Consumption of an Oil Palm Fruit Extract Promotes Large Bowel Health in Rats.

Oil palm fruit is widely used for edible oils, but the health benefits of other components are relatively unknown. We examined if consuming a polyphenol-rich extract of the fruit, from a vegetation by-product of oil processing, which also contains fibre, has gastro-intestinal benefits in rats on a Western-type diet (WD). The oil palm preparation (OPP) was added to food (OPP-F) or drinking water (OPP-D) to provide 50 mg of gallic acid equivalents (GAE)/d and compared to effects of high amylose maize starch (HAMS; 30%) in the diet or green tea extract (GT; 50 mg GAE/d) in drinking water over 4 wk. OPP treatments induced some significant effects (P < 0.05) compared to WD. OPP-D increased caecal digesta mass, caecal digesta concentrations of total SCFA, acetate and propionate (OPP-F increased caecal butyrate concentration), the numbers of mucus-producing goblet cells per colonic crypt, and caecal digesta abundance of some bacteria which may provide benefit to the host (Faecalibacterium prausnitzii, Akkermansia muciniphila and Ruminococcus gnavus). HAMS induced similar effects but with greater potency and had a broader impact on microbe populations, whereas GT had minimal impacts. These results suggest dietary OPP may benefit the large bowel.

Variability of the transition zone length in Hirschsprung disease.

BACKGROUND: Surgical management of Hirschsprung disease (HD) involves fully excising the transition zone (TZ). The literature suggests that resection of ≥5 cm of ganglionic bowel proximal to the aganglionic segment is sufficient. Our primary aim was to evaluate the lengths of the TZ in a cohort of consecutive patients with HD. We reviewed the impact this had on the need for revision surgery. We hypothesized that the TZ can be highly variable and may lead to a TZ pull-through when the proximal donut is not reviewed intraoperatively. METHODS: A retrospective review was conducted for all patients undergoing primary pull-through surgery between January 2012 and September 2018. Data was collected on demographics, need for staged surgery, and complications following surgery. RESULTS: Forty-eight patients were eligible for inclusion. 11/48 (23%) patients presented late (>6 months). 27/48 (56%) patients needed a stoma prior to definitive surgery. The median age at pull-through was 6 months (1-84 months). The median TZ length was 1.7 cm (0.3-22.9 cm). 11/48 (23%) had a TZ >5 cm. 36/48 (75%) patients did not have intraoperative review of the donut resulting in three TZ pull-throughs. CONCLUSIONS: We would advocate circumferential intraoperative frozen section review of the proximal donut to minimize the risk of a TZ pull-through. LEVEL OF EVIDENCE: Level III.

Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4.

The intestinal tract contains many commensal bacteria that modulate various physiological host functions. Dysbiosis of commensal bacteria triggers dysfunction of the intestinal epithelial barrier, leading to the induction or aggravation of intestinal inflammation. To elucidate whether microRNA plays a role in commensal microbiome-dependent intestinal epithelial barrier regulation, we compared transcripts in intestinal epithelial cells (IECs) from conventional and germ-free mice and found that commensal bacteria induced the expression of miR-21-5p in IECs. miR-21-5p increased intestinal epithelial permeability and up-regulated ADP ribosylation factor 4 (ARF4), a small GTPase, in the IEC line Caco-2. We also found that ARF4 expression was up-regulated upon suppression of phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4), which are known miR-21-5p targets, by RNAi. Furthermore, ARF4 expression in epithelial cells of the large intestine was higher in conventional mice than in germ-free mice. ARF4 suppression in the IEC line increased the expression of tight junction proteins and decreased intestinal epithelial permeability. These results indicate that commensal microbiome-dependent miR-21-5p expression in IECs regulates intestinal epithelial permeability via ARF4, which may therefore represent a target for preventing or managing dysfunction of the intestinal epithelial barrier.

Dietary fibers and associated phytochemicals in cereals.

