Risk factors for moderate acute malnutrition among children with acute diarrhoea in India and Tanzania: a secondary analysis of data from a randomized trial.

BACKGROUND: Moderate acute malnutrition (MAM) affects over 30 million children aged < 5 years worldwide. MAM may confer a greater risk of developing severe malnutrition and even mortality in children. Assessing risk factors for MAM may allow for earlier recognition of children at risk of deleterious health outcomes. OBJECTIVE: To determine risk factors associated with the prevalence and development of MAM among children aged 6 to 59 months with acute diarrhoea who received treatment with oral rehydration solution and zinc supplementation. METHODS: We conducted a secondary analysis of data from a randomized, dose-finding trial of zinc among children with acute diarrhoea in India and Tanzania. We used regression models to assess risk factors for prevalent MAM at the start of diarrhoea treatment and to identify risk factors associated with the development of MAM at 60 days. MAM was defined as weight for length (or height) Z score ≤-2 and > -3 or mid-upper arm circumference < 12.5 and ≥ 11.5 cm. RESULTS: A total of 4,500 children were enrolled; 593 (13.2%) had MAM at the baseline. MAM at baseline was significantly less common among children in Tanzania than in India (adjusted risk ratio [aRR] 0.37, 95% confidence interval [CI]: 0.30, 0.44, P < 0.001), in children aged 24- < 60 months versus 6- < 12 months (aRR 0.46, 95% CI: 0.38, 0.56, P < 0.001), and in families with household wealth index higher than the median (aRR 0.79, 95% CI: 0.68, 0.92, P = 0.002). Sixty days after outpatient treatment and follow-up, 87 (2.5%) children developed MAM. When compared to children aged 6- < 12 months, children aged 24- < 60 months had a 52% lower risk of developing MAM. Every one unit increase in weight for length (or height) Z score at enrolment was associated with a 93% lower risk of developing MAM during follow-up. CONCLUSIONS: Among children with diarrhoea, younger children and those from households with lower wealth were at greater risk of MAM. These children may benefit from targeted interventions focusing on feeding (targeted nutrition support for at-risk households) and follow up in order to reduce the occurrence of MAM and its consequences.

High frequency of antimicrobial resistance in Salmonella and Escherichia coli causing diarrheal diseases at the Yirimadio community health facility, Mali.

BACKGROUND: Diarrhoea is a public health problem, especially in developing countries where it is the second leading cause of child mortality. In Low Income Countries like in Mali, self-medication and inappropriate use of antibiotics due to the scarcity of complementary diagnostic systems can lead to the development of multidrug-resistant bacteria causing diarrhoea. The objective of this work was to determine the microorganisms responsible for diarrhoea in children under 15 years of age and to characterize their sensitivity to a panel of antibiotics used in a peri-urban community in Mali. The study involved outpatient children visiting the Yirimadio Community Health Centre and diagnosed with diarrhoea. Stool samples from those patients were collected and analysed by conventional stools culture and the susceptibility to antibiotics of detected bacteria was determined by the disc diffusion method in an agar medium. RESULT: Overall, 554 patients were included. Children under the age of 3 years accounted for 88.8% (492 of 554) of our study population. Two bacterial species were isolated in this study, Escherichia coli 31.8% (176 of 554) and Salmonella 2.9% (16 of 554). In the 176, E. coli strains resistance to amoxicillin and to cotrimoxazole was seen in 93.8% (165 of 176) and 92.6% ( 163 of 176), respectively. The ESBL resistance phenotype accounted for 39,8% (70 of 176) of E. coli. Sixteen (16) strains of Salmonella were found, of which one strain (6.3%) was resistant to amoxicillin and to amoxicillin + clavulanic acid. Another one was resistant to chloramphenicol (6.3%). Two strains of Salmonella were resistant to cotrimoxazole (12.5%) and two others were resistant to cefoxitin (12.5%). CONCLUSIONS: The data suggest that E. coli is frequently involved in diarrhoea in children under 3 years of age in this peri-urban setting of Bamako, Mali, with a high rate of resistance to amoxicillin and cotrimoxazole, the most widely used antibiotics in the management of diarrhoea in this setting.

The Impact of Rapid Handpump Repairs on Diarrhea Morbidity in Children: Cross-Sectional Study in Kwale County, Kenya.

