods for de novo enzyme generation for nonnatural or orphan reactions, focusing on AI-based enzyme functional annotation and enzyme discovery techniques based on reaction or small molecule similarity. Turning to enzyme engineering, we discuss strategies to improve enzyme thermostability, solubility, and activity, as well as the applications of AI in these fields. The shift from traditional experiment-driven models to data-driven and computationally driven intelligent models is already underway. Finally, we present potential challenges and provide a perspective on future research directions. We envision expanded applications of biocatalysis in drug development, green chemistry, and complex molecule synthesis.

Low-calorie sweeteners (LCSs) are popular sugar substitutes and have been shown to alter the gut microbiota, which raises concerns about potential impacts on intestinal permeability.

This study aimed to examine cross-sectional associations between LCS consumption and circulating biomarkers of intestinal permeability.

We analyzed data from 572 United States adults participating in the Cancer Prevention Study-3 Diet Assessment Substudy who provided ≤2 fasting blood samples, collected 6 mo apart, to measure biomarkers of intestinal permeability including antibodies to flagellin (anti-flagellin), lipopolysaccharide (anti-LPS), and total antibodies; and ≤6 24-h dietary recalls, collected over the course of 12 mo, to estimate average intake of LCS including aspartame, sucralose, acesulfame-potassium, and saccharin. Multivariable linear regression, adjusted for sociodemographic characteristics, lifestyle factors, and medical history, was used to examine associations between LCS consumption and levels of intestinal permeability biomarkers by comparing mean differences in biomarkers among lower (>0 to ≤50th percentile) (n = 158) and higher (>50th percentile) LCS consumers (n = 157) than nonconsumers. A linear trend across nonconsumers and the 2 consumption categories was evaluated using a continuous variable based on the median LCS intake (median = 0, 11.3, and 124.2 mg/d for non-, lower, and higher consumers, respectively).

Among the 572 study participants, the mean age was 52.5 y, 63.3% were female, 60.7% were on-Hispanic White, and 55.1% reported consuming LCS-containing products. Greater LCS consumption was not associated with anti-flagellin, anti-LPS, or total antibodies. Additionally, no associations between specific types of LCS and intestinal permeability biomarkers were observed.

The results of our study did not demonstrate an association between LCS consumption and intestinal permeability biomarkers. Further research with larger sample sizes and randomized controlled trials is needed to confirm our findings.

Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis (AP). Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.

To explore the biological processes and mechanisms of intestinal injury associated with AP, and to find potential targets for early prevention or treatment of intestinal barrier injury.

This study utilized single-cell RNA sequencing of the small intestine, alongside in vitro and in vivo experiments, to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.

Seventeen major cell types and 33232 cells were identified across all samples, including normal, AP1 (4x caerulein injections, animals sacrificed 2 h after the last injection), and AP2 (8x caerulein injections, animals sacrificed 4 h after the last injection). An average of 980 genes per cell was found in the normal intestine, compared to 927 in the AP1 intestine and 1382 in the AP2 intestine. B cells, dendritic cells, mast cells (MCs), and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine. Enterocytes, brush cells, enteroendocrine cells, and goblet cells maintained numbers similar to the normal intestine, while cytotoxic T cells and natural killer (NK) cells increased. Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities. Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities. Activated MCs, secreted chemokine (C-C motif) ligand 5 (CCL5), promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.

These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury, suggesting that CCL5 from MCs is a potential target for addressing dysfunction.

