Vitamin A and retinoic acid accelerate the attenuation of intestinal adaptability upon feeding induced by high-fat diet in mice.

With its unique cellular plasticity, the small intestinal mucosa exhibits efficient adaptability upon feeding. However, little is known about the effect of high-fat diet (HFD) feeding on this adaption and its underlying mechanism. Herein, we demonstrated that the cell proliferation ability, mitochondrial morphology, and global transcriptomic profile of the small intestine exhibited a prominent discrepancy between the fasted and refed state in mice, which were markedly attenuated by long-term HFD feeding. The retinol (Vitamin A, VA) metabolism pathway was dramatically affected by HFD feeding in the small intestine. Both VA and its active metabolite retinoic acid (RA), with the administration of lipid micelles, promoted the expression of genes involved in lipid absorption and suppressed the expression of genes involved in the cell proliferation of intestinal organoids. Via chip-qPCR and RT-qPCR, genes involved in lipid metabolism and cell proliferation were target genes of RARα/RXRα in small intestinal organoids treated with RA and lipid micelles. The role of VA in the in vivo attenuation of intestinal adaptability, in response to HFD, was evaluated. Mice were fed a normal chow diet, HFD, or HFD diet supplemented with additional 1.5-fold VA for 12 weeks. VA supplementation in HFD accelerated the attenuation of intestinal adaptability upon feeding induced by HFD, promoted lipid absorption gene expression, and increased body weight and serum cholesterol levels. In conclusion, the discrepancy of the small intestine between the fasted and refed state was dramatically attenuated by HFD feeding, in which VA and RA might play important roles.

COVID-19 and Hartnup disease: an affair of intestinal amino acid malabsorption.

Since the outbreak of COVID-19, clinicians have tried every effort to fight the disease, and multiple drugs have been proposed. However, no proven effective therapies currently exist, and different clinical phenotypes complicate the situation. In clinical practice, many severe or critically ill COVID-19 patients developed gastrointestinal (GI) disturbances, including vomiting, diarrhoea, or abdominal pain, even in the absence of cough and dyspnea. Understanding the mechanism of GI disturbances is warranted for exploring better clinical care for COVID-19 patients. With evidence collected from clinical studies on COVID-19 and basic research on a rare genetic disease (i.e., Hartnup disorder), we put forward a novel hypothesis to elaborate an effective nutritional therapy. We hypothesize that SARS-CoV-2 spike protein, binding to intestinal angiotensin-converting enzyme 2, negatively regulates the absorption of neutral amino acids, and this could explain not only the GI, but also systemic disturbances in COVID-19. Amino acid supplements could be recommended.Level of evidence No level of evidence: Hypothesis article.

Effect of the leaves aqueous extract of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) on intestinal function and its acute toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: In Argentine traditional medicine it is recorded the use of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) leaves for treating various affections that compromise the intestinal normal functioning. AIM OF THE STUDY: The aim of this study was to assess the effect of J. rhombifolia leaves lyophilized aqueous extract on the intestinal function by means of in vivo and ex vivo experimental assays for determinate the antidiarrheal and antispasmodic capacity. Furthermore, was to evaluate its acute toxicity potential by oral and intraperitoneal administration of extract. MATERIALS AND METHODS: The in vivo assays were conducted by the experimental techniques of intestinal transit in mice, intestinal fluid accumulation in rats and Castor oil-induced diarrhea in mice. In the ex vivo assays, isolated rat duodenum and ileum segments were used for to evaluate the antispasmodic activity through contractile concentration-response curves induced by Carbachol and CaCl2. The acute toxicity of the extract was also investigated by oral and intraperitoneal administration. RESULTS: The extract intraperitoneal administration at the doses 125, 250 and 500 mg/kg, caused a marked reduction in the normal intestinal transit and in the number of diarrheal episodes in a dose-dependent manner. However, the extract did not produce significant changes in the intestinal fluid accumulation with any of the tested dose. The extract demonstrated a non-competitive inhibitory effect on the contractions of intestinal smooth muscle experimentally provoked by the spasmogenic agents Carbachol and CaCl2 in a dose-dependent manner (IC50 = 10.57 ± 1.38 and 6.29 ± 1.54 mg extract/ml Tyrode solution in the isolated organ bath, respectively). ANOVA indicated a significative effect of treatment (p < 0.001). CONCLUSIONS: The scientific evidence achieved based in the used experimental models allows us to indicate that J. rhombifolia leaves lyophilized aqueous extract manifest an antispasmodic activity on intestinal smooth muscle without observation of apparent toxicity symptoms.