BACKGROUND: Handpumps are used by millions of people as their main source of water. Although handpumps represent only a basic form of water provision, there have been continuous efforts to improve the performance of these systems as they are likely to remain in use for many years to come. The introduction of a professional maintenance service in southern Kenya has shown an order of magnitude improvement in operational performance over community-based management, with 90% of handpump faults repaired within 3 days of being reported. One driver behind these efforts is the assumption that a more reliable water supply will lead to a reduction in water-related disease. However, it is not clear if operational improvements lead to health gains. Despite limited empirical evidence, some modeling studies suggest that even short periods of drinking contaminated water can lead to disproportionate negative health impacts. OBJECTIVE: The aim of this study was to assess whether the improvements in operational performance from the rapid professional maintenance of rural handpumps lead to improved household health outcomes. METHODS: From a sample of households using handpumps as their primary water source in Kwale County, Kenya, we measured the 2-week prevalence of World Health Organization-defined diarrhea in children, reported by the adult respondent for each household. We compared the rates before and after a period during which the households' handpumps were being professionally maintained. We then conducted a cross-sectional analysis, fitting logistic regression models with reported diarrhea as the dependent variable and speed of repair as the independent exposure of interest, adjusting for household socioeconomic characteristics; dwelling construction; and Water, Sanitation, and Hygiene (WASH)-related factors. We fitted an additional model to examine select interactions between covariates. RESULTS: Reported diarrhea in children was lower in households whose pumps had been repaired within 24 hours (adjusted odds ratio 0.35, 95% CI 0.24-0.51). This effect was robust to the inclusion of multiple categories of covariates. No reduction was seen in households whose pump repairs took more than 24 hours. Analysis of interaction terms showed that certain interventions associated with improved WASH outcomes were only associated with reductions in diarrhea in conjunction with socioeconomic improvements. CONCLUSIONS: Only pump repairs consistently made within 24 hours of failure led to a reduction in diarrhea in the children of families using handpumps. While the efficacy of reduction in diarrhea is substantial, the operational challenges of guaranteeing same-day repairs limits the effectiveness of even best-in-class pump maintenance. Maintenance regimes that cannot bring handpump downtimes close to zero will struggle to generate health benefits. Other factors that reduce diarrhea prevalence have limited effect in isolation, suggesting that WASH interventions will be more effective when undertaken as part of more holistic poverty-reduction efforts.

Prevalence and determinants of diarrhoea and acute respiratory infections among children aged under five years in West Africa: evidence from demographic and health surveys.

BACKGROUND: Diarrhoea and pneumonia are the leading causes of morbidity and mortality in children aged <5 y (under five) globally. This study sought to investigate the prevalence and determinants of diarrhoea and acute respiratory infections (ARIs) among children under five in West Africa. METHODS: The most recent demographic and health survey (DHS) standard for 13 West African countries was used in the study. We calculated the prevalence of diarrhoea and ARIs (2 wk prior to the survey) and performed multivariable complex logistic regression analysis to identify possible predictors of diarrhoea and ARIs. RESULTS: The weighted prevalence of diarrhoea and ARI was 13.7% and 15.9%, respectively. The prevalence of comorbid diarrhoea and ARI was 4.4%. Children aged <2 y (p<0.001), mothers aged <30 y (p<0.003), mothers without formal education (p<0.001), poor households (p<0.001) and poor nutritional status, wasting (p=0.005) and underweight (p<0.001), were the independent predictors of diarrhoea. The independent predictors of ARIs were children with no childhood vaccinations (p=0.002), use of solid fuel in the household (p=0.007), being underweight (p=0.05) and diarrhoea (p<0.001). CONCLUSIONS: The findings imply the need for holistic public health interventions such as increased vaccination coverage, population-based nutritional programmes and campaigns on the use of cleaner cooking fuel targeted at high-risk subgroups in the population to reduce the burden and adverse effects of diarrhoea and ARIs in the West African region.

Non-pharmacological interventions for chemotherapy-induced diarrhoea and constipation management: A scoping review.

PURPOSE: Chemotherapy-induced diarrhoea (CID) and constipation (CIC) are among the most common and severe gastrointestinal symptoms related to chemotherapy. This review aimed to identify and describe the evidence for non-pharmacological interventions for the management of CID and CIC. METHODS: The scoping review was based on the Joanna Briggs Institute methodology and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Evidence from five databases were included: CINAHL, MEDLINE, Embase, PubMed, and APA PsycInfo. Data were systematically identified, screened, extracted and synthesised narratively to describe the evidence for non-pharmacological interventions and their effects on CID and CIC. RESULTS: We included 33 studies, of which 18 investigated non-pharmacological interventions for CID management, six for CIC management, and nine for both CID and CIC management. Interventions were categorized into five groups, including (1) digital health interventions, (2) physical therapies, (3) diet and nutrition therapies, (4) education, and (5) multimodal. Diet and nutrition therapies were the most common to report potential effectiveness for CID and CIC outcomes. Most of the interventions were implemented in hospitals under the supervision of healthcare professionals and were investigated in randomised control trials. CONCLUSIONS: The characteristics of non-pharmacological interventions were diverse, and the outcomes were inconsistent among the same type of interventions. Diet and nutritional interventions show promise but further research is needed to better understand their role and to contribute to the evidence base. Nurses are well placed to assess and monitor for CIC and CID, and also deliver effective non-pharmacological interventions.

