Search Results (193)

To investigate the effects of low net-energy (NE) diets on intestinal health in Tunchang pigs, 96 animals (25.40 ± 1.11 kg) were randomly assigned to four dietary treatment groups with NE levels of 9.82 (CG), 9.57 (EY1), 9.32 (EY2), and 9.07 (EY3) MJ/kg. Each group consisted of six replicates with four pigs per replicate. The experiment lasted for 63 days. The results showed that compared with the CG, the EY2 increased jejunal villus height and villus height-to-crypt depth ratio, as well as reduced crypt depth in the colon (p < 0.05). Both the EY1 and EY2 demonstrated improved intestinal barrier function through upregulation of zonula occludens-1 and occludin expression in the jejunum, zonula occludens-1 in the ileum, and zonula occludens-1, occludin, and claudin-1 in the colon (p < 0.05). Furthermore, EY2 significantly increased the activities of superoxide dismutase, glutathione peroxidase, and catalase, while reducing malondialdehyde content in both the jejunum and colon (p < 0.05). EY2 showed significantly downregulated relative expression of pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6, in the jejunum, ileum, and colon (p < 0.05). Microbial and short-chain fatty acid (SCFA) analyses showed that the EY2 increased the abundance of beneficial bacteria such as Faecalibacterium, CF231, Coprococcus, Ruminococcus, and Blautia and elevated the concentrations of acetate, propionate, and butyrate. In summary, reducing dietary NE levels to no less than 9.32 MJ/kg improved intestinal health by modulating the gut microbiota and increasing SCFA production. Full article

Background: Lophatheri Herba, a traditional East Asian herb with documented food uses, contains bioactive flavonoids. This study investigated how Aspergillus oryzae fermentation modifies its short-chain fatty acids (SCFAs) and metabolome, and evaluated the fermented product’s impact on intestinal barrier function in mice. Methods: Fermented leaf extracts were analyzed via GC-MS/LC-MS for SCFAs and metabolites. Forty-eight mice were divided into control (standard diet) and three experimental groups (25, 50, 100 mg/kg/day fermented product). After a 4-week intervention, duodenal morphology, colonic cytokines (IL-6/IL-1β), and cecal microbiota were assessed. Results: We identified significant SCFAs optimization. Significantly increased: acetic acid; butyric acid (p < 0.001); isobutyric acid (p < 0.01); isovaleric acid (p < 0.05). No significant change: propionic acid and isohexanoic acid. Significantly decreased: valeric acid and hexanoic acid (p < 0.001). Metabolomic remodeling showed (i) flavonoid pathway activation and (ii) key metabolite upregulation (daidzein, 4,7-dihydroxyflavone, 3,7-dimethylquercetin, aloe-emodin, soyasapogenol M1, etc.). Gut function peaked at 100 mg/kg with 18% higher duodenal villus height (p < 0.05), improved villus/crypt ratio, and reduced IL-6/IL-1β. Probiotic taxa including Lactobacillus, unclassified f__Lachnospiraceae, Dubosiella, and Monoglobus increased. Conclusions: Fermented Lophatheri Herba protects gut health through synergistic SCFAs optimization, flavonoid enrichment, and probiotic proliferation, supporting its potential as a microbiota-targeting functional food ingredient. Full article

The goal of this review is to expand our understanding of how the cellular organization of the normal colonic crypt is maintained and elucidate how this intricate architecture is disrupted during tumorigenesis. Additionally, it will focus on implications for new therapeutic strategies targeting Epithelial–Mesenchymal Transition (EMT). The colonic crypt is a highly structured epithelial unit that functions in maintaining homeostasis through a complex physiological function of diverse cell types: SCs, transit-amplifying (TA) progenitors, goblet cells, absorptive colonocytes, Paneth-like cells, M cells, tuft cells, and enteroendocrine cells. These cellular subpopulations are spatially organized and regulated by multiple crucial signaling pathways, including WNT, Notch, Bone Morphogenetic Protein (BMP), and Fibroblast Growth Factor (FGF). Specifically, we discuss how these regulatory networks control the precise locations and functions of crypt cell types that are necessary to achieve cellular organization and homeostasis in the normal colon crypt. In addition, we detail how the crypt’s hierarchical structure is profoundly perturbed in colorectal cancer (CRC) development. Tumorigenesis appears to be driven by LGR5+ cancer stem cells (CSCs) and the hyperproliferation of TA cells as colonocytes undergo metabolic reprogramming. Goblet cells lose their secretory phenotype, while REG4+ Paneth-like cells foster SC niches. Tumor microenvironment is also disrupted by upregulation of M cells and by tumor-immune crosstalk that is promoted by tuft cell expansion. Moreover, the presence of enteroendocrine cells in CRC has been implicated in treatment resistance due to its contribution to tumor heterogeneity. These cellular changes are caused by the disruption of homeostasis signaling whereby: overactivation of WNT/β-catenin promotes stemness, dysregulation of Notch inhibits differentiation, suppression of BMP promotes hyperproliferation, and imbalance of FGF/WNT/BMP/NOTCH enhances cellular plasticity and invasion. Further discussion of emerging therapies targeting epithelial markers and regulatory factors, emphasizing current development in novel, precision-based approaches in CRC treatment is also included. Full article

