Regions Of Small Intestine Research Articles

GastroNet: A CNN based system for detection of abnormalities in gastrointestinal tract from wireless capsule endoscopy images

Gastrointestinal disorders are a class of prevalent disorders in the world. Capsule endoscopy is considered an effective diagnostic modality for diagnosing such gastrointestinal disorders, especially in small intestinal regions. The aim of this work is to leverage the potential of deep convolutional neural networks for automated classification of gastrointestinal abnormalities from capsule endoscopy images. This method developed a deep learning architecture, GastroNetV1, an automated classifier, to detect abnormalities in capsule endoscopy images. The gastrointestinal abnormalities considered are ulcerative colitis, polyps, and esophagitis. The curated dataset consists of 6000 images with “ground truth” labeling. The input image is automatically classified as ulcerative colitis, a polyp, esophagitis, or a normal condition by a web-based application designed with the trained algorithm. The classifier produced 99.2% validation accuracy, 99.3% specificity, 99.3% sensitivity, and 0.991 AUC. These results exceed that of the state-of-the-art systems. Hence, the GastroNetV1 could be used to identify the different gastrointestinal abnormalities in the capsule endoscopy images, which will, in turn, improve healthcare quality.

Deep Learning-Based Real-Time Organ Localization and Transit Time Estimation in Wireless Capsule Endoscopy.

Wireless capsule endoscopy (WCE) has significantly advanced the diagnosis of gastrointestinal (GI) diseases by allowing for the non-invasive visualization of the entire small intestine. However, machine learning-based methods for organ classification in WCE often rely on color information, leading to decreased performance when obstacles such as food debris are present. This study proposes a novel model that integrates convolutional neural networks (CNNs) and long short-term memory (LSTM) networks to analyze multiple frames and incorporate temporal information, ensuring that it performs well even when visual information is limited. We collected data from 126 patients using PillCam™ SB3 (Medtronic, Minneapolis, MN, USA), which comprised 2,395,932 images. Our deep learning model was trained to identify organs (stomach, small intestine, and colon) using data from 44 training and 10 validation cases. We applied calibration using a Gaussian filter to enhance the accuracy of detecting organ boundaries. Additionally, we estimated the transit time of the capsule in the gastric and small intestine regions using a combination of a convolutional neural network (CNN) and a long short-term memory (LSTM) designed to be aware of the sequence information of continuous videos. Finally, we evaluated the model's performance using WCE videos from 72 patients. Our model demonstrated high performance in organ classification, achieving an accuracy, sensitivity, and specificity of over 95% for each organ (stomach, small intestine, and colon), with an overall accuracy and F1-score of 97.1%. The Matthews Correlation Coefficient (MCC) and Geometric Mean (G-mean) were used to evaluate the model's performance on imbalanced datasets, achieving MCC values of 0.93 for the stomach, 0.91 for the small intestine, and 0.94 for the colon, and G-mean values of 0.96 for the stomach, 0.95 for the small intestine, and 0.97 for the colon. Regarding the estimation of gastric and small intestine transit times, the mean time differences between the model predictions and ground truth were 4.3 ± 9.7 min for the stomach and 24.7 ± 33.8 min for the small intestine. Notably, the model's predictions for gastric transit times were within 15 min of the ground truth for 95.8% of the test dataset (69 out of 72 cases). The proposed model shows overall superior performance compared to a model using only CNN. The combination of CNN and LSTM proves to be both accurate and clinically effective for organ classification and transit time estimation in WCE. Our model's ability to integrate temporal information allows it to maintain high performance even in challenging conditions where color information alone is insufficient. Including MCC and G-mean metrics further validates the robustness of our approach in handling imbalanced datasets. These findings suggest that the proposed method can significantly improve the diagnostic accuracy and efficiency of WCE, making it a valuable tool in clinical practice for diagnosing and managing GI diseases.

