Diarrhea Score Research Articles

Towards the quantitative characterisation of piglets’ robustness to weaning: a modelling approach

Weaning is a critical transition phase in swine production in which piglets must cope with different stressors that may affect their health. During this period, the prophylactic use of antibiotics is still frequent to limit piglet morbidity, which raises both economic and public health concerns such as the appearance of antimicrobial-resistant microbes. With the interest of developing tools for assisting health and management decisions around weaning, it is key to provide robustness indexes that inform on the animals’ capacity to endure the challenges associated with weaning. This work aimed at developing a modelling approach for facilitating the quantification of piglet resilience to weaning. A total of 325 Large White pigs weaned at 28 days of age were monitored and further housed and fed conventionally during the post-weaning period without antibiotic administration. Body weight and diarrhoea scores were recorded before and after weaning, and blood was sampled at weaning and 1 week later for collecting haematological data. A dynamic model was constructed based on the Gompertz–Makeham law to describe live weight trajectories during the first 75 days after weaning, following the rationale that the animal response is partitioned in two time windows (a perturbation and a recovery window). Model calibration was performed for each animal. Our results show that the transition time between the two time windows, as well as the weight trajectories are characteristic for each individual. The model captured the weight dynamics of animals at different degrees of perturbation, with an average coefficient of determination of 0.99, and a concordance correlation coefficient of 0.99. The utility of the model is that it provides biologically meaningful parameters that inform on the amplitude and length of perturbation, and the rate of animal recovery. Our rationale is that the dynamics of weight inform on the capability of the animal to cope with the weaning disturbance. Indeed, there were significant correlations between model parameters and individual diarrhoea scores and haematological traits. Overall, the parameters of our model can be useful for constructing weaning robustness indexes by using exclusively the growth curves. We foresee that this modelling approach will provide a step forward in the quantitative characterisation of robustness.

Antiallergic activity of Lactobacillus plantarum against peanut allergy in a Balb/c mouse model

ABSTRACTAntiallergic activities of Lactobacillus plantarum (L. plantarum) prepared from kimchi as orally administered probiotics were examined in type I peanut allergy mice models. Oral administration with L. plantarum restored the deteriorated profile of enteric flora in mice sensitized with peanut allergen and attenuated allergic symptoms, including diarrhea scores, clinical scores, serum specific immunoglobulin E (IgE) and histamine production. The mRNA expression of interleukin-10 and interferon-γ was suppressed and enhanced, respectively by L. plantarum administration. Thus, L. plantarum probably promoted anti-allergic activities via modulating enteric flora, intestinal cytokines mRNA expression in type I allergic mice, resulting in alleviation of allergic symptoms, including serum specific IgE and clinical hypersensitivity scores.

Effect of Psyllium Fiber Supplementation on Diarrhea Incidence in Enteral Tube-Fed Patients: A Prospective, Randomized, and Controlled Trial.

Diarrhea in enteral tube-fed patients is not uncommon and can lead to unfavorable outcomes. Fiber in enteral nutrition (EN) formula might play a role in postfeeding diarrhea. Theoretically, soluble fiber is beneficial for both prevention and treatment of postfeeding diarrhea, but different types of soluble fiber may not provide the same effect. This study aims to determine whether supplementation with psyllium in standard EN reduces the incidence of diarrhea in tube-fed patients. We conducted a prospective, randomized, double-blind, controlled study in general medical wards patients who were expected to receive EN for ≥5 days. Exclusion criteria were hemodynamic instability, known significant gastrointestinal problems, and recent pancreatitis. Eligible patients were randomized to receive either Mucilin SF (15.2g/L)-added Blendera (psyllium-added formula: Psyllium group [PG]) or Blendera (fiber-free formula: Control group [CG]). All patients were given EN for 10 days or until discharge/oral intake/death. Bowel movements (BMs) were monitored using King's Stool Chart. Eighty-three patients were enrolled, 42 in the PG and 41 in the CG. Baseline characteristics were similar. The proportion of patients with ≥1 day of diarrhea (King's stool score ≥15) was comparable (42.9% vs 31.7%; P = 0.41, in PG and CG, respectively). There were no significant differences in the frequency of daily BMs and the median diarrhea score between PG and CG (3 vs 2, P = 0.06 and 3.8 vs 2.4, P = 0.42, respectively). Supplementation with psyllium showed no beneficial effect on reducing incidence of diarrhea in general medical patients receiving EN. This study was registered on Thai Clinical Trials Registry (http://www.clinicaltrials.in.th: TCTR identification number TCTR20170821004).

