scholarly journals Methyl donor deficiency affects small-intestinal differentiation and barrier function in rats

2012 ◽  
Vol 109 (4) ◽  
pp. 667-677 ◽  
Author(s):  
Aude Bressenot ◽  
Shabnam Pooya ◽  
Carine Bossenmeyer-Pourie ◽  
Guillaume Gauchotte ◽  
Adeline Germain ◽  
...  
Keyword(s):  
Small Intestine ◽  
Small Bowel ◽  
Barrier Function ◽  
Paneth Cell ◽  
Cell Number ◽  
Nuclear Antigen ◽  
Methyl Donors ◽  
Distal Small Bowel ◽  
Proximal Small Bowel ◽  
Enterocyte Differentiation

Dietary methyl donors and their genetic determinants are associated with Crohn's disease risk. We investigated whether a methyl-deficient diet (MDD) may affect development and functions of the small intestine in rat pups from dams subjected to the MDD during gestation and lactation. At 1 month before pregnancy, adult females were fed with either a standard food or a diet without vitamin B12, folate and choline. A global wall hypotrophy was observed in the distal small bowel (MDD animals 0·30 mm v. controls 0·58 mm; P< 0·001) with increased crypt apoptosis (3·37 v. 0·4 %; P< 0·001), loss of enterocyte differentiation in the villus and a reduction in intestinal alkaline phosphatase production. Cleaved caspase-3 immunostaining (MDD animals 3·37 % v. controls 0·4 %, P< 0·001) and the Apostain labelling index showed increased crypt apoptosis (3·5 v. 1·4 %; P= 0·018). Decreased proliferation was observed in crypts of the proximal small bowel with a reduced number of minichromosome maintenance 6 (MDD animals 52·83 % v. controls 83·17 %; P= 0·048) and proliferating cell nuclear antigen-positive cells (46·25 v. 59 %; P= 0·05). This lack of enterocyte differentiation in the distal small bowel was associated with an impaired expression of β-catenin and a decreased β-catenin–E-cadherin interaction. The MDD affected the intestinal barrier in the proximal small bowel by decreasing Paneth cell number after immunostaining for lysosyme (MDD animals 8·66 % v. controls 21·66 %) and by reducing goblet cell number and mucus production after immunostaining for mucin-2 (crypts 8·66 v. 15·33 %; villus 7 v. 17 %). The MDD has dual effects on the small intestine by producing dramatic effects on enterocyte differentiation and barrier function in rats.

Positional specificity of defensin gene expression reveals Paneth cell heterogeneity in mouse small intestine

1996 ◽  
Vol 271 (1) ◽  
pp. G68-G74 ◽  
Author(s):  
D. Darmoul ◽  
A. J. Ouellette
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Small Bowel ◽  
Paneth Cell ◽  
Paneth Cells ◽  
Northern Blot Hybridization ◽  
Positional Specificity ◽  
Defensin Gene ◽  
Proximal Small Bowel ◽  
Mouse Small Intestine

Cryptdins are antimicrobial peptides of the defensin family that are expressed specifically by Paneth cells in small intestinal crypts (M.E. Selsted, S.I. Miller, A.H. Henschen, and A.J. Ouellette. J. Cell Biol. 118: 929-936, 1992), and at least 17 cryptdin isoforms have been reported in mouse small intestine (A.J. Ouellette, M.M. Hsieh, M.T. Nosek, D.F. Cano-Gauci, K.M. Huttner, R.N. Buick, and M.E. Selsted. Infect. Immun. 62: 5040-5047, 1994). Analysis of cryptdin gene expression in adult mouse small bowel revealed that the cryptdin-4 isoform is differentially expressed along the proximal-to-distal intestinal axis. By peptide-specific reverse transcriptase-polymerase chain reaction-based assays, cryptdin-4 mRNA was found to be absent from the proximal small bowel, increasing to maximal levels in the ileum. In contrast, intestinal content of cryptdin-1 and -5 mRNAs was equivalent in duodenum, jejunum, and ileum, and Northern blot hybridization experiments were consistent with both sets of data. Similarly, individual crypts isolated from duodenum contain cryptdin-1 mRNA but not cryptdin-4 mRNA. Taken together, the results show that Paneth cells are heterogeneous, depending on their position along the longitudinal axis of the small bowel. The positional specificity of defensin gene expression suggests that cryptdins may be useful markers for investigating the establishment and maintenance of this epithelial lineage in the mouse small intestine.

Role of TNF-α in gut mucosal changes after severe burn

2002 ◽  
Vol 283 (3) ◽  
pp. G703-G708 ◽  
Author(s):  
Marcus Spies ◽  
Vicky L. Chappell ◽  
Mohan R. Dasu ◽  
David N. Herndon ◽  
James C. Thompson ◽  
...  
Keyword(s):  
Small Bowel ◽  
Total Body Surface Area ◽  
Cell Number ◽  
Nuclear Antigen ◽  
Mucosal Cell ◽  
Severe Burn ◽  
Mucosal Atrophy ◽  
Proximal Small Bowel ◽  
Tnf Α ◽  
Mucosal Cells

Gut epithelial cell death by apoptosis is increased in the gut epithelium after severe burn associated with mucosal atrophy. We hypothesized that tumor necrosis factor (TNF)-α-TNF receptor (TNFR) interaction activates apoptosis in small bowel mucosal cells after severe burn. C57BL6 mice received a 30% total body surface area scald burn and were treated with neutralizing anti-TNF-α. The proximal small bowel was assessed for mucosal atrophy. Proliferation and apoptosis of mucosal cells were assessed by proliferative cell nuclear antigen-immunostaining and terminal deoxyuridine nick-end labeling assay, respectively. Mucosal height and mucosal cell number decreased after burn. Anti-TNF-α-treated mice showed significantly less mucosal atrophy. Proliferation of intestinal cells was not changed with burn or anti-TNF-α treatment. An over threefold increase in apoptotic cell number was seen after burn, which was diminished by anti-TNF-α treatment. Changes in gut mucosal homeostasis after severe burn are affected, in part, by the activation of apoptosis by TNF-α-TNFR interaction.

Maximal lymphatic triglyceride transport rate from the rat small intestine

1982 ◽  
Vol 242 (4) ◽  
pp. G408-G415 ◽  
Author(s):  
P. Tso ◽  
K. L. Buch ◽  
J. A. Balint ◽  
J. B. Rodgers
Keyword(s):  
Small Intestine ◽  
Small Bowel ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Transport Rate ◽  
Lymphatic Transport ◽  
Onset Of Action ◽  
Triglyceride Fatty Acid ◽  
Proximal Half ◽  
Proximal Small Bowel

In previous studies, we demonstrated that the hydrophobic surfactant Pluronic L-81 blocks lymphatic triglyceride transport from the small intestine and leads to accumulation of triglyceride in the mucosa. The onset of action of Pluronic L-81 is rapid and quickly reversed once its administration is discontinued. We have taken advantage of these effects of Pluronic L-81 on intestinal lipid transport in order to determine the apparent maximal triglyceride transport capacity of the proximal half of the rat small bowel using lymph fistula rats infused intraduodenally with a phosphate-buffered, taurocholate-stabilized emulsion containing 40 mumol [3H]triolein and 0.5 mg Pluronic L-81 at 3 ml/h for 8 h to load the proximal small bowel with lipid. Studies were done in one group of rats in order to be certain that only the proximal half of the small bowel contained 3H-lipid after this period of infusion. In other rats treated similarly, the 8 h of lipid-Pluronic L-81 infusion were followed by infusion of 3 ml/h of 0.15 M salt solution for 5 h. Lymphatic transport of lipid was determined throughout the entire period of infusion. During lipid-Pluronic L-81 infusion, transport of 3H-triglyceride fatty acid into lymph was only 22-27 mumol/h but rose steadily after substitution of saline and reached a maximal transport rate of 109 +/- 6.2 mumol/h (means +/- SE) after 3.5 h. During this 3.5-h period, the amount of 3H-lipid in the proximal mucosa declined from 530 to 263 mumol. While Pluronic L-81 was infused, only very low-density-lipoprotein-sized particles were seen in lymph by electron microscopy, whereas, at the peak of triglyceride transport during saline infusion, chylomicrons of up to 6,000 A were observed in lymph.

scholarly journals Small bowel transit of a bran meal residue in humans: sieving of solids from liquids and response to feeding

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 685-689 ◽  
Author(s):  
J M Hebden ◽  
P E Blackshaw ◽  
A C Perkins ◽  
M D’Amato ◽  
R C Spiller
Keyword(s):  
Gastric Emptying ◽  
Small Bowel ◽  
Small Bowel Transit ◽  
Motor Patterns ◽  
Solid Meal ◽  
Lower Quadrant ◽  
Distal Small Bowel ◽  
Proximal Small Bowel ◽  
Indium 111 ◽  
Right Lower Quadrant

Background—Ileal motor patterns are adapted to the propulsion of viscous meal residue, such as bran, which accumulates in the distal ileum postprandially.Aims—To examine the effects of a second liquid/solid meal on ileal emptying.Subjects and methods—Eleven healthy fasting subjects consumed a 1.47 MJ pancake containing 15 g bran and 5 MBq Technetium-99m labelled amberlite resin (meal A). Gastric emptying and transit through the left upper quadrant (proximal) and right lower quadrant (distal) small bowel regions and colon were assessed scintigraphically. Transit was compared with and without a second Indium-111 liquid/solid DTPA labelled 2.28 MJ meal (B) given three hours after the first meal.Results—Gastric emptying of meal A was slower than meal B (the time for 50% of the activity to leave the stomach (T50) being 113 (11) minutes versus 48 (3) minutes respectively, p<0.01, n=11). Both meals passed rapidly through the proximal small bowel (T50 meal A = 57 (14) minutes versus T50 meal B = 42 (11) minutes). Transit of meal A through the distal small bowel was much slower (T50 more than 390 minutes versus 176 (29) minutes for meal B, p<0.01), resulting in meal B overtaking meal A and entering the colon earlier. Ingestion of the second meal (B) resulted in significantly less meal A marker entering the colon (5 (3)%) at 11 hours than when meal A was taken alone (18 (4)%) (p<0.05, n=8).Conclusions—The distal small bowel selectively retains bran, allowing liquid phase markers through to the colon. Consuming a second liquid/solid meal does not stimulate ileal transit of bran which seems to be propelled quicker by fasting motor patterns.

Absence of Na+–H+ barrier function in mucosa of canine small bowel

1978 ◽  
Vol 56 (4) ◽  
pp. 617-623 ◽  
Author(s):  
Darlene G. Kelly ◽  
Charles F. Code
Keyword(s):  
Small Intestine ◽  
Small Bowel ◽  
Barrier Function ◽  
Hexanoic Acid ◽  
Water Soluble ◽  
Mucosal Barrier ◽  
Jejunal Mucosa ◽  
Gastric Corpus ◽  
Gastric Mucosal Barrier ◽  
Made In

The study was designed to determine whether the special Na+–H+ barrier function or the gastric mucosa is present in the mucosa of the small bowel and whether a gastric mucosal barrier breaker (hexanoic acid) would accelerate the fluxes of sodium in duodenum–jejunum and ileum as in the stomach. The observations were made in healthy conscious dogs with Thiry-Vella fistulae of the small bowel or Heidenhain pouches of the gastric corpus. These barrier characteristics of the stomach were completely absent in the small intestine where bidirectional Na fluxes were 5–10 times greater than in the stomach and were not accelerated by hexanoic acid as they were in the stomach.A comparison was made between the rates of absorption of hexanoic acid, sodium hexanoate, and HCl from the pouches and fistulae. The lipid-soluble fatty acid was transported at all sites more rapidly than its water-soluble sodium salt. In the stomach and ileum the H+ of HCl and sodium hexanoate were absorbed at similar slow rates. The duodenal–jejunal mucosa, however, transported H+ at rates nearly identical to those of hexanoic acid. In our tests HCl was not neutralized in duodenal contents while large quantities were neutralized in the contents of ileum.

Effects of bile and pancreatic secretions on intestinal mucosa after proximal small bowel resection in rats

1980 ◽  
Vol 58 (9) ◽  
pp. 1117-1123 ◽  
Author(s):  
Monique D. Gélinas ◽  
Claude L. Morin
Keyword(s):  
Small Intestine ◽  
Small Bowel ◽  
Pancreatic Juice ◽  
Bowel Resection ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Sprague Dawley ◽  
Ileal Mucosa ◽  
Distal Small Intestine ◽  
Proximal Small Bowel

After proximal small bowel resection the remaining small intestine undergoes adaptive hyperplasia. In the present study, the relative contributions of bile and (or) pancreatic juice to adaptive intestinal hyperplasia following proximal resection was studied. Using male Sprague–Dawley rats a 50% proximal intestinal resection was done starting 10 cm distal to the beginning of the jejunum. The animals were also subjected to diversion of bile and (or) pancreatic secretions to the distal ileum at 18 cm proximal to the ileocecal junction. After 8 days gut and mucosal weights, mucosal proteins, and DNA were measured in the duodenojejunum (gut segment proximal to the resection anastomosis) and in the ileum (first half of the small bowel segment distal to the diversion site). The results indicate that (1) in rats fed either chow (Purina rat chow) or a chemically defined diet diversion of pancreaticobiliary secretions to the ileum significantly stimulated ileal mucosa growth whereas no changes were observed in the duodenojejunum, (2) in rats fed a chemically defined diet neither bile nor pancreatic juice affected ileal mucosa when separately diverted to the ileum, and (3) pancreatic juice draining into the duodenum while bile was diverted to the ileum induced hypoplastic changes in the duodenojejunum. The present study suggests that following jejunectomy the regulation of mucosal growth by pancreatic and bile secretions is different in the proximal and distal small intestine. Pancreaticobiliary secretions are trophic for the ileum. However, in the proximal gut bile offers protection against a direct or indirect catabolic action of pancreatic juice.

DOES THE PRESENCE OF PROXIMAL SMALL BOWEL ARTERIOVENOUS MALFORMATION PREDICT THE EXISTENCE OF DISTAL SMALL BOWEL ARTERIOVENOUS MALFORMATION?

2004 ◽  
Vol 99 ◽  
pp. S66
Author(s):  
Nakechand Pooran ◽  
S. Devi Rampertab ◽  
Ronald Greenberg ◽  
Gerard Mullin ◽  
Pankaj Singh ◽  
...  
Keyword(s):  
Small Bowel ◽  
Arteriovenous Malformation ◽  
Distal Small Bowel ◽  
Proximal Small Bowel

Neonatal antibiotic treatment alters gastrointestinal tract developmental gene expression and intestinal barrier transcriptome

2005 ◽  
Vol 23 (2) ◽  
pp. 235-245 ◽  
Author(s):  
Alexandra Schumann ◽  
Sophie Nutten ◽  
Dominique Donnicola ◽  
Elena M. Comelli ◽  
Robert Mansourian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Barrier Function ◽  
Bacterial Colonization ◽  
Paneth Cell ◽  
Global Gene Expression ◽  
Gut Barrier ◽  
Commercial Preparation ◽  
Postnatal Maturation ◽  
Gut Barrier Function

The postnatal maturation of the gut, partially modulated by bacterial colonization, ends up in the establishment of an efficient barrier to luminal antigens and bacteria. The use of broad-spectrum antibiotics in pediatric practices alters the gut bacterial colonization and, consequently, may impair the maturation of the gut barrier function. To test this hypothesis, suckling Sprague-Dawley rats received a daily intragastric gavage of antibiotic (Clamoxyl; an amoxicillin-based commercial preparation) or saline solution from postnatal day 7 (d7) until d17 or d21. Luminal microbiota composition and global gene expression profile were analyzed on samples from small intestine and colon of each group. The treatment with Clamoxyl resulted in the almost-complete eradication of Lactobacillus in the whole intestine and in a drastic reduction of colonic total aerobic and anaerobic bacteria, in particular Enterobacteriacae and Enterococcus. The global gene expression analysis revealed that Clamoxyl affects the maturation process of 249 and 149 Affymetrix probe sets in the proximal and distal small intestine, respectively, and 163 probe sets in the colon. The expression of genes coding for Paneth cell products (defensins, matrilysin, and phospholipase A2) was significantly downregulated by the Clamoxyl treatment. A significant downregulation of major histocompatibility complex (MHC) class Ib and II genes, involved in antigen presentation, was also observed. Conversely, mast cell proteases expression was upregulated. These results suggest that early treatment with a large-spectrum antibiotic deeply affects the gut barrier function at the suckling-weaning interface, a period during which the gut is challenged by an array of novel food-borne antigens.

scholarly journals Per-rectal bleeding due to jejunal Crohn’s: a rare case report from Bangladesh

2019 ◽  
Vol 10 (1) ◽  
pp. 68-72
Author(s):  
Shireen Ahmed ◽  
Md Nazmul Hoque ◽  
Md Anisur Rahman
Keyword(s):  
Weight Loss ◽  
Small Intestine ◽  
Abdominal Pain ◽  
Gastrointestinal Tract ◽  
Small Bowel ◽  
Capsule Endoscopy ◽  
Oral Steroid ◽  
Intestinal Bleeding ◽  
Clinical Relapse ◽  
Proximal Small Bowel

Crohn’s disease (CD) is a disorder of uncertain etiology that is characterized by transmural inflammation of the gastrointestinal tract. CD may involve the entire gastrointestinal tract from mouth to the perianal area. Isolated jejunal involvement of CD is a rare entity. We describe a case of CD involving only jejunum with successful treatment in a 74-years-man who presented with melaena, abdominal pain and significant weight loss. Endoscopy of upper gastro-intestinal tract revealed gastritis and colonoscopy showed small sessile polyp at rectum and sigmoid colon, polypectomy was done accordingly. After few days of polypectomy, he again noticed melaena along with abdominal discomfort and weakness with loss of 4 kg weight within this periods. Diagnosis was confirmed by capsule endoscopy and serology. Treatment was thereafter started with oral steroid and mesalamine sachet. The patient is now on remission and is on regular follow up. CD has propensity to involve the distal small intestine and proximal large bowel. Affected persons usually experience diarrhea and abdominal pain, frequently accompanied by weight loss. Proximal small bowel involvement is less common than distal small bowel or colonic involvement in CD. CD involving proximal small intestine should be suspected in Asian patients with middle gastro-intestinal bleeding. It is associated with a high risk of clinical relapse and morbidity, including the need for abdominal surgery. Different modalities of baseline evaluation and more sophisticated diagnostic modalities may be required for patients with CD involving proximal small bowel. Capsule endoscopy (CE) currently plays an important role in CD. Birdem Med J 2020; 10(1): 68-72

scholarly journals Paneth cell–derived growth factors support tumorigenesis in the small intestine

2020 ◽  
Vol 4 (3) ◽  
pp. e202000934
Author(s):  
Qing Chen ◽  
Kohei Suzuki ◽  
Luis Sifuentes-Dominguez ◽  
Naoteru Miyata ◽  
Jie Song ◽  
...  
Keyword(s):  
Small Intestine ◽  
Growth Factors ◽  
Small Bowel ◽  
Genetic Model ◽  
Paneth Cell ◽  
Tumor Formation ◽  
Intestinal Epithelial ◽  
Α Subunit ◽  
Conditional Expression ◽  
Small Intestinal

Paneth cells (PCs) are small intestinal epithelial cells that secrete antimicrobial peptides and growth factors, such as Wnt ligands. Intriguingly, the context in which PC-derived Wnt secretion is relevant in vivo remains unknown as intestinal epithelial ablation of Wnt does not affect homeostatic proliferation or restitution after irradiation injury. Considering the importance of growth factors in tumor development, we explored here the role of PCs in intestinal carcinogenesis using a genetic model of PC depletion through conditional expression of diphtheria toxin-α subunit. PC depletion in ApcMin mice impaired adenoma development in the small intestine and led to decreased Wnt3 expression in small bowel adenomas. To determine if PC-derived Wnt3 was required for adenoma development, we examined tumor formation after PC-specific ablation of Wnt3. We found that this was sufficient to decrease small intestinal adenoma formation; moreover, organoids derived from these tumors displayed slower growth capacity. Overall, we report that PC-derived Wnt3 is required to sustain early tumorigenesis in the small bowel and identify a clear role for PC-derived Wnt production in intestinal pathology.

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