Showing papers on "Small intestine published in 2022"
TL;DR: Wang et al. as mentioned in this paper used microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system for radioprotection of the whole small intestine.
Abstract: Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.
50 citations
TL;DR: The authors showed that small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement, and this difference is determined by the degree of Wntdriven retrograde cell movement, which is largely absent in the large intestine.
Abstract: The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts1–3. Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated. Small intestinal crypts contain twice as many effective stem cells as large intestinal crypts, and this difference is determined by the degree of Wnt-driven retrograde cell movement—which is largely absent in the large intestine—counteracting conveyor-belt-like upward movement.
22 citations
TL;DR: Despite small increases in additions to the intestine transplant wait‐ list, total waitlist numbers, overall intestine transplant rates, and overall transplants performed from 2019 to 2020, the trend over the last decade is still toward less intestine transplant activity.
20 citations
TL;DR: In this article , the authors highlight recent advances in the green synthesis and applications of resistant starch (RS) and its nanoparticles, with an emphasis on their potential effects of these substances on the human GIT and health, including their ability to inhibit amylase, delay gastric emptying, exhibit prebiotic effects, and act as colon-specific delivery systems.
Abstract: Starch is an important source of dietary carbohydrates in the typical human diet, but the rapid digestion of starch promotes a rapid rise in blood sugar levels, which are looked upon negatively. Increased consumption of starchy foods with a low glycemic index is believed to give high contributions to health. Resistant starch (RS) is not digested in the mouth, stomach, or small intestine but is fermented by microbial flora in the colon, which generates short-chain fatty acids (SCFAs) that have potential health benefits. Furthermore, their RS nanoparticles as a novel type of functional dietary fibre exhibit potential for the development of health-promoting foods. In this review, we highlight recent advances in the green synthesis and applications of RS and its nanoparticles, with an emphasis on their potential effects of these substances on the human GIT and health, including their ability to inhibit amylase, delay gastric emptying, exhibit prebiotic effects, and act as colon-specific delivery systems. RS and its nanoparticles resist digestion in the upper intestine but not in the colon, they are proven to exert prebiotic effects in human body. Furthermore, RS nanoparticles have a number of attributes that are beneficial for their application as functional ingredients in foods, including good water dispersibility, small size, high biocompatibility. Moreover, RS nanoparticles can resistant to hydrolysis by digestible enzymes in the upper GIT (like amylase). As a result, RS nanoparticles can be utilized as prebiotics or as colon-specific delivery systems for bioactive agents.
18 citations
TL;DR: In this article , the authors identify druggable biological targets and small-molecule regulators of intestinal stem cell differentiation via multiplexed phenotypic screening using thousands of miniaturized organoid models.
Abstract: The cellular composition of barrier epithelia is essential to organismal homoeostasis. In particular, within the small intestine, adult stem cells establish tissue cellularity, and may provide a means to control the abundance and quality of specialized epithelial cells. Yet, methods for the identification of biological targets regulating epithelial composition and function, and of small molecules modulating them, are lacking. Here we show that druggable biological targets and small-molecule regulators of intestinal stem cell differentiation can be identified via multiplexed phenotypic screening using thousands of miniaturized organoid models of intestinal stem cell differentiation into Paneth cells, and validated via longitudinal single-cell RNA-sequencing. We found that inhibitors of the nuclear exporter Exportin 1 modulate the fate of intestinal stem cells, independently of known differentiation cues, significantly increasing the abundance of Paneth cells in the organoids and in wild-type mice. Physiological organoid models of the differentiation of intestinal stem cells could find broader utility for the screening of biological targets and small molecules that can modulate the composition and function of other barrier epithelia.
16 citations
TL;DR: In this article , the authors identify druggable biological targets and small-molecule regulators of intestinal stem cell differentiation via multiplexed phenotypic screening using thousands of miniaturized organoid models.
Abstract: The cellular composition of barrier epithelia is essential to organismal homoeostasis. In particular, within the small intestine, adult stem cells establish tissue cellularity, and may provide a means to control the abundance and quality of specialized epithelial cells. Yet, methods for the identification of biological targets regulating epithelial composition and function, and of small molecules modulating them, are lacking. Here we show that druggable biological targets and small-molecule regulators of intestinal stem cell differentiation can be identified via multiplexed phenotypic screening using thousands of miniaturized organoid models of intestinal stem cell differentiation into Paneth cells, and validated via longitudinal single-cell RNA-sequencing. We found that inhibitors of the nuclear exporter Exportin 1 modulate the fate of intestinal stem cells, independently of known differentiation cues, significantly increasing the abundance of Paneth cells in the organoids and in wild-type mice. Physiological organoid models of the differentiation of intestinal stem cells could find broader utility for the screening of biological targets and small molecules that can modulate the composition and function of other barrier epithelia.