Chronic liver disease is defined by persistent harm to the liver that might result in decreased liver function. The two prevalent chronic liver diseases are alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). There is ample evidence that the pathogenesis of these two chronic liver diseases is closely linked to gastrointestinal dysfunctions that alters the gut-liver crosstalk. These alterations are mediated through the imbalances in the gut microbiota composition/function that combined with disruption in the gut barrier integrity allows for harmful gut microbes and their toxins to enter the portal circulation and reach the liver to elicit an inflammatory response. This leads to further recruitment of systemic inflammatory cells, such as neutrophils, T-cells, and monocytes into the liver, which perpetuate additional inflammation and the development of progressive liver damage. Many therapeutic modalities, currently used to prevent, attenuate, or treat chronic liver diseases are aimed at modulating gut dysbiosis and improving intestinal barrier function. Betaine is a choline-derived metabolite and a methyl group donor with antioxidant, anti-inflammatory and osmoprotectant properties. Studies have shown that low betaine levels are associated with higher levels of organ damage. There have been several publications demonstrating the role of betaine supplementation in preventing the development of ALD and MASLD. This review explores the protective effects of betaine through its role as a methyl donor and its capacity to regulate the protective gut microbiota and maintain intestinal barrier integrity to prevent the development of these chronic liver diseases. Further studies are needed to enhance our understanding of its therapeutic potential that could pave the way for targeted interventions in the management of not only chronic liver diseases, but other inflammatory bowel diseases or systemic inflammatory conditions.

Lacto-N-neotetraose (LNnT) is a prevalent neutral core human milk oligosaccharides (HMOs) recognized for its numerous benefits to infant health. In infant formula, galactooligosaccharide (GOS) are frequently used as substitutes for HMOs. However, the regulatory roles of LNnT and GOS in early intestinal development are not yet fully understood. This study aims to elucidate the effects of LNnT and GOS on intestinal development during early life. Our findings show that administering LNnT or GOS significantly increased the spleen and liver indices of infant mice at postnatal day 21. Immunofluorescence and qPCR analysis showed that feeding LNnT significantly promoted the proliferation and differentiation of intestinal stem cells (ISCs) in the colon of infant mice at postnatal day 21, and increased the expression of differentiation markers of goblet cells, intestinal epithelial cells, Paneth cells, and intestinal endocrine cells. Conversely, feeding GOS had no significant effect on the proliferation and differentiation of ISCs. Furthermore, intestinal microbiota analysis showed that LNnT increased the microbiota associated with intestinal regeneration and ISCs proliferation and differentiation in infant mice at postnatal day 21. In conclusion, LNnT promoted ISCs proliferation and differentiation in the colon and alters the composition and function of the intestinal microbiota to support intestinal development in infant mice.

Edible and medicinal mushroom polysaccharides (EMMPs) have been widely studied for their various biological activities. It has been shown that EMMPs could modulate microbiota in the large intestine and improve intestinal health. However, the role of EMMPs in protecting the gastric barrier, regulating gastric microbiota, and improving gastric health cannot be ignored. Hence, this review will elucidate the effect of EMMPs on gastric and intestinal barriers, with emphasis on the interaction of EMMPs with microbiota in maintaining overall gastrointestinal health. Additionally, this review highlights the gastroprotective effects and underlying mechanisms of EMMPs against gastric mucosa injury, gastritis, gastric ulcer, and gastric cancer. Furthermore, the effects of EMMPs on intestinal diseases, including inflammatory bowel disease, colorectal cancer, and intestinal infection, are also summarized. This review will also discuss the future perspective and challenges in the use of EMMPs as a dietary supplement or a nutraceutical in preventing and treating gastrointestinal diseases.

