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Biological & Pharmaceutical Bulletin 2024A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from...
A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from the outer environment. The intercellular spaces between adjacent epithelial cells are sealed by bicellular and tricellular tight junctions (TJs). Although one strategy for enhancing intestinal drug absorption is to modulate these TJs, comprehensive gene (mRNA) expression analysis of the TJs components has never been fully carried out in humans. In this study, we used human biopsy samples of normal-appearing mucosa showing no endoscopically visible inflammation collected from the duodenum, jejunum, ileum, colon, and rectum to examine the mRNA expression profiles of TJ components, including occludin and tricellulin and members of the claudin family, zonula occludens family, junctional adhesion molecule (JAM) family, and angulin family. Levels of claudin-3, -4, -7, -8, and -23 expression became more elevated in each segment along the intestinal tract from the upper segments to the lower segments, as did levels of angulin-1 and -2 expression. In contrast, expression of claudin-2 and -15 was decreased in the large intestine compared to the small intestine. Levels of occludin, tricellulin, and JAM-B and -C expression were unchanged throughout the intestine. Considering their segment specificity, claudin-8, claudin-15, and angulin-2 appear to be targets for the development of permeation enhancers in the rectum, small intestine, and large intestine, respectively. These data on heterogenous expression profiles of intestinal TJ components will be useful for the development of safe and efficient intestinal permeation enhancers.
Topics: Humans; Tight Junctions; Intestinal Mucosa; MARVEL Domain Containing 2 Protein; Claudins; Occludin; Male; Adult; Middle Aged; Female; RNA, Messenger; Gene Expression; Aged
PubMed: 38925921
DOI: 10.1248/bpb.b23-00927 -
Endoscopy Dec 2024
Topics: Humans; Laparoscopy; Stents; Anastomosis, Surgical; Male; Stomach Neoplasms; Jejunal Neoplasms; Jejunum; Aged; Middle Aged; Female; Endoscopy, Gastrointestinal; Intestinal Obstruction
PubMed: 38917973
DOI: 10.1055/a-2335-6901 -
Poultry Science Jun 2024This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on inflammatory responses and intestinal health of lipopolysaccharide...
This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on inflammatory responses and intestinal health of lipopolysaccharide (LPS)-challenged broilers. One hundred and forty-four 1-day-old male broiler chicks were divided into 3 groups with 6 replicates of 8 birds each. The groups were as follows: 1) Control group: birds fed a basal diet; 2) LPS group: LPS-challenged birds fed a basal diet; 3) CGA group: LPS-challenged birds fed a CGA-supplemented diet. The LPS was intraperitoneally administered at a dose of 1 mg/kg of body weight. CGA increased the weight gain and feed intake of LPS-challenged birds by 37.05% and 24.29%, respectively (P < 0.05). CGA also alleviated LPS-induced inflammation, as evidenced by lower levels of pro-inflammatory cytokines in the serum and jejunum (tumor necrosis factor-α, interferon-γ, interleukin-1β, and interleukin-6), and the decreased myeloperoxidase activity in the jejunum (P < 0.05). These effects were accompanied by a decrease in the mRNA abundance of toll-like receptor 4 and myeloid differentiation factor 88 and an inhibition of nuclear factor kappa-B translocation in the jejunum (P < 0.05). CGA reduced circulating diamine oxidase activity and levels of D-lactate and endotoxin, and positively regulated the expression of jejunal claudin-3 and zonula occludens-1 in LPS-challenged broilers (P < 0.05). Compared to the LPS group, CGA reduced the apoptotic rate of epithelial cells and cytochrome c concentration in the jejunum, and normalized the expression of genes responsible for proliferation and apoptosis in jejunal epithelial cells, including cysteine aspartate-specific protease-9, B cell lymphoma-2, and proliferating cell nuclear antigen (P < 0.05). Furthermore, CGA normalized the altered phosphorylation of protein kinase B and glycogen synthase kinase-3β, as well as the translocation of nuclear β-catenin in the jejunum of LPS-challenged broilers (P < 0.05). These results suggested that CGA supplementation improved growth performance, alleviated inflammation, and helped maintain intestinal integrity and barrier function in LPS-challenged broilers, possibly through the regulation of the toll-like receptor 4/nuclear factor kappa-B and protein kinase B/Wnt/β-catenin pathways.
PubMed: 38917604
DOI: 10.1016/j.psj.2024.103949 -
BMC Genomics Jun 2024Modern broiler breeds allow for high feed efficiency and rapid growth, which come at a cost of increased susceptibility to pathogens and disease. Broiler growth rate,...
