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Metabolism: Clinical and Experimental Jan 2024The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the... (Review)
Review
The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the metabolic status of the host. While research on the fecal microbiome has provided valuable insights, it tells us only part of the story. This limitation arises from the substantial variations in microorganism distribution throughout the gastrointestinal tract due to changes in physicochemical conditions. Thus, relying solely on the fecal microbiome may not be sufficient to draw comprehensive conclusions about metabolic diseases. The proximal part of the small intestine, particularly the jejunum, indeed, serves as the crucial site for digestion and absorption of nutrients, suggesting a potential role of its microbiome in metabolic regulation. Unfortunately, it remains relatively underexplored due to limited accessibility. This review presents current evidence regarding the relationships between the microbiome in the upper small intestine and various phenotypes, focusing on obesity and type 2 diabetes, in both humans and rodents. Research on humans is still limited with variability in the population and methods used. Accordingly, to better understand the role of the whole gut microbiome in metabolic diseases, studies exploring the human microbiome in different niches are needed.
Topics: Humans; Diabetes Mellitus, Type 2; Microbiota; Metabolic Diseases; Obesity; Intestine, Small
PubMed: 37884078
DOI: 10.1016/j.metabol.2023.155712 -
Medical Image Analysis May 2022Cine-MRI of the abdomen is a non-invasive imaging technique allowing assessment of small intestinal motility. This is valuable for the evaluation of gastrointestinal...
Cine-MRI of the abdomen is a non-invasive imaging technique allowing assessment of small intestinal motility. This is valuable for the evaluation of gastrointestinal disorders. While 2D cine-MRI is increasingly used for this purpose in both clinical practice and in research settings, the potential of 3D cine-MRI has been largely underexplored. In the absence of image analysis tools enabling investigation of the intestines as 3D structures, the assessment of motility in 3D cine-images is generally limited to the evaluation of movement in separate 2D slices. Furthermore, while a segmentation map of the small intestine would be required for a number of automatic analysis tasks, deep learning based segmentation of the small intestine generally performs poorly due to the large variety in shapes, sizes and locations in the abdomen among different patients. Using a data set of 3D cine-MRI scans from 14 healthy volunteers, we developed a multi-task method that automatically tracks individual segments of the small intestine in a time-point from 3D cine-MRI scans, using a stochastic tracker built on top of a CNN-based orientation classifier. The method additionally performs segmentation, conditioned on the locations of intestinal centerlines. We demonstrate the benefit of our stochastic tracking strategy and we show that our proposed segmentation method performs significantly better than an identical network without centerline conditioning. Furthermore, we assess the robustness of the method through evaluation on a set of patients with severe bowel disease. In terms of centerline tracking, our method achieves a recall of 0.74±0.07, a precision of 0.80±0.06 and an F1 score of 0.77±0.05 in the set of healthy volunteers. In the set of patients, it achieves a recall of 0.76±0.12, a precision of 0.86±0.11 and an F1 score of 0.80±0.08. Segmentation achieves a Dice coefficient of 0.88±0.03 in the set of healthy volunteers and 0.79±0.09 in the set of patients. By extracting a structural representation of the small intestine, the presented method provides a major first step towards automatic detailed quantitative assessment of small intestinal motility in abdominal 3D cine-MRI.
Topics: Deep Learning; Humans; Image Processing, Computer-Assisted; Intestine, Small; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine
PubMed: 35259636
DOI: 10.1016/j.media.2022.102386 -
Tissue Engineering. Part B, Reviews Aug 2020Pathologies affecting the small intestine contribute significantly to the disease burden of both the developing and the developed world, which has motivated... (Review)
Review
Pathologies affecting the small intestine contribute significantly to the disease burden of both the developing and the developed world, which has motivated investigation into the disease mechanisms through models. Although existing models recapitulate selected features of the intestine, various important aspects have often been isolated or omitted due to the anatomical and physiological complexity. The small intestine's intricate microanatomy, heterogeneous cell populations, steep oxygen gradients, microbiota, and intestinal wall contractions are often not included in experimental models of the small intestine, despite their importance in both intestinal biology and pathology. Known and unknown interdependencies between various physiological aspects necessitate more complex models. Microfluidic technology has made it possible to mimic the dynamic mechanical environment, signaling gradients, and other important aspects of small intestinal biology. This review presents an overview of the complexity of small intestinal anatomy and bioengineered models that recapitulate some of these physiological aspects.