Effects of Chaihu-Shugan-San on Small Intestinal Interstitial Cells of Cajal in Mice.

Chaihu-Shugan-San (CSS) has been widely used as an alternative treatment for gastrointestinal (GI) diseases in East Asia. Interstitial cells of Cajal (ICCs) are pacemakers in the GI tract. In the present study, we examined the action of CSS on pacemaker potentials in cultured ICCs from the mouse small intestine in vitro and on GI motility in vivo. We used the electrophysiological methods to measure the pacemaker potentials in ICCs. GI motility was investigated by measuring intestinal transit rates (ITR). CSS inhibited the pacemaker potentials in a dose-dependent manner. The capsazepine did not block the effect of CSS. However, the effects of CSS were blocked by glibenclamide. In addition, NG-nitro-L-arginine methyl ester (L-NAME) also blocked the CSS-induced effects. Pretreatment with SQ-22536 or with KT-5720 did not suppress the effects of CSS; however, pretreatment with ODQ or KT-5823 did. Furthermore, CSS significantly suppressed murine ITR enhancement by neostigmine in vivo. These results suggest that CSS exerts inhibitory effects on the pacemaker potentials of ICCs via nitric oxide (NO)/cGMP and ATP-sensitive K+ channel dependent and transient receptor potential vanilloid 1 (TRPV1) channel independent pathways. Accordingly, CSS could provide the basis for the development of new treatments for GI motility dysfunction.

Effects of Zuojin pill on depressive behavior and gastrointestinal function in rats with chronic unpredictable mild stress: Role of the brain-gut axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM: To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS: The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1ß, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum. RESULTS: The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1ß, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1. CONCLUSION: ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .

Rikkunshito Depolarizes Pacemaker Potentials of Cultured Interstitial Cells of Cajal through Ghrelin Receptors in Murine Small Intestine.

BACKGROUND: Rikkunshito has been used to treat gastrointestinal (GI) disorders. The purpose of this study was to investigate the effects of Rikkunshito, a traditional Japanese herbal medicine, on the pacemaker potentials of interstitial cells of Cajal (ICCs) from the small intestines of mice. METHODS: We isolated ICCs from the small intestines of mice, and the whole-cell patch-clamp configuration was used to record the pacemaker potentials in cultured ICCs and membrane currents. RESULTS: Rikkunshito depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with GSK1614343 or (D-Lys3)-growth hormone-releasing peptide-6 inhibited Rikkunshito-induced depolarization of pacemaker potentials. Intracellular GDP-ß-S inhibited Rikkunshito-induced effects. In Ca2+-free solution or in the presence of thapsigargin, Rikkunshito did not depolarize pacemaker potentials. Moreover, in the presence of U-73122 or xestospongin C, Rikkunshito-induced effects were inhibited. However, in the presence of staurosporine, Go6976 or Rottlerin, Rikkunshito depolarized pacemaker potentials. Furthermore, Rikkunshito inhibited both transient receptor potentials melastatin 7 (TRPM7) and Ca2+-activated Cl- channels (ANO1) currents. CONCLUSION: Rikkunshito depolarized pacemaker potentials of ICCs via ghrelin receptor and G protein through internal or external Ca2+-, phospholipase C-, and inositol triphosphate-dependent and protein kinase C-, TRPM7-, and ANO1-independent pathways. The study shows that Rikkunshito may alleviate GI motility disorders through its depolarizing effects on ICCs.