Spatially and temporally precise microbiome profiling in the small intestine using the SIMBA capsule with X-ray tracking

IntroductionFew minimally invasive options for sampling the small intestinal (SI) luminal fluid exist to study the SI microbiota in health and disease. To address the lack of tools and methods to study GI regions that are difficult to access, Nimble Science developed a fully autonomous and passive sampling method, the Small Intestine MicroBiome Aspiration (SIMBA™) capsule, for convenient, high-quality, and reliable sampling to study the diet-microbiota interactions in the SI. MethodsThe sealing efficacy and microbial DNA preservation capacity of the SIMBA capsules was first validated through in vitro simulation assays. Then, a clinical study was conducted with 20 healthy participants to validate the in vivo use of SIMBA capsules to reliably capture samples for SI microbiome analysis before and after an intervention (NCT04489329). Briefly, participants ingested the capsules at baseline and 7 days later, with a probiotic capsule containing a blend of L. rhamnosus R0011 and B. longum R0175. Following baseline SIMBA capsule ingestion, multiple low-dosage x-ray scans were performed to track the sampling location. Fecal samples corresponding with the baseline and intervention capsule were analyzed for comparison. ResultsThe SIMBA capsules’ performance in vitro demonstrated the potential for contamination-free sampling with preservation of the microbial communities. Within the clinical study, the capsules performed safely and reliably for collection of SI content. X-ray tracking confirmed that 97.2% of the capsules completed sample collection in the SI regions before reaching the colon. Importantly, our data showed that the capsules sampled in the right area of the intestines and that baseline SIMBA microbiome profile is significantly different from fecal microbiome profile. SIMBA successfully detected a concurrent probiotic intervention in the small intestine, which was not detectable using stool samples. DiscussionsThe high accuracy of sampling location and sealing efficacy of the SIMBA capsules makes them potentially useful research tools in clinical trials for studying diet-microbiota interactions in health and disease, and perhaps eventually for the clinical diagnosis of GI tract conditions affecting the SI such as SIBO.

Biopsy samples from patients with irritable bowel syndrome, but not from those with mastocytosis or unspecific gastrointestinal complaints reveal unique nerve activation in all gut regions independent of mast cell density, histamine content or specific gastrointestinal symptoms.

We previously showed enteric nerve activation after application of colonic mucosal biopsy supernatants from patients with irritable bowel syndrome (IBS). The question remains whether this is a region-specific or a generalized sensitization. We tested the nerve-activating properties of supernatants from large and small intestinal regions of IBS patients with diarrhea (IBS-D) in comparison to those from mastocytosis patients with diarrhea (MC-D) or non-IBS/non-MC patients with GI-complaints. MC-D patients were included to test samples from patients with an established, severe mast cell disorder, because mast cells are suggested to play a role in IBS. Voltage-sensitive dye imaging was used to record the effects of mucosal biopsy supernatants from IBS-D, MC-D, and non-IBS/non-MC on guinea pig submucous neurons. Mast cell density and histamine concentrations were measured in all samples. The median neuroindex (spike frequency × % responding neurons in Hz × %) was significantly (all p < 0.001) increased for IBS-D (duodenum and colon, proximal and distal each, 49.3; 50.5; 63.7; 71.9, respectively) compared to non-IBS/non-MC (duodenum and colon, proximal and distal each, 8.7; 4.9; 6.9; 5.4, respectively) or MC-D supernatants (duodenum and colon, proximal and distal each, 9.4; 11.9; 0.0; 7.9, respectively). Nerve activation by MC-D and non-IBS/non-MC supernatants was comparable (p>0.05). Mast cell density or histamine concentrations were not different between IBS-D, MC-D, and non-IBS/non-MC samples. Nerve activation by biopsy supernatants is an IBS hallmark that occurs throughout the gut, unrelated to mast cell density or histamine concentration. At least as important is our finding that GI complaints per se were not associated with biopsy supernatant-induced nerve activation, which further stresses the relevance of altered nerve behavior in IBS.

Adaptations in Gastrointestinal Nutrient Absorption and its Determinants During Pregnancy in Monogastric Mammals: A Scoping Review.