Environmental pollution with microplastics (MPs) can have a negative impact on human health. Certain findings point to the relationship between MP and the development of inflammatory bowel diseases (IBD). We investigated the effect of MP consumption on the severity of chronic colitis in male C57BL/6 mice. The MP effect was modeled by drinking water consumption with a suspension of 5 μm PS particles at a concentration of 10 mg/L replacement for 12 weeks. Chronic colitis was induced by three seven-day cycles of 1% DSS consumption (starting from the 8th, 29th and 50th days of the experiment). We investigated inflammatory infiltration, the goblet cell volume fraction and the highly sulfated and neutral mucins content in them, the endocrine cell number, the ulcerative-inflammatory process prevalence, changes in the gene’s expression encoding tight junction proteins, glycocalyx components proapoptotic factor Bax and proliferation marker Mki67 in the colon, and TNFα, IL-1β, IL-6 and IL-10 cytokines content in the serum. In healthy mice, MP did not cause pathological changes in the colon; however, indirect data indicate an increase in colon permeability. In chronic colitis, MP leads to higher prevalence of all pathological changes in general, and ulcers in particular, in a greater number of crypt abscesses and enteroendocrine cells. MP consumption leads to a more severe chronic colitis course. Full article

Weaning is one of the most challenging stages in a piglet’s life, with multiple stressors contributing to poor gut health. For several years, zinc oxide (ZnO) was the preferred means of promoting a healthy gut and preventing post-weaning diarrhea (PWD). However, with the banning of its use at medicinal levels in the EU since 2022, alternatives are needed. Berberine (BBR), an isoquinoline alkaloid, has been used for centuries in Chinese medicine to treat diarrhea and has pharmacological properties that could make this molecule an attractive alternative to ZnO. The aim of this study was to investigate how berberine is metabolized in the intestinal tract and liver of weaned piglets; determine which metabolites are detected in intestinal contents and plasma; and whether a low dose can alter histomorphological parameters, short-chain fatty acid (SCFA) production, and gut microbiota composition. A total of 60 piglets weaned at 4 weeks were divided into two groups (Control and BBR), each consisting of six pens of five animals. After two weeks of feeding with a normal diet or a berberine-supplemented diet (30 mg berberine/kg feed), berberine and its metabolites were quantified in intestinal contents and plasma by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) on 12 animals per group (2 male piglets per pen). Moreover, villus length and crypt depth were measured in small-intestinal tissue, and 16S rRNA gene sequencing was performed to examine jejunal, cecal, and colonic gut microbiota composition. Our findings show that piglets metabolize berberine into phase I and II metabolites; however, a low dose does not affect their histomorphology, microbiota composition, or SCFA production. Full article

Background: Rice bran proteins and their hydrolysates exhibit anticancer activity. Our previous study demonstrated that Riceberry glutelin and its hydrolysates possessed potent in vitro antioxidant and antimutagenic properties. However, their cancer chemopreventive effects in animals remain unclear. Methods: This study investigated chemopreventive mechanisms in diethylnitrosamine (DEN)- and 1,2-dimethylhydrazine (DMH)-induced preneoplastic lesions, including glutathione S-transferase placental form (GST-P)-positive foci in the liver and aberrant crypt foci (ACF) in the colon of rats. Rats received GTL, GTLH, and total protein hydrolysate (TPH) at 500 mg/kg body weight, five days per week for ten weeks. Results: GTLH significantly reduced GST-P-positive foci in the liver and ACF in the colon, while GTL decreased GST-P-positive foci only in the liver. However, TPH did not affect preneoplastic lesions in both the liver and the colon. GTLH suppressed cell proliferation by reducing proliferating cell nuclear antigen (PCNA)-positive cells and promoted apoptosis, as indicated by an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in both organs. GTL also decreased PCNA-positive cells in the liver and colon. Moreover, GTLH significantly upregulated BAX and CASP3 in the liver, while only BAX in the colon was observed. Conclusions: This study highlighted the cancer chemopreventive potential of Riceberry GTLH with its underlying mechanism to reduce the number of preneoplastic lesions in the liver and colon through cell proliferation inhibition and apoptosis induction. These findings suggested that this protein hydrolysate might be used as a functional food ingredient or dietary supplement for cancer prevention. Full article