Epidermal growth factor promotes intestinal secretory cell differentiation in weaning piglets via Wnt/ß-catenin signalling.

Small intestinal epithelium homeostasis involves four principal cell types: enterocytes, goblet, enteroendocrine and Paneth cells. Epidermal growth factor (EGF) has been shown to affect enterocyte differentiation. This study determined the effect of dietary EGF on goblet, enteroendocrine and Paneth cell differentiation in piglet small intestine and potential mechanisms. Forty-two weaned piglets were used in a 2 × 3 factorial design; the major factors were time post-weaning (days 7 and 14) and dietary treatment (0, 200 or 400 µg/kg EGF supplementation). The numbers of goblet and enteroendocrine cells were generally greater with the increase in time post-weaning. Moreover, the supplementation of 200 µg/kg EGF increased (P < 0.01) the number of goblet and enteroendocrine cells in villus and crypt of the piglet small intestine as compared with the control. Dietary supplementation with 200 µg/kg EGF enhanced (P < 0.05) abundances of differentiation-related genes atonal homologue 1, mucin 2 and intestinal trefoil factor 3 messenger RNA (mRNA) as compared with the control. Piglets fed 200 or 400 µg/kg EGF diet had increased (P < 0.05) abundances of growth factor-independent 1, SAM pointed domain containing ETS transcription factor and pancreatic and duodenal homeobox 1 mRNA, but decreased the abundance (P < 0.01) of E74 like ETS transcription factor 3 mRNA as compared with the control. Animals receiving 400 µg/kg EGF diets had enhanced (P < 0.05) abundances of neurogenin3 and SRY-box containing gene 9 mRNA as compared with the control. The mRNA abundance and protein expression of lysozyme, a marker of Paneth cell, were also increased (P < 0.05) in those animals. As compared with the control, dietary supplementation with 200 µg/kg EGF increased the abundance of EGF receptor mRNA and the ratio of non-phospho(p)-ß-catenin/ß-catenin (P < 0.05) in villus epithelial cells at days 7 and 14. This ratio in crypt epithelial cells was higher (P < 0.05) on the both 200 and 400 µg/kg EGF groups during the same period. Our results demonstrated that dietary EGF stimulated goblet, enteroendocrine and Paneth cell differentiation in piglets during the post-weaning period, partly through EGFR and Wnt/ß-catenin signalling.

Dose-dependent effects of two inulin types differing in chain length on the small intestinal morphology, contractility and proinflammatory cytokine gene expression in piglets.

Inulin is a linear fructose polymer which may affect small intestinal physiology. The effects of dietary level of two inulin types on morphology, contractility and proinflammatory cytokine gene expression in the small intestine of piglets were investigated. Fifty six piglets were divided into seven groups fed diets without inulin addition or with 1%, 2% or 3% of inulin with an average degree of polymerisation of 10 (IN10) or 23 (IN23). All diets were offered from day 10 of life for 40 d. Feeding IN10 diets did not affect villous height to crypt depth ratio in the duodenum, while in the jejunum the 2% IN10 diet increased it as compared to other groups. Jejunal muscle contractions induced by electrical field stimulation were impaired by the 2% and 3% IN10 diets. The ileal expression of interleukin-12p40 was decreased by the 2% IN10 diet. There was no effect of IN23 level on villous height to crypt depth ratio in any segment of the small intestine as well as on jejunal motility. The 2% and 3% IN23 diets decreased the jejunal expression of tumour necrosis factor-α. In conclusion, IN10 is more active in the small intestine than IN23. At the 2% dietary level, it increases absorptive area in the jejunum, but may slightly impair smooth muscle contractions.