Nutraceutical Combinational Therapy for Diarrhoea Control with Probiotic Beverages from Fermented Fruits, Vegetables and Cereals to Regain Lost Hydration, Nutrition and Gut Microbiota.

This article deals with the condition of irregular bowel movements known as diarrhoea, its pathology, symptoms and aetiology. The information has been presented on causes of diarrhoea that include gut infections, food intolerances and allergies to certain ingredients, problems in the gastrointestinal tract like irritable bowel syndrome, inflammatory bowel disease and, the condition of dysbiosis which occurs due to long-term use of antibiotics, or other medicines, etc. Most cases of diarrhoea can be resolved without needing medical treatment; however, it is still important to avoid dehydration of the body and use some supplements to get necessary nutrients which are lost with frequent bowel movements before they can get absorbed and assimilated in the gastrointestinal tract. Probiotic products are reported as natural therapeutic agents, which can reduce the risk of diarrhoea in both adults and children. The intake of dietary fluid supplements in the form of fermented beverages containing probiotic strains could help in diarrhoea control. The patient would achieve benefits with the consumption of these functional beverages in three ways-by regaining lost fluids to the body, supplementing beneficial gut bacteria to restore diversity in gut microbiota, which was disturbed in the condition of diarrhoea as well as regaining a source of quick nutrition to recoup energy.

Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children.

INTRODUCTION AND OBJECTIVES: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350 + E) for constipation in critically ill children. METHODS: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72 h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350 + E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). RESULTS: The sample included 56 patients with a mean age of 48.2 ±â€¯11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350 + E and 12 (21.4%) with rectal enemas. The proportion of patients that responded well to treatment was greater in the PEG 3350 + E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P = .151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350 + E was more effective in children aged less than 2 years (100%) compared to older children (100% vs 65.4%; P < .01), with no significant differences in the development of adverse events. CONCLUSIONS: The PEG 3350 + E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years.

Understanding diarrhoeal diseases in response to climate variability and drought in Cape Town, South Africa: a mixed methods approach.

BACKGROUND: The climate of southern Africa is expected to become hotter and drier with more frequent severe droughts and the incidence of diarrhoea to increase. From 2015 to 2018, Cape Town, South Africa, experienced a severe drought which resulted in extreme water conservation efforts. We aimed to gain a more holistic understanding of the relationship between diarrhoea in young children and climate variability in a system stressed by water scarcity. METHODS: Using a mixed-methods approach, we explored diarrhoeal disease incidence in children under 5 years between 2010 to 2019 in Cape Town, primarily in the public health system through routinely collected diarrhoeal incidence and weather station data. We developed a negative binomial regression model to understand the relationship between temperature, precipitation, and relative humidity on incidence of diarrhoea with dehydration. We conducted in-depth interviews with stakeholders in the fields of health, environment, and human development on perceptions around diarrhoea and health-related interventions both prior to and over the drought, and analysed them through the framework method. RESULTS: From diarrhoeal incidence data, the diarrhoea with dehydration incidence decreased over the decade studied, e.g. reduction of 64.7% in 2019 [95% confidence interval (CI): 5.5-7.2%] compared to 2010, with no increase during the severe drought period. Over the hot dry diarrhoeal season (November to May), the monthly diarrhoea with dehydration incidence increased by 7.4% (95% CI: 4.5-10.3%) per 1 °C increase in temperature and 2.6% (95% CI: 1.7-3.5%) per 1% increase in relative humidity in the unlagged model. Stakeholder interviews found that extensive and sustained diarrhoeal interventions were perceived to be responsible for the overall reduction in diarrhoeal incidence and mortality over the prior decade. During the drought, as diarrhoeal interventions were maintained, the expected increase in incidence in the public health sector did not occur. CONCLUSIONS: We found that that diarrhoeal incidence has decreased over the last decade and that incidence is strongly influenced by local temperature and humidity, particularly over the hot dry season. While climate change and extreme weather events especially stress systems supporting vulnerable populations such as young children, maintaining strong and consistent public health interventions helps to reduce negative health impacts.