Early weaning of piglets elicits weaning stress, which in turn induces oxidative stress and consequently impairs growth and development. Hydrogen-rich water (HRW), characterized by selective antioxidant properties, mitigates oxidative stress damage and serves as an ideal intervention. This study aimed to evaluate the effects of HRW on weaned piglets, specifically investigating its impact on growth performance, diarrhea incidence, antioxidant function, intestinal morphology, gut microbiota, and hepatic metabolites. The results demonstrate that HRW significantly increased the average daily feed intake and significantly reduced the diarrhea rate in weaned piglets. Analysis of serum oxidative stress indicators revealed that HRW significantly elevated the activities of total antioxidant capacity and total superoxide dismutase while significantly decreasing malondialdehyde concentration. Assessment of intestinal morphology showed that HRW significantly increased the villus height to crypt depth ratio in the duodenum, jejunum, and ileum. Microbial analysis indicated that HRW significantly increased the abundance of Prevotella in the colon. Furthermore, HRW increased the abundance of beneficial bacteria, such as Akkermansia, in the jejunum and cecum, while concurrently reducing the abundance of harmful bacteria like Escherichia. Hepatic metabolite profiling revealed that HRW significantly altered the metabolite composition in the liver of weaned piglets. Differentially abundant metabolites were enriched in oxidative stress-related KEGG pathways, including ABC transporters; pyruvate metabolism; autophagy; FoxO signaling pathway; glutathione metabolism; ferroptosis; and AMPK signaling pathways. In conclusion, HRW alleviates diarrhea and promotes growth in weaned piglets by enhancing antioxidant capacity. These findings provide a scientific foundation for the application of HRW in swine production and serve as a reference for further exploration into the mechanisms underlying HRW’s effects on animal health and productivity. Full article

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracaseiL21 (L. paracaseiL21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracaseiL21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracaseiL21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracaseiL21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracaseiL21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies. Full article

Background: Interleukin (IL)-23 exerts its effects by activating Th17 cells, resulting in high neutrophilic infiltration in the colonic mucosal epithelium. We have developed a scoring method for refining the Geboes score Grade 3 to identify active ulcerative colitis (UC) patients with high epithelial neutrophilic infiltration (Geboes Grade 3.2 or 3.3). Methods: Colonoscopy and histology findings were assessed using the Mayo endoscopic subscore (MES) and the Geboes score Grade 3. The percentage of crypts with neutrophilic infiltration, which was calculated as the number of crypts with neutrophilic infiltration/total crypts in a glass slide, was used to subclassify the Geboes score Grade 3 into Grades 3.0, 3.1, 3.2, and 3.3. Results: This scoring method was then applied to 30 enrolled patients (20 men; median age: 46 years), yielding the following distribution: Geboes Grade 3.0 in six (20%) patients, Grade 3.1 in seven (23%) patients, Grade 3.2 in sixteen (53%) patients, and Grade 3.3 in one (3%) patient. Of the 18 UC patients with MES 2, 5 (28%) were classified as Grade 3.1 and 12 (67%) were classified as Grade 3.2. One of the IL-23 antagonists, mirikizumab treatment, resulted in clinical and endoscopic improvements in 10 active UC patients who were classified as Geboes score ≥ 3.2. Conclusions: We developed a novel Geboes score Grade 3 scoring method and applied it to 30 patients; approximately 60% were classified as Grade 3.2 or higher. This method may help to identify UC patients who are likely to respond effectively to IL-23 antagonists. Full article

Background: PTEN is a tumor suppressor that controls many pathophysiological pathways, including cell proliferation, differentiation, apoptosis and invasiveness. Although PTEN down-modulation is a critical event in neoplastic progression, it becomes apparent that transient and local inhibition of PTEN activity might be beneficial for the healing process. Methods: In the present study, we investigated the impact of PTEN invalidation in mouse intestinal epithelium under a physiological condition and after dextran sulfate sodium (DSS) treatment to induce experimental colitis. PTEN conditional knockout was induced in intestinal epithelial cells after crossing villin-Cre and PTEN^flox/flox mice. Results: PTEN invalidation alleviates experimental colitis induced by DSS, as evidenced by decreased weight loss during the acute phase, the lower expression of inflammation markers, including the proinflammatory cytokines IFN-γ, CXCL1 and CXCL2, reduced mucosal lesions, and faster recovery after resolution of inflammation. This protective effect might result in part from the sustained proliferation of colonic epithelium, leading to hyperplasia and increased colonic crypt depth under physiological conditions, which was further exacerbated in the vicinity of mucosal injury induced by DSS treatment. Furthermore, PTEN knockout decreased paracellular permeability, thereby enhancing the intestinal barrier function. This process was associated with the reinforcement of claudin-3 immunostaining, especially on the surface epithelium of villin-Cre PTEN^flox/flox mice. Conclusions: PTEN inactivation exerts a protective effect on the onset of colitis, and the transient and local down-modulation of PTEN might constitute an approach to drive recovery following acute intestinal inflammation. Full article

Background: Circadian disruption (CD) aggravates metabolic dysfunction-associated steatohepatitis (MASH), but supplementation with prebiotics inulin and oat β-glucan may mitigate its effects. However, their impact on colonic architecture and hepatic proteome remains unclear. Objectives: We aimed to investigate the effects of prebiotics inulin and oat β-glucan on colonic architecture and hepatic proteome in mice with CD-aggravated MASH. Methods: CD was induced by weekly reversal of the light–dark cycle to simulate shift work. Male C57BL/6J mice were subjected to non-shifted chow, non-shifted fructose, palmitate, cholesterol, and trans-fat (FPC) diet, shifted chow, or shifted FPC diet (SFPC) for 26 weeks. Prebiotics inulin and oat β-glucan supplementation were provided to the SFPC group in the final 10 weeks. Distal colon and serum samples were collected for histological examination and endotoxemia evaluation, respectively. Liver samples were collected for proteomic mass spectrometry analysis. Results: Mice with CD-aggravated MASH were found with colonic crypt loss and a distinct hepatic proteome structure compared to mice with non-CD MASH. Notably, inulin showed better effects than oat β-glucan in preserving colonic crypts in mice with CD-aggravated MASH. Furthermore, inulin supplementation restored the hepatic proteome structure similar to that of non-CD MASH mice, a benefit not observed with oat β-glucan. Conclusions: Given our prior findings showing oat β-glucan’s superior ability to enrich gut bacterial species associated with MASH improvement under CD, this study highlights inulin’s unique benefits for colonic architecture and hepatic proteome regulation in CD-aggravated MASH. Full article

Bioactive peptides from black soldier fly larvae (BSFL) protein hydrolysates have gained attention for their health-promoting properties. Our previous study demonstrated the chemopreventive potential of BSFL hydrolysates prepared with Alcalase (ASBP-AH) in colon cancer cells; their in vivo efficacy has not been fully elucidated. This study evaluated the chemopreventive effects of ASBP-AH, processed by spray-drying (ASBP-AHS) or freeze-drying (ASBP-AHF), in a diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH)-induced rat model of early-stage colorectal carcinogenesis. Oral administration of ASBP-AHS or ASBP-AHF significantly reduced aberrant crypt foci (ACF) and downregulated PCNA, COX-2, and NF-κB expression, without affecting apoptosis. Furthermore, both treatments restored microbial species richness and shifted gut microbial diversity disrupted by carcinogen exposure. ASBP-AHS specifically enriched short-chain fatty acid (SCFA)-producing bacteria, while ASBP-AHF favored anti-inflammatory microbial signatures. Likewise, correlation analysis revealed positive associations between microbial changes and SCFA levels, particularly with ASBP-AHS. Peptidomic profiling identified identical peptides in both hydrolysates, including stable pyroglutamyl-containing sequences with potential anti-inflammatory and microbiota-modulating effects. These findings support the in vivo chemopreventive potential of ASBP-AH and its promise as a functional food ingredient for promoting gut health and reducing colorectal cancer risk. Full article

