Pathophysiologic Role of Neurotransmitters in Digestive Diseases

Neurotransmitters are special molecules that serve as messengers in chemical synapses between neurons, cells, or receptors, including catecholamines, serotonin, dopamine, and other neurotransmitters, which play an important role in both human physiology and pathology. Compelling evidence has indicated that neurotransmitters have an important physiological role in various digestive diseases. They act as ligands in combination with central or peripheral receptors, and transmits signals through chemical synapses, which are involved in regulating the physiological and pathological processes of the digestive tract organs. For instance, neurotransmitters regulate blood circulation and affect intestinal movement, nutrient absorption, the gastrointestinal innate immune system, and the microbiome. In this review, we will focus on the role of neurotransmitters in the pathogenesis of digestive tract diseases to provide novel therapeutic targets for new drug development in digestive diseases.

Changes in the Gut Microbiome after Galacto-Oligosaccharide Administration in Loperamide-Induced Constipation

Unbalanced dietary habits and the consumption of high protein and instant foods cause an increase in constipation. Here, we evaluated the effects of galacto-oligosaccharide (GOS) on a rat model of loperamide-induced constipation by measuring various biological markers and cecal microbiota. The fecal water content and intestinal transit ratio significantly increased in the GOS-administered (GL and GH) groups than in the control group (p < 0.05, p < 0.01, and p < 0.001, respectively). The length of intestinal mucosa (p < 0.05 and p < 0.01, respectively) and area of crypt cells were (p < 0.01, both) significantly increased in the GOS-administered groups compared to the control group. The distribution of interstitial cells of Cajal, which is related to the intestinal movement, showed a significant increase in GOS-administered groups than in the control group (p < 0.01, both). The relative abundance of lactic acid bacteria (LAB), especially Lactobacillus and Lactococcus, significantly increased in the GL group than in the control group. Furthermore, there was a positive correlation between short chain fatty acids (SCFAs) and the gut microbiota in the GL groups. These results demonstrated that GOS administration effectively alleviates constipation by increasing LAB proliferation in the intestinal microbiota and SCFA production.

Effect of sham feeding on postoperative ileus

Background: To evaluate the effects of different sham feeding methods on postoperative ileus after low anterior resection and diverting ileostomy for rectal cancer.Methods: 72 patients who underwent low anterior resection with a diverting ileostomy were randomized into 4 groups as: control (n = 16), ice cream (n = 18), gum (n = 17) and nicotine gum (n = 17). Four patients were excluded due to a lack of data. Patients’ demographics, constipation scores, neoadjuvant treatment, amount of perioperative bleeding, fluid administration, drain placement, time of intestinal movement, ileostomy discharge, and return of appetite were compared.Results: Patients’ demographics, constipation scores, neoadjuvant treatment existence, amount of perioperative bleeding, fluid administration, drain placement were similar between groups (p > 0,05). The first sense of intestinal movement was shorter in the nicotine group than control and gum groups (p=0,004 and 0,046, respectively). The average time to first ileostomy discharge and first appetite was shortest in the nicotine gum group. Diverting ileostomy discharge time was significantly shorter in the nicotine gum group than the control group (p=0,011). Return of appetite time was shorter in the nicotine gum group when compared to the gum group (p=0.036).Conclusions: Nicotine gum chewing is an effective method to resolve postoperative ileus after rectal surgery. Other methods such as ice-cream feeding and gum chewing showed no benefit compared to control.

Identification of Important Proteins and Pathways Affecting Feed Efficiency in DLY Pigs by iTRAQ-Based Proteomic Analysis

Feed efficiency is an economically important trait controlled by multiple genes in pigs. The small intestine is the main organ of digestion and nutrient absorption. To explore the biological processes by which small intestine proteomics affects feed efficiency (FE), we investigated the small intestinal tissue proteomes of high-FE and low-FE pigs by the isobaric tag for relative and absolute quantification (iTRAQ) method. In this study, a total of 225 Duroc × (Landrace × Yorkshire) (DLY) commercial pigs were ranked according to feed efficiency, which ranged from 30 kg to 100 kg, and six pigs with extreme phenotypes were selected, three in each of the high and low groups. A total of 1219 differentially expressed proteins (DEPs) were identified between the high-FE and low-FE groups (fold change ≥1.2 or ≤0.84; p ≤ 0.05), of which 785 were upregulated, and 484 were downregulated. Enrichment analysis indicated that the DEPs were mainly enriched in actin filament formation, microvilli formation, and small intestinal movement pathways. Protein functional analysis and protein interaction networks indicated that RHOA, HCLS1, EZR, CDC42, and RAC1 were important proteins that regulate FE in pigs. This study provided new insights into the important pathways and proteins involved in feed efficiency in pigs.

Effects of Allium mongolicum Regel and Its Flavonoids on Constipation

Constipation is a common bowel disease in adults with the symptoms of dry stool or difficulty passing stool. Compared with medication therapy, patients show more compliance with the diet therapy, and thus the diet therapy normally exhibits better therapeutic effect. Allium mongolicum Regel s a perennial herb of Liliaceae native to Mongolia, Kazakhstan, and China, which is traditionally used for constipation. In this paper, we partly clarify the effectiveness of A. mongolicum on constipation from two aspects, including maintaining colon water content and increasing intestinal transit. In loperamide-induced constipation mice model, nine days oral administration of A. mongolicum 50% ethanolic extract increased luminal side water content and regulated intestinal movement rhythm to normalize stools. The activity at least partly related to down-regulation of colon aquaporins 3 (AQP3) expression, and up-regulation and activation of G protein alpha (Gα) and phosphoinositide 3-kinases (PI3K). Further, activities on intestine movements were tested using compounds isolated from A. mongolicum. Three kinds of major flavonoids significantly increased cellular calcium flux in HCT116 cells and promoted mice intestine smooth muscle contraction. The activity may be related to M choline receptor, μ opioid receptor, 5-HT3 receptor, and inositol 1,4,5-trisphosphate (IP3) receptor.

Effects of Electroacupuncture on the Daily Rhythmicity of Intestinal Movement and Circadian Rhythmicity of Colonic Per2 Expression in Rats with Spinal Cord Injury

Background. Spinal cord injury (SCI) leads to bowel dysfunction. Electroacupuncture (EA) may improve bowel function. Objective. To assess EA on daily rhythmicity of intestinal movement and circadian rhythmicity of colonic Per2 expression in rats with SCI. Methods. Rats were randomized to the sham, SCI, and SCI+EA groups. EA was performed at bilateral Zusanli point (ST36) during daytime (11:00–11:30) for 14 days following SCI. Intestinal transit and daily rhythmicity of intestinal movement were assessed. Circadian rhythmicity of colonic Per2 expression was assessed by real-time RT-PCR. Results. EA shortened the stool efflux time and increased the dry fecal weight within 24 h in SCI rats. Daily rhythmicity of intestinal movements was unaffected by SCI. The expression of colonic Per2 peaked at 20:00 and the nadir was observed at 8:00 in the SCI and sham groups. In the SCI+EA group, colonic Per2 expression peaked at 12:00 and 20:00, and the nadir was observed at 8:00. Conclusion. SCI did not change the circadian rhythmicity of colonic Per2 expression in rats, and daily intestinal movement rhythmicity was retained. EA changed the daily rhythmicity of intestinal movement and the circadian rhythmicity of colonic Per2 expression in rats with SCI, increasing Per2 expression shortly after EA treatment.

Generating Situation-Dependent Behavior: Decentralized Control of Multi-Functional Intestine-Like Robot that can Transport and Mix Contents

Most robots are designed to perform a specific task in a predefined environment and have difficulty in producing situation-dependent behavior. To tackle this problem, we focus here on a mammal intestine that either transports or mixes the contents depending on the encountered circumstances. We propose a simple model for the intestinal movement and design an autonomous decentralized control scheme for an intestine-like robot by using coupled oscillators with local sensory feedback. Simulation results show that different types of motions are generated depending on the the physical conditions of the intestine and its contents. Our simulated robot does not require any input from a higher center to switch between different types of motions but determines autonomously which motion to generate. This study thus paves the way for developing “multi-functional robots” whose behavior is changed flexibly and spontaneously depending on circumstances.