13 citations
TL;DR: The colonization of GF mice activated small intestinal eosinophils as mentioned in this paper , which led to the activation of colonized mice in response to microbes regulated villous size alterations, macrophage maturation, epithelial barrier integrity and intestinal transit.
13 citations
TL;DR: In this article , a battery-free smart capsule is designed to sample inflammatory biomarkers inside the colon lumen of the small intestine, where a swelling polyacrylamide hydrogel is placed inside the capsule as a milieu to collect the sampled GI fluid.
Abstract: Although serum and fecal biomarkers (e.g., lactoferrin, and calprotectin) have been used in management and distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), none are proven to be a differential diagnostic tool between Crohn's disease (CD) and ulcerative colitis (UC). The main challenge with laboratory-based biomarkers in the stool test is the inability to indicate the location of the disease/inflammation in the gastrointestinal (GI) tract due to the homogenous nature of the collected fecal sample. For the first time, we have designed and developed a battery-free smart capsule that will allow targeted sampling of inflammatory biomarkers inside the gut lumen of the small intestine. The capsule is designed to provide a simple and non-invasive complementary tool to fecal biomarker analysis to differentiate the type of IBD by pinpointing the site of inflammatory biomarkers secretion (e.g., small or large bowel) throughout the GI tract. The capsule takes advantage of the rapid change from an acidic environment in the stomach to higher pH levels in the small intestine to dissolve a pH-sensitive polymeric coating as a means to activate the sampling process of the capsule within the small intestine. A swelling polyacrylamide hydrogel is placed inside the capsule as a milieu to collect the sampled GI fluid while also providing the required mechanical actuation to close the capsule once the sampling is completed. The hydrogel component along with the collected GI fluid can be easily obtained from the capsule through the screw-cap design for further extraction and analysis. As a proof of concept, the capsule's performance in sampling and extraction of bovine serum albumin (BSA) and calprotectin - a key biomarker of inflammation - was assessed within the physiologically relevant ranges. The ratio of extracted biomarkers relative to that in the initial sampling environment remained constant (∼3%) and independent of the sampling matrix in both in vitro and ex vivo studies. It is believed that the demonstrated technology will provide immediate impact in more effective IBD type differential diagnostic and treatment strategies by providing a non-invasive assessment of inflammation biomarkers profile throughout the digestive tract.
11 citations
01 Jan 2022
TL;DR: In this article , 2'-fucosyllactose (2'-FL), an abundant oligosaccharide in human milk, protects intestinal integrity and ameliorates intestinal mucositis.
Abstract: Intestinal mucositis, a severe complication of antineoplastic therapeutics, is characterized by mucosal injury and inflammation in the small intestine. Therapies for the prevention and treatment of this disease are needed. We investigated whether 2'-fucosyllactose (2'-FL), an abundant oligosaccharide in human milk, protects intestinal integrity and ameliorates intestinal mucositis.A mouse small intestinal epithelial (MSIE) cell line, mouse enteroid cultures, and human gastrointestinal tumor cell lines (AGS and HT29) were co-treated with the chemotherapy agent 5-fluorouracil (5-FU) and 2'-FL. Mice were injected intraperitoneally with 5-FU to induce intestinal mucositis. 2'-FL was administered in the drinking water to mice before (pretreatment) or concurrently with 5-FU injection. Body weight and pathologic changes were analyzed.2'-FL alleviated 5-FU inhibition of cell growth in MSIE cells, but not in AGS and HT29 cells. The 5-FU-induced apoptosis in MSIE cells and enteroids was suppressed by 2'-FL. Compared with 5-FU treatment alone, 2'-FL pretreatment protected against body weight loss, and ameliorated inflammation scores, proinflammatory cytokine production, shortening of villi, epithelial cell apoptosis, goblet cell loss, and tight junctional complex disruption in the small intestine. 2'-FL concurrent treatment had less of an effect on intestinal mucositis than 2'-FL pretreatment. Interestingly, no effect of 2'-FL was observed on 5-FU-induced S-phase arrest in MSIE, AGS, and HT29 cells. Neither pretreatment nor concurrent treatment with 2'-FL affected 5-FU-induced inhibition of proliferation in MSIE cells.This study shows a novel direct effect of 2'-FL in protecting small intestinal epithelial cells against apoptosis stimulated by 5-FU, which may contribute to prevention of 5-FU-induced intestinal mucositis.