Risk factors associated with post-weaning diarrhoea in Austrian piglet-producing farms.

Post-weaning diarrhoea (PWD) is a frequent, multifactorial disease of piglets leading to increased mortality rates and high economic losses. Due to the emergence of multi-resistant Escherichia coli isolates and the ban of zinc oxide (ZnO) in the EU since June 2022, alternative measures to prevent PWD are urgently needed. While an abundance of feed supplements is described to prevent PWD, there are hardly any studies reflecting the current situation of PWD in the field. Thus, we aimed to identify differences in management practices, housing and feeding strategies between farms with PWD and farms without PWD. Data were personally collected using a semi-structured questionnaire in 257 Austrian piglet-producing farms. Farms with PWD in more than 10% of all weaned groups within twelve months prior to data collection were defined as case farms (n = 101), while the remaining 136 farms were defined as control farms. Data from 237 farms and 69 explanatory variables were analysed via penalized binary logistic regression using elastic-net in 100 different splits into randomly selected training and test datasets (80:20). Treatment with ZnO and/or colistin (136 farms) was negatively associated with PWD in all splits and had the biggest estimated absolute log odds ratio out of all tested variables. Implementation of an all-in/all-out system in the nursery units and administration of probiotics or horseradish also had preventive effects in most splits (≥ 97%). A higher number of feeding phases for piglets within the first seven weeks of life and housing on fully slatted floors was associated negatively with the occurrence of PWD as well in > 95% of all splits. PWD was more likely to occur on farms having problems with neonatal diarrhoea or postpartum dysgalactia syndrome. While our data demonstrate that treatment with ZnO or colistin had the biggest statistical effect on PWD, we were able to identify other preventive measures like supplementation with probiotics or horseradish. Since implementation of all-in/all-out measures and fully slatted floors were also negatively associated with the occurrence of PWD on visited farms, we assume that reduction of bacterial load by the implementation of simple hygiene measures are still crucial to prevent PWD.

Faecal microbiome transplantation improves clinical signs of chronic idiopathic large bowel diarrhoea in working dogs.

BACKGROUND: Chronic diarrhoea is a common clinical sign in dogs with chronic enteropathy, and psyllium husk has been shown to improve clinical signs in affected dogs. The aim of this study was to investigate whether faecal microbiome transplant has a similar effect in alleviating clinical signs in dogs with chronic large bowel diarrhoea. METHOD: Thirty large-breed working dogs with chronic large bowel diarrhoea were divided into a psyllium group (PG) and a faecal microbiome transplant group (FMTG). To the PG, 16 g/day of psyllium husk was administered for 30 days. The FMTG received faecal microbiome transplantation (FMT) once via enema. A daily log of faecal characteristics was kept, and the dogs' canine inflammatory bowel disease index (CIBDAI) and body condition scores (BCS) were determined. A Wilcoxon-Mann-Whitney test was used to compare group results. In addition, the Kaplan-Meier test was used to evaluate the occurrence rate of 1 day or more of diarrhoea and 2 days or more of diarrhoea by day 30. RESULTS: The sample had a mean age of 3.9 ± 2.1 years and a bodyweight of 25.3 ± 6.8 kg. The FMTG showed a more rapid onset of CIBDAI improvement but no difference in other measures. At 30 days, the FMTG showed a greater improvement in bodyweight and BCS, but no differences were observed in faecal scores, defaecation frequency and time of appearance of episodes of diarrhoea. Time played a significant positive role in the results observed across both groups (p < 0.05). LIMITATIONS: This study did not compare the microbiomes of the dogs before and after treatment, so the role of specific types of bacteria cannot be determined. CONCLUSION: Psyllium husk and FMT had similar effects in improving clinical signs of chronic large bowel diarrhoea.

Blidingia sp. extracts improve intestinal health and reduce diarrhoea in weanling piglets.

Blidingia sp. is a prominent fouling green macroalga and we previously found that extracts from Blidingia sp. alleviated intestinal inflammation in mice challenged with lipopolysaccharides. However, whether these extracts are effective in weanling piglets remains unknown. In the present study, Blidingia sp. extracts were supplemented in the diet and their effects on growth performance, incidence of diarrhoea and intestinal function in weanling piglets were explored. The results showed that diets supplemented with 0.1% or 0.5% Blidingia sp. extract significantly increased average daily body weight gain and feed intake in weanling piglets. Meanwhile, piglets supplemented with 0.5% Blidingia sp. extract showed decreased incidence of diarrhoea as well as reduced fecal water and Na+ content. Furthermore, the diet supplemented with 0.5% Blidingia sp. extracts improved intestinal morphology, as indicated by the results of hematoxylin and eosin staining. Diet supplemented with 0.5% Blidingia sp. extracts also improved tight junction function, as indicated by increased expression of Occludin, Claudin-1 and Zonula occludens-1, and alleviated the inflammatory response, as indicated by decreased tumor necrosis factor-α and interleukin-6 (IL6) contents and increased IL10 levels. Taken together, our results showed that Blidingia sp. extracts had beneficial effects in weanling piglets and we suggest that Blidingia sp. extracts could be potentially used as an additive for piglets.