Epidemiological studies have linked whole-grain (WG) cereal consumption to a reduced risk of developing several chronic diseases-coronary heart disease, arteriosclerosis, type-2 diabetes, and some form of cancers. The underlying physiological mechanisms behind the protective effects of WG are unclear, but can most likely be assigned to a concerted action of dietary fiber (DF) and a wide variety of phytochemicals. Physiologically, it is important that soluble nonstarch polysaccharides contribute to higher viscosity in the small intestine as this may influence rate and extent of digestion and absorption. Associated with the DF matrix of cereals is an array of nonnutritive constituents predominantly concentrated in the bran fraction. Among them, the phenolic phytochemicals, benzoic acid and cinnamic derivatives and lignans, are of importance in a nutritional-health perspective. Only a small fraction of the phenolics is absorbed in the small intestine, but the availability can be increased by bioprocessing. The major part, however, is passed to the large intestine where the microbiota, which degrade and metabolize DF to SCFAs and gases, also convert the phenolic compounds into a range of other metabolites that are absorbed into the body and with the capability of influencing the metabolism at the cellular level.

Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.

The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5+ intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.

The Hippo pathway in intestinal regeneration and disease.

The Hippo pathway is a signalling cascade conserved from Drosophila melanogaster to mammals. The mammalian core kinase components comprise MST1 and MST2, SAV1, LATS1 and LATS2 and MOB1A and MOB1B. The transcriptional co-activators YAP1 and TAZ are the downstream effectors of the Hippo pathway and regulate target gene expression. Hippo signalling has crucial roles in the control of organ size, tissue homeostasis and regeneration, and dysregulation of the Hippo pathway can lead to uncontrolled cell growth and malignant transformation. Mammalian intestine consists of a stem cell compartment as well as differentiated cells, and its ability to regenerate rapidly after injury makes it an excellent model system to study tissue homeostasis, regeneration and tumorigenesis. Several studies have established the important role of the Hippo pathway in these processes. In addition, crosstalk between Hippo and other signalling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this Review, we summarize studies on the role of the Hippo pathway in the intestine on these physiological processes and the underlying mechanisms responsible, and discuss future research directions and potential therapeutic strategies targeting Hippo signalling in intestinal disease.

Buckling of a growing tissue and the emergence of two-dimensional patterns.

The process of biological growth and the associated generation of residual stress has previously been considered as a driving mechanism for tissue buckling and pattern selection in numerous areas of biology. Here, we develop a two-dimensional thin plate theory to simulate the growth of cultured intestinal epithelial cells on a deformable substrate, with the goal of elucidating how a tissue engineer might best recreate the regular array of invaginations (crypts of Lieberkühn) found in the wall of the mammalian intestine. We extend the standard von Kármán equations to incorporate inhomogeneity in the plate's mechanical properties and surface stresses applied to the substrate by cell proliferation. We determine numerically the configurations of a homogeneous plate under uniform cell growth, and show how tethering to an underlying elastic foundation can be used to promote higher-order buckled configurations. We then examine the independent effects of localised softening of the substrate and spatial patterning of cellular growth, demonstrating that (within a two-dimensional framework, and contrary to the predictions of one-dimensional models) growth patterning constitutes a more viable mechanism for control of crypt distribution than does material inhomogeneity.

Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome.

BACKGROUND: Intestinotrophic therapies, such as glucagon-like peptide-2 (GLP-2) analogs, may enhance intestinal adaptation and reduce dependence on parenteral nutrition (PN) in patients with intestinal failure associated with short bowel syndrome (SBS-IF). However, because GLP-2 enhances cellular growth, there is concern that GLP-2 analogs may also encourage growth of malignant cells. AIMS: To histologically examine the effects of teduglutide, a recombinant human GLP-2 analog, on the mucosa of the small and large intestine for indications of dysplastic transformation. METHODS: In a multicenter, prospective, randomized, placebo-controlled study, 83 PN-dependent patients with SBS-IF were monitored for several weeks to ensure optimal and stable PN. Patients were then randomized to receive 24 weeks of placebo (n=16), teduglutide (0.5 mg/kg/d; n=35), or teduglutide (0.10 mg/kg/d; n=32). RESULTS: Biopsies were obtained from 77 patients to yield 390 individual histologic interpretations. After 6 months of treatment, no features of dysplasia were found in any biopsy from the large or small intestine of patients receiving placebo or either dose of teduglutide. New secondary diagnoses, such as eosinophilic colitis or Crohn's disease, were found at a low frequency overall: teduglutide (0.05 mg/kg/d; range, 3.1% to 6.3%); teduglutide (0.10 mg/kg/d, 3.3%); placebo (range, 6.7% to 13.3%). CONCLUSIONS: Although this histologic substudy of biopsy samples was not powered to detect differences in occurrence of dysplasia between teduglutide-treated patients and those randomized to placebo, it demonstrated that no dysplasia or other pathologic processes were evident within the intestinal mucosa in the placebo group or the 2 teduglutide groups after 6 months of treatment.