Child compound Endothelium corneum attenuates gastrointestinal dysmotility through regulating the homeostasis of brain-gut-microbiota axis in functional dyspepsia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, there is no specific effective western medicine for functional dyspepsia (FD), especially in children. Clinically, child compound Endothelium corneum (CCEC) has shown to be effective for the therapy of FD, however, the underlying mechanism has not been elucidated yet. MATERIALS AND METHODS: FD was induced in rats by irregular diet plus dilute hydrochloric acid feeding. Gastric emptying and small intestinal transit were examined by intragastric gavage with Evans blue. Histopathology was assessed by H&E staining. Gastrointestinal hormones and brain gut peptides were measured by ELISA assay. mRNA expression level was quantified by real-time PCR. Protein expression level was detected by western blotting assay. Gut microbiota was analyzed by 16S rRNA miseq sequencing. RESULTS: CCEC significantly enhanced gastric emptying and small intestinal transit of FD rats, and prominently suppressed gastrointestinal microinflammation. At phylum level, CCEC prevented the decrease of Firmicutes and the increase of Bacteroidetes in gut of FD rats. In stomach of FD rats, MTL, CCK and VIP levels were significantly increased, which could be repressed by CCEC; however, the decreased GAS level could not be elevated by CCEC. In small intestine of FD rats, MTL and GAS levels were decreased, while VIP content was increased. These alterations could be effectively reversed by CCEC. NPY levels in serum, small intestine and hypothalamus of FD rats were significantly decreased, which could be rescued by CCEC. Moreover, the over-activated POMC/Stat3/Akt pathway in hypothalamus of FD rats could be suppressed by CCEC. CONCLUSION: CCEC enhanced gastrointestinal motility probably through rebalancing the homeostasis of brain-gut-microbiota axis in FD rats. The novel findings may provide insightful theoretical basis for its clinical employment.

High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine.

The lumen of the small intestine (SI) is filled with particulates: microbes, therapeutic particles, and food granules. The structure of this particulate suspension could impact uptake of drugs and nutrients and the function of microorganisms; however, little is understood about how this suspension is re-structured as it transits the gut. Here, we demonstrate that particles spontaneously aggregate in SI luminal fluid ex vivo. We find that mucins and immunoglobulins are not required for aggregation. Instead, aggregation can be controlled using polymers from dietary fiber in a manner that is qualitatively consistent with polymer-induced depletion interactions, which do not require specific chemical interactions. Furthermore, we find that aggregation is tunable; by feeding mice dietary fibers of different molecular weights, we can control aggregation in SI luminal fluid. This work suggests that the molecular weight and concentration of dietary polymers play an underappreciated role in shaping the physicochemical environment of the gut. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Impact of a dietary challenge with peroxidized oil on the glutathione redox status and integrity of the small intestine in weaned piglets.

Glutathione (GSH) is considered to play an important role in maintaining the integrity of the small intestine. In piglets, altered mucosal GSH levels might therefore be involved in weaning-induced changes of the small intestinal morphology and barrier function. To test this hypothesis, we aimed to challenge the mucosal GSH redox status during the first 28 days after weaning, by feeding diets containing 5% fresh linseed oil (CON), or 2.5% (OF1) or 5% (OF2) peroxidized linseed oil (peroxide value 225 mEq O2/kg oil) and exploring the effects on gut integrity. Piglets were pair-fed and had a total daily feed allowance of 32 g/kg BW. A fourth treatment included animals that were fed the control diet ad libitum (ACON). Animals were sampled at days 5 and 28 post-weaning. The malondialdehyde (MDA) concentration and GSH redox status (GSH/GSSG Eh) were determined in blood, liver and small intestinal mucosa. Histomorphology of the duodenal and jejunal mucosa was determined, and Ussing chambers were used to assess fluorescein isothiocyanate dextran (FD4) and horseradish peroxidase (HRP) fluxes across the mucosa. Results show that peroxidized linseed oil imposed an oxidative challenge at day 28, but not at day 5 post-weaning. At day 28, increasing levels of dietary peroxides to pair-fed pigs linearly increased MDA levels in duodenal and jejunal mucosa. Moreover, FD4 fluxes were significantly increased in OF1 (+75%) and OF2 (+64%) in the duodenum, and HRP fluxes tended (P=0.099) to show similar differences, as compared to CON. This co-occurred with a significant 11 mV increase of the hepatic GSH/GSSG Eh, potentiated by a significantly increased GSH peroxidase activity for treatments OF1 (+47%) and OF2 (+63%) in liver as compared to CON. Furthermore; duodenal HRP flux significantly correlated with the hepatic glutathione disulphide (GSSG) level (r=0.650), as also observed in the jejunum for hepatic GSSG (r=0.627) and GSH/GSSG Eh (r=0.547). The jejunal permeability was not affected, but FD4 and HRP fluxes significantly correlated with the local GSH (r=0.619; r=0.733) and GSSG (r=0.635; r=0586) levels. Small intestinal histomorphology was not affected by dietary lipid peroxides, nor were there any correlations found with the GSH redox system. To conclude, under oxidative stress conditions, jejunal barrier function is related to the local and hepatic GSH redox system. It is suggested that the hepatic GSH system participates in the elimination of luminal peroxides, and thereby impacts on duodenal barrier function.

