Acceptability of an Orange-Flavoured Zinc Sulphate Dispersible Tablet in the Management of Acute Diarrhoea in Under-five Children in Lagos, Nigeria.

BACKGROUND: Acute diarrhoea is a significant cause of morbidity and mortality in children under five, especially in subSaharan Africa. The WHO recommends using oral rehydration solution (ORS) and zinc therapy for its management, but the metallic taste of zinc often hinders adherence. METHOD: This prospective open-label intervention study took place at three health facilities in Lagos, Southwest Nigeria, involving children aged 3 to 59 months with acute diarrhoea. Sociodemographic and diarrhoea-related data were obtained. Palatability was assessed using a 5-point hedonic scale, and adherence was determined by the proportion of prescribed zinc sulfate tablets consumed. Caregivers received a 10-day supply of the study drug and ORS sachets for each child, along with participant diaries for tracking drug intake, palatability scores, and adverse events. Follow-up was conducted on Days 3 and 7, and diaries were collected between Days 10 and 14. RESULTS: Out of the 294 participants, most caregivers were mothers (86.0%), had at least a secondary education (88.1%), and were employed (70.7%). The majority of children were male (54.2%), and under 18 months old (52.2%). The average palatability score was 2.65 (±0.78), with no significant differences based on age or gender. Mean adherence was 93.03%, with 89.3% achieving ≥80% adherence, and adherence did not significantly differ by age or gender. The only reported adverse event, vomiting, decreased from 18.8% on Day 1 to 0.5% on Day 10. CONCLUSION: The study indicates that the orange-flavored dispersible zinc sulfate tablet is well-accepted by children aged 3 to 59 months with acute diarrhoea in Lagos, Nigeria.

CONTEXTE: La diarrhée aiguë est une cause significative de morbidité et de mortalité chez les enfants de moins de cinq ans, en particulier en Afrique subsaharienne. L'OMS recommande l'utilisation de la solution de réhydratation orale (SRO) et de la thérapie au zinc pour sa prise en charge, mais le goût métallique du zinc entrave souvent l'observance. MÉTHODE: L'étude d'intervention prospective à ciel ouvert a eu lieu dans trois établissements de santé à Lagos, dans le sud-ouest du Nigeria, impliquant des enfants de 3 à 59 mois souffrant de diarrhée aiguë. Des données sociodémographiques et liées à la diarrhée ont été obtenues. La palatabilité a été évaluée à l'aide d'une échelle hédonique à 5 points, et l'observance a été déterminée par la proportion de comprimés de sulfate de zinc prescrits consommés. Les aidants ont reçu une provision de 10 jours du médicament de l'étude et des sachets de SRO pour chaque enfant, ainsi que des journaux de suivi pour noter la prise du médicament, les scores de palatabilité et les événements indésirables. Un suivi a été effectué aux jours 3 et 7, et les journaux ont été collectés entre les jours 10 et 14. RÉSULTATS: Sur les 294 participants, la plupart des aidants étaient des mères (86,0%), avaient au moins une éducation secondaire (88,1%), et étaient employées (70,7%). La majorité des enfants étaient de sexe masculin (54,2%) et avaient moins de 18 mois (52,2%). La note moyenne de palatabilité était de 2,65 (±0,78), sans différences significatives en fonction de l'âge ou du sexe. L'observance moyenne était de 93,03%, avec 89,3% atteignant une observance ≥ 80%, et l'observance ne différait pas de manière significative en fonction de l'âge ou du sexe. Le seul événement indésirable signalé, les vomissements, est passé de 18,8% le jour 1 à 0,5% le jour 10. CONCLUSION: L'étude indique que le comprimé de sulfate de zinc dispersible à l'arôme d'orange est bien accepté par les enfants de 3 à 59 mois souffrant de diarrhée aiguë à Lagos, au Nigeria. MOTS-CLÉS: Diarrhée, moins de cinq ans, Enfants, Arôme d'orange, Comprimés de zinc, Palatabilité, Acceptabilité, Échelle hédonique, Lagos, Nigeria.

Factors associated with the co-utilization of oral rehydration solution and zinc for treating diarrhea among under-five children in 35 sub-saharan Africa countries: a generalized linear mixed effect modeling with robust error variance.