Modern broiler breeds allow for high feed efficiency and rapid growth, which come at a cost of increased susceptibility to pathogens and disease. Broiler growth rate, feed efficiency, and health are affected by the composition of the gut microbiota, which in turn is influenced by diet. In this study, we therefore assessed how diet composition can affect the broiler jejunal gut microbiota. A total of 96 broiler chickens were divided into four diet groups: control, coated butyrate supplementation, medium-chain fatty acid supplementation, or a high-fibre low-protein content. Diet groups were sub-divided into age groups (4, 12 and 33 days of age) resulting in groups of 8 broilers per diet per age. The jejunum content was used for metagenomic shotgun sequencing to determine the microbiota taxonomic composition at species level. The composed diets resulted in a total of 104 differentially abundant bacterial species. Most notably were the butyrate-induced changes in the jejunal microbiota of broilers 4 days post-hatch, resulting in the reduced relative abundance of mainly Enterococcus faecium (-1.8 l2fc, P = 9.9E-05) and the opportunistic pathogen Enterococcus hirae (-2.9 l2fc, P = 2.7E-08), when compared to the control diet. This effect takes place during early broiler development, which is critical for broiler health, thus exemplifying the importance of how diet can influence the microbiota composition in relation to broiler health. Future studies should therefore elucidate how diet can be used to promote a beneficial microbiota in the early stages of broiler development.
Topics: Animals; Chickens; Enterococcus faecium; Gastrointestinal Microbiome; Jejunum; Enterococcus hirae; Animal Feed; Diet; Metagenomics; Dietary Supplements
PubMed: 38910254
DOI: 10.1186/s12864-024-10496-8 -
International Journal of Pharmaceutics Jun 2024Labrafac™ MC60 (glycerol monocaprylocaprate) is a lipid-based excipient used in oral formulations as a solubiliser. Due to the high proportions of established...
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) and caprate (C), 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) of [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.
PubMed: 38909926
DOI: 10.1016/j.ijpharm.2024.124353 -
International Journal of Surgery Case... Jun 2024Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, with jejunal GISTs being particularly uncommon. Jejunal GISTs causing perforation and acute diffuse...
INTRODUCTION
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, with jejunal GISTs being particularly uncommon. Jejunal GISTs causing perforation and acute diffuse peritonitis is rare.
CASE PRESENTATION
A 53-year-old female with a history of hypertension presented with severe, acute abdominal pain and vomiting. Examination revealed abdominal distension, tenderness, and guarding, with imaging suggestive of gastrointestinal perforation. Emergency laparotomy revealed a 9 cm × 8 cm mass with perforation in the jejunum, which was resected which on histopathological examination confirmed a low-grade GIST. The postoperative course was complicated by a wound infection, managed with antibiotics and secondary suturing. At one-year follow-up, the patient remained disease-free without the need for adjuvant therapy.
CLINICAL DISCUSSION
The most common symptoms of jejunal GISTs include vague abdominal pain or discomfort, early satiety, obstruction or hemorrhage. Preoperative diagnosis and confirmation of GIST is difficult due to nonspecific symptoms and none of the radiographic procedures can establish the diagnosis with certainty. The surgical excision of the tumor along with infiltrated tissues is the treatment of choice for GIST.
CONCLUSION
This case underscores the necessity of considering GISTs in differential diagnoses of acute abdomen and the critical role of prompt surgical management and multidisciplinary care in achieving favorable outcomes.
PubMed: 38908159
DOI: 10.1016/j.ijscr.2024.109922 -
BMC Gastroenterology Jun 2024The primary objective of this study is to comparatively assess the safety of nasogastric (NG) feeding versus nasojejunal (NJ) feeding in patients with acute pancreatitis... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative safety assessment of nasogastric versus nasojejunal feeding initiated within 48 hours post-admission versus unrestricted timing in moderate or severe acute pancreatitis: a systematic review and meta-analysis.
BACKGROUND
The primary objective of this study is to comparatively assess the safety of nasogastric (NG) feeding versus nasojejunal (NJ) feeding in patients with acute pancreatitis (AP), with a special focus on the initiation of these feeding methods within the first 48 h of hospital admission.
METHODS
Studies were identified through a systematic search in PubMed, EMbase, Cochrane Central Register of Controlled Trials, and Web of Science. Four studies involving 217 patients were included. This systematic review assesses the safety and efficacy of nasogastric versus nasojejunal feeding initiated within 48 h post-admission in moderate/severe acute pancreatitis, with a specific focus on the timing of initiation and patient age as influential factors.
RESULTS
The results showed that the mortality rates were similar between NG and NJ feeding groups (RR 0.86, 95% CI 0.42 to 1.77, P = 0.68). Significant differences were observed in the incidence of diarrhea (RR 2.75, 95% CI 1.21 to 6.25, P = 0.02) and pain (RR 2.91, 95% CI 1.50 to 5.64, P = 0.002) in the NG group. The NG group also showed a higher probability of infection (6.67% vs. 3.33%, P = 0.027) and a higher frequency of multiple organ failures. Subgroup analysis for early intervention (within 48 h) showed a higher risk of diarrhea in the NG group (RR 2.80, P = 0.02). No significant differences were found in the need for surgical intervention, parenteral nutrition, or success rates of feeding procedures.