Perioperative systemic lidocaine for postoperative analgesia and recovery after abdominal surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative pain management remains a significant challenge after abdominal surgery. OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy of systemic lidocaine for postoperative pain management and recovery after abdominal surgery. DATA SOURCE: Data were derived from Medline (1966-2010), CINAHL, The Cochrane Central Register of Controlled Trials, and Scopus. STUDY SELECTION: Randomized controlled trials of systemic administration of lidocaine for postoperative analgesia and recovery after abdominal surgery in adults, ie, >18 years, were considered. INTERVENTIONS: Combined data were analyzed with use of a random-effects model. MAIN OUTCOMES MEASURES: Data on opioid consumption, postoperative pain intensity, opioid-related side effects, time to first flatus, time to first bowel movement, and length of hospital stay were extracted. RESULTS: Twenty-one trials comparing systemic lidocaine with placebo or blank control for postoperative analgesia and recovery after abdominal surgery were included in this meta-analysis. Weighted mean difference for cumulative analgesic opioid (morphine) consumption 48 hours after surgery was -7.04 mg (95% CI: -10.40, -3.68, I2= 46.1%).Systemic lidocaine also significantly reduced postoperative pain intensity(visual analog scale, 0-100 mm) 6 hours after surgery at rest (weighted mean difference: -8.07 mm (95% CI: -14.69, -1.49); I2 = 90.6%) and during activity (weighted mean difference: -10.56 mm (95% CI: -16.89, -4.23), I2 = 82%). The time to first flatus and bowel movement was significantly shortened with lidocaine intervention by 6.92 hours (95% CI: -9.21, -4.63, I2 = 62.8%) and 11.74 hours (95% CI:-16.97, -6.51, I2 = 0). Moreover, systemic lidocaine also reduced hospital length of stay following the open procedure (weighted mean difference: -0.71 days (95% CI: -1.35, -0.07); I2 = 37.3%). LIMITATIONS: Heterogeneity of study results is the main limitation of this meta-analysis. CONCLUSION: Perioperative systemic lidocaine may be a useful adjunct for postoperative pain management by decreasing postoperative pain intensity, reducing opioid consumption, facilitating GI function, and shortening length of hospital stay.

Phenotypic and functional profiles of CRIg (Z39Ig)-expressing macrophages in the large intestine.

Intestinal macrophages (Mφ) play significant roles in maintaining homeostasis by the efficient elimination of foreign particles in the large intestine. However, functional complement receptors have not been fully identified. In this study, we showed that a complement receptor of the Ig superfamily (CRIg, also known as Z39Ig), a receptor for complement fragments (C3b and iC3b), was expressed on a subset of intestinal M in murine and human large intestine. When abilities of uptake of antigens of murine CRIg(+) Mφ were examined, intestinal CRIg(+) Mφ displayed less endocytic and similar phagocytic abilities compared to resident peritoneal F4/80(+)CRIg(-) Mφ and F4/80(+)CRIg(+) Mφ. Additionally, we found that a significant portion of C3b-dependent phagocytosis by large intestinal M involves CRIg, emphasizing the importance of efficient mechanisms to eliminate foreign particles in the large intestine. On the other hand, intestinal Mφ from 2,4,6-trinitrobenzene sulfonic acid-treated mice had decreased CRIg expression but increased CD11b expression, implying some contribution to the removal of immune complexes. This study will shed new light on opsonization and phagocytosis by large intestinal Mφ.

Intestinal health functions of colonic microbial metabolites: a review.

This review tries to find a scientific answer on the following two questions: (1) to what extent do we understand the specific role of colonic microbial metabolites, especially short-chain fatty acids (SCFA), in maintaining the health status and prevention of diseases of the colon and the host; (2) to what extent can we influence or even control the formation of colonic microbial metabolites which are beneficial for the health status. The review focuses on the following topics: energy source, intestinal motility, defence barrier, oxidative stress with special attention for antiinflammatory and anti-carcinogen functions, and satiety. Also the risk of overproduction of SCFA is discussed. Reviewing the literature as present today, it can be concluded that physiological levels of SCFA are vital for the health and well-being of the host and that the presence of carbohydrates (dietary fibre, prebiotics) is essential to favour the metabolic activity in the direction of carbohydrate fermentation. For optimal motor activity of the ileum and colon, to regulate the physiological intestinal mobility, steadily fermentable dietary fibres or prebiotics are crucial. The formation of SCFA, especially propionate and butyrate, up to high physiological levels in the colon, much likely also contributes to the defence mechanisms of the intestinal wall. No final answer can be given yet about the role of SCFA in anti-inflammation and anti-carcinogenicity, but recently published research shows possible mechanisms in this field. The intake of prebiotics or specific dietary fibres promotes the formation of SCFA within the physiological range, and more or less specifically increases the levels of propionate and butyrate. In this way, they provide benefit to the host, especially the natural regulation of the digestive system.