INTRODUCTION: Even though childhood diarrhea is treated with a simple treatment solution, it continues to be one of the leading causes of under-five child mortality and malnutrition globally. In resource-limited settings such as Sub-Saharan Africa (SSA), the combination of oral rehydration salts (ORS) and zinc is regarded as an effective treatment for diarrhea; however, its utilization is very low. The purpose of this study was to determine the proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA. METHODS: The proportion and associated factors of co-utilization of ORS and zinc among under-five children with diarrhea in SSA were determined using secondary data analysis of recent Demographic and Health Surveys (DHS) of 35 SSA countries. The study included a total of 44,341 under-five children with diarrhea in weighted samples. A generalized linear mixed-effects model with robust error variance was used. For the variables included in the final model, adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) were estimated. A model with the lowest deviance value were considered as the best-fitted model. RESULT: The pooled proportion of co-utilization of ORS and zinc for the treatment of diarrhea among under five children in SSA countries was 43.58% with a 95% CI (43.15%, 44.01%). Sex of the child, maternal age, residence, maternal educational and employment status, wealth index, media exposure, perceived distance to health facility and insurance coverage were statistically significant determinants of ORS and Zinc co-utilization for treating diarrhea among under five children in SSA. CONCLUSION: Only less than half of under-five children with diarrhea in SSA were treated with a combination of ORS and zinc. Thus, strengthening information dissemination through mass media, and community-level health education programs are important to scale up the utilization of the recommended combination treatment. Furthermore, increasing health insurance coverage, and establishing strategies to address the community with difficulty in accessing health facilities is also crucial in improving the use of the treatment.

Da-Jian-Zhong decoction alleviates diarrhea-predominant irritable bowel syndrome via modulation of gut microbiota and Th17/Treg balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. AIM OF THE STUDY: We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. MATERIALS AND METHODS: An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. RESULTS: We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. CONCLUSIONS: These results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

Pharmaceutical activity of sappan wood extract (Caesalpinia sappan L.) for treating Escherichia coli infection in piglets.

Background: Escherichia coli infection is one of the major diarrheal diseases resulting in the loss of pigs at a young age. Aim: This research investigated the antimicrobial activity of Caesalpinia sappan wood extract against E. coli infection as an antibiotic replacement. Methods: E. coli was cultured from diarrheal piglets and then used to find the minimal inhibition concentration (MIC). Caesalpinia sappan wood extract (500 mg/kg) was used for the treatment of diarrheal piglets compared to antibiotics (enrofloxacin 5 mg/kg) by oral administration. Another three groups of diarrheal piglets were used supplemented feed with 1% and 2% extract compared with commercial feed. Subsequently, E. coli enumeration, fecal shape, fecal color, and growth rate were recorded from day 1 to 7. Results: Based on the results, C. sappan wood extract could inhibit E. coli growth at a MIC of 16-34 mg/ml. The number of colonies did not significantly differ between C. sappan wood extract and enrofloxacin treatment groups. A supplemented feed with 1% and 2% C. sappan wood extract could improve the fecal shape and fecal score compared to the control group, albeit only in suckling pigs. There were significant differences from the control group on days 4, 5, 6, and 7 (p < 0.05). However, the average daily gain did not significantly differ among the three groups. Conclusion: The results indicate that C. sappan wood extract could improve diarrheal signs in suckling pigs and can be used as a replacement for antibiotics for organic pig production.

Research in revealing the effects on Cuscuta chinensis to diarrhea type irritable bowel syndrome based on network pharmacology and molecular docking potential mechanism.