Irritable Bowel Syndrome (IBS) is a complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits, often linked to disruptions in intestinal barrier function. Increased intestinal permeability plays a key role in IBS pathogenesis, affecting immune responses, gut microbiota, and inflammation. This study conducts a bibliometric analysis to explore global research trends on intestinal permeability in IBS, focusing on key contributors, collaboration networks, and thematic shifts, particularly the interplay between the intestinal barrier, gut microbiota, and dietary components. A total of 411 articles were retrieved from Scopus, with 232 studies analyzed using Bibliometrix in R. To optimize screening, ASReview, a machine learning tool, was employed, utilizing the Naïve Bayes algorithm combined with Term Frequency-Inverse Document Frequency (TF-IDF) for adaptive ranking of articles by relevance. This approach significantly improved screening step efficacy. The analysis highlights growing research interest, with China and the USA as leading contributors. Key themes include the role of gut microbiota in modulating permeability, the impact of dietary components (fiber, probiotics, bioactive compounds) on tight junction integrity, and the exploration of therapeutic agents. Emerging studies suggest integrating gut barrier modulation with nutritional and microbiome-targeted strategies for IBS management. This study provides a comprehensive overview of research on intestinal permeability in IBS, mapping its evolution and identifying major trends. By highlighting key contributors and thematic areas, it offers insights to guide future investigations into the interplay between gut permeability, diet, and microbiota, advancing understanding of IBS pathophysiology and management.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.

Ulcerative colitis (UC) is a recurrent intestinal disease caused by a complex of factors, and there are serious adverse effects and tolerance problems associated with the current long-term use of therapeutic drugs. The development of natural food sources and multi-targeted drugs for the treatment of UC is imminent. Portulaca oleracea L. (PO), as a vegetable, has been shown in studies to have an anti-UC effects. However, the relationship between the abundant active ingredients contained in Portulaca oleracea L. and the improvement of intestinal barrier, gut microbiota and metabolites is unclear. In the present study, Portulaca oleracea L. which was found to be rich in phenolic acid-based active ingredients, were effective in alleviating dextran sulfate sodium (DSS)-induced body weight loss, disease activity index (DAI) score and colon length in mice. It also decreased C-reactive protein (CRP) and myeloperoxidase (MPO) responses, reduced the permeation of fluorescein isothiocyanate (FITC)-dextran, lipopolysaccharide (LPS) and evans blue (EB), and improved histopathological scores. Meanwhile, in vitro and in vivo validation revealed the protective effects of purslane on the intestinal barrier indicators ZO-1, Occludin and Claudin-1, and inhibited the expression of inflammation-associated iNOS and NLRP3 proteins through the NF-κB signaling pathway. In addition, purslane increased the diversity of the intestinal flora, enhancing the proportion of the genera Butyricoccus, Dorea and Bifidobacterium and decreasing the percentage of Bacteroides, Turicibacter and Parabacteroides. Serum metabolomics analysis showed that the imbalance of 39 metabolites was significantly reversed after PO deployment. Enrichment analysis showed that Pentose phosphate pathway and Pyruvate metabolism pathway were the key pathways of PO against UC. Overall, purslane effectively improved the intestinal barrier disruption and intestinal inflammation by inhibiting the NF-κB signaling pathway, and adjusted the disorder of gut microbiota and metabolites to exert anti-UC effects.

Enterotoxigenic Escherichia coli (ETEC) is a major pathogen causing neonatal diarrhea in livestock, with antibiotics commonly used for control. However, antibiotic overuse has led to issues such as residues and bacterial resistance, underscoring the need for alternative prevention strategies. This study investigated the potential of Bacillus safensis (B. safensis) M01, isolated from healthy porcine feces in Shandong, China, to prevent ETEC infections. M01 exhibited over 80% inhibition of ETEC in vitro and was selected for further analysis. Pre-treatment of IPEC-J2 cells with M01 significantly reduced ETEC-induced cellular damage, enhanced cell viability, and inhibited bacterial adhesion. It modulated inflammatory responses by down-regulating IL-1β and TNF-α while up-regulating IL-10. Additionally, M01 promoted the expression of tight junction proteins, including Claudin-1, Occludin, and ZO-1. In the C57BL/6 mouse model, pre-feeding with M01 for 14 days improved jejunal injury caused by ETEC, as indicated by increased villus height/crypt depth ratios. Similar to in vitro findings, M01 reduced IL-1β and TNF-α expression while enhancing tight junction protein levels. These results suggest that B. safensis M01 is a promising probiotic candidate for preventing ETEC infections in livestock, offering an effective alternative to antibiotics.