Evaluation of tributyrin supplementation in milk replacer on diarrhoea occurrence in preweaning Holstein calves.

Neonatal calf diarrhoea is one of the most important health challenges in cattle herds causing substantial economic losses and antimicrobial use. Due to the raising problem of antimicrobial resistance, effective alternatives are urgently required, in line with European policies. The aim of this study was to evaluate the effect of tributyrin supplementation in milk replacer on diarrhoea, performance and metabolic status in preweaning Holstein calves. Twelve newborn calves, after colostrum administration, were randomly allotted in two experimental groups for 42 days: control (CTRL) fed milk replacer, tributyrin (TRIB) fed milk replacer supplemented with 0.3% of liquid tributyrin on milk powder weight. Calves BW was recorded on a weekly basis from day 7 to day 42, and feed intake was recorded daily to calculate zootechnical performance. Faecal consistency was assessed daily through the faecal score (0-3 scale; considering diarrhoea moderate = 2 and severe = 3). Faecal samples were collected weekly from rectal ampulla for microbiological analysis by plate counting method evaluating the number of total bacteria, lactic acid bacteria and coliform bacteria. On day 0 and day 42, individual blood samples were collected from jugular vein for metabolic profile analysis. Serum samples of day 42 were also evaluated for the antioxidant barrier using a colorimetric test, while glucagon-like peptide 2 and diamine oxidase concentrations were measured through immunoenzymatic assays. Tributyrin supplementation did not influence the zootechnical performance of calves over 42 days of trial. Diarrhoea frequency was significantly lower in TRIB compared to CTRL group (27.91 and 38.37%; P < 0.01) considering the whole experimental period. In particular, the major effect was observed for moderate diarrhoea in TRIB group that showed a significantly reduced frequency compared to CTRL (P < 0.01) thus suggesting a preventive effect of tributyrin. Faecal total bacterial, lactic acid and coliform bacteria counts did not show differences between groups. Urea serum concentrations tended to be lower in TRIB compared to CTRL, indicating an efficient utilisation of dietary protein. Antioxidant barrier and glucagon-like peptide 2 were comparable between CTRL and TRIB on day 42. Diamine oxidase concentrations were significantly decreased in TRIB compared to CTRL group after 42 days of trial (P < 0.01), suggesting a higher gut epithelial integrity probably due to lower diarrhoea frequency and the nourish effect of tributyrin on enterocytes. In conclusion, tributyrin could be considered as a valuable bioactive feed additive to decrease the neonatal diarrhoea occurrence and support intestinal integrity in preweaning calves.

Use and perceived effectiveness of non-pharmacological home remedies for digestive symptoms: a questionnaire-based survey among primary care patients.

BACKGROUND: Patients frequently visit their primary care physician (PCP) for digestive symptoms. We aimed to compile a list of non-pharmacological home remedies (NPHRs) that patients frequently use and find effective so that PCPs can then propose them to their patients with various digestive symptoms. METHODS: In this questionnaire-based survey on the use and perceived effectiveness of NPHRs for digestive symptoms, 50 randomly selected Swiss or French PCPs consecutively recruited 20-25 patients between March 2020 and July 2021. These patients were given a list of 53 NPHRs previously developed by our research team. They were asked whether they used them (Y/N) and whether they considered them to be ineffective, not very effective, moderately effective, or very effective in treating abdominal pain (14 NPHRs), bloating (2), constipation (5), diarrhoea (10), digestion trouble (12), nausea/vomiting (2) and stomach pain (8). We considered NPHRs to be perceived as effective if patients reported that they were moderately or very effective. RESULTS: A total of 1,012 patients agreed to participate in the study (participation rate = 84.5%, median age = 52 years, women = 61%). The two most frequently used NPHRs were rice cooking water for diarrhoea (29% of patients) and prunes for constipation (22%). The perceived effectiveness of the NPHRs ranged from 82% (fennel infusions for abdominal pain) to 95% (bicarbonate for stomach pain). CONCLUSION: Our data could be useful to PCPs interested in proposing NPHRs to their patients suffering from digestive disorders, and more generally to all PCPs interested in learning more about patients' use of NPHRs in primary care.

Effects of opium tincture on the enteric and central nervous systems: A randomized controlled trial.

Opioids change gut motility, and opium tincture has been used for treatment of chronic diarrhoea for centuries. However, the effects have never been documented in controlled trials. We aimed to investigate the effects of opium tincture on gastrointestinal transit and motility, frequency of bowel movements, stool consistency, gastrointestinal symptoms and sedation. Twenty healthy subjects were included in this randomized controlled trial. Opium tincture or placebo was each applied for 9 days. Gastrointestinal transit and motility were investigated with the 3D-transit system. Bowel movements and gastrointestinal symptoms were recorded daily. General cognition, reaction time, memory and electroencephalography were used to assess effects on the central nervous system. Opium tincture doubled colonic transit (49 vs. 23 h, p < 0.001), decreased antegrade colonic movements (p < 0.05), reduced daily bowel movements (0.7 vs. 1.2, p < 0.001) and increased stool consistency (Type 3 vs. Type 4, p < 0.001). No changes in general cognition, reaction time or memory were observed, and minor changes of power observed by electroencephalography did not indicate sedation. This study is the first to show that opium tincture has anti-propulsive properties in the healthy gut, while no sedative effects were seen. This indicates that opium tincture is a relevant and safe treatment option in chronic diarrhoea.

CYX-5, a G-protein biassed MOP receptor agonist, DOP receptor antagonist and KOP receptor agonist, evokes constipation but not respiratory depression relative to morphine in rats.

BACKGROUND: Strong opioid analgesics such as morphine alleviate moderate to severe acute nociceptive pain (e.g. post-surgical or post-trauma pain) as well as chronic cancer pain. However, they evoke many adverse effects and so there is an unmet need for opioid analgesics with improved tolerability. Recently, a prominent hypothesis has been that opioid-related adverse effects are mediated by ß-arrestin2 recruitment at the µ-opioid (MOP) receptor and this stimulated research on discovery of G-protein biassed opioid analgesics. In other efforts, opioids with MOP agonist and δ-opioid (DOP) receptor antagonist profiles are promising for reducing side effects c.f. morphine. Herein, we report on the in vivo pharmacology of a novel opioid peptide (CYX-5) that is a G-protein biassed MOP receptor agonist, DOP receptor antagonist and kappa opioid (KOP) receptor agonist. METHODS: Male Sprague-Dawley received intracerebroventricular bolus doses of CYX-5 (3, 10, 20 nmol), morphine (100 nmol) or vehicle, and antinociception (tail flick) was assessed relative to constipation (charcoal meal and castor oil-induced diarrhoea tests) and respiratory depression (whole body plethysmography). RESULTS: CYX-5 evoked naloxone-sensitive, moderate antinociception, at the highest dose tested. Although CYX-5 did not inhibit gastrointestinal motility, it reduced stool output markedly in the castor oil-induced diarrhoea test. In contrast to morphine that evoked respiratory depression, CYX-5 increased tidal volume, thereby stimulating respiration. CONCLUSION: Despite its lack of recruitment of ß-arrestin2 at MOP, DOP and KOP receptors, CYX-5 evoked constipation, implicating a mechanism other than ß-arrestin2 recruitment at MOP, DOP and KOP receptors, mediating constipation evoked by CYX-5 and potentially other opioid ligands.

Effects of sodium humate and glutamine on growth performance, diarrhoea incidence, blood parameters, and faecal microflora of pre-weaned calves.

This study aimed to evaluate the effects of administration of sodium humate (HNa) and glutamine (Gln) on growth performance, diarrhoea incidence, serum parameters, and faecal microflora of pre-weaned Holstein calves. In a 57-day experiment, 28 healthy newborn female calves were randomly allocated to four treatment groups: (1) CON (control); (2) HNa (basal diet + 5% HNa); (3) Gln (basal diet + 1% Gln); and (4) HNa + Gln (basal diet + 5% HNa + 1% Gln). The calves in the CON group were fed with basal diet. HNa and Gln were alone or together mixed with milk (Days 1-20) or milk replacer (Days 21-57) and orally administered to each calf. The results indicated that calves combined supplemented with HNa and Gln had a higher average daily gain at 0-21 days, 21-57 days, and 0-57 days, and starter intake at 21-57 days and 0-57 days (p < 0.05). Compared with the CON group, calves in HNa, Gln, and HNa + Gln groups showed lower faecal scores and diarrhoea incidence at 0-21 days and 0-57 days (p < 0.05). Combined administration of HNa and Gln increased the concentration of IgG and IgA, activities of glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) but decreased the concentration of diamine oxidase (DAO), D-lactic acid (D-lac), TNF-α, and malondialdehyde (MDA) in the serum of calves compared with the CON group throughout the entire period (p < 0.05). Furthermore, the abundances of Bifidobacterium and Lactobacillus were increased but the Escherichia coli was decreased in faecal grab samples of HNa + Gln group calves in comparison with the CON group (p < 0.05). In conclusion, combined administration of HNa and Gln effectively improved the growth performance, antioxidant and immune status, and intestinal beneficial bacteria, and further reduced the diarrhoea incidence of the pre-weaned calves.

Effects of dietary supplementation with bioactive peptides derived from rapeseed protein on the growth performance, serum biochemistry and faecal micro-organism composition of weaned piglets.

The present study investigated the effects of supplementing bioactive peptides derived from rapeseed protein (rapeseed peptide, Rsp) on the growth performance, serum biochemistry and faecal micro-organism composition of weaned piglets. Sixty Duroc × Landrace × Yorkshire weaned piglets of similar weights were randomly divided into three groups. The control group (NC) was fed a basal diet, and the two treatment groups, Rsp-1 and Rsp-2, were fed a basal diet supplemented with 1% or 2% Rsp, respectively, for 28 days. Each treatment consisted of five replicates with four piglets per replicate. The results showed that Rsp treatment significantly improved the average daily gain and had a better feed-to-gain ratio (p < 0.05). The diarrhoea incidence and indices of Rsp-1 and Rsp-2 groups were significantly lower than the NC group (p < 0.05), and the effect of Rsp-2 on reducing the incidence of diarrhoea was significantly higher than that of Rsp-1 (p < 0.05). The serum albumin, serum immunoglobulin A and catalase levels of the Rsp-1 and Rsp-2 groups were significantly better than the NC group (p < 0.05). Additionally, Rsp treatment significantly gained the relative abundance of faecal Lactobacillaceae and decreased the relative abundance of faecal Eubacterium_coprostanoligenes_group, Treponema and Coprococcus (p < 0.05). In summary, Rsp supplementation improved the growth performance, ameliorated the diarrhoea, enhanced the immune and antioxidant functions and changed the composition of faecal micro-organisms in piglets. These findings indicate that Rsp positively affected the health of weaned piglets.

Dietary Qi-Weng-Huangbo powder enhances growth performance, diarrhoea and immune function of weaned piglets by modulating gut health and microbial profiles.

Introduction: The evolution of nutritional strategies to improve the gut health and microbiota profiles of early-weaned piglets is essential to reduce diarrhoea caused by weaning stress. Therefore, the aim of this study was to determine the effects of dietary supplementation of Qi-Weng-Huangbo powder, a traditional herbal medicine consisting of a mixture of Pulsatilla chinensis, Chinese Schneid and Astragalus extracts (PCE), on the growth performance, diarrhoea rate, immune function and intestinal health of weaned piglets. Methods: 162 piglets were randomly assigned to the CON group (no PCE added), the PCEL group (300 mg/kg PCE) and the PCEH group (500 mg/kg PCE) at the end of the third week post farrowing. There were 9 replicates of each group with 6 pigs per replicate. The experiment lasted for 28 days and sampling was performed on the final day. Results: The results showed that the PCE diet increased the average daily gain (ADG) and final body weight (BW) compared to the CON group. Both supplemented doses of PCE reduced the faecal scores of piglets, and the diarrhoea rate in the PCEL group was significantly lower than that in the CON group. The application of PCE diets promoted the development of the spleen in piglets and up-regulated serum immunoglobulin concentrations to enhance immune function, which was also reflected in the down-regulated gene expression of the colonic TLR/MyD88/NF-κB pathway. Supplementation with PCE improved intestinal morphology, and all doses of PCE significantly increased villus height (VH) in the ileum, whereas colonic crypt depth (CD) was significantly lower in the PCEH group than in the CON group. The PCEH diet significantly increased the levels of valeric and isovaleric acid in the colon content. Dietary PCEH also improved the colonic microbial community profile, reflected by a significant increase in Shannon's index compared with CON group. The abundance of Veillonellaceae and Rhodospirillales was significantly increased in the PCEH group at the family level. Discussion: In conclusion, dietary PCE reduced diarrhoea rates, improved growth performance and enhanced immune function in weaned piglets. These improvements were potentially supported by altered ileum and colonic morphology, elevated colonic VFA levels, and modulation of colonic microbial profiles.

Effects of Massa Medicata Fermentata on the intestinal pathogenic flagella bacteria and visceral hypersensitivity in rats with irritable bowel syndrome.

Objective: To investigate the effect of Massa Medicata Fermentata (MMF) on the changes of pathogenic flagellar bacteria and visceral hypersensitivity in rats with diarrhea irritable bowel syndrome (IBS-D). Methods: Thirty adult SD rats were randomly divided into normal control group (n = 10), model control group (n = 10), and MMF group (n = 10). Acetic acid enema combined with restraint stress was used to build the IBS-D visceral hypersensitivity model; Abdominal withdrawal reflex (AWR) test was used to assess the visceral sensitivity of rats; 16SrRNA sequencing was used to analyze the changes of intestinal bacteria in each group, and the content of pathogenic flagellated bacteria were quantitatively counted; The content of flagellin in colonic mucosa was detected by ELISA; TLR5 protein in colonic mucosa of rats was detected by Western Blot. Results: After IBS-D modeling, the visceral sensitivity of rats was significantly higher in the model control group than that in the normal control group (p = 0.0061), while it was significantly decreased in MMF group compared with the model control group (p = 0.0217), but without significant difference compared with the normal control group (p = 0.6851). The number of fecal Bifidobacterium and Lactobacillus in the model group were significantly decreased compared with the normal control group (p < 0.0001); While they were significantly increased in the MMF group compared with the model control group and normal control group (p = 0.009; p < 0.0001). The amount of fecal pathogenic flagellated bacteria in the model group was significantly increased compared with the normal control group (p = 0.001); However it was significantly reduced in MMF group compared with the model group (p = 0.026), which has no statistically difference with the normal control group (p = 0.6486). The content of flagellin in colonic mucosa was significantly increased in the model group when compared with the normal control group (p < 0.0001), and it was decreased in MMF group compared with the normal control group (p < 0.0001), but there was no statistical difference with the normal control group (p = 0.6545). The expression level of TLR5 protein in colonic mucosa of rat was significantly increased in model control group compared with the normal control group (p = 0.0034), However, it was significantly decreased in MMF group compared with normal control group (p = 0.0019), but it was no statistical difference with the normal control group (p = 0.7519). Conclusion: MMF can reduce visceral hypersensitivity by decreasing the content of pathogenic flagellated bacteria and their flagellin and inhibiting its specific receptor TLR5 protein expression in colonic mucosa in IBS-D rats.

Efficacy of neomycin dosing regimens for treating enterotoxigenic Escherichia coli-related post-weaning diarrhoea in a Danish nursery pig herd not using medicinal zinc oxide.

Neomycin is a concentration-dependant aminoglycoside antimicrobial used to treat enterotoxigenic Escherichia coli (ETEC)-related post-weaning diarrhoea (PWD) in pigs. The objective was to compare the efficacy of neomycin administered in a single high dose (50,000 IU/kg) and a standard dose and frequency (25,000 IU/kg daily for 3 consecutive days) in reducing the number of pigs with clinical PWD. We also aimed to evaluate the development of antimicrobial resistance in E. coli following neomycin treatment. The study was performed in a Danish herd not using medicinal zinc oxide and experiencing outbreaks of PWD caused by ETEC in the first week after weaning. Pigs from six batches with perianal faecal staining on days 4-6 after weaning and a faecal score of 3-4 were ear tagged and treated with neomycin. Pens were randomly assigned to a treatment group before inclusion. A total of 772 pigs (471 in the control group and 301 in the experimental group) were included and treated orally. The apparent prevalence of diarrhoea on the first day of inclusion across six batches (n = 1,875) was 27%. The efficacy of the neomycin treatment strategy was 86% for the control group and 91% for the single high-dose group (p = 0.043), and the mean percentage (standard deviation (sd)) of haemolytic E. coli-like colonies was 12% (26) and 26% (37) (p < 0.001), respectively. Neomycin resistance did not differ between groups. Before treatment, all analysed isolates were identified as ETEC (n = 142), while after treatment, 91% were identified as ETEC (n = 69) and 9% (n = 7) as non-ETEC E. coli (without fimbria or toxins). A higher cure rate in the single high-dose group suggests that ETEC-related PWD can be treated with a single high dose of 50,000 IU/kg of neomycin, thereby reducing antimicrobial use by 33% compared to the standard treatment of 25,000 IU/kg for 3 consecutive days. The study indicated a higher number of haemolytic E. coli in the single high-dose group after treatment, but no evidence of increased neomycin resistance in coliforms was observed compared to the standard treatment.