Total nutrient digestibility and small intestine starch digestion in Nellore and Angus young bulls fed a whole shelled corn diet.

Eighteen Nellore and 18 Angus young bulls with BW of 381 ± 12 kg were randomly assigned into two feeding groups (whole shelled corn [WSC] or ground corn with silage [GC]) to evaluate the interaction of breed and diet on total nutrient digestibility, pancreatic α-amylase, and maltase activity and SLC5A1expression in the small intestine. Experimental diets (DM basis) included (a) a diet containing 30% corn silage and 70% GC and soya bean meal-based concentrate and (b) a diet containing 85% WSC and 15% of a soya bean meal- and mineral-based pelleted supplement. The treatments were Nellore fed GC diet; Nellore fed WSC diet; Angus fed GC diet; and Angus fed WSC diet. Total faecal collection for the digestibility trial occurred from day 48 until day 50 of the experimental period. Feeding the WSC diet reduced DM and NDF intake (p < 0.01). Angus had greater DM and nutrient intake in kg/day (p < 0.01). However, there was no breed effect on DM and nutrient intakes based on percentage of BW (p > 0.19). Angus had greater starch digestibility (p = 0.03) than Nellore. Cattle fed the WSC diet had greater DM, NDF and starch digestibility (p < 0.01) compared with those fed the GC diet. The activity of pancreatic α-amylase (U/g of protein) was greater in Nellore (p < 0.01) and was not affected by diet (p = 0.52). In duodenum, maltase activity (U/g of protein) was greater in bulls fed GC diet (p = 0.02). Expression of the gene SLC5A1was not affected by breed or diet (p > 0.05). In conclusion, Nellore had less capacity to digest starch. However, they did not have less pancreatic α-amylase and duodenal maltase activity compared to Angus. The use of the WSC diet increases DM and total nutrient digestibility.

The Effect of Gastric Electrical Stimulation on Small Bowel Motility in Patients With Gastroparesis and Concomitant Pancreatic and Small Bowel Dysfunction: From Animal Model to Human Application.

BACKGROUND/AIMS: Patients with gastroparesis often have biliary/pancreatic and small bowel symptoms but the effects of gastric electrical stimulation on small bowel electrical activity of the mid-gut have not been studied. Animal model aim: Establish gastric and upper small bowel/biliary slow wave activity relationships with electrical stimulation. Human study aim: Demonstrate improvement in symptoms associated with proximal small bowel dysmotility in gastric stimulated patients. MATERIALS AND METHODS: Animal model: In vivo evoked responses of duodenal and Sphincter of Oddi measures recorded during gastric electrical stimulation in a nonsurvival swine model (N = 3). High-resolution electrical slow wave mapping of frequency, amplitude, and their ratio, for duodenal and Sphincter of Oddi electrical activity were recorded. Human study: Patients (N = 8) underwent temporary gastric stimulation with small bowel electrodes. Subjective and objective data was collected before and after temporary gastric stimulation. Symptom scores, gastric emptying times, and mucosal electrograms via low-resolution mapping were recorded. RESULTS: Animal gastric stimulation resulted in some changes in electrical activity parameters, especially with the highest energies delivered but the changes were not statistically significant. Human study revealed improvement in symptom and illness severity scores, and changes in small bowel mucosal slow wave activity. CONCLUSIONS: Gastric electrical stimulation in an animal model seems to show nonsignificant effects small bowel slow wave activity and myoelectric signaling, suggesting the existence of intrinsic neural connections. Human data shows more significance, with possible potential for therapeutic use of electrical stimulation in patients with gastroparesis and pancreato-biliary and small bowel symptoms of the mid-gut. This study was limited by the nonsurvival pig model, small sample size, and open label human study.