CONCLUSION
This meta-analysis highlights the importance of considering the method and timing of nutritional support in acute pancreatitis. While NG feeding within 48 h of admission increases the risk of certain complications such as diarrhea and infection, it does not significantly impact mortality or the need for surgical intervention.
Topics: Humans; Intubation, Gastrointestinal; Enteral Nutrition; Pancreatitis; Time Factors; Acute Disease; Diarrhea; Hospitalization; Jejunum
PubMed: 38902639
DOI: 10.1186/s12876-024-03290-z -
World Journal of Gastroenterology Jun 2024Obesity is associated with a significantly increased risk for chronic diarrhea, which has been proposed as Linghu's obesity-diarrhea syndrome (ODS); however, its...
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 (, , , , , , , and ) may play a key regulatory role in the pathological process of ODS, and their expression levels were significantly decreased in ODS patients ( < 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 ( < 0.01), but were higher in the SOD group than in the SO group ( < 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.
Topics: Humans; Jejunum; Male; Pilot Projects; Female; Diarrhea; Adult; Intestinal Mucosa; Obesity; Middle Aged; Gene Expression Profiling; Transcriptome; Case-Control Studies; Syndrome; Amine Oxidase (Copper-Containing); Computational Biology; Lactic Acid; Chronic Disease
PubMed: 38899329
DOI: 10.3748/wjg.v30.i21.2777 -
International Journal of Molecular... Jun 2024Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been...
Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been shown to modify some epithelial cell kinetics parameters, less is known about the role of the human intestinal microbiota. Here, we investigated the rate of intestinal cell proliferation in C3H/HeN germ-free mice associated with human flora (HFA, n = 8), and in germ-free (n = 15) and holoxenic mice (n = 16). One hour before sacrifice, all mice were intraperitoneally inoculated with 5-bromodeoxyuridine (BrdU), and the number of BrdU-positive cells/total cells (labelling index, LI), both in the jejunum and the colon, was evaluated by immunohistochemistry. Samples were also observed by scanning electron microscopy (SEM). Moreover, the microbiota composition in the large bowel of the HFA mice was compared to that of of human donor's fecal sample. No differences in LI were found in the small bowels of the HFA, holoxenic, and germ-free mice. Conversely, the LI in the large bowel of the HFA mice was significantly higher than that in the germ-free and holoxenic counterparts ( = 0.017 and = 0.048, respectively). In the holoxenic and HFA mice, the SEM analysis disclosed different types of bacteria in close contact with the intestinal epithelium. Finally, the colonic microbiota composition of the HFA mice widely overlapped with that of the human donor in terms of dominant populations, although and disappeared. Despite the small sample size analyzed in this study, these preliminary findings suggest that human intestinal microbiota may promote a high proliferation rate of colonic mucosa. In light of the well-known role of uncontrolled proliferation in colorectal carcinogenesis, these results may deserve further investigation in a larger population study.
Topics: Animals; Humans; Gastrointestinal Microbiome; Intestinal Mucosa; Cell Proliferation; Mice; Colon; Male; Germ-Free Life; Female; Mice, Inbred C3H; Feces
PubMed: 38892368
DOI: 10.3390/ijms25116182 -
Animals : An Open Access Journal From... May 2024Eggs are a vital dietary component for humans, and it is beneficial to increase egg production to support poultry farming. Initially, the egg production rate rises...
Eggs are a vital dietary component for humans, and it is beneficial to increase egg production to support poultry farming. Initially, the egg production rate rises rapidly with young hens until it reaches its peak, and then it declines gradually. By extending the duration of peak egg production, the hens' performance can be enhanced significantly. Previous studies found dynamic changes in gut microbiota during egg-laying, and several species of microbiota isolated from the chicken gut improved egg-laying performance. However, the interaction between microbes and host gene expression is still unclear. This study provides a more comprehensive understanding of chicken egg-laying by examining dynamic alterations in the microbiota of the entire intestinal tract (i.e., duodenum, jejunum, and ileum) and gene expression. The microbial community in the intestine underwent significant changes during different egg-laying periods (i.e., pre-, peak-, and late-laying periods). Metagenomic functional analysis showed that the relative abundance of biosynthesis of amino acids, secondary metabolites, and cofactors decreased significantly in the duodenum, jejunum, and ileum of aging hens. The relative levels of aldosterone, GnRH, insulin, growth hormone, and other hormone-related pathways increased dramatically in the intestinal microbiota during egg-laying, but only in the microbiota located in the duodenum and ileum. Transcriptome analysis suggested that genes associated with various transport processes were upregulated consistently in the small intestine during egg-laying; genes involved in the development of intestinal structure were down-regulated; and genes involved in response to DNA damage and stress were consistent with changes in laying rate. The abundance of Lactobacillus was related to the expression of , , , and in the duodenum; was correlated significantly with , , and expression in the jejunum; and was correlated positively with the expression of and in the ileum. These results indicated that the intestinal microbiota and host gene expression may influence egg production jointly.
PubMed: 38891577
DOI: 10.3390/ani14111529