[Adhesive process in the abdominal cavity in patients with end colostomies and its influence on the reestablishment of the large intestine continuity].

Under analyses there were reparative operations on 79 patients with end colostomies performed using medial access in 42 patients and parastomal access in 37 patients. The investigation of prevalence of the adhesive process in 61 patients has shown that marked adhesions were formed in the area of the medial scar in 41 (67.2%) patients, the stump of the suppressed gut--in 31 (50.9%) patients and colostomy--in 27 (44.3%) Reestablishment of intestine continuity from the parastomal access allowed avoidance of adhesions in the zone of the medial postoperative scar which shortened the time of operation and decreased the level of intra- and postoperative complications.

Intestinal and renal effects of low-volume phosphate and sulfate cathartic solutions designed for cleansing the colon: pathophysiological studies in five normal subjects.

OBJECTIVES: Ingestion of a concentrated low-volume phosphate solution produces copious diarrhea, which cleanses the colon, but it occasionally causes renal failure due to calcium phosphate precipitation in renal tubules. We hypothesized that a concentrated low-volume sulfate solution would be an equally effective cathartic, and that urine produced after sulfate would have less tendency to precipitate calcium salts than urine produced after phosphate. METHODS: Hydrated subjects ingested 75 ml of phosphosoda or an equimolar dose of sulfate salts in a small volume of solution. Four liters of PEG (polyethylene glycol) lavage solution was the control. All solutions were administered in split doses, 10 h apart. Propensity of urine to precipitate at pH 6.4 (the pH of renal tubular fluid) was assessed by determining the minimal calcium concentration that caused precipitation. RESULTS: Average diarrheal stool weight was 2,004 g after phosphate, 2,854 g after sulfate, and 3,021 g after PEG (P<0.001). Average calcium concentration (in mg/dl) required to induce urine precipitation at pH 6.4 was 43 after PEG, 10 after PO(4), and 187 after SO(4) (P=0.009). CONCLUSIONS: (i) In equimolar doses, sulfate produced 42% more diarrheal stool weight than phosphate. (ii) Phosphate increased the propensity for calcium salt precipitation in urine at pH 6.4, whereas sulfate did not. (iii) These results suggest that a hypertonic low-volume sulfate solution would be an effective cathartic for colon cleansing and that sulfate-induced catharsis would be less likely than phosphate catharsis to produce calcium salt deposition in renal tubules.

Distribution of neuroendocrine cells in the small and large intestines of the one-humped camel (Camelus dromedarius).

The distribution and relative frequency of neuroendocrine cells in the small and large intestines of one-humped camel were studied using antisera against 5-hydroxytryptamine (5-HT), cholecystokinin (CCK-8), somatostatin (SOM), peptide tyrosine tyrosine (PYY), gastric inhibitory polypeptide (GIP), neuronal nitric oxide synthase (nNOS), gastrin releasing peptide (GRP), substance P (SP), and neurokinin A (NKA). Among these cell types, CCK-8 immunoreactive (IR) cells were uniformly distributed in the mucosa, while others showed varied distribution in the villi or crypts of the small intestine. Immunoreactive cells like 5HT, CCK-8, and SOM showed peak density in the villi and crypts of the small intestine and in the colonic glands of the large intestine, while cells containing SP were discerned predominately in the crypts. 5-HT, CCK-8 and SOM cells were mainly flask-shaped and of the open-variety, while PYY and SP immunoreactive cells were mainly rounded or basket-shaped and of the closed variety. Basically the distribution pattern of the endocrine cells in the duodenum, jejunum and colon of the one-humped camel is similar to that of other mammals. Finally, the distribution of these bioactive agents may give clues as to how these agents aid in the function of the intestinal tract of this desert animal.

The Wnt antagonist sFRP1 is downregulated in premalignant large bowel adenomas.