Medium-chain glycerides affect gut morphology, immune- and goblet cells in post-weaning piglets: In vitro fatty acid screening with Escherichia coli and in vivo consolidation with LPS challenge.

The influence of medium-chain glycerides on performance and gastrointestinal well-being in weaning piglets was assessed. First, caproic (C6), caprylic (C8) and capric (C10) acid activity against Escherichia coli was screened in vitro. Pig flora of the whole small intestine was used as inoculum. Seven in vitro incubations were done in duplicate at pH = 3 and 5: C10 (15 mM), C8 (12 mM), C6 (15, 12, 10 mM), a non-incubated-negative control and incubated negative control. Culture suspensions were plated on E. coli-selective agar. Controls showed bacterial growth. C6 and C8 showed no growth at both pH-values, where C10 showed growth at pH = 5. Secondly, an in vivo study was done with 80 weaned piglets over 42 days, housed in pens of eight animals (five pens/treatment), fed a basal diet containing broken rice/soya bean meal/fish meal and supplemented with C6 and C8 in medium-chain glyceride form (MCT6/8, 0.175%) or antibiotic growth promoter (AGP, 0.020%) (Kasetsart University, Thailand) serving as control. Feed intake, daily gain and feed-to-gain ratio did not differ between MCT6/8 and AGP. Per replicate, two random selected piglets were challenged intravenously with E. coli-lipopolysaccharide (LPS) or saline solution (S) at Days 21 and 28. All challenged animals were sacrificed; blood and digestive tract samples (jejunum/ileum) were collected at Day 35. LPS challenge consistently reduced villus height and crypt depth for MCT6/8 and AGP. However, LPS-challenged piglets supplemented with MCT6/8 restored villus height, where AGP did not. MCT6/8 piglets had higher serum IgA, more jejunal IgA-positive plasma cells and goblet cells than AGP. At the ileal level, results were similar, though less pronounced. The present study offers new insight in the benefits of MCT6/8 over AGP in the post-weaning period. There is in vitro anti-microbial action of C6 and C8 on E. coli. In vivo, MCT6/8 also has protective effects in the small intestine that may result in growth promotion.

The Rate at Which Digested Protein Enters the Small Intestine Modulates the Rate of Amino Acid Digestibility throughout the Small Intestine of Growing Pigs.

Background: Actinidin, a cysteine protease in kiwifruit (KF), increases both the gastric digestion and gastric-emptying rate of beef muscle protein. Objective: This study aimed to determine the relation between the rate of digested nitrogen entering the small intestine (SI; a function of the extent of gastric digestion and gastric-emptying rate) and the disappearance of amino acids (AAs) in different parts of the SI at set times postfeeding. Methods: Male 9-wk-old pigs (n = 90; mean ± SD body weight: 28 ± 2.9 kg) were fed a diet containing 14% beef for 3 d. The beef-based diet was supplemented with green KF pulp (containing actinidin), gold KF pulp supplemented with actinidin, or gold KF pulp alone (no actinidin). The KF or actinidin amounts corresponded to the intake of 2 KFs/human meal. On day 3, pigs were killed at 0.5, 1, 3, 5, and 7 h postprandially. Stomach chyme was analyzed to determine the rate of digested nitrogen entering the SI. Apparent AA digestibility at set times was determined in the proximal, medial, and distal SI. Polynomial and correlation analyses were conducted. Results: The rate of digested nitrogen entering the SI was higher (P < 0.001) with actinidin (e.g., >44% at 5 h postprandially). Actinidin also increased the apparent AA digestibility at the proximal and medial SI (P ≤ 0.05) at set times (e.g., 42% and 15% greater for arginine, respectively), but not in general for the distal SI (P > 0.05). At the proximal SI, apparent AA digestibility was correlated more strongly with the digested nitrogen entering the SI (r = 0.73, P < 0.001; n = 57) than with gastric emptying (r = 0.64, P < 0.001) or gastric protein digestion (r = 0.57, P < 0.001). Similar trends were observed for the medial SI. Conclusion: The rate of digested nitrogen entering the SI is an accurate predictor of the rate of AA digestibility and the location of AA absorption in the pig SI.