11 citations
TL;DR: In this article , the effects of chemically protected sodium butyrate (CSB) on growth performance and the early development and function of small intestine in broilers as one potential substitute for antibiotics were investigated.
Abstract: The purpose of this study was to investigate the effects of chemically protected sodium butyrate (CSB) on growth performance and the early development and function of small intestine in broilers as one potential substitute for antibiotics. A total of 192 one-day-old Arbor Acres male broilers were randomly assigned into three dietary treatment groups (eight replicates per treatment): the control (CON) diet; ANT diet, CON diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg); CSB diet, CON diet supplemented with 1000 mg/kg CSB, respectively. The results showed that dietary CSB and antibiotics addition significantly improved the growth performance of broilers by increasing the body weight gain (BWG) and feed conversion ratio (FCR) during different stages (p < 0.05). On day 21, the supplement of CSB in diet improved the structure of small intestine (duodenum, jejunum, and ileum) in broilers by increasing the ratio of villus height to crypt depth (VH/CD) (p < 0.05) and enhanced the butyric acid (BA) (p < 0.05) and total short chain fatty acids (SCFA) concentrations of small intestine (jejunum and ileum) compared with the CON and ANT diets. Besides that, the superoxide dismutase (SOD), total antioxidant capacity (TAC) and TAC to malondialdehyde (TAC/MDA) ratio of the ileal and jejunal mucosa were significantly higher (p < 0.05) in the CSB and ANT than in the CON. In addition, the supplement of CSB in diet markedly significantly enhanced α-amylase, lipase, and trypsin activities of the ileum (p < 0.05) as compared to the ANT diet. 16S rRNA gene sequencing indicated that CSB markedly increased the microbiota diversity of ileum in broilers at 21 days of age as compared to CON and ANT (p < 0.05). Furthermore, we found that Firmicutes was the predominant phyla and Lactobacillus was the major genus in the ileum of broilers. Compared with the ANT diet, the supplement of CSB in diet increased the relative abundance of some genera microbiota (e.g., Candidatus_Arthromitus, Romboutsia) by decreasing the relative abundance of Lactobacillus. Moreover, Akkermansia in the CSB was the highest in comparison to that in the CON and ANT. In addition, Kitasatospora that belongs to the phylum Actinobacteriota was only found in ileum of broilers fed the ANT diet. In summary, the supplement of 1000 mg/kg CSB in the diet improved the growth performance by promoting early development and function of the small intestine, which is associated with the regulation of intestinal flora and reestablishment of micro-ecological balance in broilers. Thus, CSB has great potential value as one of effective substitutes for in-feed antibiotics in the broiler industry.
11 citations
TL;DR: In this article , the authors used a mouse model of antibody-deficiency to demonstrate that a relationship exists between dysbiosis, defects in bile acid homeostasis, and gluten-sensitive enteropathy of the small intestine.
Abstract: Mucosal antibodies maintain gut homeostasis by promoting spatial segregation between host tissues and luminal microbes. Whether and how mucosal antibody responses influence gut health through modulation of microbiota composition is unclear. Here, we use a CD19-/- mouse model of antibody-deficiency to demonstrate that a relationship exists between dysbiosis, defects in bile acid homeostasis, and gluten-sensitive enteropathy of the small intestine. The gluten-sensitive small intestine enteropathy that develops in CD19-/- mice is associated with alterations to luminal bile acid composition in the SI, marked by significant reductions in the abundance of conjugated bile acids. Manipulation of bile acid availability, adoptive transfer of functional B cells, and ablation of bacterial bile salt hydrolase activity all influence the severity of small intestine enteropathy in CD19-/- mice. Collectively, results from our experiments support a model whereby mucosal humoral immune responses limit inflammatory disease of the small bowel by regulating bacterial BA metabolism.
