Search

This study elucidated the unique pathological features of tissue healing by magnamosis and revealed the changes in landmark molecule expression levels related to collagen synthesis and tissue hypoxia. Forty-eight male Sprague-Dawley rats were divided into the magnamosis and suture anastomosis groups, and gastrojejunal anastomosis surgery was performed. Rats were dissected at 6, 24, and 48 h and 5, 6, 8, 10, and 12 days postoperatively. Hematoxylin, eosin, and Masson's trichrome staining were used to evaluate granulation tissue proliferation and collagen synthesis density at the anastomosis site. Immunohistochemistry was used to measure TGF-β1 and HIF-1α expression levels. Magnamosis significantly shortened the operation time, resulting in weaker postoperative abdominal adhesions (P < 0.0001). Histopathological results showed a significantly lower granulation area in the magnamosis group than in the suture anastomosis group (P = 0.0388), with no significant difference in the density of collagen synthesis (P = 0.3631). Immunohistochemistry results indicated that the magnamosis group had significantly lower proportions of TGF-β1-positive cells at 24 (P = 0.0052) and 48 h (P = 0.0385) postoperatively and HIF-1α-positive cells at 24 (P = 0.0402) and 48 h postoperatively (P = 0.0005). In a rat model of gastrojejunal anastomosis, magnamosis leads to improved tissue healing at the gastrojejunal anastomosis, associated with downregulated expression levels of TGF-β1 and HIF-1α., (© 2024. The Author(s).)

Carnosine is a physiologically important molecule in normal human body functions. Chicken meat is an excellent source of carnosine; especially slow-growing Korat chicken (KR) females have a high carnosine content in their meat. The carnosine content of chicken meat can be increased by dietary supplementation of β-alanine (βA) and L-histidine (L-His). Our objective was to reveal the pathways and genes through jejunal transcriptomic profiling related to βA and L-His absorption and transportation. We collected whole jejunum samples from 5 control and 5 experimental KR chicken, fed with 1% βA and 0.5% L-His supplementation. A total of 407 differentially expressed genes (P < 0.05, log 2 fold change ≥2) were identified, 272 of which were down-regulated and 135 up-regulated in the group with dietary supplementation compared to the control group. Based on the integrated analysis of the protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway maps, 87 gene ontology terms were identified and 6 KEGG pathways were significantly (P < 0.05) enriched in the jejunum. The analyses revealed 6 key genes, KCND3, OPRM1, CCK, GCG, TRH, and GABBR2, that are related to neuroactive ligand-receptor interaction and the calcium signaling pathway. These findings give insight regarding the molecular mechanism related to carnosine precursor absorption and transportation in the jejunum and help to identify useful molecular markers for improving the carnosine content in slow-growing KR chicken meat., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the developmental change of body growth and gene expression related to fatty acid uptake and oxidation in the yolk sac membrane (YSM) and jejunum during embryogenesis in Muscovy ducks. The weights of embryos and yolk sac (YS) (5 embryos per replicate, n = 6) were recorded on embryonic days (E)16, E19, E22, E25, E28, E31, and the day of hatch (DOH). The fat and fatty acid contents in YSM, jejunal histology, and gene expression related to fatty acid metabolism in YSM and jejunum were determined in each sampling time. Among the nonlinear models, the maximum growth is estimated at 2.83 (E22.5), 2.67 (E22.1), and 2.60 (E21.3) g/d using logistic, Gompertz, and Von Bertalanffy models, respectively. The weight of YS, and ether extract-free YS as well as the amounts of fat and fatty acids in YS decreased (P < 0.05) linearly, whereas the villus height, crypt depth, villus height/crypt depth, and musculature thickness in jejunum increased (P < 0.05) linearly during embryogenesis. The mRNA expression of CD36, SLC27A4, and FABP1 related to fatty acid uptake as well as the mRNA and protein expressions of PPARα and CPT1 related to fatty acid oxidation increased in a quadratic manner (P < 0.05) in both YS and jejunum, and the maximum values were achieved during E25 to E28. In conclusion, the maximum growth rate of Muscovy duck embryos was estimated at 2.60 to 2.83 g/d on E21.3 to E23.5, while the accumulations of lipid and fatty acid in YS were decreased in association with the increased absorptive area of morphological structures in jejunum. The gene and protein expression involved in fatty acid metabolism displayed a similar enhancement pattern between YSM and jejunum during E25 to E28, suggesting that fatty acid utilization could be strengthened to meet the energy demand for embryonic development., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Enteroendocrine cells (EECs) and vagal afferent neurons constitute functional sensory units of the gut, which have been implicated in bottom-up modulation of brain functions. Sodium oligomannate (GV-971) has been shown to improve cognitive functions in murine models of Alzheimer's disease (AD) and recently approved for the treatment of AD patients in China. In this study, we explored whether activation of the EECs-vagal afferent pathways was involved in the therapeutic effects of GV-971. We found that an enteroendocrine cell line RIN-14B displayed spontaneous calcium oscillations due to TRPA1-mediated calcium entry; perfusion of GV-971 (50, 100 mg/L) concentration-dependently enhanced the calcium oscillations in EECs. In ex vivo murine jejunum preparation, intraluminal infusion of GV-971 (500 mg/L) significantly increased the spontaneous and distension-induced discharge rate of the vagal afferent nerves. In wild-type mice, administration of GV-971 (100 mg· kg -1  ·d -1 , i.g. for 7 days) significantly elevated serum serotonin and CCK levels and increased jejunal afferent nerve activity. In 7-month-old APP/PS1 mice, administration of GV-971 for 12 weeks significantly increased jejunal afferent nerve activity and improved the cognitive deficits in behavioral tests. Sweet taste receptor inhibitor Lactisole (0.5 mM) and the TRPA1 channel blocker HC-030031 (10 µM) negated the effects of GV-971 on calcium oscillations in RIN-14B cells as well as on jejunal afferent nerve activity. In APP/PS1 mice, co-administration of Lactisole (30 mg ·kg -1  ·d -1 , i.g. for 12 weeks) attenuated the effects of GV-971 on serum serotonin and CCK levels, vagal afferent firing, and cognitive behaviors. We conclude that GV-971 activates sweet taste receptors and TRPA1, either directly or indirectly, to enhance calcium entry in enteroendocrine cells, resulting in increased CCK and 5-HT release and consequent increase of vagal afferent activity. GV-971 might activate the EECs-vagal afferent pathways to modulate cognitive functions., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

This study aimed to determine the effects of Saccharomyces yeast postbiotics on cell turnover, immune responses, and oxidative stress in the jejunal mucosa of pigs. Thirty-two newly weaned pigs at 6.05 ± 0.24 kg were assigned to two dietary treatments based on a randomized complete block design. The treatments were control group receiving a basal diet and a group supplemented with Saccharomyces yeast postbiotics (175 g/ton diet) in the basal diet. After 35 d of the study, pigs were euthanized and jejunal mucosa were collected to assess immune status, oxidative stress, barrier markers, cell proliferation, and apoptosis. Saccharomyces yeast postbiotics reduced (P < 0.05) the fecal score from d 3 to d 7 and tended to increase the gene expression of interferon-γ (IFN-γ) (P = 0.071) and mammalian/mechanistic target of rapamycin (mTOR) (P = 0.080), decrease the gene expression of B-cell lymphoma 2-associated X protein 1 (BAX1) (P < 0.05), tended to decrease the gene expression of serum and glucocorticoid-induced protein kinase 1 (SGK1) (P = 0.066), increased (P < 0.05) cell proliferation in the crypts, and tended to increase the villus height (P = 0.078) and crypt depth (P = 0.052) in the jejunum. In conclusion, the supplementation of Saccharomyces yeast postbiotics in nursery diets reduced diarrhea within the first week after weaning and provided protection to the villi in the jejunum by enhancing the immune responses of nursery pigs, promoting crypt cell proliferation, and reducing the expression of genes associated with apoptosis without affecting inflammatory and oxidative stress status in the jejunum of the nursery pigs., (© 2024. The Author(s).)

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationships between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG ( LGG ) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3s) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3s and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor influences various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, to promote their growth and development, suggesting that AhR has a broad impact on intestinal health. In conclusion, our study demonstrated the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock.IMPORTANCEWe observed high expression of the AhR receptor on pig and human ILC3s, although its expression was negligible in mouse ILC3s. ILC3s are closely related to the gut microbiota, particularly the secretion of IL-22 stimulated by microbial signals, which plays a crucial regulatory role in intestinal immunity. In our study, we found that metabolites produced by beneficial gut bacteria interact with ILC3s through AhR, thereby maintaining intestinal immune homeostasis in pigs. Moreover, LGG feeding can enhance the activation of ILC3s and promote IL-22 secretion in the intestines of piglets, ultimately preventing PEDV infection., Competing Interests: The authors declare no conflict of interest.

