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The Keio Journal of Medicine Dec 2022Our understanding of the biology of the intestinal epithelium has advanced since the establishment of an organoid culture system. Although organoids have enabled... (Review)
Review
Our understanding of the biology of the intestinal epithelium has advanced since the establishment of an organoid culture system. Although organoids have enabled investigation of the mechanism of self-renewal of human intestinal stem cells in vitro, it remains difficult to clarify the behavior of human normal and diseased intestinal epithelium in vivo. Recently, we developed a xenotransplantation system in which human intestinal organoids are engrafted onto epithelium-depleted mouse colons. This xenograft recapitulated the original tissue structures. Upon xenotransplantation, normal colon organoids developed normal colon crypt structures without tumorigenesis, whereas tumor-derived organoids formed colonic tumors resembling the original tumors. The non-tumorigenicity of human intestinal organoids highlights the safety of organoid-based regenerative medicine. As an example of regenerative medicine for short bowel syndrome, we devised a unique organ-repurposing approach to convert colons into small intestines by organoid transplantation. In this approach, the transplanted rat small intestinal organoids not only engrafted onto the rat colons but also remodeled the colon subepithelial structures into a small intestine-like conformation. Luminal flow accelerated the maturation of villi in the small intestine, which promoted the formation of a lymphovascular network mimicking lacteals. In this review, we provide an overview of recent advances in gastrointestinal organoid transplantation and share our understanding of human disease biology and regenerative medicine derived from these studies.
Topics: Animals; Mice; Humans; Intestines; Intestinal Mucosa; Organoids; Colon; Intestine, Small
PubMed: 36450523
DOI: 10.2302/kjm.2022-0019-IR -
International Journal of Molecular... Feb 2023Pure cultures of chicken intestinal microbial species may still be crucial and imperative to expound on the function of gut microbiota, and also contribute to the...
Pure cultures of chicken intestinal microbial species may still be crucial and imperative to expound on the function of gut microbiota, and also contribute to the development of potential probiotics and novel bioactive metabolites from gut microbiota. In this study, we isolated and identified 507 chicken intestinal bacterial isolates, including 89 previously uncultured isolates. Among these, a total of 63 strains, belonging to , , , , , and , exhibited antibacterial activity against . Acid tolerance tests showed strain YPG14 ( strain YPG14) has a particularly strong tolerance to acid. We further characterized other probiotic properties of strain YPG14. In simulated intestinal fluid, the growth of strain YPG14 remained stable after incubation for 4 h. The auto-aggregation test showed the auto-aggregation percentage of strain YPG14 was recorded as 15.0 ± 0.38%, 48.3 ± 2.51%, and 75.1 ± 4.44% at 3, 12, and 24 h, respectively. In addition, the mucin binding assay showed strain YPG14 exhibited 12.07 ± 0.02% adhesion to mucin. Antibiotic sensitivity testing showed that strain YPG14 was sensitive to the majority of the tested antibiotics. The anti- Pullorum (. Pullorum) infection effect in vivo revealed that the consumption of strain YPG14 could significantly improve body weight loss and survival rate of chicks infected by . Pullorum; reduce the loads of . Pullorum in the jejunum, liver, spleen, and feces; and alleviate the jejunum villi morphological structure damage, crypt loss, and inflammatory cell infiltration caused by . Pullorum. Overall, this study may help us to understand the diversity of chicken intestinal microflora and provide some insights for potential probiotic development from gut microbiota and may find application in the poultry industry.
Topics: Animals; Gastrointestinal Microbiome; Chickens; Intestines; Limosilactobacillus reuteri; Anti-Bacterial Agents; Probiotics; Mucins
PubMed: 36769368
DOI: 10.3390/ijms24033045 -
Seminars in Cell & Developmental Biology Jun 2017The intestine is a vital organ responsible for nutrient absorption, bile and waste excretion, and a major site of host immunity. In order to keep up with daily demands,... (Review)
Review
The intestine is a vital organ responsible for nutrient absorption, bile and waste excretion, and a major site of host immunity. In order to keep up with daily demands, the intestine has evolved a mechanism to expand the absorptive surface area by undergoing a morphogenetic process to generate finger-like units called villi. These villi house specialized cell types critical for both absorbing nutrients from food, and for protecting the host from commensal and pathogenic microbes present in the adult gut. In this review, we will discuss mechanisms that coordinate intestinal development, growth, and maturation of the small intestine, starting from the formation of the early gut tube, through villus morphogenesis and into early postnatal life when the intestine must adapt to the acquisition of nutrients through food intake, and to interactions with microbes.
Topics: Cell Differentiation; Endoderm; Humans; Intestines; Morphogenesis
PubMed: 28161556
DOI: 10.1016/j.semcdb.2017.01.011 -
Pathologica Feb 2022The neonatal and paediatric spectrum of small bowel disorders encompass a wide variety of conditions, ranging from food allergies to life-threatening surgical... (Review)
Review
The neonatal and paediatric spectrum of small bowel disorders encompass a wide variety of conditions, ranging from food allergies to life-threatening surgical emergencies or life-long medical conditions and, as such, it comes with a whole set of diagnostic challenges for the non-paediatric pathologist. Histologic examination is a cornerstone of diagnosis in a large number of diseases and may still provide important diagnostic clues in the appropriate clinical context. In this review, divided in two sections, we aim to provide a comprehensive histopathological summary of paediatric small bowel alteration and their differential diagnoses with a reference to the main clinical aspects required for appropriate interpretation. Specifically, in this first part, we describe congenital and metabolic disorders, intestinal lymphangiectasia, immunodeficiencies, GVHD, and necrotising enterocolitis.
Topics: Child; Duodenum; Enterocolitis, Necrotizing; Humans; Infant, Newborn; Intestine, Small
PubMed: 34856604
DOI: 10.32074/1591-951X-337 -
British Medical Journal May 1965
Topics: Anatomy; Humans; Intestinal Mucosa; Intestine, Small
PubMed: 14278836
DOI: No ID Found -
The Journal of Surgical Research May 2022Murine ileocecal resection (ICR) has been used to investigate intestinal adaptation. The established model often includes the sacrifice of significant length of the...
BACKGROUND
Murine ileocecal resection (ICR) has been used to investigate intestinal adaptation. The established model often includes the sacrifice of significant length of the proximal colon. Here, we optimized a highly selective vascular approach to the ICR, with primary jejunal-colic anastomosis yielding maximal colonic preservation.
MATERIALS AND METHODS
Forty C57BL/6 mice underwent a highly vascularly selective ICR. The terminal branches of the ileocecal artery are isolated apart from the mesenteric branches supplying the small bowel to be resected. The distal 50% of small bowel and cecum are resected; a primary jejuno-colonic anastomosis is performed. Animals were sacrificed at postoperative weeks 2 (n = 10) and 10 (n = 29). Proximal 50% small bowel resection (SBR) with jejuno-ileal anastomosis was also performed for comparison.
RESULTS
The entire colon (with exception of the cecum) was preserved in 100% of animals. Ninety-seven percent of animals survived to postoperative week 10, and all exhibited structural adaptation in the remnant small intestine epithelium. Crypts deepened by 175%, and villi lengthened by 106%, versus 39% and 29% in the proximal SBR cohort, respectively. Colonic proliferation, structural adaptation, and functional adaptation (measured by p-histone 3, luminal-facing apical crypt border size, and sucrase isomaltase, respectively) were increased in ICR compared with proximal SBR.
CONCLUSIONS
Highly selective isolation of the cecal vasculature allows for greater colon preservation and yields enhanced remnant intestine epithelial adaptation. ICR is also associated with greater colonic adaptation and unique plasticity toward an intestinal phenotype. These findings underscore major differences between resection sites and offer insights into the critical adaptive mechanisms in response to massive intestinal loss.
Topics: Adaptation, Physiological; Animals; Colon; Humans; Intestinal Mucosa; Intestine, Small; Jejunum; Mice; Mice, Inbred C57BL; Short Bowel Syndrome
PubMed: 35033819
DOI: 10.1016/j.jss.2021.11.015 -
Advanced Science (Weinheim,... Oct 2023Intestinal retentive devices have applications ranging from sustained oral drug delivery systems to indwelling ingestible medical devices. Current strategies to retain...
Intestinal retentive devices have applications ranging from sustained oral drug delivery systems to indwelling ingestible medical devices. Current strategies to retain devices in the small intestine primarily focus on chemical anchoring using mucoadhesives or mechanical coupling using expandable devices or structures that pierce the intestinal epithelium. Here, the feasibility of intestinal retention using devices containing villi-inspired structures that mechanically interlock with natural villi of the small intestine is evaluated. First the viability of mechanical interlocking as an intestinal retention strategy is estimated by estimating the resistance to peristaltic shear between simulated natural villi and devices with various micropost geometries and parameters. Simulations are validated in vitro by fabricating micropost array patches via multistep replica molding and performing lap-shear tests to evaluate the interlocking performance of the fabricated microposts with artificial villi. Finally, the optimal material and design parameters of the patches that can successfully achieve retention in vivo are predicted. This study represents a proof-of-concept for the viability of micropost-villi mechanical interlocking strategy to develop nonpenetrative multifunctional intestinal retentive devices for the future.
Topics: Intestinal Mucosa; Drug Delivery Systems
PubMed: 37449425
DOI: 10.1002/advs.202301084 -
Pathologica Feb 2022In this paper, we will continue the description of histological findings of infantile and paediatric small bowel alterations with the main clinical pictures and... (Review)
Review
In this paper, we will continue the description of histological findings of infantile and paediatric small bowel alterations with the main clinical pictures and differential diagnosis. We emphasise once again the need to evaluate the biopsies in an adequate clinical contest and with a systematic approach, including epithelial alterations, lamina propria changes, mucosal architecture, and the distribution of inflammation, together with other morphological signs more specific of certain diseases. We describe the histological findings of coeliac and Crohn's disease, gastrointestinal food allergic diseases, Langerhans cell histiocytosis, nutritional deficiencies and infections. Finally, we suggest the principal issues in the drafting the pathological report for appropriate interpretation and usefulness in clinical practice.
Topics: Child; Crohn Disease; Duodenum; Humans; Inflammation; Intestinal Mucosa; Intestine, Small
PubMed: 34856605
DOI: 10.32074/1591-951X-338 -
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 -
World Journal of Gastroenterology Oct 2022The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma.... (Review)
Review
The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.
Topics: Animals; Intestine, Small; Adenocarcinoma; Colorectal Neoplasms; Duodenal Neoplasms; Intestinal Mucosa; Risk Factors; Carcinogenesis
PubMed: 36338888
DOI: 10.3748/wjg.v28.i39.5658