01 Apr 2022
TL;DR: A 62‐year‐old male with severe COVID‐19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO), revealed extensive mucosal sloughing in the lower intestinal tract, which suggested a significant elevation of IL‐6, which could be involved in the pathophysiology of the GI involvement in CO VID‐19.
Abstract: Abstract Patients with coronavirus disease 2019 (COVID‐19) primarily cause respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. The endoscopic characteristics of the GI tract in COVID‐19 patients remain unclear. We herein report a 62‐year‐old male with severe COVID‐19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO). Despite the improvement in his respiratory status, GI bleeding developed. Capsule endoscopy and colonoscopy revealed extensive mucosal sloughing in the lower intestinal tract. Additionally, we performed a comprehensive analysis of the mRNA expression levels of various proinflammatory cytokines in the intestinal mucosal tissues. The results suggested a significant elevation of IL‐6, which could be involved in the pathophysiology of the GI involvement in COVID‐19. Further investigation with more clinical data, including endoscopic findings and molecular analyses, will contribute to a comprehensive understanding of COVID‐19‐associated GI injury.
TL;DR: In this article , an oral colon-targeted adhesion core-shell nanoparticles were designed by applying FA-Zein as the core and using pectins as the shell to enhance the low bioavailability exhibited by glycyrrhizic acid (GA) and the anti-inflammatory effect in specific parts of the intestine.
TL;DR: This review intends to give a comprehensive look into three main branches of NPs delivery through the oral route: the functionalization of NPS drug carriers for systemic targets; NPs for the delivery of drugs locally active in the intestine, for the treatment of inflammatory bowel diseases and colon cancer; and the potential concerns and side effects of the accidental and uncontrolled exposure to NPs employed as food additives.
Abstract: The use of nanoparticles (NPs) has surely grown in recent years due to their versatility, with a spectrum of applications that range from nanomedicine to the food industry. Recent research focuses on the development of NPs for the oral administration route rather than the intravenous one, placing the interactions between NPs and the intestine at the centre of the attention. This allows the NPs functionalization to exploit the different characteristics of the digestive tract, such as the different pH, the intestinal mucus layer, or the intestinal absorption capacity. On the other hand, these same characteristics can represent a problem for their complexity, also considering the potential interactions with the food matrix or the microbiota. This review intends to give a comprehensive look into three main branches of NPs delivery through the oral route: the functionalization of NPs drug carriers for systemic targets, with the case of insulin carriers as an example; NPs for the delivery of drugs locally active in the intestine, for the treatment of inflammatory bowel diseases and colon cancer; finally, the potential concerns and side effects of the accidental and uncontrolled exposure to NPs employed as food additives, with focus on E171 (titanium dioxide) and E174 (silver NPs).
TL;DR: Compared with the standard administration of the same antibiotics, the oral administration of nanoparticle-encapsulated ampicillin, chloramphenicol or vancomycin in mice with bacterial infections in the lungs effectively eliminated the infections, and decreased adverse effects on the intestinal microbiota by protecting the animals from dysbiosis-associated metabolic syndromes and from opportunistic pathogen infections.
TL;DR: In this article , the authors investigated inherent instability, temporal dynamics, and the contribution of fed and fasted states using stoma samples from cured colorectal cancer patients as a non-invasive access route to the otherwise inaccessible small and large intestines.
TL;DR: In this article , the authors review the relevant literature and critically discuss absorption pathways with a focus on the role of specific intestinal epithelial and immune cells, concluding that while Microfold (M) cells are a valid target for oral vaccines, enterocytes play a greater role in the systemic bioavailability of orally administrated particulate formulations, particularly within the sub-micron size range.
TL;DR: This study developed small intestine-specific CIDEC (SI-CIDEC-/-) knockout C57BL/6J mice by Cre/LoxP recombination to investigate the in vivo effects of intestinal CID EC on lipid metabolism, and identified a new interacting protein and previously unreported C IDEC mechanisms that revealed its activity in lipid metabolism of the small intestine.