We previously demonstrated that postruminal casein infusion and exogenous glucagon-like peptide 2 (GLP-2) administration independently stimulated growth and carbohydrase activity of the pancreas and jejunal mucosa in cattle. The objective of the current study was to profile the jejunal mucosal transcriptome of cattle using next-generation RNA sequencing in response to postruminal casein infusion and exogenous GLP-2. Twenty-four Holstein steers [250 ± 23.1 kg body weight (BW)] received a continuous abomasal infusion of 3.94 g raw corn starch/kg of BW combined with either 0 or 1.30 g casein/kg of BW for 7 d. Steers received subcutaneous injections at 0800 and 2000 h to provide either 0 or 100 μg GLP-2/kg of BW per day. At the end of the 7-d treatment period, steers were slaughtered for collection of the jejunal mucosa. Total RNA was extracted from jejunal mucosal tissue, strand-specific cDNA libraries were prepared, and RNA sequencing was conducted to generate 150-bp paired-end reads at a depth of 40 M reads per sample. Differentially expressed genes (DEG), KEGG pathway enrichment, and gene ontology enrichment were determined based on the FDR-corrected P-value (padj). Exogenous GLP-2 administration upregulated (padj < 0.05) 667 genes and downregulated 1,101 genes of the jejunal mucosa. Sphingolipid metabolism, bile secretion, adherens junction, and galactose metabolism were among the top KEGG pathways enriched with upregulated DEG (padj < 0.05) in response to exogenous GLP-2 administration. The top gene ontologies enriched with upregulated DEG (padj < 0.05) in response to exogenous GLP-2 administration included nutrient metabolic processes, brush border and bicellular tight junction assembly, and enzyme and transporter activities. Exogenous GLP-2 administration increased or tended to increase (padj < 0.10) brush border carbohydrase (MGAM, LCT, TREH), hexose transporter (SLC5A1, SLC2A2), and associated transcription factor (HNF1, GATA4, KAT2B) mRNA expression of the jejunal mucosa. Gene ontologies and KEGG pathways that were downregulated (padj < 0.05) in response to exogenous GLP-2 were related to genetic information processing. Postruminal casein infusion downregulated (padj < 0.05) 7 jejunal mucosal genes that collectively did not result in enriched KEGG pathways or gene ontologies. This study highlights some of the transcriptional mechanisms associated with increased growth, starch assimilation capacity, and barrier function of the jejunal mucosa in response to exogenous GLP-2 administration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Labrafac™ MC60 (glycerol monocaprylocaprate) is a lipid-based excipient used in oral formulations as a solubiliser. Due to the high proportions of established permeability enhancers, caprylate (C 8 ) and caprate (C 10 ), in Labrafac™ MC60, we hypothesised that it might behave as an intestinal permeation enhancer. We therefore evaluated this using two paracellular markers (ex vivo) and insulin (in vivo) as model molecules. Ex vivo studies were conducted in isolated muscle-stripped rat colonic mucosae mounted in Ussing chambers. Apical addition of Labrafac™ MC60 (8, 12, and 16 mg/ml) enhanced the apparent permeability coefficients (P app ) of [ 14 C] mannitol and FITC-dextran 4 kDa (FD4) across colonic mucosae. Similar effects were observed in isolated jejunal mucosae, but at higher concentrations (40 mg/ml). The enhancing capacity of Labrafac™ MC60 was transient due to reversibility of reductions in transepithelial electrical resistance (TEER) upon wash-out and effects on fluxes were molecular weight-dependent (MW) as suggested by fluxes of a set of high MW FITC-dextrans. The permeability enhancing effects of Labrafac™ MC60 ex vivo were maintained in the presence of simulated intestinal fluids, FaSSIF and FaSSCoF, in both jejunal and colonic mucosae, respectively. Following intra-intestinal regional instillations to rats, the relative bioavailability of 50 IU/kg insulin ad-mixed with Labrafac™ MC60 was 5 % in jejunum (40 mg/ml) and 6 % in colon (8 mg/ml). When Labrafac™ MC60 was combined with PEG-60 hydrogenated castor oil (1 % v/v), this further increased the bioavailability of insulin to 8 % in jejunum. Absorption enhancement was also maintained in the presence of FaSSIF in jejunal instillations. Histology after 120 min exposure to Labrafac™ MC60 in vivo for both jejunum and colon was similar to untreated control. Labrafac™ MC60 therefore acts as a non-damaging intestinal permeation enhancer for macromolecules and can be considered as another excipient in screening programmes to develop orally administered macromolecules., Competing Interests: Declaration of competing interest FM was funded by a Postdoctoral Fellowship from Gattefossé (St. Priest, France). CD was employed by Gattefossé SAS during the time of this study. DB acts as a consultant to Pharma companies working on oral formulations of peptides., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Early weaning is prone to damage intestinal barrier function, resulting in diarrhea, whereas rutin, as a natural flavonoid with multiple biological functions, shows potential in piglets. Therefore, the effects of dietary rutin on growth, antidiarrheal, barrier function, antioxidant status and cecal microbiota of weaned piglets were investigated with the control group (CON) (basal diet) and Rutin (basal diet+500 mg kg -1 rutin) groups fed for 14 days., Results: The results showed that dietary 500 mg kg -1 rutin significantly decreased diarrhea index, serum diamine oxidase activity and total aerobic bacterial population in mesenteric lymph nodes, whereas it significantly increased the gain-to-feed ratio (G:F) and serum growth hormone content, jejunal villus height and villus height to crypt depth ratio, and also enhanced jejunal claudin-1 and zonula occludens-1 mRNA and protein expression. Meanwhile, dietary rutin significantly decreased inflammation-associated mRNA expression, malondialdehyde (MDA) content, swollen mitochondrial number and mitochondrial area in the jejunum, whereas it increased the total superoxide dismutase (T-SOD) and glutathione peroxidase activities and activated the Nrf2 signaling pathway. Moreover, dietary rutin significantly increased Firmicutes abundance and decreased Campylobacterota abundance, which were closely associated with the decreased diarrhea index and MDA content or increased Claudin-1 expression and T-SOD activity., Conclusion: Dietary 500 mg kg -1 rutin increased G:F by improving intestinal morphology, and alleviated diarrhea by enhancing intestinal barrier, which might be associated with the enhanced antioxidant capacity via activating the Nrf2/Keap1 signaling pathway and the improved cecal microbial composition in weaned piglets. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

This study reports the synthesis of 2-thioxo-1,3-dithiol-carboxamides ( TDTCAs ) under mild conditions at room temperature using HBTU as a coupling agent, which significantly improved amide bond formation. The synthesized compounds were characterized using several analytical techniques, including 1 H and 13 C NMR spectroscopy, and HRMS, confirming their intended structures and structural integrity. A DFT computational study at the B3LYP/6-31G(d,p) level was conducted on the four synthesized compounds to compare their electronic properties and molecular structures. The results showed that these compounds demonstrated antispasmodic effects on jejunum contractions. Molecular docking revealed that compounds c and d displayed the highest docking scores on potassium and voltage-gated calcium channels and adrenergic receptors. In summary, compounds c and d exhibit antispasmodic effects, potentially blocking alpha-adrenergic receptors and calcium channels, thus providing a scientific basis for their potential use in treating gastrointestinal disorders.

We aimed to characterize the anti-obesity and anti-atherosclerosis effects of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 using high-fat diet (HFD)-fed obese C57BL/6 mice. We divided the mice into control (CON), HFD, HFD with 10 8 CFU/kg/day probiotics (HFD + KL, HY7301:KY1032 = 1:1), and HFD with 10 9 CFU/kg/day probiotics (HFD + KH, HY7301:KY1032 = 1:1) groups and fed/treated them during 7 weeks. The body mass, brown adipose tissue (BAT), inguinal white adipose tissue (iWAT), and epididymal white adipose tissue (eWAT) masses and the total cholesterol and triglyceride concentrations were remarkably lower in probiotic-treated groups than in the HFD group in a dose-dependent manner. In addition, the expression of uncoupling protein 1 in the BAT, iWAT, and eWAT was significantly higher in probiotic-treated HFD mice than in the HFD mice, as demonstrated by immunofluorescence staining and Western blotting. We also measured the expression of cholesterol transport genes in the liver and jejunum and found that the expression of those encoding liver-X-receptor α, ATP-binding cassette transporters G5 and G8, and cholesterol 7α-hydroxylase were significantly higher in the HFD + KH mice than in the HFD mice. Thus, a Lactobacillus HY7601 and KY1032 mixture with 10 9 CFU/kg/day concentration can assist with body weight regulation through the management of lipid metabolism and thermogenesis.