Modulation of Pacemaker Potentials in Murine Small Intestinal Interstitial Cells of Cajal by Gamisoyo-San, a Traditional Chinese Herbal Medicine.

BACKGROUND: The Gamisoyo-san (GSS) has been used for -improving the gastrointestinal (GI) symptoms. The purpose of this study was to investigate the effects of GSS, a traditional Chinese herbal medicine, on the pacemaker potentials of mouse small intestinal interstitial cells of Cajal (ICCs). METHODS: ICCs from the small intestines were dissociated and cultured. Whole-cell patch-clamp configuration was used to record pacemaker potentials and membrane currents. RESULTS: GSS depolarized ICC pacemaker potentials in a dose-dependent manner. Pretreatment with 4-diphenylacetoxypiperidinium iodide completely inhibited GSS-induced pacemaker potential depolarizations. Intracellular GDP-ß-S inhibited GSS-induced effects, and in the presence of U-73122, GSS-induced effects were inhibited. Also, GSS in the presence of a Ca2+-free solution or thapsigargin did not depolarize pacemaker potentials. However, in the presence of calphostin C, GSS slightly depolarized pacemaker potentials. Furthermore, GSS inhibited both transient receptor potential melastatin7 and Ca2+-activated Cl- channel (anoctamin1) currents. CONCLUSION: GSS depolarized pacemaker potentials of ICCs via G protein and muscarinic M3 receptor signaling pathways and through internal or external Ca2+-, phospholipase C-, and protein kinase C-dependent and transient receptor potential melastatin 7-, and anoctamin 1-independent pathways. The study shows that GSS may regulate GI tract motility, suggesting that GSS could be a basis for developing novel prokinetic agents for treating GI motility dysfunctions.

Insights Into the Different Effects of Food on Intestinal Secretion Using Magnetic Resonance Imaging.

BACKGROUND: Plant foods may stimulate intestinal secretion through chemicals designed to deter herbivores, including lactucins in lettuce and rhein in rhubarb. This may increase ileostomy output and induce diarrhoea in people with intact bowels. OBJECTIVE: We aimed to determine the effect of food on intestinal water content using Magnetic Resonance Imaging (MRI). DESIGN: A three period crossover trial of isocaloric meals in adults without bowel disorders. Meals: 2 slices white bread with 10 g butter; 300 g rhubarb with 60 mL lactose free cream; 300 g lettuce with 30 mL mayonnaise. PRIMARY OUTCOME: Area under curve (AUC) small bowel water content (SBWC) using MRI. SECONDARY OUTCOMES: ascending colon water content; T1 relaxation time of ascending colon (T1AC); gastric volume; visual analogue scales of bloating and satiety (0-100). MRI analysts were blinded. Scanned fasting and hourly to 180 min postprandial. Symptoms scored half-hourly. RESULTS: 9 female and 6 male subjects completed the study. AUC SBWC fell after bread but rose after lettuce and even more after rhubarb, difference from baseline being (Bread AUC -5662 (1209) ml.min vs Lettuce 3194 (1574) ml.min and Rhubarb 10586 (1629) ml.min (P < 0.01). Rhubarb induced a rise in T1AC but differences at 3 hours were not significant (P = 0.06). Gastric volume at T = 0 significantly was higher for both lettuce and rhubarb (571 ± 92 and 558 ± 89 mls) respectively compared to bread (314 ± 108 mls) (p < 0.0001). Symptom scores were higher for lettuce > rhubarb > bread. CONCLUSION: Lettuce and rhubarb meals increased intestinal water content, demonstrating how different foods can alter ileal flow and stool consistency.