Abstract: The small intestine is main site of exogenous lipid digestion and absorption, and it is important for lipid metabolic homeostasis. Cell death-inducing DNA fragmentation-factor like effector C (CIDEC) is active in lipid metabolism in tissues other than those in the intestine. We developed small intestine-specific CIDEC (SI-CIDEC-/-) knockout C57BL/6J mice by Cre/LoxP recombination to investigate the in vivo effects of intestinal CIDEC on lipid metabolism. Eight-week-old SI-CIDEC-/- mice fed a high-fat diet for 14 weeks had 15% lower body weight, 30% less body fat mass, and 79% lower liver triglycerides (TG) than wild-type (WT) mice. In addition, hepatic steatosis and fatty liver inflammation were less severe in knockout mice fed a high-fat diet (HFD) compared with wild-type mice fed an HFD. SI-CIDEC-/- mice fed an HFD diet had lower serum TG and higher fecal TG and intestinal lipase activity than wild-type mice. Mechanistic studies showed that CIDEC accelerated phosphatidic acid synthesis by interacting with 1-acylglycerol-3-phosphate-O-acyltransferase to promote TG accumulation. This study identified a new interacting protein and previously unreported CIDEC mechanisms that revealed its activity in lipid metabolism of the small intestine.
TL;DR: It can be concluded that 2.4 μg of 25OHD3, when administrated in ovo at 18 doi, may be used to decrease the inflammatory reaction as well as to enhance the small intestine morphology of broilers during a coccidiosis challenge.
Abstract: Simple Summary Vitamin D3 sources serve as immunomodulators and improve intestinal morphology, which can promote broiler performance. The in ovo injection of vitamin D3 sources has been shown to enhance immunity as well as histomorphological variables in unchallenged conditions. One of the main diseases affecting poultry production is coccidiosis. Because of this, the current study was designed to determine the effects vitamin D3 (D3) and 25-hydroxyvitamin D3 (25OHD3) alone or together on the inflammatory reaction and small intestine morphology of broilers that were challenged with coccidiosis. In this study, it is shown that the in ovo administration of 2.4 μg of 25OHD3 alone increased villus length to crypt depth ratio (VCR) with the D3 + 25OHD3 treatment being intermediate two weeks post-challenge (28 day of age). Furthermore, chickens that received of 25OHD3 alone experienced lower plasma nitric oxide concentration as a systemic inflammatory indicator in comparison to all other treatments. It is concluded that the in ovo injection of 2.4 μg of 25OHD3 at 18 days of incubation can enhance intestinal histomorphology as well as inflammatory reaction of broilers when infected with coccidiosis. Abstract In broilers challenged with coccidiosis, effects of in ovo vitamin D3 (D3) and 25-hydroxyvitamin D3 (25OHD3) administration on their inflammatory response and small intestine morphology were evaluated. At 18 d of incubation (doi), a 50 μL volume of the following 5 in ovo injection treatments was administrated: non-injected (1) and diluent injected (2) controls, or diluent injection containing 2.4 μg D3 (3) or 2.4 μg 25OHD3 (4), or their combination (5). Four male broilers were randomly allocated to each of eight isolated replicate wire-floored battery cages at hatch, and birds were challenged at 14 d of age (doa) with a 20x live coccidial vaccine dosage. One bird from each treatment–replicate (40 birds in each of 8 replicates per treatment) was bled at 14 and 28 doa in order to collect blood for the determination of plasma IL-1β and nitric oxide (NO) concentrations. The duodenum, jejunum, and ilium from those same birds were excised for measurement of villus length, crypt depth, villus length to crypt depth ratio (VCR), and villus surface area. In ovo injection of 2.4 μg of 25OHD3 resulted in a reduction in plasma NO levels as compared to all other treatments at 28 doa. Additionally, duodenal VCR increased in response to the in ovo injection of 25OHD3 when compared to the diluent, D3 alone, and the D3 + 25OHD3 combination treatments at two weeks post-challenge (28 doa). Therefore, it can be concluded that 2.4 μg of 25OHD3, when administrated in ovo at 18 doi, may be used to decrease the inflammatory reaction as well as to enhance the small intestine morphology of broilers during a coccidiosis challenge.
TL;DR: In this article , the authors investigated the hydrolysis of IMOs by small intestinal α-glucosidases from rat and human recombinant sucrase-isomaltase complex.
TL;DR: In this article , the authors found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes and reduced the expression suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues.
Abstract: Lipid peroxidation-induced ferroptosis is a newly recognized type of programmed cell death. With the method of RNA sequencing, we found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes, whereas reduced the expression of ferroptosis suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues. By using ferroptosis inducer RSL-3 and inhibitor liproxstatin-1, we found that ferroptosis is essential for IR-induced intestinal injury. Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) is an important component for ferroptosis execution, and we found that ACSL4 expression was significantly upregulated in irradiated intestine tissues, but not in liver or lung tissues. Antibacterial and antifungal regents reduced the expression of ASCL4 and protected against tissue injury in irradiated intestine tissues. Further studies showed that troglitazone, a ACSL4 inhibitor, succeeded to suppresses intestine lipid peroxidation and tissue damage after IR.
TL;DR: In this article , essential genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip lined by organoid-derived intestinal epithelial cells from patients with EED and cultured in nutrient-deficient medium lacking niacinamide and tryptophan.
Abstract: Abstract Environmental enteric dysfunction (EED)—a chronic inflammatory condition of the intestine—is characterized by villus blunting, compromised intestinal barrier function and reduced nutrient absorption. Here we show that essential genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip lined by organoid-derived intestinal epithelial cells from patients with EED and cultured in nutrient-deficient medium lacking niacinamide and tryptophan. Exposure of the organ chip to such nutritional deficiencies resulted in congruent changes in six of the top ten upregulated genes that were comparable to changes seen in samples from patients with EED. Chips lined with healthy epithelium or with EED epithelium exposed to nutritional deficiencies resulted in severe villus blunting and barrier dysfunction, and in the impairment of fatty acid uptake and amino acid transport; and the chips with EED epithelium exhibited heightened secretion of inflammatory cytokines. The organ-chip model of EED‐associated intestinal injury may facilitate the analysis of the molecular, genetic and nutritional bases of the disease and the testing of candidate therapeutics for it.
TL;DR: In this article , the authors investigated whether Gln, Glu, and Asp improved the intestinal morphology via regulating the energy metabolism in weaning piglets, and found that Gln and Glu improved small intestinal morphology by increasing villus height, goblet cell number and decreasing crypt depth.
TL;DR: The study demonstrated that microplastics induced small intestinal wall degeneration, but recovery in young fish occurred slowly, which likely compromised its digestive function, which may affect growth and reproduction.
Abstract: The histopathological effects of microplastics (MPs) in the gastrointestinal tracts of fish following long-term exposure and depuration are relatively understudied. This study investigated histomorphological damage in the small intestine of Oreochromis urolepis larvae following 65 d exposure to 38–45 μm of polyethylene microspheres (PE MPs) and after a recovery period of 60 d. Larval fish were assigned to each treatment group (control, 1, 10 and 100 PE MPs), where ingestion and degenerative changes in the small intestine were examined using a routine hematoxylin and eosin staining technique. The results highlighted significant PE MPs ingestion and retention proportional to exposure dose (χ2 = 49.54; df = 2). Villi height and width and epithelial cell height were significantly affected and differed between treatment groups. Indices of damage to the small intestine organ (χ2 = 47.37; df = 2; p < 0.05) and reaction patterns of villi, epithelial, goblet and cryptic glandular cells, leucocytic infiltration and blood congestion revealed significant occurrence of alteration as PE MPs exposure dose increased. After the recovery period, no PE MPs were observed, and villi height, width and epithelial cells showed recovery with no significant difference between treatment groups. Organ indices declined (χ2 = 12; df = 2; p < 0.05) but remained significantly different between treatment groups, largely due to leucocytic infiltration (χ2 = 9.08; df = 2; p < 0.05). The study demonstrated that microplastics induced small intestinal wall degeneration, but recovery in young fish occurred slowly. The damage likely compromised its digestive function, which may affect growth and reproduction. This requires further research.
TL;DR: The results showed that torularhodin entered the intestine faster from micelles, and part of it was metabolized into retinol in the anterior segment of the intestine, and the expression of genes indicated that absorption of torular Rhodin in the intestine might require transporter CD36 and SR-B1.
Abstract: Torularhodin, as a new functional carotenoid, possesses great application potential in disease intervention. However, its absorption process and corresponding mechanism have not been studied. In this study, a rat postprandial model was established to explore the absorption and mechanism of torularhodin by investigating the bioavailability of torularhodin in different tissues, the expression of related enzymes and several transporters in the intestine. The results showed that torularhodin entered the intestine faster from micelles (45.21 ± 2.61% was absorbed in the duodenum), and part of it was metabolized into retinol in the anterior segment of the intestine. The expression of genes indicated that absorption of torularhodin in the intestine might require transporter CD36 and SR-B1. The special structure and target organ might be speculated to be the main reason for the low bioavailability of torularhodin in the serum and liver. The results could lay a theoretical foundation for the chemical modification, carrier and subsequent development of torularhodin.
TL;DR: In this article , the effects of replacing antibiotics with postbiotics and paraprobiotics on growth performance, small intestine morphology, immune status, and hepatic growth gene expression in broiler chickens were investigated.
Abstract: Simple Summary This study aimed to determine the effects of replacing antibiotics with postbiotics and paraprobiotics on growth performance, small intestine morphology, immune status, and hepatic growth gene expression in broiler chickens. Different strains of postbiotics and paraprobiotics were prepared from the active culture of Lactiplantibacillus plantarum and incorporated into the broiler starter and finisher diets at a 0.2% level. Birds were fed with the formulated diets for a period of 35 days. Bodyweight (BW) and feed intake (FI) were measured weekly, and the data were used to calculate body weight gain (BWG) and feed conversion ratio (FCR). The European Broiler Index (EBI) was used to compare the broiler results from different treatments. The EBI is a factor that standardizes technical results by taking into account feed conversion, mortality, and daily gain. EBI was calculated using the formula: (Average grams gained/day × % survival rate)/Feed conversion × 10. At the end of the feeding trial, birds were euthanized, and samples were collected for small intestine morphology, immune status, and hepatic growth gene expression determination. The results revealed that growth performance parameters were not affected by the dietary treatments. However, feed intake was significantly affected both at the starter and finisher phases. The abdominal fat, colon mucosa sIgA, histomorphology, and growth gene expression were significantly affected by the treatment diets. IgM was only significantly different at the finisher phase. Abstract Background: This experiment was designed to investigate how replacing antibiotics with postbiotics and paraprobiotics could affect growth performance, small intestine morphology, immune status, and hepatic growth gene expression in broiler chickens. Methods: The experiment followed a completely randomized design (CRD) in which eight treatments were replicated six times with seven birds per replicate. A total of 336, one-day-old (COBB 500) chicks were fed with the eight treatment diets, which include T1 = negative control (Basal diet), T2 = positive control (Basal diet + 0.01% (w/w) Oxytetracycline), T3 = Basal diet + 0.2% (v/w) postbiotic TL1, T4 = Basal diet + 0.2% (v/w) postbiotic RS5, T5 = Basal diet + 0.2% (v/w) paraprobiotic RG11, T6 = Basal diet + 0.2% (v/w) postbiotic RI11, T7 = Basal diet + 0.2% (v/w) paraprobiotic RG14, T8 = Basal diet + 0.2% (v/w) paraprobiotic RI11, for 35 days in a closed house system. Results: The growth performance indicators (final body weight, cumulative weight gain, and feed conversion ratio) were not significantly (p > 0.05) affected by the dietary treatments. However, feed intake recorded a significant (p < 0.05) change in the starter and finisher phases across the dietary treatments. Paraprobiotic RG14 had significantly (p < 0.05) lower abdominal fat and intestines. Villi heights were significantly (p < 0.05) increased, while the crypt depth decreased significantly due to dietary treatments. The dietary treatments significantly influenced colon mucosa sIgA (p < 0.05). Similarly, plasma immunoglobulin IgM level recorded significant (p < 0.05) changes at the finisher phase. In this current study, the hepatic GHR and IGF-1 expressions were significantly (p < 0.05) increased by postbiotics and paraprobiotics supplementation. Conclusions: Therefore, it was concluded that postbiotics and paraprobiotics differ in their effect on broiler chickens. However, they can replace antibiotics without compromising the growth performance, carcass yield, and immune status of broiler chickens.
TL;DR: To characterize the effects of blocking calcitonin gene‐related peptide (CGRP) activity in a mouse model of gastrointestinal transport, a novel ‘spatially aggregating’ mechanism is proposed.
Abstract: To characterize the effects of blocking calcitonin gene‐related peptide (CGRP) activity in a mouse model of gastrointestinal transport.
TL;DR: In this paper , the authors found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes and reduced the expression suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues.
Abstract: Lipid peroxidation-induced ferroptosis is a newly recognized type of programmed cell death. With the method of RNA sequencing, we found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes, whereas reduced the expression of ferroptosis suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues. By using ferroptosis inducer RSL-3 and inhibitor liproxstatin-1, we found that ferroptosis is essential for IR-induced intestinal injury. Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) is an important component for ferroptosis execution, and we found that ACSL4 expression was significantly upregulated in irradiated intestine tissues, but not in liver or lung tissues. Antibacterial and antifungal regents reduced the expression of ASCL4 and protected against tissue injury in irradiated intestine tissues. Further studies showed that troglitazone, a ACSL4 inhibitor, succeeded to suppresses intestine lipid peroxidation and tissue damage after IR.