Topics: Animals; Cell Differentiation; Humans; Intestine, Small; Models, Biological; Tissue Engineering
PubMed: 32046599
DOI: 10.1089/ten.TEB.2019.0334 -
Journal of Controlled Release :... Mar 2022Micro- and nano-scale particulate formulations are widely investigated towards improving the oral bioavailability of both biologics and drugs with low solubility and/or... (Review)
Review
Micro- and nano-scale particulate formulations are widely investigated towards improving the oral bioavailability of both biologics and drugs with low solubility and/or low intestinal permeability. Particulate formulations harnessing physiological intestinal transport pathways have recently yielded remarkably high oral bioavailabilities, illustrating the need for better understanding the specific pathways underpinning particle small intestinal absorption and the relative role of intestinal cells. Mechanistic knowledge has been hampered by the well acknowledged limitations of current in vitro, in vivo and ex vivo models relevant to the human intestinal physiology and the lack of standardization in studies reporting absorption data. Here we review the relevant literature and critically discusses absorption pathways with a focus on the role of specific intestinal epithelial and immune cells. We conclude 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. We also comment on less-reported mechanisms such as paracellular permeability of particles, persorption due to cell damage and uptake by migratory immune cells.
Topics: Administration, Oral; Biological Availability; Biological Transport; Humans; Intestinal Absorption; Intestine, Small; Permeability
PubMed: 35149142
DOI: 10.1016/j.jconrel.2022.02.006 -
Physiological Reports Feb 2021Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The... (Comparative Study)
Comparative Study
BACKGROUND
Obesity is associated with the development of insulin resistance (IR) and type-2 diabetes mellitus (T2DM); however, not all patients with T2DM are obese. The Goto-Kakizaki (GK) rat is an experimental model of spontaneous and non-obese T2DM. There is evidence that the intestine contributes to IR development in GK animals. This information prompted us to investigate small intestine remodeling in this animal model.
METHODS
Four-month-old male Wistar (control) and GK rats were utilized for the present study. After removing the small intestine, the duodenum, proximal jejunum, and distal ileum were separated. We then measured villi and muscular and mucosa layer histomorphometry, goblet cells abundance, total myenteric and submucosal neuron populations, and inflammatory marker expression in the small intestinal segments and intestinal transit of both groups of animals.
KEY RESULTS
We found that the GK rats exhibited decreased intestinal area (p < 0.0001), decreased crypt depth in the duodenum (p = 0.01) and ileum (p < 0.0001), increased crypt depth in the jejunum (p < 0.0001), longer villi in the jejunum and ileum (p < 0.0001), thicker villi in the duodenum (p < 0.01) and ileum (p < 0.0001), thicker muscular layers in the duodenum, jejunum, and ileum (p < 0.0001), increased IL-1β concentrations in the duodenum and jejunum (p < 0.05), and increased concentrations of NF-κB p65 in the duodenum (p < 0.01), jejunum and ileum (p < 0.05). We observed high IL-1β reactivity in the muscle layer, myenteric neurons, and glial cells of the experimental group. GK rats also exhibited a significant reduction in submucosal neuron density in the jejunum and ileum, ganglionic hypertrophy in all intestinal segments studied (p < 0.0001), and a slower intestinal transit (about 25%) compared to controls.
CONCLUSIONS
The development of IR and T2DM in GK rats is associated with small intestine remodeling that includes marked alterations in small intestine morphology, local inflammation, and reduced intestinal transit.
Topics: Animals; Blood Glucose; Cytokines; Diabetes Mellitus, Type 2; Disease Models, Animal; Duodenum; Gastrointestinal Transit; Ileum; Inflammation Mediators; Insulin Resistance; Intestine, Small; Jejunum; Male; Myenteric Plexus; Rats, Wistar; Submucous Plexus; Rats
PubMed: 33580916
DOI: 10.14814/phy2.14755 -
Biochemical and Biophysical Research... Jun 2022Macroscopic lipid observation in the organs of living small animals has not been realized. Here, we visualized sphingomyelin (SM) in the intestines of living mice using...
Macroscopic lipid observation in the organs of living small animals has not been realized. Here, we visualized sphingomyelin (SM) in the intestines of living mice using an SM-binding protein (EqtII-EGFP-His) under two-photon microscopy. The SM was identified as 10 μm spots in glands of the lamina propria of the mucosa in the large and small intestines. The spots vertically penetrated from the serosa toward the mucosal side. At the edge of the mucosal side in the small intestine, these spots connected with each other and formed horizontal lines. For the large intestine, the horizontal lines became a surface, indicating that SM covered the whole crypt membrane. Detailed observation revealed thin SM-positive lines that connected the spots and the blood vessels in the small intestine. Thus, SM exists at crypt surfaces and inside crypts of the intestines and can regulate the functions of the digestion system.