Beneficial effects of water-soluble chestnut (Castanea sativa Mill.) tannin extract on chicken small intestinal epithelial cell culture.

Feed and water supplementation with powdered hydrolyzable tannins from chestnut represents a valuable alternative strategy to antibiotics in animal nutrition. In this study, we evaluated the effects and safety of a water-soluble form of chestnut tannin (WST) in an in vitro model of chicken small intestinal epithelial cells (CSIEC). A chicken cell culture was established, and WST in concentrations of 0.025, 0.05, 0.1, and 0.2% were tested for cytotoxicity, cell proliferation, metabolic activity, production of reactive oxygen species, intracellular antioxidative potential, genotoxicity, and influence on the epithelia cell cycle. The tested concentrations showed a significant (P < 0.05) greater proliferative effect on CSIEC than the control medium (maximal proliferation at 0.1% WST as determined by optical density measurements). The 0.2% concentration of WST was cytotoxic, causing significantly higher (P < 0.05) nitric oxide and hydrogen peroxide production but with no short-term genotoxicity. Although increasing the concentration caused a decline in the metabolism of challenged cells (the lowest at 0.1% WST), metabolic activity remained higher than that in control cells. The antioxidant potential was 75% better and significantly (P < 0.05) higher in the 0.1% WST cultured cells compared to control. In conclusion, the cultured CSIEC are useful tools in basic and clinical research for the study of intestinal physiology, as they retain physiological and biochemical properties and epithelial morphology close to the original tissue and, in many ways, reflect the in vivo state. Our results indicate that WST exert a beneficial effect on intestinal epithelia, since they: i) stimulate proliferation of enterocytes; ii) increase antioxidative potential; iii) have no genotoxic effect; and iv) do not affect cellular metabolism. Our results reinforce the importance of WST as promising candidates for further evaluation and use in commercial broiler farm production.

Acceleration of small bowel motility after oral administration of dai-kenchu-to (TJ-100) assessed by cine magnetic resonance imaging.

Dai-kenchu-to (TJ-100) is an herbal medicine used to shorten the duration of intestinal transit by accelerating intestinal movement. However, intestinal movement in itself has not been evaluated in healthy volunteers using radiography, fluoroscopy, and radioisotopes because of exposure to ionizing radiation. The purpose of this study was to evaluate the effect of TJ-100 on intestinal motility using cinematic magnetic resonance imaging (cine MRI) with a steady-state free precession sequence. Ten healthy male volunteers received 5 g of either TJ-100 or lactose without disclosure of the identity of the substance. Each volunteer underwent two MRI examinations after taking the substances (TJ-100 and lactose) on separate days. They drank 1200 mL of tap water and underwent cine MRI after 10 min. A steady-state free precession sequence was used for imaging, which was performed thrice at 0, 10, 20, 30, 40, and 50 min. The bowel contraction frequency and distention score were assessed. Wilcoxon signed-rank test was used, and differences were considered significant at a P-value <0.05. The bowel contraction frequency tended to be greater in the TJ-100 group and was significantly different in the ileum at 20 (TJ-100, 8.95 ± 2.88; lactose, 4.80 ± 2.92; P < 0.05) and 50 min (TJ-100, 9.45 ± 4.49; lactose, 4.45 ± 2.65; P < 0.05) between the groups. No significant differences were observed in the bowel distention scores. Cine MRI demonstrated that TJ-100 activated intestinal motility without dependence on ileum distention.

Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity.

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation.