scholarly journals Proximal colon–derived O-glycosylated mucus encapsulates and modulates the microbiota

Science ◽  
2020 ◽  
Vol 370 (6515) ◽  
pp. 467-472 ◽  
Author(s):  
Kirk Bergstrom ◽  
Xindi Shan ◽  
David Casero ◽  
Albert Batushansky ◽  
Venu Lagishetty ◽  
...  
Keyword(s):  
Distal Colon ◽  
Goblet Cells ◽  
Proximal Colon ◽  
Fecal Material ◽  
Mucin Production ◽  
Major Form ◽  
Minor Form ◽  
A Minor ◽  
And Function ◽  
Host Tissues

Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon–derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.

scholarly journals Loss of NHE8 expression impairs intestinal mucosal integrity

2015 ◽  
Vol 309 (11) ◽  
pp. G855-G864 ◽  
Author(s):  
Aiping Wang ◽  
Jing Li ◽  
Yang Zhao ◽  
Malin E. V. Johansson ◽  
Hua Xu ◽  
...  
Keyword(s):  
Periodic Acid ◽  
Paneth Cell ◽  
Distal Colon ◽  
Goblet Cells ◽  
Paneth Cells ◽  
Wild Type ◽  
Periodic Acid Schiff ◽  
Mucin Production ◽  
Mucosal Integrity ◽  
Mucin 2

The newest member of the Na+/H+ exchanger (NHE) family, NHE8, is abundantly expressed at the apical membrane of the intestinal epithelia. We previously reported that mucin 2 expression was significantly decreased in the colon in NHE8−/− mice, suggesting that NHE8 is involved in intestinal mucosal protection. In this study, we further evaluated the role of NHE8 in intestinal epithelial protection after dextran sodium sulfate (DSS) challenge. Compared with wild-type mice, NHE8−/− mice have increased bacterial adhesion and inflammation, especially in the distal colon. NHE8−/− mice are also susceptible to DSS treatment. Real-time PCR detected a remarkable increase in the expression of IL-1β, IL-6, TNF-α, and IL-4 in DSS-treated NHE8−/− mice compared with DSS-treated wild-type littermates. Immunohistochemistry showed a disorganized epithelial layer in the colon of NHE8−/− mice. Periodic acid-Schiff staining showed a reduction in the number of mature goblet cells and the area of the goblet cell theca in NHE8−/− mice. Phyloxine/tartrazine staining revealed a decrease in functional Paneth cell population in the NHE8−/− small intestinal crypt. The expression of enteric defensins was also decreased in NHE8−/− mice. The reduced mucin production in goblet cells and antimicrobial peptides production in Paneth cells lead to disruption of the intestinal mucosa protection. Therefore, NHE8 may be involved in the establishment of intestinal mucosal integrity by regulating the functions of goblet and Paneth cells.

Mammalian U6 small nuclear RNA undergoes 3' end modifications within the spliceosome

1993 ◽  
Vol 13 (3) ◽  
pp. 1641-1650
Author(s):  
J Tazi ◽  
T Forne ◽  
P Jeanteur ◽  
G Cathala ◽  
C Brunel
Keyword(s):  
Single Species ◽  
Small Nuclear Rna ◽  
U6 Snrna ◽  
Major Form ◽  
Nuclear Extracts ◽  
Nuclear Rna ◽  
Minor Form ◽  
Multiple Species ◽  
A Minor ◽  
Selection Of

Mammalian U6 small nuclear RNA (snRNA) is heterogeneous with respect to the number of 3' terminal U residues. The major form terminates with five U residues and a 2',3' cyclic phosphate. Because of the presence in HeLa cell nuclear extracts of a terminal uridylyl transferase, a minor form of U6 snRNA is elongated, producing multiple species containing up to 12 U residues. In this study we have used glycerol gradients to demonstrate that these U6 snRNA forms are assembled into U6 ribonucleoprotein (RNP), U4/U6 snRNPs, and U4/U5/U6 tri-snRNP complexes. Furthermore, glycerol gradients combined with affinity selection of biotinylated pre-mRNAs led us to show that elongated forms of U6 snRNAs enter the spliceosome and that some of these become shortened with time to a single species having the same characteristics as the major form of U6 snRNA present in mammalian nuclear extracts. We propose that this elongation-shortening process is related to the function of U6 snRNA in mammalian pre-mRNA splicing.

scholarly journals Mammalian U6 small nuclear RNA undergoes 3' end modifications within the spliceosome.