Studies have reported the occurrence of gastrointestinal (GI) symptoms, primarily diarrhea, in COVID-19. However, the pathobiology regarding COVID-19 in the GI tract remains limited. This work aimed to evaluate SARS-CoV-2 Spike protein interaction with gut lumen in different experimental approaches. Here, we present a novel experimental model with the inoculation of viral protein in the murine jejunal lumen, in vitro approach with human enterocytes, and molecular docking analysis. Spike protein led to increased intestinal fluid accompanied by Cl - secretion, followed by intestinal edema, leukocyte infiltration, reduced glutathione levels, and increased cytokine levels [interleukin (IL)-6, tumor necrosis factor-α, IL-1β, IL-10], indicating inflammation. Additionally, the viral epitope caused disruption in the mucosal histoarchitecture with impairment in Paneth and goblet cells, including decreased lysozyme and mucin, respectively. Upregulation of toll-like receptor 2 and toll-like receptor 4 gene expression suggested potential activation of local innate immunity. Moreover, this experimental model exhibited reduced contractile responses in jejunal smooth muscle. In barrier function, there was a decrease in transepithelial electrical resistance and alterations in the expression of tight junction proteins in the murine jejunal epithelium. Additionally, paracellular intestinal permeability increased in human enterocytes. Finally, in silico data revealed that the Spike protein interacts with cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride conductance (CaCC), inferring its role in the secretory effect. Taken together, all the events observed point to gut impairment, affecting the mucosal barrier to the innermost layers, establishing a successful experimental model for studying COVID-19 in the GI context., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Variances in the biological functions of astaxanthin geometric isomers (i.e., all- E , Z ) are related to their intestinal absorption, but the mechanism of isomer absorption mediated by transporters remains unclear. Here, models of in vitro cell overexpression, in situ intestinal perfusion, and in vivo mouse inhibition were employed to investigate the impact of cluster of differentiation 36 (CD36) on the absorption of astaxanthin isomers. Cells overexpressing CD36 notably enhanced the uptake of Z -astaxanthin, particularly the 9- Z -isomer (47.76%). The absorption rate and permeability of Z -astaxanthin surpassed that of the all- E -isomer by the in situ model. Furthermore, the addition of the CD36-specific inhibitor sulfo- N -succinimidyl oleate significantly reduced the absorption of Z -astaxanthin in the mouse duodenum and jejunum, especially the 9- Z -isomer (57.66%). Molecular docking and surface plasmon resonance techniques further validated that 9- Z -astaxanthin binds to more amino acids of CD36 with higher affinity and in a fast-binding, fast-dissociating mode, thus favoring transport. Our findings elucidate, for the first time, the mechanism of the CD36-mediated transmembrane transport of astaxanthin geometric isomers.

Human noroviruses (HuNoVs) are a diverse group of RNA viruses that cause endemic and pandemic acute viral gastroenteritis. Previously, we reported that many HuNoV strains require bile or bile acid (BA) to infect human jejunal intestinal enteroid cultures. BA was not essential for the replication of a pandemic-causing GII.4 HuNoV strain. We found the hydrophobic BA glycochenodeoxycholic acid (GCDCA) promotes the replication of the BA-dependent strain GII.3 in jejunal enteroids. Furthermore, we found that inhibition of the G-protein-coupled BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), by JTE-013, reduced GII.3 infection dose-dependently and inhibited GII.3 cellular uptake in enteroids. Herein, we sought to determine whether S1PR2 is required for other BA-dependent HuNoV strains, the BA-independent GII.4, and whether S1PR2 is required for BA-dependent HuNoV infection in HIEs from other small intestinal segments. We found a second S1PR2 inhibitor, GLPG2938, reduces GII.3 infection dose-dependently, and an S1PR2 agonist (CYM-5520) enhances GII.3 replication in the absence of GCDCA. GII.3 replication also is abrogated in the presence of JTE-013 and CYM-5520. JTE-013 inhibition of S1PR2 in jejunal HIEs reduces GI.1, GII.3, and GII.17 (BA-dependent) but not GII.4 Sydney (BA-independent) infection, providing additional evidence of strain-specific differences in HuNoV infection. Finally, GII.3 infection of duodenal, jejunal, and ileal lines derived from the same individual is reduced with S1PR2 inhibition, indicating a common mechanism of BA-dependent infection among multiple segments of the small intestine. Our results support a model where BA-dependent HuNoVs exploit BA effects on S1PR2 to infect the entire small intestine.IMPORTANCEHuman noroviruses (HuNoVs) are important viral human pathogens that cause both outbreaks and sporadic gastroenteritis. These viruses are diverse, and many strains are capable of infecting humans. Our previous studies have identified strain-specific requirements for hydrophobic bile acids (BAs) to infect intestinal epithelial cells. Moreover, we identified a BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), required for infection by a BA-dependent strain. To better understand how various HuNoV strains enter and infect the small intestine and the role of S1PR2 in HuNoV infection, we evaluated infection by additional HuNoV strains using an expanded repertoire of intestinal enteroid cell lines. We found that multiple BA-dependent strains, but not a BA-independent strain, all require S1PR2 for infection. In addition, BA-dependent infection requires S1PR2 in multiple segments of the small intestine. Together, these results indicate that S1PR2 has value as a potential therapeutic target for BA-dependent HuNoV infection., Competing Interests: The authors declare no conflict of interest.

The microbiological environment and their corresponding secreted metabolite spectrum are an essential modulator of the enterocyte function, effecting the whole organism. Intestinal porcine jejunal epithelial cell line (IPEC-J2) is an established in vitro model for differentiation of enterocytes in different cell culture models. An improved oxygen supply seems to be the main reason for differentiation in an air-liquid-interface culture, but this has not yet been conclusively clarified. In this context, the nutrition of the cell and its influence on the metabolism is also of crucial importance. The interest in short-chain fatty acids (SCFAs) has grown steadily in recent years due to their clinical relevance in certain diseases such as multiple sclerosis and other inflammatory diseases, but not much is known of FFAR2 and FFAR3 (free fatty acid receptor 2 and 3) in pigs. We want to address the questions: 1. about the distribution of FFAR2 and FFAR3 in vivo and in vitro in sus scrofa 2. whether there is an influence of propionic acid, glucose content and cultivation on metabolism of enterocytes? The morphological analysis of FFAR2 and FFAR3 in vivo was investigated through immunostaining of frozen sections of the porcine gut segments jejunum, ileum and colon. Both receptors are expressed along the gut and were found in the smooth muscle cells of the tunica muscularis and lamina muscularis mucosae. Furthermore, a high expression of FFAR2 and a low expression of FFAR3 in the enteric nerve system was also observed in jejunum, ileum and colon of sus scrofa. In addition, FFAR2 and FFAR3 within the vessels was investigated. FFAR3 showed a strong expression on endothelial cells of veins and lymphatic vessels but was not detectable on arteries. Furthermore, we demonstrate for the first time, FFAR2 and FFAR3 in IPEC-J2 cells on RNA- and protein level, as well as with confocal microscopy. In addition, ENO1 and NDUFA4 were investigated on RNA-level in IPEC-J2 cells as 2 important genes, which play an essential role in metabolism. Here, NDUFA4 is detected in the model animal sus scrofa as well as in the porcine cell line IPEC-J2. A potential impact of propionic acid and/or glucose and/or cultivation method on the metabolism of the cells was tested with the Seahorse analyzer. Here, a significant higher ECAR was observed in the SMC than in the OCR. In summary, we were able to show that the cultivation system appears to have a greater influence than the medium composition or nutrition of the cells. However, this can be modulated by incubation time or combination of different SCFAs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shokr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plastics are present in almost every aspect of our lives. Polyethylene terephthalate (PET) is commonly used in the food industry. Microparticles can contaminate food and drinks, posing a threat to consumers. The presented study aims to determine the effect of microparticles of PET on the population of neurons positive for selected neurotransmitters in the enteric nervous system of the jejunum and histological structure. An amount of 15 pigs were divided into three groups (control, receiving 0.1 g, and 1 g/day/animal orally). After 28 days, fragments of the jejunum were collected for immunofluorescence and histological examination. The obtained results show that histological changes (injury of the apical parts of the villi, accumulations of cellular debris and mucus, eosinophil infiltration, and hyperaemia) were more pronounced in pigs receiving a higher dose of microparticles. The effect on neuronal nitric oxide synthase-, and substance P-positive neurons, depends on the examined plexus and the dose of microparticles. An increase in the percentage of galanin-positive neurons and a decrease in cocaine and amphetamine-regulated transcript-, vesicular acetylcholine transporter-, and vasoactive intestinal peptide-positive neurons do not show such relationships. The present study shows that microparticles can potentially have neurotoxic and pro-inflammatory effects, but there is a need for further research to determine the mechanism of this process and possible further effects.