Pregnancy increases nutrient demand, but how nutrient uptake and its determinants adapt to facilitate this is unclear. This review aimed to identify and characterize evidence and evidence gaps regarding changes in gastrointestinal nutrient absorption and its determinants during pregnancy in monogastric mammals. A scoping review of peer-reviewed sources was conducted across PubMed, Scopus, Web of Science, Embase, and ProQuest (theses and dissertations) databases. Data extracted included species, pregnancy stages and outcomes. Where sufficient data for a given outcome was available, relative values were summarized graphically or in tables, to allow comparison across pregnancy stages and/or small intestine regions. Searches identified 26 855 sources, of which only 159 were eligible. Mechanistic studies were largely restricted to rodents, and most compared non- and late-pregnant groups, with fewer studies including early- or mid-pregnant groups. During pregnancy, there is some evidence for greater capacity for glucose uptake but unchanged amino acid uptake, and good evidence for increased uptake of calcium, iron, and zinc, and slower gastrointestinal passage of nutrients. The available evidence indicates that acute glucose uptake, gastric emptying, and the activities of sucrase, maltase, and lactase do not change during pregnancy. Gaps in the knowledge include the effects of pregnancy on uptake of specific amino acids, lipids, and most minerals and vitamins. The results indicate that the gastrointestinal tract adapts during pregnancy to facilitate increased nutrient absorption. Additional data is required in order to assess the underlying mechanisms for and impacts on the absorption of many nutrients, as well as to determine the timing of these adaptations.

Effect of chronic stress on gel-forming mucins in the small intestine of BALB/c mice.

Intestinal homeostasis involves the collaboration of gut barrier components, such as goblet cells and IgA-microbiota complexes, that are under the control of stress that promotes inflammatory responses addressed primarily in the colon. The aim of this study was to evaluate the effect of stress on mucins, goblet cells, and proinflammatory parameters in the proximal and distal regions of the small intestine. A group (n = 6) of female 8-week-old BALB/c mice underwent board immobilization stress (2 h per day for 4 days) and were sacrificed with isoflurane. Samples from proximal and distal small segments were collected to analyze the following: 1) goblet cells stained with periodic acid-Schiff (PAS) and with alcian blue (AB) to visualize histologically neutral and acidic mucins, respectively; 2) IgA-microbiota complexes identified by flow cytometry in intestinal lavages; and 3) MUC2, MUC5AC, and IL-18 mRNA levels in whole mucosal scrapings by reverse transcription-qPCR. Regarding the unstressed group, in the proximal region of small intestine both PAS+ and AB+ goblet cells were unchanged; however, MUC5AC and IL-18 mRNA levels were increased, and the percentage of IgA-microbiota complexes was reduced. In the distal segment, the number of PAS+ goblet cells was increased, whereas the number of AB+ goblet cells was reduced and did not affect the remaining parameters. The data suggest that stress induces inflammation in the proximal small intestine; these findings may provide an experimental reference for human diseases that may affect the proximal small intestine, such as Crohn's disease, in which stress contributes to the progression of intestinal inflammation or relapse.

Bland–Altman agreement analysis between CT predicted and surgical peritoneal cancer index in pseudomyxoma peritonei of appendiceal origin

Peritoneal cancer index (PCI) is the surgical variable most commonly used to quantify the extent of peritoneal metastases for pseudomyxoma peritonei (PMP) patients. The present study aimed to investigate the agreement between CT predicted and surgical PCI by the Bland–Altman method for PMP of appendiceal origin. A total of 167 PMP patients of appendiceal origin were included between 2016 and 2021. Bland–Altman analysis was performed for both total PCI and selected PCI (regions 2 + 9–12). After the Bland–Altman plot was drawn, the mean bias and its 95% limit of agreements (LoAs) was quantified. Besides, the correlation coefficients between CT-PCI and surgical PCI were also been calculated. The Bland–Altman plot showed the mean bias ± SD between total CT-PCI and surgical PCI as 0.431 ± 3.005, with the LoAs from − 5.459 to 6.321. There were nine points of difference in total PCI exceeded the 95% LoAs, with the rate of 5.39% (9/167). As for selected CT-PCI, Bland–Altman plot showed the mean bias ± SD between selected CT-PCI and surgical PCI as − 0.287 ± 1.955, with the LoAs from − 4.118 to 3.544. There were ten points of difference in selected PCI exceeded the 95% LoAs, with the rate of 5.99% (10/167). The Spearman's rank correlation coefficient between total CT-PCI and surgical PCI was 0.911, P < 0.001, as for selected CT-PCI and surgical PCI, the coefficient was 0.909, P < 0.001. Although there was a strong correlation for both total and selected CT-PCI with surgical PCI, however, the agreement is still not good in Bland–Altman analysis, which suggested that CT-PCI cannot predict surgical PCI accurately even in professional PMP treatment centers. In brief explanation, CT makes it difficult to distinguish the borderline between tumor tissue and mucus and to detect tumor lesions in the small intestine regions, which caused overestimation or underestimation by CT-PCI. In the future, a multiple linear regression model based on CT-PCI might accurately predict surgical PCI preoperatively.