1993 ◽  
Vol 13 (3) ◽  
pp. 1641-1650 ◽  
Author(s):  
J Tazi ◽  
T Forne ◽  
P Jeanteur ◽  
G Cathala ◽  
C Brunel
Keyword(s):  
Single Species ◽  
Small Nuclear Rna ◽  
U6 Snrna ◽  
Major Form ◽  
Nuclear Extracts ◽  
Nuclear Rna ◽  
Minor Form ◽  
Multiple Species ◽  
A Minor ◽  
Selection Of

Mammalian U6 small nuclear RNA (snRNA) is heterogeneous with respect to the number of 3' terminal U residues. The major form terminates with five U residues and a 2',3' cyclic phosphate. Because of the presence in HeLa cell nuclear extracts of a terminal uridylyl transferase, a minor form of U6 snRNA is elongated, producing multiple species containing up to 12 U residues. In this study we have used glycerol gradients to demonstrate that these U6 snRNA forms are assembled into U6 ribonucleoprotein (RNP), U4/U6 snRNPs, and U4/U5/U6 tri-snRNP complexes. Furthermore, glycerol gradients combined with affinity selection of biotinylated pre-mRNAs led us to show that elongated forms of U6 snRNAs enter the spliceosome and that some of these become shortened with time to a single species having the same characteristics as the major form of U6 snRNA present in mammalian nuclear extracts. We propose that this elongation-shortening process is related to the function of U6 snRNA in mammalian pre-mRNA splicing.

scholarly journals Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

2014 ◽  
Vol 306 (11) ◽  
pp. G1002-G1010 ◽  
Author(s):  
Verónica Ramírez-Alcántara ◽  
Marshall H. Montrose
Keyword(s):  
Distal Colon ◽  
Proximal Colon ◽  
Myeloperoxidase Activity ◽  
Aminosalicylic Acid ◽  
Patient Response ◽  
Dss Colitis ◽  
Therapeutic Outcomes ◽  
Mrna Ratio ◽  
Enzyme Isoforms ◽  
And Function

Pharmacotherapy based on 5-aminosalicylic acid (5-ASA) is a preferred treatment for ulcerative colitis, but variable patient response to this therapy is observed. Inflammation can affect therapeutic outcomes by regulating the expression and activity of drug-metabolizing enzymes; its effect on 5-ASA metabolism by the colonic arylamine N-acetyltransferase (NAT) enzyme isoforms is not firmly established. We examined if inflammation affects the capacity for colonic 5-ASA metabolism and NAT enzyme expression. 5-ASA metabolism by colonic mucosal homogenates was directly measured with a novel fluorimetric rate assay. 5-ASA metabolism reported by the assay was dependent on Ac-CoA, inhibited by alternative NAT substrates (isoniazid, p-aminobenzoylglutamate), and saturable with Km (5-ASA) = 5.8 μM. A mouse model of acute dextran sulfate sodium (DSS) colitis caused pronounced inflammation in central and distal colon, and modest inflammation of proximal colon, defined by myeloperoxidase activity and histology. DSS colitis reduced capacity for 5-ASA metabolism in central and distal colon segments by 52 and 51%, respectively. Use of selective substrates of NAT isoforms to inhibit 5-ASA metabolism suggested that mNAT2 mediated 5-ASA metabolism in normal and colitis conditions. Western blot and real-time RT-PCR identified that proximal and distal mucosa had a decreased mNAT2 protein-to-mRNA ratio after DSS. In conclusion, an acute colonic inflammation impairs the expression and function of mNAT2 enzyme, thereby diminishing the capacity for 5-ASA metabolism by colonic mucosa.

Digestive Physiology of the Ground Cuscus (Phalanger gymnotis), a New Guinean Phalangerid Marsupial

1997 ◽  
Vol 45 (6) ◽  
pp. 561 ◽  
Author(s):  
I. D. Hume ◽  
M. J. Runcie ◽  
J. M. Caton
Keyword(s):  
Small Intestine ◽  
Nitrogen Concentration ◽  
Distal Colon ◽  
Short Chain Fatty Acids ◽  
Proximal Colon ◽  
Brushtail Possum ◽  
Daily Production ◽  
Natural Diet ◽  
Digestible Energy ◽  
And Function

Digestive-tract morphology and function were studied in the ground cuscus (Phalanger gymnotis), reported to be the most frugivorous of eight species of New Guinean phalangerid marsupials. When offered a mixed diet of fruit and foliage, captive animals selected a diet of more than 90% fruit. Fibre digestibility was low and variable, but apparent digestibilities of both dry matter (90%) and energy (87%) were high, and intake of digestible energy was similar to that of the Australian phalangerid Trichosurus vulpecula (common brushtail possum) in captivity. The small intestine of P. gymnotis was the longest and heaviest region of the gastrointestinal tract, but the stomach contained more digesta. The total nitrogen content of digesta was low in the stomach and small intestine, but increased four-fold in the hindgut, because of microbial activity. No difference in nitrogen concentration or in the proportions of small or medium particles was found along the hindgut, but the caecum contained a smaller proportion of large particles than the distal colon. The transit time of a large particle marker was much longer than that of a solute marker, but mean retention times (MRTs) of the two markers did not differ. Both transit times and MRTs were long relative to those reported in T. vulpecula. Although fermentation rates in the caecum and proximal colon were similar to those in T. vulpecula on a foliage diet, fluid volumes were less than one-third those of T. vulpecula, and, consequently, daily production of short-chain fatty acids (SCFAs) was less than half that in T. vulpecula, and contributed only 5% of digestible energy intake (v. 15% in T. vulpecula). These results are consistent with reports that the natural diet of P. gymnotis is based largely on fruit rather than on foliage.

scholarly journals Food restriction beginning at lactation interferes with the cellular dynamics of the mucosa and colonic myenteric innervation in adult rats

2014 ◽  
Vol 86 (4) ◽  
pp. 1833-1848 ◽  
Author(s):  
JOÃO PAULO F. SCHOFFEN ◽  
FERNANDO A. VICENTINI ◽  
CAROLINA G. MARCELINO ◽  
EDUARDO J.A. ARAÚJO ◽  
MARIA M.D. PEDROSA ◽  
...  
Keyword(s):  
Food Restriction ◽  
Goblet Cells ◽  
Neuronal Population ◽  
Proximal Colon ◽  
Enteroendocrine Cells ◽  
Adult Rats ◽  
Mucin Production ◽  
Histological Processing ◽  
Neutral Mucin ◽  
Tunica Muscularis

The effects of food restriction (FR) on the morphoquantitative aspects of the wall and myenteric neurons of the proximal colon in adult rats were analysed. FR was imposed by duplication of the experimental brood size in relation to the control brood during lactation. The FR group received a 50% reduction of food from weaning until 90 days of age. Samples of the colon underwent histological processing to morphometrically analyze the crypts, muscularis mucosae, tunica mucosa, and muscularis externa. We determined the number of goblet cells and serotoninergic enteroendocrine cells, and morphoquantitatively studied the myenteric neuronal population. FR caused hypertrophy in the tunica mucosa, increase in crypt depth and in the muscular layer of the mucosa, a decrease in the thickness of the tunica muscularis and in the number of goblet cells and an increase in serotoninergic cells. A higher neuronal density in the ganglia and a reduction of the cell profile area were observed in the FR group. FR imposed since lactation led to hypertrophy of the tunica mucosa, a reduction of neutral mucin production, atrophy of the tunica muscularis, and an increase in the survival neuronal in adult rats, attributable to an increase in the number of serotoninergic enteroendocrine cells in mucosa.

scholarly journals Distribution and function of monoacylglycerol lipase in the gastrointestinal tract

2008 ◽  
Vol 295 (6) ◽  
pp. G1255-G1265 ◽  
Author(s):  
Marnie Duncan ◽  
Adam D. Thomas ◽  
Nina L. Cluny ◽  
Annie Patel ◽  
Kamala D. Patel ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Distal Colon ◽  
Proximal Colon ◽  
Nerve Fibers ◽  
Activity Levels ◽  
Monoacylglycerol Lipase ◽  
And Function ◽  
Endogenous Cannabinoid ◽  
Oxide Synthase

The endogenous cannabinoid system plays an important role in the regulation of gastrointestinal function in health and disease. Endocannabinoid levels are regulated by catabolic enzymes. Here, we describe the presence and localization of monoacylglycerol lipase (MGL), the major enzyme responsible for the degradation of 2-arachidonoylglycerol. We used molecular, biochemical, immunohistochemical, and functional assays to characterize the distribution and activity of MGL. MGL mRNA was present in rat ileum throughout the wall of the gut. MGL protein was distributed in the muscle and mucosal layers of the ileum and in the duodenum, proximal colon, and distal colon. We observed MGL expression in nerve cell bodies and nerve fibers of the enteric nervous system. There was extensive colocalization of MGL with PGP 9.5 and calretinin-immunoreactive neurons, but not with nitric oxide synthase. MGL was also present in the epithelium and was highly expressed in the small intestine. Enzyme activity levels were highest in the duodenum and decreased along the gut with lowest levels in the distal colon. We observed both soluble and membrane-associated enzyme activities. The MGL inhibitor URB602 significantly inhibited whole gut transit in mice, an action that was abolished in cannabinoid 1 receptor-deficient mice. In conclusion, MGL is localized in the enteric nervous system where endocannabinoids regulate intestinal motility. MGL is highly expressed in the epithelium, where this enzyme may have digestive or other functions yet to be determined.

Histological examination of rat small intestine after surgical removal of obturation small bowel obstruction and peptide stimulation of lymph flow

2018 ◽  
pp. 157-162
Author(s):  
А.А. Коваленко ◽  
Г.П. Титова ◽  
В.К. Хугаева
Keyword(s):  
Small Intestine ◽  
Surgical Treatment ◽  
Survival Rate ◽  
Small Bowel ◽  
Goblet Cells ◽  
Intestinal Wall ◽  
Structure And Function ◽  
Lymph Flow ◽  
Intestinal Lumen ◽  
And Function

Оперативное лечение различных заболеваний кишечника сопровождается осложнениями в виде нарушений микроциркуляции в области анастомоза кишки. Ранее нами показана способность лимфостимуляторов пептидной природы восстанавливать нарушенную микроциркуляцию, что послужило основой для настоящего исследования. Цель работы - оценка влияния стимуляции лимфотока в стенке кишки на процессы восстановления микроциркуляции, структуры и функции тонкой кишки в области оперативного вмешательства. Методика. В экспериментах на наркотизированных крысах (хлоралгидрат в дозе 0,6 г/кг в 0,9% растворе NaCl) моделировали различные поражения тонкой кишки (наложение лигатуры, перевязка 1-3 брыжеечных артерий, перекрут петли кишки вокруг оси брыжейки, сочетание нескольких видов повреждений). Резекция поврежденного участка через 1 сут. с последующим созданием тонкокишечного анастомоза завершалась орошением операционного поля раствором пептида-стимулятора лимфотока (40 мкг/кг массы животного в 1 мл 0,9% раствора NaCl). На 7-е сут. после операции проводили гистологическое исследование фрагмента кишки в области анастомоза. Результаты. На 7-е сут. после резекции у выживших животных (летальность вследствие кишечной непроходимости составляла 30%) имеют место морфологические признаки острых сосудистых нарушений стенки кишки, изменений кровеносных и лимфатических микрососудов, интерстициальный отек всех слоев стенки кишки, дилатация просвета кишки, повреждение всасывающего эпителия ворсин с истончением щеточной каемки клеток, морфологические признаки гиперфункции бокаловидных клеток. Использование лимфостимулятора пептидной природы после операции увеличивало выживаемость животных на 24%. У части животных отмечалось уменьшение расширения просвета кишки, у других практически полная его нормализация. Восстанавливалась форма кишечных ворсин и распределение бокаловидных клеток. Отсутствовали признаки внутриклеточного и межмышечного отека. Отмечено умеренное полнокровие венул. Заключение. Использование лимфостимулятора при хирургическом лечении кишечной непроходимости увеличивает выживаемость животных на 24% по сравнению с контролем, способствует более раннему восстановлению структуры и функции тонкой кишки. Полученные результаты свидетельствуют о перспективности использования стимуляции лимфотока при операциях на кишечнике. Surgical treatment of bowel diseases is associated with complications that cause microcirculatory disturbances in the anastomosis area and may lead to a fatal outcome. This study was based on our previous finding that peptide-type lymphatic stimulators are able to restore impaired microcirculation. The aim of this work was stimulating the lymph flow in the intestinal wall to facilitate recovery of microcirculation, structure and function of the small intestine in the area of surgical intervention. Methods. In experiments on anesthetized rats (0.6 g/kg chloral hydrate in 0.9% NaCl), various small bowel lesions were modeled (bowel ligation, ligation of 1-3 mesenteric arteries, gut torsion, combination of several lesion types). In 24 h, the damaged area was resected, and a small intestine anastomosis was creased. The surgery was completed with irrigation of the operative field with a solution of lymph flow stimulating peptide (40 мg/kg body weight in 1 ml of 0.9% NaCl). A gut fragment from the anastomosis area was examined histologically on day 7 after the surgery. Results. On the 7th day after removing the intestinal obstruction, the surviving animals (lethality 30%) had morphological signs of acute vascular disorders in the intestinal wall; changes in blood and lymphatic microvessels; interstitial edema of all intestinal wall layers; dilatation of the intestinal lumen; damage to the absorptive epithelium of villi with thinning of the brush border, and hyperfunction of mucous (goblet) cells. The use of the peptide after surgery increased the survival rate of animals by 24% and provided a smaller dilatation of the intestinal lumen in some animals. In other animals, the lumen recovered. The shape of intestinal villi and distribution of goblet cells were restored. Signs of intracellular and intermuscular edema were absent. Moderate venular congestion was noticed. Conclusion. Using the lymphatic stimulator in surgical treatment of intestinal obstruction increases the survival rate of animals by 24% compared to the control, facilitates earlier restoration of the small intestine structure and function. The obtained results indicated the effectiveness of lymphatic stimulation in intestinal surgery.

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