Topics: Animals; Intestinal Mucosa; Intestine, Small; Mice; Microscopy; Sphingomyelins
PubMed: 35472605
DOI: 10.1016/j.bbrc.2022.03.128 -
Disease Models & Mechanisms Jun 2020Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and remains stubbornly difficult to treat in many cases.... (Review)
Review
Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and remains stubbornly difficult to treat in many cases. Much of our understanding of NEC pathogenesis has been gained through the study of highly translational animal models. However, most models of NEC are limited by their overall complexity and by the fact that they do not incorporate human tissue. To address these limitations, investigators have recently developed precision-based models of NEC, also termed 'NEC-in-a-dish' models, which provide the opportunity to increase our understanding of this disease and for drug discovery. These approaches involve exposing intestinal cells from either humans or animals with or without NEC to a combination of environmental and microbial factors associated with NEC pathogenesis. This Review highlights the current progress in the field of NEC model development, introduces NEC-in-a-dish models as a means to understand NEC pathogenesis and examines the fundamental questions that remain unanswered in NEC research. By answering these questions, and through a renewed focus on precision model development, the research community may finally achieve enduring success in improving the outcome of patients with this devastating disease.
Topics: Animals; Cell Culture Techniques; Cells, Cultured; Disease Models, Animal; Enterocolitis, Necrotizing; Humans; Intestine, Small; Organoids; Signal Transduction; Toll-Like Receptor 4
PubMed: 32764156
DOI: 10.1242/dmm.044388 -
Nature Cell Biology Feb 2024A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different...
A key aspect of nutrient absorption is the exquisite division of labour across the length of the small intestine, with individual nutrients taken up at different proximal:distal positions. For millennia, the small intestine was thought to comprise three segments with indefinite borders: the duodenum, jejunum and ileum. By examining the fine-scale longitudinal transcriptional patterns that span the mouse and human small intestine, we instead identified five domains of nutrient absorption that mount distinct responses to dietary changes, and three regional stem cell populations. Molecular domain identity can be detected with machine learning, which provides a systematic method to computationally identify intestinal domains in mice. We generated a predictive model of transcriptional control of domain identity and validated the roles of Ppar-δ and Cdx1 in patterning lipid metabolism-associated genes. These findings represent a foundational framework for the zonation of absorption across the mammalian small intestine.
Topics: Humans; Mice; Animals; Intestine, Small; Duodenum; Intestines; Jejunum; Ileum; Mammals
PubMed: 38321203
DOI: 10.1038/s41556-023-01337-z -
The American Journal of the Medical... Dec 2021
Topics: Hemangioma; Humans; Intestinal Neoplasms; Intestine, Small
PubMed: 34010621
DOI: 10.1016/j.amjms.2021.05.008 -
The Journal of Medical Investigation :... 2022Small bowel neoplasms are rare and account for 3-6% of all gastrointestinal neoplasms. For the diagnosis of small bowel neoplasms, differentiating normal bowel tissue... (Review)
Review
Small bowel neoplasms are rare and account for 3-6% of all gastrointestinal neoplasms. For the diagnosis of small bowel neoplasms, differentiating normal bowel tissue from tumor is critical and depends on imaging modality and scanning techniques. The detection and characterization of small bowel neoplasms have recently improved with the advance of computed tomography (CT) technology. Post-contrast multiphasic CT is an aid to detection and recognition of the vascular nature of small bowel neoplasms. Understanding the typical post-contrast multiphasic CT features of small bowel neoplasms is important because of overlapping features and the necessity of evaluating associated complications and metastases to lymph node and other organs. However, accurate classification of pathologies is still challenging in clinical practice. Texture analysis can quantify complex mathematical patterns within the gray-level distribution of the pixels and voxels of digital images, and texture analysis of the post-contrast multidetector CT data of various tumors has been attracting attention in recent years. The aim of this article is to provide a comprehensive guide to the relevant imaging features for different types of malignant small bowel neoplasms. J. Med. Invest. 69 : 19-24, February, 2022.
Topics: Contrast Media; Humans; Intestinal Neoplasms; Intestine, Small; Multidetector Computed Tomography
PubMed: 35466141
DOI: 10.2152/jmi.69.19