Evaluation of a Plant-Based Infant Formula Containing Almonds and Buckwheat on Gut Microbiota Composition, Intestine Morphology, Metabolic and Immune Markers in a Neonatal Piglet Model.

A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus delbrueckii, Lactobacillus crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.

Loss of Endothelial Cell RIPK3 Leads to Increased Vascular Permeability Following Intestinal Ischemia‐Reperfusion Injury

The receptor‐interacting serine/threonine‐protein kinase 3 (RIPK3) is primarily known for promoting necroptosis, but recent findings suggest that RIPK3 has non‐necroptotic roles as well, particularly in endothelial cells (ECs). Our lab has reported both beneficial and detrimental roles for endothelial RIPK3 during vascular development, which has prompted us to study RIPK3 in the context of different postnatal vascular pathologies. Our current study focuses on roles for endothelial RIPK3 following intestinal ischemia‐reperfusion (I/R) injury in mice. First‐order branches of the superior mesenteric artery that feeds the ileum were clamped for 1 hr to induce ischemia, and clamps were removed subsequently to allow 24 hr reperfusion in tamoxifen‐induced Ripk3;Cdh5(PAC)‐CreERT2 mice (RIPK3ECKO) compared to wildtype littermate control mice (WT) (males and females, 12 weeks old). Unclamped small intestinal regions were considered as sham control in the same mouse. An Evans blue permeability assay was utilized in assessing small intestinal and distal organ vascular permeability. Small intestinal vascular permeability directly downstream of I/R injury was significantly increased in both RIPK3ECKO and WT mice (n=6 mice/group), however permeability was also significantly increased in sham small intestinal regions and in livers of RIPK3ECKO unlike in WT controls (n=6 mice/group). No difference in vascular permeability was observed between RIPK3ECKO and WT mice (n=5 mice/group) at baseline without I/R injury in all organs assessed. However, in uninjured RIPK3ECKO mice we do observe an increase in the CD68+ proinflammatory macrophage marker in the liver and submucosal layer of the small intestine compared to uninjured WT mice (n=5 mice/group). When clodronate liposomes were administered to deplete macrophages and determine whether this CD68+ macrophage population was contributing to the increased permeability in RIPK3ECKO mice following I/R injury, we observed a permeability rescue in the small intestine but not in the liver (n=4‐5 mice/group). This finding suggests that there are organ‐specific differences in macrophage contribution to vascular permeability following I/R injury. Our current studies are evaluating circulating and tissue specific cytokines and endothelial cell adhesion molecules to understand why RIPK3ECKO vasculature becomes more permeable in response to I/R injury. Discovering cellular mechanisms for vascular endothelial RIPK3 following I/R injury could provide novel therapeutic targets to promote vessel recovery after I/R injury.

Oxygen concentration of gut luminal contents varies post-prandially in growing pigs.

The oxygen (O2 ) concentration of gastrointestinal tract (GIT) contents decreases distally, but little is known about how O2 concentrations are influenced by ingestion of a meal. The O2 concentration in luminal contents at different GIT locations (stomach [cardia and pylorus], proximal, mid- and distal small intestine and caecum) and how these concentrations changed post-prandially were determined. Fifty entire male pigs (22kg bodyweight at the start of study) were fed semi-synthetic diets containing casein, α-lactalbumin, whey protein isolate or zein as the sole source of protein for 8days. A further group of pigs received the casein diet for six days and a semi-synthetic protein-free diet for a further 2days. On day 8, pigs (n=2 per diet and time point) were euthanized post-prandially (0, 1, 2, 4 and 6h), and the stomach, small intestine and caecum were isolated and O2 determined in the GIT contents. Observations at each time point were averaged across the diets (n=10). The mean O2 concentration was markedly higher (p≤0.05) in the stomach compared with the rest of the GIT. The O2 concentration was similar in the small intestinal regions (p>0.05; 1.0%-1.1%) and the caecum (0.9%), apart for the proximal small intestine which had a 24% higher (p≤0.05) O2 concentration than the caecum. The mean O2 concentration in the GIT varied post-prandially (p≤0.05). The O2 concentration in the cardia decreased 1.8%/h over the first two hours post-feeding and thereafter increased 0.3%/h (p≤0.05). In the caecum, the O2 concentration was constant during the first 4h and thereafter increased slightly (p≤0.05). The flow of food through the GIT influenced both the concentration and amount of O2 in GIT luminal contents.

Anesthetic Preconditioning of the Small Intestine in Hemorrhagic Hypotension

Aim of the study. To investigate the preconditioning effect of sevoflurane on small intestinal mucosa in experimental hemorrhagic hypotension.Material and methods. The study was performed on a cohort of 106 male rats that included two experimental groups: one exposed to ether (Group 1, n=40) and another one exposed to sevoflurane (Group 2, n=40); two control groups included 20 intact animals, of which 10 were anesthetized with ether and 10 with sevoflurane. Six animals were excluded from the study because they died by the 2nd hour of hemorrhagic hypotension under ether anesthesia. The study parameters were measured at 15 min, 30 min, 1 h, and 2 h of hemorrhagic hypotension. Amylolytic activity of the small intestine mucosa was determined by E. A. Zabelinsky, B. W. Smith and I. M. Roe technique modified by A. M. Ugolev. The data were statistically analyzed using the nonparametric Mann-Whitney method.Results. By 15 min of hemorrhagic hypotension, the activity of amylase fractions in all small intestine regions in Group 2 animals was significantly lower vs the Group 1 rats. By 30 min of hemorrhagic hypotension, the activity of the enzyme fractions in all small intestine regions in Group 2 animals remained significantly lower than in Group 1, by an average of 2 to 9 times (P=0.01; P&lt;0.001), and after 1 h of hemorrhagic hypotension, it was 2 and 4 times lower (P=0.02; P&lt;0.001). By the 2nd hour of hemorrhagic hypotension, the activity of nearly all duodenal amylase fractions in the Group 2 animals remained 3-4 times lower compared to Group 1. Meanwhile, a significantly higher activity of slowly desorbing and intracellular amylase fractions vs the control group was observed in jejunum and ileum.Conclusion. In hemorrhagic hypotension under sevoflurane anesthesia, a decrease of the pancreas excretory function, stabilization of the brush border of the mucosa of all small intestine regions, including enterocyte membranes, was found during the first hour of experiment. Two hours after the hemorrhage, the biochemical evidence of brush border damage in the jejunum and ileum was revealed.

Evaluation of organ glucose metabolism by 18F-FDG accumulation with insulin loading in aged mice compared with young normal mice

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-d-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

Primary and Metastatic Malignant Melanomas of the Digestive System

Purpose: Primary and metastatic digestive system malignant melanomas are extremely rare. In our study, we aimed to compare lymph node metastasis with clinical and pathological parameters in gallbladder, stomach, small intestine and anorectal region malignant melanomas. Materials and methods: This retrospective study included 20 cases diagnosed with malignant melanoma in the gastrointestinal tract organs between January 2010 and January 2020 at XXXXXXXXXXXX. In our study, we wanted to evaluate the relationship between regional lymph node metastasis and age, gender, tumor localization, tumor size, extraintestinal melanoma history, melanin pigment, neutrophil-lymphocyte ratio and post-diagnosis life span in primary and metastatic malignant melanoma cases. We also reviewed the origin and literature of the cells from which melanoma originates in the digestive system. Results: There was a statistical relationship between tumor diameter and regional lymph node metastasis (p =0.000). As the tumor diameter increased, the lymph node metastasis rate increased. There was a relationship between survival and gender, tumor localization, distant metastasis, primary and metastatic digestive system melanoma (all p <0.05). Most of the men and those who did not metastasize away from the digestive system were alive. All patients with melanoma metastases to the digestive system and all patients with gallbladder and small intestine localization were alive. Our 70 year old patient with gallbladder primary malignant melanoma was the oldest patient we could identify in the literature. Conclusions: Regardless of cutaneous or origin, all melanomas originate from melanocytes, cells derived from embryological nerve crest. Malignant melanoma can be primary in every region, more frequently in the anorectal region in the gastrointestinal tract. The most common metastasis is to the small intestine. Accurate diagnosis is vital in places where it is rarely seen, such as the digestive system. Recently, in metastatic melanoma, immuno-oncological agents are used in adjuvant therapy to help prevent metastatic spread of the disease. Thanks to these treatments, it is reported that more than half of patients with melanoma who have the risk of metastasis after surgical resection provide recurrence-free survival. Although it is very rare, it should be kept in mind that there may be primary or metastatic malignant melanoma in the evaluation of digestive system biopsies.

An Ingestible Self-Polymerizing System for Targeted Sampling of Gut Microbiota and Biomarkers.

A proof-of-concept for the fabrication of a self-polymerizing system for sampling of gut microbiome in the upper gastrointestinal (GI) tract is presented. An orally ingestible microdevice is loaded with the self-polymerizing reaction mixture to entrap gut microbiota and biomarkers. This polymerization reaction is activated in the aqueous environment, like fluids in the intestinal lumen, and causes site-specific microsampling in the gastrointestinal tract. The sampled microbiota and protein biomarkers can be isolated and analyzed via high-throughput multiomic analyses. The study utilizes a hollow microdevice (Su-8, ca. 250 μm), loaded with an on-board reaction mixture (iron chloride, ascorbic acid, and poly(ethylene glycol) diacrylate monomers) for diacrylate polymerization in the gut of an animal model. An enteric-coated rat capsule was used to orally gavage these microdevices in a rat model, thereby, protecting the microdevices in the stomach (pH 2), but releasing them in the intestine (pH 6.6). Upon capsule disintegration, the microdevices were released in the presence of luminal fluids (in the small intestine region), where iron chloride reacts with ascorbic acid, to initiate poly(ethylene glycol) diacrylate polymerization via a free radical mechanism. Upon retrieval of the microdevices, gut microbiota was found to be entrapped in the polymerized hydrogel matrix, and genomic content was analyzed via 16s rRNA amplicon sequencing. Herein, the results show that the bacterial composition recovered from the microdevices closely resemble the bacterial composition of the gut microenvironment to which the microdevice is exposed. Further, histological assessment showed no signs of local tissue inflammation or toxicity. This study lays a strong foundation for the development of untethered, non-invasive microsampling technologies in the gut and advances our understanding of host-gut microbiome interactions, leading to a better understanding of their commensal behavior and associated GI disease progression in the near future.

Changes in expression of antimicrobial peptides and Fc receptors in the small intestines of neonatal calves during the passive immunity period

The contribution of colostrum to passive immunity transfer and intestinal protection is well known; however, the effects of colostrum intake on the expression of antimicrobial peptides (AP) and Fc receptors in the intestine of neonatal calves are unclear. Our aim was to investigate changes in the expression of AP and Fc receptor in the small intestine of calves in the first 36 h postpartum. Twenty-four Holstein bull calves were used in this study, of which 18 calves were administered 3.2 L of pooled colostrum for each calf per meal via an esophageal tube. Calves were slaughtered at 8 h (1 meal at 1-2 h), 24 h (2 meals at 1-2 h and 10-12 h), and 36 h (3 meals at 1-2 h, 10-12 h, and 22-24 h) postpartum. The remaining 6 calves without any milk administration were slaughtered at 2 h postpartum. Samples of blood and jejunum digesta were collected to determine immunoglobulin concentration using ELISA. Samples of the duodenum, jejunum, and ileum tissues after slaughter were collected to determine AP and Fc receptor expression using quantitative real-time PCR. In calves administered colostrum, IgG concentration in jejunum digesta rapidly decreased in an age-dependent manner (33.41, 9.47, and 0.34 mg/mL at 8, 24, and 36 h, respectively), whereas serum IgG concentration increased significantly, from 0.25 μg/mL at 2 h to 21.72 mg/mL at 24 h. Cathelicidin-4, β-defensin (DEFB)-7, and enteric β-defensin expression was upregulated at 8 h postpartum in the duodenum and jejunum compared with that at 2 h, but progressive recovery was detected from 24 h onward. Higher expression of cathelicidin-4, regenerating family member 3γ, lysozyme (LYZ), LYZ1, and LYZ2 and lower expression of DEFB, DEFB1, DEFB7, DEFB10, and enteric β-defensin were observed in the duodenum and jejunum compared with the ileum. Differences in AP expression between intestinal regions suggested that the innate immune defense mechanism varied significantly among the duodenum, jejunum, and ileum. No difference in the expression of Fc fragment of the IgG receptor was observed either among ages or small intestinal regions. The Fcγ receptor (FcγR)Ia and FcγRIIb expression was the highest at 8 h compared with that at 2, 24, and 36 h, and expression of FcγRIa, FcγRIIb, and FcγRIIIa was higher in the duodenum and jejunum than in the ileum. These results indicated that AP and Fcγ receptors might play important roles in intestinal defense during the passive immunity period.

Self-recovery study of the adverse effects of fluoride on small intestine: Involvement of pyroptosis induced inflammation

Increasing investigations suggest that fluoride (F) exposure was associated with gastrointestinal diseases, but related literatures were still largely insufficient and the underlying mechanisms have not been fully elucidated. Moreover, previous study in our lab reported F toxicity has the reversible tendency, but it still needs to be further explored. To address this issue, we established a 90 days F exposure and 15 days & 30 days self-recovery mice model, including control and three F groups (25, 50 and 100 mg/L sodium fluoride (NaF)) in each period. The results revealed that after 90 days F exposure, histological structure and ultrastructure of small intestine were markedly disrupted; the value of villus height to crypt depth, and expressions of tight junctions related mRNA and proteins were significantly decreased; intestinal permeability, pro-inflammatory cytokines and pyroptosis related mRNA and proteins were notably increased in duodenum, jejunum and ileum. However, intriguingly, after 30 days recovery period, indices in F groups almost all have recovered towards normalcy. Collectively, this study demonstrated that F exposure could impair the structure and epithelial barrier function of small intestine, leading to the intestinal inflammation, and pyroptosis may contribute to this damage; Furthermore, F toxicity on small intestine is reversible, and could be restored when off the F exposure environment for a certain period of time. Additionally, among the three regions of small intestine, duodenum seems more vulnerable to F exposure than jejunum and ileum.

Vitamin D signaling maintains intestinal innate immunity and gut microbiota: potential intervention for metabolic syndrome and NAFLD.

A lack of sunlight exposure, residence in the northern latitudes, and dietary vitamin D insufficiency are coprevalent with metabolic syndrome (MetS), Type 2 diabetes (T2D), and nonalcoholic fatty liver diseases (NAFLD), implying a potential causality and underlying mechanism. Whether vitamin D supplementation or treatment can improve these disorders is controversial, in part, because of the absence of large-scale trials. Experimental investigations, on the other hand, have uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin that maintained calcium homeostasis. While the large intestine harbors massive numbers of microbes, the small intestine has a minimal quantity of bacteria, indicating the existence of a gating system located in the distal region of the small intestine that may restrain bacterial translocation to the small intestine. Vitamin D receptor (VDR) was found to be highly expressed at the distal region of small intestine, where the vitamin D signaling promotes innate immunity, including the expression of α-defensins by Paneth cells, and maintains the intestinal tight junctions. Thus, a new hypothesis is emerging, indicating that vitamin D deficiency may impair the intestinal innate immunity, including downregulation of Paneth cell defensins, leading to bacterial translocation, endotoxemia, systemic inflammation, insulin resistance, and hepatic steatosis. Here, we review the studies for vitamin D for innate immunity and metabolic homeostasis, and we outline the clinical trials of vitamin D for mitigating MetS, T2D, and NAFLD.

Hepatoid Adenocarcinoma presenting in the colon with an unknown primary: A rare tumor case report

Hepatoid adenocarcinoma (HAC) is a very rare malignant tumor of extrahepatic origin which is characterized by having foci with features of both hepatocellular differentiation as well as adenomatous differentiation. It is most commonly seen in the stomach, however, few cases of HAC originating in the ovary, small intestine, colon, lung, uterus, pancreas, gallbladder, oesophagus and periampullary region have also been reported. Interestingly, it morphologically and functionally resembles Hepatocellular carcinoma, which can make the diagnosis challenging. Identification of HAC is necessary as it is associated with a dismal prognosis. We report here a case of a metastatic hepatoid adenocarcinoma of an unknown primary presenting in the ascending colon with both hepatoid and mucinous adenocarcinomatous areas on morphology. Keywords: Gastrointestinal tract, Hepatic like, Tumor.

NF-\u03baB2 signalling in enteroids modulates enterocyte responses to secreted factors from bone marrow-derived dendritic cells

Alternative pathway NF-κB signalling regulates susceptibility towards developing inflammatory bowel disease (IBD), colitis-associated cancer and sepsis-associated intestinal epithelial cell apoptosis and shedding. However, the cell populations responsible for the perturbed alternative pathway NF-κB signalling in intestinal mucosal pathology remain unclear. In order to investigate the contribution of the epithelial compartment, we have tested whether NF-κB2 regulated transcription in intestinal epithelial cells controls the intestinal epithelial response to cytokines that are known to disrupt intestinal barrier permeability. Enteroids were generated from the proximal, middle and distal regions of small intestine (SI) from C57BL/6J wild-type mice and displayed region-specific morphology that was maintained during sub-culture. Enteroids treated with 100 ng/mL TNF were compared with corresponding regions of SI from C57BL/6J mice treated systemically with 0.33 mg/kg TNF for 1.5 h. TNF-induced apoptosis in all regions of the intestine in vitro and in vivo but resulted in Paneth cell degranulation only in proximal tissue-derived SI and enteroids. TNF also resulted in increased enteroid sphericity (quantified as circularity from two-dimensional bright field images). This response was dose and time-dependent and correlated with active caspase-3 immunopositivity. Proximal tissue-derived enteroids generated from Nfκb2−/− mice showed a significantly blunted circularity response following the addition of TNF, IFNγ, lipopolysaccharide (LPS) activated C57BL/6J-derived bone marrow-derived dendritic cells (BMDC) and secreted factors from LPS-activated BMDCs. However, Nfκb1−/− mouse-derived enteroids showed no significant changes in response to these stimuli. In conclusion, the selection of SI region is important when designing enteroid studies as region-specific identity and response to stimuli such as TNF are maintained in culture. Intestinal epithelial cells are at least partially responsible for regulating their own fate by modulating NF-κB2 signalling in response to stimuli known to be involved in multiple intestinal and systemic diseases. Future studies are warranted to investigate the therapeutic potential of intestinal epithelial NF-κB2 inhibition.

Mucins are Involved in the Intestinal Permeation of Lipophilic Drugs in the Proximal Region of Rat Small Intestine.

Mucins are the principal glycoproteins in mucus and have been implicated in the limitation of intestinal drug absorption; however, the contribution of these molecules to intestinal drug absorption remains unclear. In this study, the relationship between the effect of the mucus layer on intestinal drug permeation and mucin distribution in different parts of the rat gastrointestinal tract was evaluated. The intestinal permeability of various lipophilic drugs in rat small intestine was evaluated using the in vitro sac method. The expression profiles of mucin mRNA and proteins were evaluated by quantitative real-time RT-PCR and western blotting, respectively. The intestinal permeability of griseofulvin and antipyrine was enhanced by dithiothreitol (DTT) treatment in the proximal small intestine, such as duodenum and jejunum, but not in the distal regions. The mRNA expression analysis of rat mucin genes revealed that the intestinal expression of Muc5ac was considerably higher in the duodenum, whereas that of Muc1, Muc2, and Muc3A was gradually increased toward the lower intestine. In addition, Muc5ac protein was detected only in the luminal fluids from the proximal small intestine after DTT treatment. Mucus limits the intestinal permeation of lipophilic drugs in the rat proximal small intestine, in which Muc5ac may be involved.