Galacto-oligosaccharides (GOS) are recognized prebiotics with extensive applications in animal nutrition. This study aimed to elucidate the effects of chlortetracycline (CTC) supplementation alongside GOS on growth performance, intestinal morphology, and microbiota composition in weaned piglets. A total of 72 weaned piglets [(Duroc × (Landrace × Yorkshire)] with an initial body weight of 7.64 ± 0.15 kg were randomly assigned to three dietary treatments: a corn–soybean meal-based diet (CON), a corn–soybean meal-based diet supplemented with chlortetracycline (CTC) at 75 mg/kg, and a diet with 1500 mg/kg GOS. The experiment spanned 14 days, divided into early (1–7 days) and late (7–14 days) stages. The results indicated that the GOS group exhibited a significant increase in body weight (BW) by day 14 and improved average daily gain (ADG) from day 1 to 14, alongside a decreased feed-to-gain ratio and diarrhea incidence (p < 0.05). Notably, GOS supplementation enhanced the villus height of the jejunum and increased the ratio of villus height to crypt depth compared to the CON group, although no significant differences were observed between GOS and AntB groups. Additionally, the number of goblet cells in the colonic crypts increased significantly with GOS supplementation. High-throughput 16S rRNA gene sequencing revealed an increased relative abundance of Firmicutes in the GOS group, coupled with a decrease in Bacteroidetes and Spirochaetota. Beneficial bacteria such as Lactobacillus and Faecalibacterium were significantly enriched, while potentially pathogenic bacteria, including Clostridium_sensu_stricto_1 and Treponema, were reduced. In summary, dietary GOS supplementation can enhance beneficial microbiota while diminishing harmful species, thereby improving intestinal morphology and growth performance in weaned piglets. Consequently, GOS emerges as a promising alternative to in-feed antibiotics in contemporary animal husbandry. Full article

Background/Objectives: Indigo naturalis (IN) is a traditional Chinese medicine concocted from medicinal plants such as Baphicacanthus cusia (Nees) Bremek. IN has multifaceted pharmacological activities. Recent research highlights the remarkable efficacy of IN in treating ulcerative colitis (UC). This study investigates the efficacy of Indigo Naturalis prepared using a novel method (NIN) in ameliorating UC. Methods: We have developed a new IN processing technology without the use of lime. Correspondingly, the content of active ingredients has relatively increased in NIN. In this study, dextran sulfate sodium salt (DSS) induced UC models among male KM mice, and the protective effects of NIN on UC were verified. Results: NIN could significantly improve weight loss, diarrhea and prolapse, bloody stools, elevated Disease Activity Index (DAI) and alleviate the colitis symptoms of mice; it could also improve the shortening of colon, disappearance of intestinal crypts, epithelial cell destruction and inflammatory infiltration caused by UC; and it could also significantly reduce the Histological Index (HI). In addition, NIN relieved the inflammatory response by decreasing the content of pro-inflammatory cytokines TNF-α and IL-1β and elevating the content of anti-inflammatory cytokines IL-10 and IL-22. It also restored the intestinal mucosal barrier by increasing the level of MUC2 protein expression at the site of colonic injury. Conclusions: The significant effects of NIN on UC were verified for the first time, suggesting that NIN was worth further developing into a novel therapeutic drug and, necessarily, further safety evaluations and comparisons with traditional IN will help in the application of NIN. Full article

Enterotoxigenic Escherichia coli (ETEC), a common intestinal pathogen, can colonize the intestines and induce diarrhea in piglets, which brings great economic losses to the swine industry. Antibiotics are recommended to the treatment for diarrhea caused by ETEC in weaned piglets. However, with the emergence and spread of multidrug-resistant ETEC, there is an urgent need to develop alternatives to antibiotics. Due to the unique antibacterial mechanism of targeting bacterial membranes, antimicrobial peptides (AMPs) are promising candidates. In this study, the activity of crude recombinant porcine β-defensin 2 (rPBD2) expressed in Pichia pastoris (P. pastoris) was measured in vitro. Mice infected with ETEC were orally administered 16, 8, and 4 AU crude rPBD2 for 7 consecutive days to evaluate its anti-infective activity in vivo. The results showed that in addition to broad antibacterial activity against Gram-positive and -negative bacteria, crude rPBD2 displayed high tolerance to temperatures ranging from 20 to 60 °C, a broad range of pH, trypsin, pepsin, and physiological concentrations of salts. In an ETEC-induced mouse model, the oral administration of crude rPBD2 decreased diarrhea scores and the intestinal/carcass ratio and alleviated body weight loss. Additionally, crude rPBD2 decreased bacterial loads in stools and the colon (HP group), and the levels of serum pro-inflammatory cytokines IL-6 (HP group) and TNF-α (HP and MP groups), and increased the villus height and the ratio of villus height to crypt depth (VH/CD) in the ileum (HP and MP groups). Our study provides a cost-effective way for PBD2 production and identifies it as a promising candidate to combat ETEC-induced infection. Full article