Disease Burden Subgroup Analysis of Health-Related Quality of Life of Blinatumomab Versus Standard-of-Care Chemotherapy in Patients with Relapsed or Refractory Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia in a Randomized, Open-Label Phase 3 Study (TOWER)

Disease Burden Subgroup Analysis of Health-Related Quality of Life of Blinatumomab Versus Standard-of-Care Chemotherapy in Patients with Relapsed or Refractory Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia in a Randomized, Open-Label Phase 3 Study (TOWER)

1464. The Clinical Features of Pneumonia Caused by Legionella pneumophila vs. Streptococcus pneumoniae: A Retrospective Study

BackgroundLegionnaires’ disease (LD) is a serious and often lethal pneumonia caused by Legionella bacteria. From 2001 to 2016, the incidence of Legionnaires’ disease has tripled in the United States. The clinical manifestations of pneumonia caused by L. pneumophilia (LP) may be similar to those caused by Streptococcus pneumoniae (SP). As mortality from Legionella pneumonia is high (15–50%), an investigation of factors that differentiate these two types of pneumonia is required.Methods(1) To determine the clinical features that differentiate community-acquired pneumonia (CAP) caused by LP SG 1 vs. SP; and (2) to assess outcomes associated with CAP caused by LP serogroup 1 vs. SP. W conducted a retrospective chart review of adult patients admitted between January 1, 2013 and October 31, 2017 for confirmed LP or SP pneumonia. Data were collected on demographic and clinical characteristics, comorbidities, month of admission, laboratory values, vital signs, and outcomes. Data were analyzed using Student’s t-test, the chi-squared test and logistic regression with the forward likelihood ratio algorithm.ResultsOf 106 patients, 48.1% had LP, 64.4% were male, 56.6% were black and the mean age was 59.1 ± 15.3 years. The incidence of LP peaked in the summer. Results of univariable analysis are shown in the table.FactorLPSP P-ValueMean Temp. (°F)102.3 ± 1.799.0 ± 9.00.009Diarrhea50%20.4%0.002Male gender78.4%43.6%<0.0001Median CWIC score0.0 (1–4)1.0 (0–13)0.02Mean Na (mEq/L)130.2 ± 4.6132.1 ± 18.90.5From multivariable analysis, predictors of LP were male gender (OR=18.2, P < 0.0001), diarrhea (OR = 3.7, P = 0.05), BMI (OR = 1.2, P = 0.05) and CWIC score (OR = 0.57, P = 0.004). Patients with SP were more likely to require intubation (P = 0.04), an ICU stay (P = 0.004) and to die (P = 0.002).ConclusionOur data suggest that high temperature and diarrhea may be used to help differentiate LP and SP pneumonia. The higher incidence among men requires further investigation. LP demonstrated a higher morbidity and mortality than SP.Disclosures All authors: No reported disclosures.

Effect of Bismuth Subsalicylate on Gastrointestinal Tolerability in Healthy Volunteers Receiving Oral Delayed-release Dimethyl Fumarate: PREVENT, a Randomized, Multicenter, Double-blind, Placebo-controlled Study

PurposeFlushing and gastrointestinal (GI) events are commonly associated with the use of delayed-release dimethyl fumarate (DMF) treatment for relapsing multiple sclerosis. MethodsPREVENT (A Multicenter, Double-Blind, Placebo-Controlled Study of Pepto-Bismol [Bismuth Subsalicylate] on Gastrointestinal Tolerability in Healthy Volunteers Receiving Oral TECFIDERA [Dimethyl Fumarate] Delayed-Release Capsules Twice Daily) is a double-blind, placebo-controlled, 8-week study that evaluated the effect of bismuth subsalicylate on DMF-related GI events. Bismuth subsalicylate 524 mg or placebo were administered 30 min before DMF (weeks 1–4). DMF was dosed twice-daily (BID) at 120 mg (week 1) and 240 mg (weeks 2–8). Using an e-diary device, participants recorded GI and flushing events on the Modified Overall Gastrointestinal Symptom Scale once daily for the preceding 24 h. The primary end point was time to first GI-related event. Secondary end points included frequency and severity of GI-related events. FindingsA total of 175 participants were enrolled (placebo, n = 87; bismuth subsalicylate, n = 88), and 17 discontinued treatment (placebo, n = 8; bismuth subsalicylate n = 9). A total of 146 participants reported ≥1 GI event: placebo, n = 72 (82.8%); and bismuth subsalicylate, n = 74 (84.1%). There was no statistical difference in risk of a GI event between the groups (P = 0.8292). Mean (SD) time from DMF initiation to first GI event was similar: placebo, 5.4 (8.73) days; and bismuth subsalicylate, 5.6 (10.87) days. Incidence of flatulence (38.6% vs 50.6%) and diarrhea (36.4% vs 48.2%) during weeks 1–4 was numerically lower in the bismuth subsalicylate group compared with the placebo group. Mean worst severity scores for flatulence (1.1 vs 1.8; P = 0.0219) and diarrhea (1.0 vs 1.6; P = 0.0500) were lower with bismuth subsalicylate than with placebo. ImplicationsAlthough coadministration of bismuth subsalicylate did not affect the occurrence of DMF-related GI events overall, it reduced the severity and incidence of flatulence and diarrhea. ClinicalTrials.gov identifier: NCT01915901.

Differential Longitudinal Symptom and Quality of Life (QOL) Outcomes on Selected Medications in Patients With Suspected Gastroparesis With Delayed versus Normal Colon Transit on Wireless Motility Capsule Testing

Introduction: Patients with suspected gastroparesis may also report intestinal symptoms such as constipation and/or show delayed colon transit on wireless motility capsules (WMC) testing. However, the impact of colonic dysfunction on gastroparesis and whether its treatment improves upper and lower GI symptoms and quality of life (QOL) in patients with delayed vs. normal colon transit is unknown. This prospective multicenter study determined if treatment decisions based on the results of WMC testing are associated with improvements in upper and lower GI symptoms and QOL in patients with suspected gastroparesis. Methods: 150 subjects with suspected gastroparesis underwent concurrent WMC and gastric emptying scintigraphy. Based on test results, investigators recommended treatment(s) (prokinetic, neuromodulator, constipation therapies). The clinical outcomes for various treatment modalities as assessed by symptoms (PAGI-SYM/GCSI) and QOL (PAGI-QOL) at 6 months were compared between the normal (NCT) and delayed colon transit (DCT)(>59 hours by WMC) groups. Results: 53 (35%) had delayed gastric transit; 45 (30%) subjects had DCT; 100 (67%) had NCT; 5 (3%) did not have colonic transit data. 50 subjects received prokinetics; 71 received neuromodulators; 54 received constipation therapies (linaclotide 22, lubiprostone 9, PEG 19, others 4). Overall PAGI-SYM scores improved on prokinetics and neuromodulators with both NCT and DCT, but improved on constipation therapies only with DCT (Table).PAGI-QOL scores improved on all 3 drug classes with DCT, but improved only on prokinetics with NCT. When comparing individual symptoms, constipation therapies were associated with reduced GCSI, fullness, and constipation scores and trends towards less bloating with DCT, but did not affect N/V, pain, or diarrhea (Figures A-B). Diarrhea (P=0.049) and upper abdominal pain (P=0.048) scores were higher on constipation therapies in DCT group. Conversely, constipation therapies were associated with trends to less fullness with NCT and no benefits for other symptoms. Conclusion: Delayed colon transit was found in 30% of patients with suspected gastroparesis and treatment with neuromodulators and constipation therapies was associated with selective overall improvements in gastroparetic and bowel symptoms and QOL in this group. By identifying colonic dysfunction, wireless motility capsule tests could provide improved overall treatment benefit(s) in patients with suspected gastroparesis.158_A Figure 1. Longitudinal Outcomes on Different Medication Classes in Normal vs. Delayed Colon Transit by Wireless Motility Capsule158_B Figure 2. Normal Colon Transit158_C Figure 3. Delayed Colon Transit

Improving the Reliability and Utility of Streptozotocin-Induced Rat Diabetic Model.

The Streptozotocin- (STZ-) induced diabetic model is widely used; however, unexplained acute toxicity has given the model an unreliable reputation. To improve the reliability and utility of this model, we characterize the age dependence of STZ toxicity and introduce novel endpoints to assess diabetic complications and reveal possible mechanisms for diabetic development. Diabetes was induced by STZ injection into male, 6 to 23 weeks old, Sprague-Dawley rats. Their metabolic (glucose, lipids, and hormones), inflammatory (cytokines), histologic and behavioral endpoints were observed for 1.2 years. Analgesic compounds were assessed for efficacy treating neuropathy. Acute mortality, within a week of STZ injection (50–65 mg/kg i.v.), was inversely correlated to animal age. Only 3% of rats, age 6–11 weeks, died in the week following STZ injection, whereas 83% of rats 12 to 17 weeks old and 91% of rats 18 weeks or older died in the same week. Partial model recovery (normalized insulin, glucose and food/water intake) was observed starting at week 36; however, pain scores, kidney enlargement, and cataract formation continued to show progression consistent with the diabetic state. Unique noninvasive observational measurements, such as haircoat quality and diarrhea scores, served as useful endpoints for this model. The increased plasma cytokines (such as TNF-α, IL-4, and IL-6) and inflammatory cell infiltration into the pancreatic islets are strong evidence of inflammation in the STZ-induced diabetic model. Pancreatic tissue staining revealed total islet area reduction and confirmed STZ-specific pancreatic toxicity; however, the β-cell density per area in pancreatic islets and insulin levels statistically increased over time in the diabetic rats, suggesting a mechanism for partial recovery of diabetic symptoms. Voltage-gated sodium channel (NaV1.7 specific, peripherally restricted) blocker, CC4148, inhibited neuropathy without side effects as compared to a nonspecific sodium channel inhibitor, Mexiletine, or GABA analog, Pregabalin, which inhibited neuropathy with side effects.

DIETARY SUPPLEMENTATION OF GANODERMA LUCIDUM POWDER ENHANCES SURVIVAL AND IMMUNOCOMPETENCE OF WEANING PIGS

The study was conducted to investigate the effects of Ganoderma lucidum (GL) on growth performance, survival rates, and immunocompetence of the weaning pigs. A total of 45, 28-day-old Landrace weaning pigs were randomly divided into three groups of 15 pigs each. A corn–soybean meal-based control diet was formulated and the experimental diets included 0.3% and 0.6% GL powder. The groups were treated for 38 days. Pigs which fed both concentration of GL powder had significantly higher ([Formula: see text]) survival rates than the control group. Besides, pigs which fed 0.3% and 0.6% GL powder had increased lymphocyte proliferation indexes ([Formula: see text]) and the titer of neutralizing antibody against hog cholera (HC) ([Formula: see text]) on day 66 compared with pigs which fed control diet. No differences were found between treatments regarding the average daily gain (ADG), gain:feed (G:F) ratio and diarrhea score. Supplementation of GL powder showed no effects on aspartate aminotransferase (AST) and blood urea nitrogen (BUN), which suggested that GL treatment has no immediate harm on liver or kidney. Based on these results, GL could be suggested as a potential feed additive of weaning pig diets to increase survival rate and immunocompetence.

Effects of dietary Clostridium butyricum supplementation on growth performance, intestinal development, and immune response of weaned piglets challenged with lipopolysaccharide

BackgroundWeanling pigs, with immature immune system and physiological function, usually experience post-weaning diarrhea. This study determined the effects of dietary Clostridium butyricum supplementation on growth performance, diarrhea, and immunity of weaned pigs challenged with lipopolysaccharide (LPS).MethodsIn Experiment (Exp.) 1, 144 weaned piglets were weaned at 21 d and randomly assigned to six groups, with six replicates per group and four pigs per replicate, receiving a control diet (CON) or diet supplemented with antibiotics (AB) or C. butyricum (CB) (0.1%, 0.2%, 0.4%, or 0.8%), respectively. All diets in Exp. 1 were a highly digestible basal diet, with 3,000 mg/kg zinc oxide supplied in the first 2 wk only. In Exp. 2, 180 piglets were weaned at 21 d and randomly assigned to five groups, with six replicates per group and six pigs per replicate, receiving CON, AB, or CB (0.2%, 0.4%, or 0.6%) diets. The digestibility of diets was lower than those in Exp. 1, and did not include zinc oxide. At 36 d of Exp. 2, 12 piglets were selected from each of the CON and 0.4% CB groups, six piglets were intraperitoneally injected with LPS (50 μg/kg body weight) and the other six piglets with normal saline; animals were killed at 4 h after injection to collect blood, intestine, and digesta samples for biochemical analysis.ResultsIn Exp. 1, CB and AB diets had no effect on growth performance of piglets. In Exp. 2, 0.4% CB decreased feed-gain ratio (P < 0.1), diarrhea score (P < 0.05), and increased duodenal, jejunal, and ileal villus height and jejunal villus height/crypt depth (P < 0.05). The 0.4% CB decreased the plasma tumor necrosis factor (TNF) α (P < 0.05) but increased ileal mucosa IL-10 and TLR2 mRNA expression (P < 0.05). Furthermore, 0.4% CB altered the microbial profile, with Bacillus and Ruminococcaceae UGG-003 at genus level and Lactobacillus casei and Parasutterella secunda at species level were higher than CON in colonic content (P < 0.05).ConclusionsDietary C. butyricum supplementation had positive effects on growth of weaned piglets with less digestible diets. There was a tendency to reduce the feed-gain ratio, which could reduce feed costs in pig production. Moreover, C. butyricum decreased post-weaning diarrhea by improving the intestinal morphology, intestinal microflora profile, and immune function.

Folate-producing lactic acid bacteria reduce inflammation in mice with induced intestinal mucositis.

To evaluate two folate-producing strains, Streptococcus (Strep.) thermophilus CRL 808 and Strep. thermophilus CRL 415, against chemically induced mucositis in mice. In vitro assays with Caco-2 cells were performed to evaluate the effect of the bacteria in the presence of 5-fluorouracil (5-FU). For invivo studies, mice were daily injected with 5-FU to induce intestinal mucositis (IM) and orally administered with folate-producing strains during 6days. Clinical symptoms, histological parameters and cytokine profiles were assessed. The results showed that Strep. thermophilus CRL 808 increased the cytotoxicity of 5-FU against Caco-2 cells. Administration of this strain in mice with chemically induced IM resulted in a reduction in diarrhoea score and restoration of the intestinal architecture. Cytokine analysis showed that the anti-inflammatory effect by the bacterium is not associated with an immune mechanism. Regarding Strep. thermophilus CRL 415, no improvements were observed in any of the parameters evaluated. The administration of the folate-producing Strep. thermophilus CRL 808 has the potential to prevent IM induced by 5-FU in mice. Folate-producing LAB could be used in chemotherapy patients to reduce the symptoms of IM, improve their nutritional status and increase the effectiveness of 5-FU.

SCID/NOD mice model for 5-FU induced intestinal mucositis: Safety and effects of probiotics as therapy

For chemotherapy patients, intestinal mucositis is a frequent complication. Previously, we evaluated the beneficial effect of oral probiotics in 5-Fluorouracil (5-FU) induced mucositis in BALB/c mice. Here, we used SCID/NOD mice instead to simulate the immunodeficiency of chemotherapy patients: first, to evaluate the safety of probiotic supplementation and second, to determine the probiotic effect in response to 5-FU intestinal mucositis. Thirty-six SCID/NOD mice were injected with saline (three control groups) or 5-FU (three experimental groups) intraperitoneally daily for five days. Mice were given either oral saline daily, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35, Antibiophilus™, France) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi, Infloran™, Italy). Blood, liver, spleen, and lymph node tissue samples were evaluated for probiotic translocation via culture and Q-PCR. Weight change, diarrhea score, jejunal villus height (VH) and crypt depth (CD), and serum cytokine levels of TNF-α, IFNγ, IL-1β, IL-6, IL-4, IL-10, IL-13, and IL-17 were also assessed. No weight loss was found in the SCID control group. Mean weight loss of 10.63±0.87% was noted by day five in 5-FU group without probiotics but it was only 6.2±0.43% if mice were given Lcr35 (p<0.01) and 7.1±1.80% (p<0.01) if they were given LaBi. Diarrhea score of 5-FU group without probiotics was 2.0±0.0 by day five, which dropped to 1.33±0.17 (p<0.05) and 1.42±0.24 (p<0.05) with Lcr35 and LaBi, respectively. Average VH significantly decreased and CD significantly increased in SCID mice given 5-FU. With probiotics, average CD improved (p<0.05) while VH lengthened as well. Besides IL-13, all cytokine levels increased in 5-FU SCID mice. Both Lcr35 and LaBi significantly inhibited serum cytokines (p<0.05). No probiotic strains were detected in blood cultures of any mice. Using SCID/NOD mice as a novel model for 5-FU induced intestinal mucositis, we find that probiotics Lcr35 and LaBi do not lead to bacteremia, can improve diarrhea and body weight, can restore jejunal crypt depth, and significantly inhibit cytokines TNF-α, IL-1β, IFNγ, IL-6, IL-4, IL-10, and IL-17.

Human Milk Fortification with Bovine Colostrum Is Superior to Formula-Based Fortifiers to Prevent Gut Dysfunction, Necrotizing Enterocolitis, and Systemic Infection in Preterm Pigs.

Fortification of donor human milk (DHM) is required for optimal growth of very preterm infants, but there are concerns of more gut dysfunction and necrotizing enterocolitis (NEC) when using formula-based fortifiers (FFs), especially soon after birth. Intact bovine colostrum (BC) is rich in nutrients and bioactive factors, and protects against NEC in preterm pigs. We hypothesized that fortification of DHM with BC is superior to FFs to prevent gut dysfunction and infections when provided shortly after preterm birth. Two FF products, Enfamil (ENF; intact protein, vegetable oil) and PreNAN+Nutrilon (NAN; extensively hydrolyzed protein, maltodextrin), were compared with BC as fortifier to DHM fed to preterm pigs for 5days. Relative to the DHM+BC group, DHM+FF groups had higher diarrhea score and lower hexose uptake and lactase activity, and specifically the DHM+NAN group showed higher gut permeability, NEC score, more mucosa-adherent bacteria with altered gut microbiota structure (ie, lower diversity, increased Enterococcus, decreased Staphylococcus abundance). Both DHM+FF groups showed higher expression of intestinal cytokine and inflammation-related genes, more gut-derived bacteria in the bone marrow, lower density of mucin-containing goblet cells, and slightly higher colon lactate, stomach pH and acetate, and blood neutrophil-to-lymphocyte levels than the DHM+BC group. Used as a fortifier to DHM, BC is superior to FFs to support gut function, nutrient absorption, and bacterial defense mechanisms in preterm pigs. It is important to optimize the composition of nutrient fortifiers for preterm infants fed human milk.

Establishment of an Endogenous Clostridium difficile Rat Infection Model and Evaluation of the Effects of Clostridium butyricum MIYAIRI 588 Probiotic Strain.

Clostridium difficile is well known as an agent responsible for pseudomembranous colitis and antibiotic-associated diarrhea. The hamster model utilizing an oral route for infection of C. difficile has been considered to be the standard model for analysis of C. difficile infection (CDI) but this model exhibits differences to human CDI, most notably as most hamsters die without exhibiting diarrhea. Therefore, we attempted to develop a new non-lethal and diarrheal rat CDI model caused by endogenous C. difficile using metronidazole (MNZ) and egg white. In addition, the effects of probiotic strain Clostridium butyricum MIYAIRI 588 (CBM) on CDI were examined using this model. Syrian Golden hamsters received clindamycin phosphate orally at 30 mg/kg on 5 days before challenge with either C. difficile VPI10463 (hypertoxigenic strain) or KY34 (low toxigenic clinical isolate). Mortality and the presence of diarrhea were observed twice a day for the duration of the experiment. Wistar rats received 10% egg white dissolved in drinking water for 1 week ad libitum following intramuscular administration of 200 mg/kg MNZ twice a day for 3 days. Diarrhea score was determined for each day and fecal water content, biotin concentration, and cytotoxin titer in feces were examined. More than 70% of hamsters orally infected with C. difficile died without exhibiting diarrhea regardless of toxigenicity of strain. The rats receiving egg white after MNZ administration developed diarrhea due to overgrowth of endogenous C. difficile. This CDI model is non-lethal and diarrheal, and some rats in this model were spontaneously cured. The incidence of diarrhea was significantly decreased in C. butyricum treated rats. These results indicate that the CDI model using egg white and MNZ has potentially better similarity to human CDI, and implies that treatment with C. butyricum may reduce the risk of CDI.

The aqueous extract of Ocimum gratissimum leaves ameliorates acetic acid-induced colitis via improving antioxidant status and hematological parameters in male Wistar rats

The beneficial effects of Ocimum gratissimum, have been attributed mainly to its antioxidant and anti-inflammatory properties. This study investigated the protective effects of aqueous extract of Ocimum gratissimum leaves (AEOGL) on acetic acid induced colitis in male rats. Twenty male Wistar rats, 100–180 g were divided into four groups as follows: Group 1 (control) (n = 5) received 2 ml/kg of distilled water for 21 consecutive days. Group 2 (n = 5) received 2 ml of 6% acetic acid solution once intra rectally for induction of colitis. Group 3 and 4 (n = 5 each) were treated as group 2 and thereafter received AEOGL orally at 200 and 400 mg/kg/day respectively for 20 consecutive days. All the animals from each group were sacrificed 24 h after the induction of colitis and administration of AEOGL. The diarrhea score, ulcer score, hematological parameters, nitric oxide (NO), myeloperoxidase (MPO), superoxide dismutase (SOD), reduced glutathione (GSH) markers and histopathological alteration were evaluated. Acetic acid-induced colitis significantly caused alteration in diarrhea score, ulcer score, hematological parameters, MPO and SOD activities, NO and GSH levels (p < 0.05). It induced significant inflammation of the colonic tissue. AEOGL administration significantly decreased diarrhea score and ulcer score to normal (p < 0.05). It prevented alteration effect of acetic acid on hematological parameters and significant decreases the activities of MPO, SOD, NO and increase GSH levels (p < 0.05) in colitis rats. In conclusion, Ocimum gratissimum leaves possesses ameliorative effects against acetic acid-induced colitis as a consequence of its anti-inflammatory and anti-oxidative properties.

In vivo effect of a TLR5 SNP (C1205T) on Salmonella enterica serovar Typhimurium infection in weaned, specific pathogen-free Landrace piglets.

Toll-like receptor 5 is a pattern-recognition receptor for bacterial flagellin. We previously reported that a single nucleotide polymorphism (SNP) of swine TLR5, C1205T, impairs recognition of Salmonella typhimurium (ST) flagellin and ethanol-killed Salmonella Choleraesuis (SC). In the present study, weaned, specific pathogen-free (SPF) Landrace piglets with CC, CT or TT genotypes were orally infected with ST (L-3569 strain) to determine the effect of this specific SNP on ST infection in vivo. Eighteen ST-infected piglets (six each with CC, CT, or TT) exhibited fever and diarrhea for 1 week after infection. TT piglets had the longest duration of fever. TT piglets had the greatest mean diarrhea score during the experimental period, followed by CT and CC piglets. Fecal ST shedding was greater in CT and TT pigs than CC pigs from 2 days after infection. Serum haptoglobin concentration increased in ST-infected piglets and to greater extents in CT and TT pigs than CC pigs. Daily weight gain was lower in infected pigs, particularly TT piglets, than control pigs. To the best of our knowledge, this study is the first to demonstrate that impairment of TLR recognition affects pig susceptibility to disease in vivo. Thus, piglets with the T allele of swine TLR5 (C1205T) exhibit impaired resistance to ST infection. Furthermore, elimination of the T allele of this SNP from Landrace pigs would lead to enhancement of their resistance to ST infection.

Lactobacillus casei Variety rhamnosus Probiotic Preventively Attenuates 5-Fluorouracil/Oxaliplatin-Induced Intestinal Injury in a Syngeneic Colorectal Cancer Model.

Adjuvant 5-fluorouracil (5-FU)-based chemotherapy, including FOLFOX (5-FU, leucovorin, and oxaliplatin), is recommended for colorectal cancer. However, intestinal mucositis remains a common adverse effect for which no effective preventive strategies are available. To develop a convenient and novel way to alleviate mucositis, we investigated the effect of Lactobacillus casei variety rhamnosus (Lcr35) on FOLFOX-induced mucosal injury. BALB/c mice subcutaneously injected with syngeneic CT26 colorectal adenocarcinoma cells were orally administered Lcr35 daily before, during, and after 5-day injection of FOLFOX regimen, for 14 days. The following methods were used: diarrhea score for toxicity, ELISA for cytokine production, histopathology for intestinal injury, immunohistochemistry for apoptosis/proliferation and regulatory proteins, RT-PCR for cytokine mRNA expression, and DNA sequencing for fecal gut microbiota. FOLFOX administration to colorectal cancer-bearing mice significantly inhibited tumor growth and the accompanying marked diarrhea and intestinal injury histologically characterized by the shortening of villi and destruction of intestinal crypts. Preventive administration of Lcr35 dose-dependently reduced the severity of diarrhea and intestinal mucositis without affecting the anti-tumor effect of FOLFOX. The numbers of apoptotic, NF-κB-, and BAX-activated cells increased after FOLFOX, and these responses were mitigated by Lcr35. TNF-α and IL-6 upregulation by FOLFOX treatment was attenuated by Lcr35. The fecal gut microbiota composition of Firmicutes and Bacteroidetes disturbed by FOLFOX was significantly reversed by Lcr35 toward a preferential profile. In conclusion, the oral probiotic Lcr35 prevented FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism might involve modulation of gut microbiota and proinflammatory responses with suppression of intrinsic apoptosis in intestinal injury.

Kolaviron, A Flavonoid From Garcinia Kola Seeds, Ameliorates Experimental Colitis In Rats Exposed To Cadmium

Cadmium has been shown to potentiate experimental ulcers in laboratory animals. Its ability to predispose humans to ulcerative colitis has also been postulated. Polyphenols and flavonoids found in plants possess antioxidant and metal binding potentials and may therefore, be beneficial in pathological conditions of oxidative stress resulting from exposure to heavy metals. In the present study, the effect of kolaviron, a biflavonoid complex from the seeds of Garcinia kola (Heckel) on colitis in cadmium‐exposed rats was investigated. Male Wistar rats (110–120 g) were randomly divided into five groups. Group 1 received distilled water, Group 2 received dimethyl sulphoxide, and served as negative and positive controls respectively. Group 3 received cadmium (10 mg/kg) while group 4 animals received Cadmium (10 mg/kg) in addition to kolaviron (200 mg/kg). The last group received kolaviron (200 mg/kg) alone. After four weeks of exposure to cadmium with or without kolaviron, colitis was induced in all animals in groups 2–5 by intrarectal administration of 2 mL of 4% Acetic acid (AA). Rats were sacrificed and colons resected at days 0, 3, 7 and 14 days of colitis induction. Assessment was based on symptoms of colitis such as weight loss and stool consistency using a diarrhoea score scale. Colon sample homogenates were analysed for concentrations of Malondialdehyde (MDA), Nitric oxide (NO), Glutathione (GSH), Sulfhydryl, activities of Superoxide dismutase (SOD), Na+‐K+ ATPase, Myeloperoxidase (MPO) by spectrophotometry and histology by hematoxylin and eosin staining. The weight loss (%) in Cadmium group by week 3 was (31.05 ± 0.04). Intrarectal administration of AA resulted in increased stool score in Cadmium group (0.80 ± 0.00) till day 14 post colitis induction. Macroscopic score was significantly (p &lt; 0.05) increased in Cadmium group till day 14. MDA were significantly (p &lt; 0.05) increased in Cadmium group at days 7 and 14. The notable increases in MPO and NO during AA‐induced colitis and cadmium exposure were significantly (p &lt; 0.05) reduced by Kolaviron. Significant (p &lt; 0.05) decreases in SOD, Na+‐K+ ATPase activities, sulfhydryl and GSH concentrations upon AA administration were attenuated in other groups except Cadmium group. Histology showed healing in all groups post colitis induction except in Cadmium group where histopathological damage was still evident at day 14. Kolaviron ameliorated the delayed healing of Acetic acid‐induced colitis during cadmium exposures in Wistar rats and may therefore, be useful as dietary intervention in cases of cadmium exposures.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Er Shen Wan extract reduces diarrhea and regulates AQP 4 and NHE 3 in a rat model of spleen-kidney Yang deficiency–induced diarrhea

IntroductionEr Shen Wan (ESW), a traditional Chinese medicinal formula comprised of Psoraleae Fructus (Babchi seeds, from Psoralea corylifolia Linn.) and Myristicae Semen (Nutmeg, from Myristica fragrans Houtt.), is widely used to treat spleen-kidney Yang deficiency (SKYD)-induced diarrhea. Previous studies have demonstrated preliminarily that the petroleum ether extract of ESW (ESWP) exhibits significant anti-diarrheal activity. The present study aimed to evaluate the anti-diarrhea activity of ESWP and to explore the underlying mechanisms with respect to fluid metabolism in a rat model of SKYD-induced diarrhea. Materials and methodsA high-performance liquid chromatography–diode array detector (HPLC–DAD) approach was developed and validated for qualitative and quantitative analyses of the main constituents of ESWP. SKYD model rats were established and treated with an effective dose (3.5 g/kg) of the extract for two weeks. Anti-diarrheal activity and stool properties were observed. After the experiment, the appearance and histology of the intestines were evaluated. Serum levels of neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were also determined. Furthermore, to characterize the regulation of aquaporin-4 (AQP 4) and Na+/H+ exchanger isoform 3 (NHE 3) in the colon, quantitative real-time RT-PCR (qRT-PCR), immunohistochemistry (IHC) and Western blotting (WB) were employed to detect mRNA and protein expression levels. ResultsIn the rat models, oral ESWP administration significantly reduced the diarrhea score and the number and weight of wet stools. Jejunal and ileac histological damage was impeded, and the histology score decreased. Serum VIP levels were significantly decreased, in contrast to NPY levels. In addition, AQP 4 and NHE 3 expression levels increased significantly. ConclusionsThese results showed that ESWP’s anti-diarrheal effect might at least partially involve the regulation of hormones intimately involved in maintaining fluid and electrolyte levels, as well as by increasing AQP 4 and NHE 3 expression levels and enhancing the absorption of Na+ and water.

The TPH1 rs211105 gene polymorphism affects abdominal symptoms and quality of life of diarrhea-predominant irritable bowel syndrome.

The gastrointestinal symptoms of irritable bowel syndrome are strongly related to impaired quality of life (QOL), especially in diarrhea-predominant. The gene polymorphisms associated with serotonin, or 5-hydroxytryptamine, alter gastrointestinal symptoms and mental status. We aimed to evaluate the effects of gene polymorphisms on gastrointestinal symptoms, psychological conditions, and QOL, and compare these between patients with diarrhea-predominant irritable bowel syndrome (n = 62) and healthy controls (n = 64). The gene polymorphisms of 5-HTTLPR, 5-HTTVNTR, TPH1 rs453773, and TPH1 rs211105 were evaluated. Gastrointestinal symptoms, depressive state, and QOL were assessed using the Gastrointestinal Symptom Rating Scale, Self-rating Depression Scale, and Short-Form-36. Gene polymorphisms did not significantly differ in frequency between the two groups. The scores for diarrhea, abdominal pain, and indigestion significantly correlated with the physical component summary score. Only the group of patients with diarrhea-predominant irritable bowel syndrome showed a significant correlation between the TPH1 rs211105 T/T genotype and lower scores for role physical and mental health, and higher scores for indigestion and diarrhea. 5-HTTLPR l/s was associated with lower score of role emotional in the diarrhea-predominant irritable bowel syndrome and higher scores in the controls. The gene polymorphisms of 5-hydroxytryptamine signaling effected gastrointestinal symptoms and QOL, especially of the patients with diarrhea-predominant irritable bowel syndrome.