Our previous studies have implicated the Wnt antagonist, sFRP1, as a tumour suppressor gene in advanced colorectal cancer. In this study, we set out to investigate the relationship between sFRP1 expression and large bowel adenomas, a precursor of colorectal cancer. The induction of beta-catenin/TCF mediated transcription is both a frequent early event in colorectal neoplasia, and a key downstream effect of wnt growth factor signalling. Lithium treatment of a small bowel mucosal cell line (FHs 74 int) induced sFRP1 within 8 h, indicating that this gene is positively regulated by beta-catenin, contrasting with the suppression of sFRP1 expression, we saw previously in advanced colorectal cancers. We therefore investigated a series of 12 adenomas and matched large bowel mucosa samples. Real-time RT-PCR analysis showed a reduction in sFRP1 expression in all 12 dysplastic lesions (median 485-fold, IQR 120- to 1500-fold), indicating factors other than beta-catenin influence sFRP1 levels. In a second series of 11 adenomas, we identified methylation of the sFRP1 promotor region in all 11 samples, and this was increased compared with the surrounding normal mucosa in seven cases. Immunohistochemical analysis using a polyclonal antibody supported these findings, with sFRP1 expression reduced in many of the adenoma samples examined. sFRP1 staining in normal mucosa adjacent to the dysplastic tissue was also reduced compared with the normal controls, suggesting that sFRP1 expression may be suppressed in a field of mucosa rather than in individual cells. This study identifies sFRP1 inactivation at the premalignant stage of colorectal cancer development, indicating that these pathways may be useful targets for chemoprevention strategies in this common solid tumour.

Acute colitis induction by oil of mustard results in later development of an IBS-like accelerated upper GI transit in mice.

Oil of mustard (OM) is a potent neuronal activator that promotes allodynia and hyperalgesia within minutes of application. In this study, OM was used to induce an acute colitis. We also investigated whether intracolonic OM-induced inflammation alters gastrointestinal (GI) function over a longer time frame as a model of postinflammatory irritable bowel syndrome (PI-IBS). Mice given a single administration of 0.5% OM developed a severe colitis that peaked at day 3, was reduced at day 7, and was absent by day 14. At the peak response, there was body weight loss, colon shrinkage, thickening and weight increases, distension of the proximal colon, and diarrhea. Macroscopic inspection of the distal colon revealed a discontinuous pattern of inflammatory damage and occasional transmural ulceration. Histological examination showed loss of epithelium, an inflammatory infiltrate, destruction of mucosal architecture, edema, and loss of circular smooth muscle architecture. OM administration increased transit of a carmine dye bolus from 58% of the total length of the upper GI tract in untreated age-matched controls to as high as 74% when tested at day 28 post-OM. Mice in the latter group demonstrated a significantly more sensitive response to inhibition of upper GI transit by the mu-opioid receptor agonist loperamide compared with normal mice. OM induces a rapid, acute, and transient colitis and, in the longer term, functional changes in motility that are observed when there is no gross inflammation and thereby is a model of functional bowel disorders that mimic aspects of PI-IBS in humans.

Microbial-gut interactions in health and disease. Gastrointestinal cancer.

A combination of both environmental and genetic factors contributes to the vast majority of human cancers and in particular cancers of the gastrointestinal tract, including the stomach, colon and rectum. The mechanisms associated with cancer causation or prevention are largely unknown and the subject of much research. Many of these mechanisms implicate the metabolic activities of the bacterial flora normally resident in the gastrointestinal tract. This paper examines both the detrimental and beneficial consequences of bacterial activity of the gastrointestinal tract, focusing in particular on the stomach and large intestine.

A study of the lengthening and contractility of the surgical margins in digestive tract cancer.

BACKGROUND: The lengthening and the contractility of the digestive tract were studied. METHODS: The stretched length of specimens was measured under pull weights of 500 g and 1000 g; the contracted length was measured in natural status and in 10% formalin fixation in vitro. The lengthening or contractility rate was calculated as the length difference divided by the natural length in vivo. RESULTS: The esophagus lengthened 16.5% at 500 g and 30.5% at 1,000 g, stomach 15% and 22.6%, small intestine 66.4% and 120%, large intestine 36% and 56%. In natural status in vitro, the esophagus contracted 44.5%, stomach 13.6%, small intestine 11.4%, and large intestine 15.6%; they continued to contract 12 to 24 hours after formalin fixation. CONCLUSIONS: The lengthening and contractility of the digestive tract should be considered in evaluating the resection margin at surgery. The length of different conditions can be converted by the formula: Y = alphaX.