The intestinal microbiota plays a pivotal role in digestive processes and maintains gut health and intestinal homeostasis. These functions may be compromised by increased environmental heat, which in turn reduces feed intake and gut integrity and activates the intestinal immune system. It remains unknown whether high ambient temperatures, which cause heat stress (HS) in dairy cows, disturb the eubiosis of the microbial community, and if so, to which extent the reduction in feed intake and the impairment of circulating and intestinal metabolites account for the alterations of the jejunal microbiota. To address these questions, jejunal digesta, mucosa, and plasma samples were collected from cows exposed to heat stress (HS; 28°C, temperature-humidity index [THI] = 76, n = 10), control conditions (CON; 16°C, THI = 60, n = 10), or pair-fed (PF; 16°C, THI = 60, n = 10) for 7 d. Digesta fluids were examined for pH, acetate, nonesterified fatty acids (NEFA), glucose, and lactate, and plasma samples were analyzed for glucose, lactate, BHB, triglycerides, NEFA, creatinine, and urea. The microbiota of the digesta and mucosa samples were analyzed by 16S rRNA sequencing. The α-diversity was higher in mucosa than digesta but was not affected by high ambient temperatures. However, the mucosa-associated microbiota appeared more responsive to ambient heat than the digesta microbiome. The adaptive responses under HS conditions comprised an increased mucosal abundance of Bifidobacteriaceae, Succinivibrionaceae UCG-001, Clostridia and Lactobacillus. In the digesta, HS has exerted effects on microbial abundance of Colidextribacter, and Lachnospiraceae UCG-008. Several correlations between plasma or intestinal metabolites and microbiota were elucidated, including Methanobacteriaceae correlating positively with plasma BHB and digesta glucose concentrations. Moreover, the reduction in feed intake during HS had non-negligible effects on microbial diversity and the abundance of certain taxa, underpinning the importance of nutrient supply on maintaining intestinal homeostasis., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Human breast milk promotes maturation of the infant gastrointestinal barrier, including the promotion of mucus production. In the quest to produce next generation infant milk formula (IMF), we have produced IMF by membrane filtration (MEM-IMF). With a higher quantity of native whey protein, MEM-IMF more closely mimics human breast milk than IMF produced using conventional heat treatment (HT-IMF). After a 4-week dietary intervention in young pigs, animals fed a MEM-IMF diet had a higher number of goblet cells, acidic mucus and mucin-2 in the jejunum compared to pigs fed HT-IMF (P < 0.05). In the duodenum, MEM-IMF fed pigs had increased trypsin activity in the gut lumen, increased mRNA transcript levels of claudin 1 in the mucosal scrapings and increased lactase activity in brush border membrane vesicles than those pigs fed HT-IMF (P < 0.05). In conclusion, MEM-IMF is superior to HT-IMF in the promotion of mucus production in the young gut., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although there are several types of radiation exposure, it is debated whether low‑dose‑rate (LDR) irradiation (IR) affects the body. Since the small intestine is a radiation‑sensitive organ, the present study aimed to evaluate how it changes when exposed to LDR IR and identify the genes sensitive to these doses. After undergoing LDR (6.0 mGy/h) γ radiation exposure, intestinal RNA from BALB/c mice was extracted 1 and 24 h later. Mouse whole genome microarrays were used to explore radiation‑induced transcriptional alterations. Reverse transcription‑quantitative (RT‑q) PCR was used to examine time‑ and dose‑dependent radiation responses. The histopathological status of the jejunum in the radiated mouse was not changed by 10 mGy of LDR IR; however, 23 genes were upregulated in response to LDR IR of the jejunum in mice after 1 and 24 h of exposure. Upregulated genes were selected to validate the results of the RNA sequencing analysis for RT‑qPCR detection and results showed that only Na + /K + transporting subunit α4, glucose‑6‑phosphatase catalytic subunit 2 (G6PC2), mucin 6 (MUC6) and transient receptor potential cation channel subfamily V member 6 levels significantly increased after 24 h of LDR IR. Furthermore, G6PC2 and MUC6 were notable genes induced by LDR IR exposure according to protein expression via western blot analysis. The mRNA levels of G6PC2 and MUC6 were significantly elevated within 24 h under three conditions: i) Exposure to LDR IR, ii) repeated exposure to LDR IR and iii) exposure to LDR IR in the presence of inflammatory bowel disease. These results could contribute to an improved understanding of immediate radiation reactions and biomarker development to identify radiation‑susceptible individuals before histopathological changes become noticeable. However, further investigation into the specific mechanisms involving G6PC2 and MUC6 is required to accomplish this.

Background: Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats., Methods: High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro., Results: DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors., Conclusions: DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway-and not solely by improving blood glucose-to improve oxidative stress in the heart of diabetic cardiomyopathy rats., (© 2023 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

MicroRNAs (miRNAs) were identified to be involved in various biological functions by regulating the degradation or suppressing the translation of their downstream target genes. Recent studies have identified miR-29a play a key role in functions of mammal cell differentiation, proliferation, apoptosis, and signal transduction. However, the underlying functions for miR-29a in jejunal epithelial cells biological function still to be investigated. In order to explore the yak jejunal epithelial cells proliferation and barrier dysfunction with over expression of miR-29a gene, three 0-day-old Pamir male yaks were randomly selected and slaughtered in present study, and the jejunal epithelial cells were isolated and cultured to determine yak jejunal epithelial cells proliferation and protein composition on differential expression of miR-29a gene in Pamir plateau. Here, we demonstrated that the overexpression of miR-29a gene could inhibit the proliferation of Pamir yaks jejunum epithelial cells, and contribute to the apoptosis of Pamir yaks jejunal epithelial cells with some extent. A total of 133 differentially expressed proteins were identified in different expression of miR-29a groups by label-free Mass Spectrometry (MS), which could be concluded to two predominant themes: cell proliferation and inflammatory response. Interestingly, GPR41, as a bridge protein, was contacted two predominant themes to involved in Pamir Yaks jejunal mechanical barrier PPI network, and the target proteins displayed strong mutual interactions in the complex PPI network. Overall, our study suggested that the over-expression miR-29a inhibited the jejunal epithelial cells proliferation and the expressions of specific proteins, which damaged jejunal barrier function to slow down the intestine structure and function advanced mature development during young livestock period for influence the enhanced performance of production efficiency.

Despite the significant threat of heat stress to livestock animals, only a few studies have considered the potential relationship between broiler chickens and their microbiota. Therefore, this study examined microbial modifications, transcriptional changes and host-microbiome interactions using a predicted metabolome data-based approach to understand the impact of heat stress on poultry. After the analysis, the host functional enrichment analysis revealed that pathways related to lipid and protein metabolism were elevated under heat stress conditions. In contrast, pathways related to the cell cycle were suppressed under normal environmental temperatures. In line with the transcriptome analysis, the microbial analysis results indicate that taxonomic changes affect lipid degradation. Heat stress engendered statistically significant difference in the abundance of 11 microorganisms, including Bacteroides and Peptostreptococcacea . Together, integrative approach analysis suggests that microbiota-induced metabolites affect host fatty acid peroxidation metabolism, which is correlated with the gene families of Acyl-CoA dehydrogenase long chain ( ACADL ), Acyl-CoA Oxidase ( ACOX ) and Acetyl-CoA Acyltransferase ( ACAA ). This integrated approach provides novel insights into heat stress problems and identifies potential biomarkers associated with heat stress.

Background: Increasing epidemiologic studies have shown a positive correlation between obesity and chronic diarrhea. Nevertheless, the precise etiology remains uncertain., Methods: We performed a comprehensive proteomics analysis utilizing the data-independent acquisition (DIA) technique on jejunal tissues from patients with obesity and chronic diarrhea (OD, n = 33), obese patients (OB, n = 10), and healthy controls (n = 8). Differentially expressed proteins (DEPs) in OD vs. control and OD vs. OB comparisons were subjected to pathway enrichment and protein-protein interaction (PPI) network analysis. Machine learning algorithms were adopted on overlapping DEPs in both comparisons. The candidate protein was further validated using Western blot, immunohistochemistry (IHC), and in vitro experiments., Results: We identified 189 and 228 DEPs in OD vs. control and OD vs. OB comparisons, respectively. DEPs in both comparisons were co-enriched in extracellular matrix (ECM) organization. Downregulated DEPs were associated with tight junction and ECM-receptor interaction in OD vs. control and OD vs. OB comparisons, respectively. Machine learning algorithms selected 3 proteins from 14 overlapping DEPs in both comparisons, among which collagen alpha-1(III) chain (COL3A1) was identified as a core protein in PPI networks. Western blot and IHC verified the expression of COL3A1. Moreover, the tight junction-related proteins decreased after the knockdown of COL3A1 in Caco2 intestinal cells upon PA challenge, consistent with the proteomics results., Conclusions: We generated in-depth profiling of a proteomic dataset from samples of OD patients and provided unique insights into disease pathogenesis. COL3A1 was involved in the crosstalk between obesity and intestinal homeostasis via the ECM-receptor interaction pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Rosmarinus officinalis L. (Rosemary) is a popular herb with reported effectiveness against diarrhea, anxiety and constipation, albeit with limited pharmacological evidence., Aim of the Study: The current study was aimed at evaluating the therapeutic potential, possible pharmacological mechanisms of action and active constituents of hydro-ethanolic extract of rosemary (Rs.Cr), as potential anti-diarrheal, laxative and anxiolytic agent., Method: Rs.Cr was analyzed through reverse-phase high pressure liquid chromatography (RP-HPLC). Laxative, antidiarrheal, and anxiolytic activities were assessed using in vivo models. Spasmogenic and spasmolytic mechanisms were studied on isolated guinea pig ileum and rabbit jejunum tissues, respectively. Possible role of diosmetin, one of the active constituents of Rs.Cr was also evaluated., Results: RP-HPLC analysis revealed presence of diosmetin, rutin and apigenin in Rs.Cr. Laxative effect was seen at low doses, which was partially reversed in atropinized mice. The spasmogenic mechanism was mediated by cholinergic and histaminergic receptors stimulation. At higher doses, antidiarrheal activity was evident, with reduction in gastrointestinal motility and secretions using charcoal meal and enteropooling assays, respectively. Rs.Cr also showed dose-dependent anxiolytic effect. The antispasmodic mechanisms were mediated by anti-muscarinic and K + channel opening-like effect (predominant K ATP -dependent). Diosmetin exhibited antidiarrheal and antispasmodic activities, but spasmogenic effect was not seen., Conclusion: Rosemary leaves have dual antidiarrheal and laxative effects, and as well as anxiolytic activity. In addition, the possible modulation of muscarinic and histaminergic receptors, and K ATP channels show it as potential herb to be explored for irritable bowel syndrome. Diosmetin is possibly one of its constituents that contributes to its antidiarrheal activity., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bisphenols are dangerous endocrine disruptors that pollute the environment. Due to their chemical properties, they are globally used to produce plastics. Structural similarities to oestrogen allow bisphenols to bind to oestrogen receptors and affect internal body systems. Most commonly used in the plastic industry is bisphenol A (BPA), which also has negative effects on the nervous, immune, endocrine, and cardiovascular systems. A popular analogue of BPA-bisphenol S (BPS) also seems to have harmful effects similar to BPA on living organisms. Therefore, with the use of double immunofluorescence labelling, this study aimed to compare the effect of BPA and BPS on the enteric nervous system (ENS) in mouse jejunum. The study showed that both studied toxins impact the number of nerve cells immunoreactive to substance P (SP), galanin (GAL), vasoactive intestinal polypeptide (VIP), the neuronal isoform of nitric oxide synthase (nNOS), and vesicular acetylcholine transporter (VAChT). The observed changes were similar in the case of both tested bisphenols. However, the influence of BPA showed stronger changes in neurochemical coding. The results also showed that long-term exposure to BPS significantly affects the ENS.

A total of ninety-six weaned piglets were assigned to four dietary treatments in a 2 × 2 design. The treatments included: a standard milk formula (CTR); CTR + probiotics (6.4 × 10 8 cfu L -1 Bifidobacterium longum subsp. infantis CECT 7210 and 1.1 × 10 8 cfu L -1 Lactobacillus rhamnosus NH001) + prebiotics (galacto-oligosaccharides 4.36 g L -1 and human-milk-oligosaccharide 0.54 g L -1 ) (SYN); CTR + osteopontin (0.43 g L -1 ) (OPN); and CTR + SYN + OPN (CON). Daily records including feed intake, body weight, and clinical signs, were maintained throughout the 15-day trial. At the end of the study samples from blood, digestive content, and gut tissues were collected to determine serum TNF-α, intestinal fermentative activity (SCFA and ammonia), colonic microbiota (16S rRNA Illumina-MiSeq), histomorphology, and jejunal gene expression (Open-Array). No statistical differences were found in weight gain; however, the animals supplemented with osteopontin exhibited higher feed intake. In terms of clinical signs, synbiotic supplementation led to a shorter duration of diarrhoea episodes. Regarding gut health, the sequenced faecal microbiota revealed better control of potentially dysbiotic bacteria with the CON diet at day 15. In the colon compartment, a significant increase in SCFA concentration, a decrease in ammonia concentration, and a significant decrease in intraepithelial lymphocyte counts were particularly observed in CON animals. The supplemented diets were also associated with modified jejunal gene expression. The synbiotic combination was characterized by the upregulation of genes related to intestinal maturation (ALPI, SI) and nutrient transport (SLC13A1, SLC15A1, SLC5A1, SLC7A8), and the downregulation of genes related to the response to pathogens (GBP1, IDO, TLR4) or the inflammatory response (IDO, IL-1β, TGF-β1). Osteopontin promoted the upregulation of a digestive function gene (GCG). Correlational analysis between the microbiota population and various intestinal environmental factors (SCFA concentration, histology, and gene expression) proposes mechanisms of communication between the gut microbiota and the host. In summary, these results suggest an improvement in the colonic colonization process and a better modulation of the immune response when milk formula is supplemented with the tested synbiotic combined with osteopontin, benefiting from a synergistic effect.

Consumption of a high-fat diet (HFD) has been suggested as a contributing factor behind increased intestinal permeability in obesity, leading to increased plasma levels of microbial endotoxins and, thereby, increased systemic inflammation. We and others have shown that HFD can induce jejunal expression of the ketogenic rate-limiting enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS). HMGCS is activated via the free fatty acid binding nuclear receptor PPAR-α, and it is a key enzyme in ketone body synthesis that was earlier believed to be expressed exclusively in the liver. The function of intestinal ketogenesis is unknown but has been described in suckling rats and mice pups, possibly in order to allow large molecules, such as immunoglobulins, to pass over the intestinal barrier. Therefore, we hypothesized that ketone bodies could regulate intestinal barrier function, e.g., via regulation of tight junction proteins. The primary aim was to compare the effects of HFD that can induce intestinal ketogenesis to an equicaloric carbohydrate diet on inflammatory responses, nutrition sensing, and intestinal permeability in human jejunal mucosa. Fifteen healthy volunteers receiving a 2-week HFD diet compared to a high-carbohydrate diet were compared. Blood samples and mixed meal tests were performed at the end of each dietary period to examine inflammation markers and postprandial endotoxemia. Jejunal biopsies were assessed for protein expression using Western blotting, immunohistochemistry, and morphometric characteristics of tight junctions by electron microscopy. Functional analyses of permeability and ketogenesis were performed in Caco-2 cells, mice, and human enteroids. Ussing chambers were used to analyze permeability. CRP and ALP values were within normal ranges and postprandial endotoxemia levels were low and did not differ between the two diets. The PPARα receptor was ketone body-dependently reduced after HFD. None of the tight junction proteins studied, nor the basal electrical parameters, were different between the two diets. However, the ketone body inhibitor hymeglusin increased resistance in mucosal biopsies. In addition, the tight junction protein claudin-3 was increased by ketone inhibition in human enteroids. The ketone body β-Hydroxybutyrate (βHB) did not, however, change the mucosal transition of the large-size molecular FD4-probe or LPS in Caco-2 and mouse experiments. We found that PPARα expression was inhibited by the ketone body βHB. As PPARα regulates HMGCS expression, the ketone bodies thus exert negative feedback signaling on their own production. Furthermore, ketone bodies were involved in the regulation of permeability on intestinal mucosal cells in vitro and ex vivo. We were not, however, able to reproduce these effects on intestinal permeability in vivo in humans when comparing two weeks of high-fat with high-carbohydrate diet in healthy volunteers. Further, neither the expression of inflammation markers nor the aggregate tight junction proteins were changed. Thus, it seems that not only HFD but also other factors are needed to permit increased intestinal permeability in vivo. This indicates that the healthy gut can adapt to extremes of macro-nutrients and increased levels of intestinally produced ketone bodies, at least during a shorter dietary challenge.

Background: Obesity is associated with a significantly increased risk for chronic diarrhea, which has been proposed as Linghu's obesity-diarrhea syndrome (ODS); however, its molecular mechanisms are largely unknown., Aim: To reveal the transcriptomic changes in the jejunum involved in ODS., Methods: In a cohort of 6 ODS patients (JOD group), 6 obese people without diarrhea (JO group), and 6 healthy controls (JC group), high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes. In another cohort of 16 ODS patients (SOD group), 16 obese people without diarrhea (SO group), and 16 healthy controls (SC group), serum diamine oxidase (DAO) and D-lactate (D-LA) concentrations were detected to assess changes in intestinal barrier function., Results: The gene expression profiles of jejunal mucosa in the JO and JC groups were similar, with only 1 differentially expressed gene (DEG). The gene expression profile of the JOD group was significantly changed, with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group, 129 of which overlapped. The enrichment analysis of these DEGs showed that the biological processes such as digestion, absorption, and transport of nutrients (especially lipids) tended to be up-regulated in the JOD group, while the biological processes such as rRNA processing, mitochondrial translation, antimicrobial humoral response, DNA replication, and DNA repair tended to be down-regulated in the JOD group. Eight DEGs ( CDT1 , NHP2 , EXOSC5 , EPN3 , NME1 , REG3A , PLA2G2A , and PRSS2 ) may play a key regulatory role in the pathological process of ODS, and their expression levels were significantly decreased in ODS patients ( P < 0.001). In the second cohort, compared with healthy controls, the levels of serum intestinal barrier function markers (DAO and D-LA) were significantly increased in all obese individuals ( P < 0.01), but were higher in the SOD group than in the SO group ( P < 0.001)., Conclusion: Compared with healthy controls and obese individuals without diarrhea, patients with Linghu's ODS had extensive transcriptomic changes in the jejunal mucosa, likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes., Competing Interests: Conflict-of-interest statement: Dr. Linghu has nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Coccidiosis, a protozoan disease that substantially impacts poultry production, is characterized by an intracellular parasite. The study utilized 48 one-day-old Horro chickens, randomly divided into the infected (I) and control (C) groups. The challenge group of chickens were administered Eimeria maxima oocysts via oral gavage at 21-days-old, and each chicken received 2 mL containing 7×10 4 sporulated oocysts. The total RNAs of chicken jejunum and cecum tissues were isolated from three samples, each from I and C groups. Our study aimed to understand the host immune-parasite interactions and compare immune response mRNA profiles in chicken jejunum and cecum tissues at 4 and 7 days postinfection with Eimeria maxima. The results showed that 823 up- and 737 down-regulated differentially expressed mRNAs (DEmRNAs) in jejunum at 4 d infection and control (J4I vs. J4C), and 710 up- and 368 down-regulated DEmRNAs in jejunum at 7 days infection and control (J7I vs. J7C) were identified. In addition, DEmRNAs in cecum tissue, 1424 up- and 1930 down-regulated genes in cecum at 4 days infection and control (C4I vs. C4C), and 77 up- and 191 down-regulated genes in cecum at 7 days infection and control (C7I vs. C7C) were detected. The crucial DEmRNAs, including SLC7A5, IL1R2, GLDC, ITGB6, ADAMTS4, IL1RAP, TNFRSF11B, IMPG2, WNT9A, and FOXF1, played pivotal roles in the immune response during Eimeria maxima infection of chicken jejunum. In addition, the potential detection of FSTL3, RBP7, CCL20, DPP4, PRKG2, TFPI2, and CDKN1A in the cecum during the host immune response against Eimeria maxima infection is particularly noteworthy. Furthermore, our functional enrichment analysis revealed the primary involvement of DEmRNAs in small molecule metabolic process, immune response function, inflammatory response, and toll-like receptor 10 signaling pathway in the jejunum at 4 and 7 days postinfection. Similarly, in the cecum, DEmRNAs at 4 and 7 days postinfection were enriched in processes related to oxidative stress response and immune responses. Our findings provide new insights and contribute significantly to the field of poultry production and parasitology., (Copyright © 2024. Published by Elsevier Inc.)

The postprandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium-glucose cotransporter 1 (SGLT1). This study uses Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1,547 subjects with class II/III obesity from the Atlas Biologique de l'Obésité Sévère cohort, the study uses SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression. A loss-of-function SGLT1 haplotype serves as the instrumental variable, with intestinal SGLT1 expression as the exposure and the change in 30-min postload glycemia from fasting glycemia (Δ30 glucose) as the outcome. Results show that 12.8% of the 1,342 genotyped patients carried the SGLT1 loss-of-function haplotype, associated with a mean Δ30 glucose reduction of -0.41 mmol/L and a significant decrease in intestinal SGLT1 expression. The observational study links a 1-SD decrease in SGLT1 expression to a Δ30 glucose reduction of -0.097 mmol/L. MR analysis parallels these findings, associating a statistically significant reduction in genetically instrumented intestinal SGLT1 expression with a Δ30 glucose decrease of -0.353. In conclusion, the MR analysis provides genetic evidence that reducing intestinal SGLT1 expression causally lowers early postload glucose response. This finding has a potential translational impact on managing early glucose response to prevent or treat type 2 diabetes., (© 2024 by the American Diabetes Association.)

This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra , jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. The ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using Western blotting, immunohistochemistry, and qPCR. The results indicated a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure and an increase in NFκB from 7 to 90 days in the substantia nigra , while in the jejunum, a significant increase was observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 showed an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of alpha-synuclein and induces the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.

This study aimed to assess the antioxidant capacity of lemon flavonoid extract Eriomin ® (LE) and its impact on cholesterol metabolism in the context of healthy aging. We orally treated 24-month-old male Wistar rats with an LE (40 mg/kg) suspended in 0.3 mL of sunflower oil. At the same time, control groups received an equal volume of sunflower oil (CON) or remained untreated (ICON) daily for 4 weeks. We examined LE's effects on superoxide dismutase and catalase- and glutathione-related enzyme activities, the concentration of lipid peroxides and protein carbonyls, total oxidant status (TOS) and antioxidant status (TAS), and oxidative stress index (OSI) in the liver, jejunum, and ileum. We also measured total cholesterol, its biosynthetic precursors (lanosterol, lathosterol, desmosterol), its degradation products (bile acid precursors) in the serum, liver, jejunum, and ileum, and serum phytosterols (intestinal absorption markers). LE reduced TOS, TAS, and OSI ( p < 0.05) compared with control values, indicating its consistent antioxidant action in all examined organs. LE lowered hepatic desmosterol ( p < 0.05) while also reducing 7α- and 24-hydroxycholesterol levels in the liver and ileum ( p < 0.01). Serum cholesterol, hepatic gene expression, and the immunostaining intensity of CYP7A1 were unchanged. In conclusion, LE exerted non-enzymatic antioxidant effects and reduced cholesterol degradation, reducing its biosynthesis products, thereby maintaining serum cholesterol levels.

Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/β-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated β-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.

In the large poultry industry, where farmed chickens are fed at high density, the prevalence of pathogens and repeated vaccinations induce immune stress, which can significantly decrease the production performance and increase the mortality. This study was designed to shed light on the molecular mechanisms and metabolic pathways involved in immune stress through an in-depth analysis of transcriptomic and metabolomic changes in jejunum samples from the broilers. Two groups were established for the experiment: a control group and an LPS group. LPS group received an intraperitoneal injection of LPS solution at a dose of 250 μg per kg at 12, 14, 33, and 35 d of age, whereas the control group received a sterile saline injection. The severity of immune stress was assessed using the Disease Activity Index. A jejunal section was collected to measure the intestinal villus structure (villus length and crypt depth). RNA sequencing and metabolomics data analysis were conducted to reveal differentially expressed genes and metabolites. The results showed that the DAI index was increased and jejunal villus height/crypt depth was decreased in the LPS group. A total of 96 differentially expressed genes and 672 differentially accumulating metabolites were detected in the jejunum by LPS group compared to the control group. The comprehensive analysis of metabolomic and transcriptomic data showed that 23 pathways were enriched in the jejunum and that appetite, nutrient absorption, energy and substance metabolism disorders and ferroptosis play an important role in immune stress in broilers. Our findings provide a deeper understanding of the molecular and metabolic responses in broilers to LPS-induced immune stress, suggesting potential targets for therapeutic strategies to improve the production performance of broiler chickens., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Calprotectin (CP), a heterodimer of S100A8 and S100A9, is expressed by neutrophils and a number of innate immune cells and is used widely as a marker of inflammation, particularly intestinal inflammation. CP is a ligand for toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, CP can act as a microbial modulatory agent via a mechanism termed nutritional immunity, depending on metal binding, most notably Zn 2+ . The effects on the intestinal epithelium are largely unknown. In this study we aimed to characterize the effect of calprotectin on mouse jejunal organoids as a model epithelium, focusing on Zn 2+ metabolism and cell proliferation. CP addition upregulated the expression of the Zn 2+ absorptive transporter Slc39a4 and of methallothionein Mt1 in a Zn 2+ -sensitive manner, while downregulating the expression of the Zn 2+ exporter Slc30a2 and of methallothionein 2 (Mt2). These effects were greatly attenuated with a CP variant lacking the metal binding capacity. Globally, these observations indicate adaptation to low Zn 2+ levels. CP had antiproliferative effects and reduced the expression of proliferative and stemness genes in jejunal organoids, effects that were largely independent of Zn 2+ chelation. In addition, CP induced apoptosis modestly and modulated antimicrobial gene expression. CP had no effect on epithelial differentiation. Overall, CP exerts modulatory effects in murine jejunal organoids that are in part related to Zn 2+ sequestration and partially reproduced in vivo, supporting the validity of mouse jejunal organoids as a model for mouse epithelium., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Duodenal-jejunal bypass (DJB) is an experimental procedure in metabolic surgery that does not have a restrictive component. Changes in bile acid (BA) dynamics and intestinal microbiota are possibly related to metabolic improvement after DJB. Our previous studies involving obese diabetic rats showed the crucial role of the biliopancreatic limb (BPL) in metabolic improvement after DJB caused by BA reabsorption. We established a new DJB procedure to prevent bile from flowing into the BPL and aimed to elucidate the importance of bile in the BPL after DJB., Methods: Otsuka Long-Evans Tokushima Fatty rats with diabetes were divided into three groups: two DJB groups and a sham group (n = 11). Duodenal-jejunal anastomosis was performed proximal to the papilla of Vater in the DJB group (n = 11). However, the DJB-D group (n = 11) underwent a new procedure with duodenal-jejunal anastomosis distal to the papilla of Vater for preventing bile flow into the BPL., Results: Glucose metabolism improved and weight gain was suppressed in the DJB group, but not in the DJB-D and sham groups. Serum BA level and conjugated BA concentration were elevated in the DJB group. The gut microbiota was altered only in the DJB group; the abundance of Firmicutes and Bacteroidetes decreased and that of Actinobacteria increased. However, the DJB-D group exhibited no apparent change in the gut microbiota, similar to the sham group., Conclusion: BAs are essential in the BPL for metabolic improvement after DJB; they can improve the gut microbiota in these processes., (© 2024. The Author(s).)

This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1β and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Methionine (Met) supplementation is common practice in broilers to support nutrition, yet there are gaps in the understanding of its role in systemic physiology. Furthermore, several different Met sources are available that may have different physiological effects. This study evaluated the mode of action of Met deficiency (no Met-supplementation) and supplementation (0.25% DL- or L-Met, 0.41% liquid methionine hydroxy analog-free acid (MHA-FA)), and of Met source (DL-, L- or MHA-FA) in broiler chickens, via host transcriptomics. Biological pathway activation modeling was performed to predict the likely phenotypic effects of differentially expressed genes (DEGs) in tissue samples from the jejunum, liver and breast obtained at 10, 21 and 34/35 d of age from three experiments in a combined analysis. Animal performance data showed that Met deficiency reduced BW, daily BW gain, daily feed intake, and breast yield, and increased feed conversion ratio in all experiments (P < 0.05). Effects of Met deficiency on gene expression were least evident in the jejunum and most evident in the liver and breast, as evidenced by the number of DEG and activated pathways. Activated pathways suggested Met deficiency was associated with inhibited protein turnover, gut barrier integrity, and adaptive immunity functions in the jejunum, that predicted reduced breast yield. There was an interaction with age; in Met-deficient birds, there were 333 DEGs in the jejunum of starter vs finisher birds suggesting young birds were more sensitive to Met deficiency than older birds. In the liver, Met deficiency activated pathways associated with lipid turnover, amino acid metabolism, oxidative stress, and the immune system, whereas in breast, it activated pathways involved in metabolic regulation, hemostasis, the neuronal system, and oxidative stress, again predicting a negative impact on breast yield. In the starter phase, supplementation with DL-Met compared to MHA-FA inhibited gamma-aminobutyric acid activity and oxidative stress in breast tissue. When data from all tissues were integrated, increased expression of a liver gene (ENSGALG00000042797) was found to be correlated with the expression of several genes that best explained variation due to the Met deficiency in jejunum and breast muscle. Some of these genes were involved in anti-oxidant systems. Overall, the findings indicate that impaired growth performance due to Met deficiency results from an array of tissue-specific molecular mechanisms in which oxidative stress plays a key systemic role. Young birds are more sensitive to Met-deficiency and DL-Met was a preferential source of Met than L- or MHA-FA during the starter phase., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Olmesartan medoxomil (olmesartan-MX), an ester-type prodrug of the angiotensin II receptor blocker (ARB) olmesartan, is predominantly anionic at intestinal pH. Human organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in the small intestine and is involved in the absorption of various acidic drugs. This study was designed to test the hypothesis that OATP2B1-mediated uptake contributes to the enhanced intestinal absorption of olmesartan-MX, even though olmesartan itself is not a substrate of OATP2B1., Methods: Tetracycline-inducible human OATP2B1- and rat Oatp2b1-overexpressing HEK 293 cell lines (hOATP2B1/T-REx-293 and rOatp2b1/T-REx-293, respectively) were established to characterize OATP2B1-mediated uptake. Rat jejunal permeability was measured using Ussing chambers. ARBs were quantified by liquid chromatography-tandem mass spectrometry., Results: Significant olmesartan-MX uptake was observed in hOATP2B1/T-REx-293 and rOatp2b1/T-REx-293 cells, whereas olmesartan uptake was undetectable or much lower than olmesartan-MX uptake, respectively. Furthermore, olmesartan-MX exhibited several-fold higher uptake in Caco-2 cells and greater permeability in rat jejunum compared to olmesartan. Olmesartan-MX uptake in hOATP2B1/T-REx-293 cells and in Caco-2 cells was significantly decreased by OATP2B1 substrates/inhibitors such as 1 mM estrone-3-sulfate, 100 µM rifamycin SV, and 100 µM fluvastatin. Rat Oatp2b1-mediated uptake and rat jejunal permeability of olmesartan-MX were significantly decreased by 50 µM naringin, an OATP2B1 inhibitor. Oral administration of olmesartan-MX with 50 µM naringin to rats significantly reduced the area under the plasma concentration-time curve of olmesartan to 76.9%., Conclusion: Olmesartan-MX is a substrate for OATP2B1, and the naringin-sensitive transport system contributes to the improved intestinal absorption of olmesartan-MX compared with its parent drug, olmesartan., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus , Lachnoclostridium , Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified&#95;f&#95;&#95;Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

Human noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs. Membrane proteins were extracted, trypsin digested, and glycopeptides enriched by hydrophilic interaction liquid chromatography and analyzed by nanoLC-MS/MS. The Byonic software was used for glycopeptide identification followed by hands-on verifications and interpretations. Glycan structures and attachment sites were identified from MS2 spectra obtained by higher-energy collision dissociation through analysis of diagnostic saccharide oxonium ions (B-ions), stepwise glycosidic fragmentation of the glycans (Y-ions), and peptide sequence ions (b- and y-ions). Altogether 694 unique glycopeptides from 93 glycoproteins were identified. The N-glycans encompassed pauci- and oligomannose, hybrid- and complex-type structures. Notably, polyfucosylated HBGA-containing glycopeptides of the four glycoproteins tetraspanin-8, carcinoembryonic antigen-related cell adhesion molecule 5, sucrose-isomaltase and aminopeptidase N were especially prominent and were characterized in detail and related to donor ABO, Lewis and secretor types of each HIE. Virtually no sialylated N-glycans were identified for these glycoproteins suggesting that terminal sialylation was infrequent compared to fucosylation and HBGA biosynthesis. This approach gives unique site-specific information on the structural complexity of N-linked glycans of glycoproteins of human HIEs and provides a platform for future studies on the role of host glycoproteins in gastrointestinal infectious diseases., (© The Author(s) 2024. Published by Oxford University Press.)

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) is a quinone derivative of a common tire additive 6PPD, whose occurrence has been widely reported both in the environment and human bodies including in adults, pregnant women and children. Yet, knowledge on the potential intestinal toxicity of 6PPD-Q in mammals at environmentally relevant dose remain unknown. In this study, the effects of 6PPD-Q on the intestines of adult ICR mice were evaluated by orally administering environmentally relevant dose or lower levels of 6PPD-Q (0.1, 1, 10, and 100 μg/kg) for 21 days. We found that 6PPD-Q disrupted the integrity of the intestinal barrier, mostly in the jejunum and ileum, but not in the duodenum or colon, in a dose-dependent manner. Moreover, intestinal inflammation manifested with elevated levels of TNF-α, IL-1, and IL-6 mostly observed in doses at 10 and 100 μg/kg. Using reverse target screening technology combining molecular dynamic simulation modeling we identified key cannabinoid receptors including CNR2 activation to be potentially mediating the intestinal inflammation induced by 6PPD-Q. In summary, this study provides novel insights into the toxic effects of emerging contaminant 6PPD-Q on mammalian intestines and that the chemical may be a cannabinoid receptor agonist to modulate inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

First pass metabolism by phase I and phase II enzymes in the intestines and liver is a major determinant of the oral bioavailability of many drugs. Several studies analyzed expressions of major drug-metabolizing enzymes (DMEs), such as CYP3A4 and UGT1A1 in the human gut and liver. However, there is still a lack of knowledge regarding other DMEs (i.e., "minor" DMEs), although several clinically relevant drugs are affected by those enzymes. Moreover, there is very limited intra-subject data on hepatic and intestinal expression levels of minor DMEs. To fill this gap of knowledge, we analyzed gene expression (quantitative real-time polymerase chain reaction) and protein abundance (targeted proteomics) of 24 clinically relevant DMEs, that is, carboxylesterases (CES), UDP-glucuronosyltransferases (UGT), and cytochrome P450 (CYP)-enzymes. We performed our analysis using jejunum and liver tissue specimens from the same 11 healthy organ donors (8 men and 3 women, aged 19-60 years). Protein amounts of all investigated DMEs, with the exception of CYP4A11, were detected in human liver samples. CES2, CYP2C18, CYP3A4, and UGT2B17 protein abundance was similar or even higher in the jejunum, and all other DMEs were found in higher amounts in the liver. Significant correlations between gene expression and protein levels were observed only for 2 of 15 jejunal, but 13 of 23 hepatic DMEs. Intestinal and hepatic protein amounts only significantly correlated for CYP3A4 and UGT1A3. Our results demonstrated a notable variability between the individuals, which was even higher in the intestines than in the liver. Our intrasubject analysis of DMEs in the jejunum and liver from healthy donors, may be useful for physiologically-based pharmacokinetic-based modeling and prediction in order to improve efficacy and safety of oral drug therapy., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study evaluated the effects of supplementation with Antrodia cinnamomea mycelium by-product (ACBP) on growth performance and immune response in weaning piglets. Total available content and antioxidant capacity of ACBP were determined. Ninety-six black pigs were randomly distributed to 24 pens. Study compared four groups which were supplemented with ACBP at 0%, 2.5%, 5%, or 10% for 6 weeks after weaning at 4 weeks. Results showed that ACBP on total phenolic, total flavonoid, and total triterpenoids contents were 13.68 mg GAE/g DW, 1.67 μg QE/g DW, and 15.6 mg/g, respectively. Weaning piglets fed 2.5% ACBP showed a significant decreased body weight gain compared with those supplemented with 5% ACBP, 10% ACBP, and control groups. Results showed that all ACBP groups increased the villi height of jejunum significantly. Incidence of diarrhea in 11 weeks with supplementation with 5% and 10% ACBP diets were lower than in control group. The 10% ACBP group showed significantly lower expression of immune response genes (IL-1β, IL-6, IL-8, TNF-α, and IFN-γ) than the 2.5% and 5% ACBP groups. Based on results, dietary supplementation with 10% ACBP did not significantly affect body weight but could decrease piglet diarrhea condition and expression of IL-1β and IL-6 genes., (© 2024 Japanese Society of Animal Science.)

Heat stress in chickens caused by high temperatures in summer is a serious issue faced by the poultry industry globally, which reduces product quality. The aim of this study is to investigate the role of resveratrol in alleviating heat stress injury and inflammatory response of jejunal mucosa in black-boned chickens through TLR4/MAPK signaling pathway. In total, 240 black-boned chickens (28-day old) were randomly divided into 4 treatment groups as follows. The normal temperature (NT) and normal temperature with resveratrol (NT+Res) groups received a basal diet without and with 400 mg/kg resveratrol, respectively, and treated at 24℃ ± 2℃, 24 h/d. The high temperature (HT) and high temperature with resveratrol (HT+Res) groups received basal diet without and with 400 mg/kg resveratrol, respectively, and treated at 37℃ ± 2℃ for 8 h/d and 24°C ± 2°C for the rest of the time for 12 d. The results revealed the heat-stress responses impaired the villous structure of the jejunum, causing a rough and uneven surface of the jejunal villus, and local intestinal villi were even more prone to rupture. However, resveratrol significantly improved the morphology and structure of jejunal mucosa under heat stress. Heat stress increased the mRNA levels of toll-like receptor 4 (TLR4), c-Jun, c-fos, caspase-3, and p38 (P < 0.05), reduced mRNA level of Bcl-2, and reduced the expression of tight junction proteins Occludin, ZO-1, and Claudin1 (P < 0.05) in the jejunal mucosa. However, resveratrol inhibited the TLR4/ mitogen-activated protein kinase (MAPK) signaling pathway via downregulating TLR4, c-Jun, p38, and caspase-3 (P < 0.05); upregulating Bcl-2 (P < 0.05); decreasing the protein levels of MKK3, p53, and myeloid differentiation factor 88 (MYD88); and increasing the protein levels of Occludin, ZO-1, and Claudin1. In addition, it reduced the levels of JNK and p38 proteins (P < 0.05) and inflammatory factors like tumor necrosis factor-α (TNF-α) in the jejunal mucosa of black-boned chickens under heat stress. In conclusion, resveratrol may play a regulatory role in heat-stress-induced damage and inflammatory response in the intestinal mucosa of black-boned chickens under heat stress., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Functional bowel disorders (FBD) have a major potential to degrade the standards of public life. Juniperus oxycedrus L. (J. oxycedrus) (Cupressaceae) has been described as a plant used in traditional medicine as an antidiarrheal medication. The present study is the first to obtain information on the antispasmodic and antidiarrheic effects of J. oxycedrus aqueous extract through in vitro and in vivo studies. An aqueous extract of J. oxycedrus (AEJO) was extracted by decoctioning air-dried aerial sections of the plant. Antispasmodic activity was tested in an isolated jejunum segment of rats exposed to cumulative doses of drogue extract. The antidiarrheic activity was tested using diarrhea caused by castor oil, a transit study of the small intestine, and castor oil-induced enteropooling assays in mice. In the jejunum of rats, the AEJO (0.1, 0.3 and 1 mg/ml) diminished the maximum tone induced by low K + (25 mM), while it exhibited a weak inhibitory effect on high K + (75 mM) with an IC 50 =0.49 ± 0.01 mg/ml and IC 50 =2.65 ± 0.16 mg/ml, respectively. In the contractions induced by CCh (10 -6 M), AEJO diminished the maximum tone, similar to that induced by low K + (25 mM). with an IC 50 =0.45 ± 0.02 mg/ml. The inhibitory effect of AEJO on low K + induced contractions was significantly diminished in the presence of glibenclamide (GB) (0.3 µM) and 4-aminopyrimidine (4-AP) (100 µM), with IC 50 values of 1.84 ± 0.09 mg/ml. and 1.63 ± 0.16 mg/ml, respectively). The demonstrated inhibitory effect was similar to that produced by a non-competitive antagonist acting on cholinergic receptors and calcium channels. In castor oil-induced diarrhea in mice, AEJO (100, 200, and 400 mg/kg) caused an extension of the latency time, a reduced defecation frequency, and a decrease in the amount of wet feces compared to the untreated group (distilled water). Moreover, it showed a significant anti-motility effect and reduced the amount of fluid accumulated in the intestinal lumen at all tested doses. These findings support the conventional use of Juniperus oxycedrus L. as a remedy for gastrointestinal diseases.

Jejunal diverticulosis is uncommon and so are gastrointestinal stromal tumours (GIST) arising in the jejunum. GIST arising in a jejunal diverticulum is a rarity and to date there are only 7 cases in the English literature. Our case of GIST occurring in a jejunal diverticulum of a 48-year-old lady would be the first reported in Malaysia and the 8th in the world. As in most cases, the clinical presentation and radiological findings of this patient were non-specific. With a history of acute abdominal pain, vomiting and fever, the patient was provisionally diagnosed as a case of twisted ovarian cyst and subjected to laparotomy. An intact roundish jejunal diverticulum 5.0 cm x 5.0 cm, about 50 cm distal to the duodeno-jejunal junction was found and resected with a segment of small intestine. Microscopic examination showed a tumour of the cut open diverticular wall, with epithelioid to spindled cells, demonstrating a mitotic rate of 1-2 per 5 mm2, confined to, while infiltrating the wall of the diverticulum. The immunohistochemical profile of positive staining for CD117, DOG-1, smooth muscle actin and CD34, and negative expression of desmin and S100 protein, clinched the diagnosis of GIST. Based on the AFIP Criteria for risk stratification, 1 the patient was categorised as having moderate risk for disease progression, and was not offered further targeted imatinib as an immediate measure. The patient has remained well at the time of writing i.e. 8 months following excision, and continues on active surveillance by the surgical and oncological teams, with the option of imatinib, should the necessity arise. This case is presented not merely for the sake of documenting its rarity, but as a reminder to stay alert for uncommon conditions in histopathology practice.

Efforts to achieve sustainable phosphorus (P) inputs in broiler farming which meet the physiological demand of animals include nutritional intervention strategies that have the potential to modulate and utilize endogenous and microbiota-associated capacities. A temporal P conditioning strategy in broiler nutrition is promising as it induces endocrinal and transcriptional responses to maintain mineral homeostasis. In this context, the current study aims to evaluate the composition of the jejunal microbiota as a functional entity located at the main absorption site involved in nutrient metabolism. Starting from a medium or high P supply in the first weeks of life of broilers, a depletion strategy was applied at growth intervals from d 17 to 24 and d 25 to 37 to investigate the consequences on the composition of the jejunal microbiota. The results on fecal mineral P, calcium (Ca), and phytate contents showed that the diets applied to the depleted and non-depleted cohorts were effective. Microbial diversity in jejunum was represented by alpha diversity indices which appeared unaffected between dietary groups. However, chickens assigned to the dietary P depletion groups showed significantly higher abundances of Facklamia, Lachnospiraceae, and Ruminococcaceae compared to non-depleted control groups. Based on current knowledge of microbial function, these microorganisms make only a minor contribution to the birds' adaptive mechanism in the jejunum following P depletion. Microbial taxa such as Brevibacterium, Brachybacterium, and genera of the Staphylococcaceae family proliferated in a P-enriched environment and might be considered biomarkers for excessive P supply in commercial broiler chickens., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The slow-growing Korat chicken (KR) has been developed to provide an alternative breed for smallholder farmers in Thailand. Carnosine enrichment in the meat can distinguish KR from other chicken breeds. Therefore, our aim was to investigate the effect of enriched carnosine synthesis, obtained by the β-alanine and L-histidine precursor supplementation in the diet, on changes to metabolomic profiles and biochemical compounds in slow-growing KR jejunum tissue. Four hundred 21-day-old female KR chickens were divided into 4 experimental groups: a group with a basal diet, a group with a basal diet supplemented with 1.0% β-alanine, 0.5% L-histidine, and a mix of 1.0% β-alanine and 0.5% L-histidine. The feeding trial lasted 70 d. Ten randomly selected chickens from each group were slaughtered. Metabolic profiles were analyzed using proton nuclear magnetic resonance spectroscopy. In total, 28 metabolites were identified. Significant changes in the concentrations of these metabolites were detected between the groups. Partial least squares discriminant analysis was used to distinguish the metabolites between the experimental groups. Based on the discovered metabolites, 34 potential metabolic pathways showed differentiation between groups, and 8 pathways (with impact values higher than 0.05, P < 0.05, and FDR < 0.05) were affected by metabolite content. In addition, biochemical changes were monitored using synchrotron radiation-based Fourier transform infrared microspectroscopy. Supplementation of β-alanine alone in the diet increased the β-sheets and decreased the α-helix content in the amide I region, and supplementation of L-histidine alone in the diet also increased the β-sheets. Furthermore, the relationship between metabolite contents and biochemical compounds were confirmed using principal component analysis (PCA). Results from the PCA indicated that β-alanine and L-histidine precursor group was highly positively correlated with amide I, amide II, creatine, tyrosine, valine, isoleucine, and aspartate. These findings can help to understand the relationships and patterns between the spectral and metabolic processes related to carnosine synthesis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)