TL;DR: The Zn-Prot M enhanced the Zn absorption in the small intestine partially via upregulating the expression of ZnT4,ZnT7, ZNT9, ZIP3, ZIP5, y + LAT2, and rBAT in the duodenum of broilers.
Abstract: Our previous study demonstrated that the absorption of zinc (Zn) from the organic Zn proteinate with moderate chelation strength was significantly higher than that of Zn from the inorganic Zn sulfate in the in situ ligated duodenal segment of broilers, but the underlying mechanisms are unknown. The present study aimed to determine the effect of organic Zn with moderate chelation strength and inorganic Zn on the Zn absorption in the small intestine and the expression of related transporters in the duodenum of broilers. The Zn-deficient broilers (13 days old) were fed with the Zn-unsupplemented basal diets (control) containing 25.72 and 25.64 mg Zn/kg by analysis or the basal diets supplemented with 60 mg Zn/kg as the Zn sulfate or the Zn proteinate with moderate chelation strength (Zn-Prot M) for 26 days. The results showed that the plasma Zn contents from the hepatic portal vein of broilers at 28 days and 39 days of age were increased (p < 0.05) by Zn addition and greater (p < 0.05) in the Zn-Prot M than in the Zn sulfate. On d 28, Zn addition upregulated (p < 0.05) mRNA expression of zinc transporter 1 (ZnT1), Zrt-irt-like protein 5 (ZIP5), y + L-type amino transporter 2 (y + LAT2) and b0,+-type amino acid transporter (rBAT), zinc transporter 4 (ZnT4) protein expression, and zinc transporter 9 (ZnT9) mRNA and protein expression in the duodenum. Moreover, ZnT9 mRNA expression, ZnT4, ZIP5, and rBAT protein expression, zinc transporter 7 (ZnT7), and y + LAT2 mRNA and protein expression in the duodenum of broilers on 28 days were higher (p < 0.05) in the Zn-Prot M than in the Zn sulfate. On d 39, supplemental Zn increased (p < 0.05) peptide-transporter 1 (PepT1) mRNA expression and y + LAT2 protein expression, while the mRNA expression of ZnT7 and Zrt-irt-like protein 3 (ZIP3) were higher (p < 0.05) for the Zn-Prot M than for the Zn sulfate in the duodenum. It was concluded that the Zn-Prot M enhanced the Zn absorption in the small intestine partially via upregulating the expression of ZnT4, ZnT7, ZnT9, ZIP3, ZIP5, y + LAT2, and rBAT in the duodenum of broilers.
TL;DR: Gut-derived LPS and oxidized phospholipids may be responsible for persistent inflammation seen in some persons with human immunodeficiency virus on potent antiretroviral therapy with undetectable virus levels as discussed by the authors .
Abstract: This review explores mechanisms by which gut-derived bacteriallipopolysaccharide (LPS) and oxidized phospholipids contribute to chronic systemic inflammation and atherosclerosis.Gut-derived LPS enters through the small intestine via two distinct pathways that involve high density lipoproteins (HDL) and chylomicrons. Gut-derived LPS can bind to the LPS-binding protein (LBP) and to HDL 3 in the small intestine and travel through the portal vein to the liver where it does not elicit an inflammatory reaction, and is inactivated or it can bind to HDL 2 and travel through the portal vein to the liver where it elicits an inflammatory reaction. Alternatively, in the small intestine, LPS can bind to LBP and chylomicrons and travel through the lymphatics to the systemic circulation and enhance inflammatory processes including atherosclerosis. Oxidized phospholipids formed in the small intestine regulate the levels and uptake of LPS in small intestine by regulating antimicrobial proteins such as intestinal alkaline phosphatase. Gut-derived LPS and oxidized phospholipids may be responsible for the persistent inflammation seen in some persons with human immunodeficiency virus on potent antiretroviral therapy with undetectable virus levels.By targeting gut-derived oxidized phospholipids, the uptake of gut-derived LPS may be reduced to decrease systemic inflammation and atherosclerosis.