To explore the potential mechanism in Cuscuta sinensis on diarrhea-type irritable bowel syndrome using network pharmacology and molecular docking techniques. First, the active components and related targets of Cuscuta were found setting oral utilization >30% and drug-like properties greater than or equal to 0.18 as filter information from TCMSP database. The targets of diarrheal irritable bowel syndrome were compiled by searching DrugBank, GeneCards, OMIM, PharmGkb, and TTD databases. The intersections of drugs and targets related to the disease were taken for gene ontology enrichment and Kyoto encyclopedia of genes and genomes enrichment analyses, to elucidate the potential molecular mechanisms and pathway information of Cuscuta sinensis for the treatment of diarrheal irritable bowel syndrome. The protein-protein interaction network was constructed by using the STRING database and visualized with Cytoscape_v3.10.0 software to find the protein-protein interaction network core At last, molecular docking was performed to validate the combination of active compounds with the core target. The target information of Cuscuta and diarrhea-type irritable bowel syndrome was compiled, which can be resulted in 11 active compounds such as quercetin, kaempferol, isorhamnetin, ß-sitosterol, and another 17 core targets such as TP53, IL6, AKT1, IL1B, TNF, EGFR, etc, whose Kyoto encyclopedia of genes and genomes was enriched in the pathways of lipids and atherosclerosis, chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, and fluid shear stress and atherosclerosis, etc. Docking demonstrated that the core targets and the active compounds were able to be better combined. Cuscuta chinensis may exert preventive effects on diarrhea-type irritable bowel syndrome by reducing intestinal inflammation, protecting intestinal mucosa, and playing an important role in antioxidant response through multi-targets and multi-pathways.

A situational assessment of treatments received for childhood diarrhea in the Federal Republic of Nigeria.

We assess progress towards improved case management of childhood diarrhea in Nigeria over a period of targeted health systems reform from 2013 to 2018. Individual and community data from three Demographic and Health Survey rounds are leveraged in a geospatial model designed for stratified estimation by venue of treatment seeking and State. Our analysis reveals a highly regionalised health system undergoing rapid change. Nationally, there have been substantial increases in the proportion of children under 5 years old with diarrhea receiving the recommended oral rehydration therapy after seeking treatment at either a health clinic (0.57 [0.44-0.69; 95% CI] in 2008; 0.70 [0.54-0.83] in 2018) or chemist/pharmacy (0.28 [0.17-0.42] in 2008; 0.48 [0.31-0.64] in 2018). Yet State-level variations in venue attendance and performance by venue have conspired to hold the overall proportion receiving this potentially life-saving therapy (0.45 [0.35-0.55] in 2018) to well-below ideal coverage levels. High performing states that have demonstrated significant improvements include Kano, Jigawa and Borno, while under-performing states that have suffered declines in coverage include Kaduna and Taraba. The use of antibiotics is not recommended for mild cases of childhood diarrhea yet remains concerningly high nationally (0.27 [0.19-0.36] in 2018) with negligible variation between venues. Antibiotic use rates are particularly high in Enugu, Kaduna, Taraba, Kano, Niger and Kebbi, yet welcome reductions were identified in Jigawa, Adamawa and Osun. These results support the conclusions of previous studies and build the strength of evidence that urgent action is needed throughout the multi-tiered health system to improve the quality and equity of care for common childhood illnesses in Nigeria.

Antispasmodic and antidiarrheal effects of Juniperus oxycedrus L. on the jejunum in rodents.

Functional bowel disorders (FBD) have a major potential to degrade the standards of public life. Juniperus oxycedrus L. (J. oxycedrus) (Cupressaceae) has been described as a plant used in traditional medicine as an antidiarrheal medication. The present study is the first to obtain information on the antispasmodic and antidiarrheic effects of J. oxycedrus aqueous extract through in vitro and in vivo studies. An aqueous extract of J. oxycedrus (AEJO) was extracted by decoctioning air-dried aerial sections of the plant. Antispasmodic activity was tested in an isolated jejunum segment of rats exposed to cumulative doses of drogue extract. The antidiarrheic activity was tested using diarrhea caused by castor oil, a transit study of the small intestine, and castor oil-induced enteropooling assays in mice. In the jejunum of rats, the AEJO (0.1, 0.3 and 1 mg/ml) diminished the maximum tone induced by low K+ (25 mM), while it exhibited a weak inhibitory effect on high K+ (75 mM) with an IC50=0.49 ± 0.01 mg/ml and IC50=2.65 ± 0.16 mg/ml, respectively. In the contractions induced by CCh (10-6 M), AEJO diminished the maximum tone, similar to that induced by low K+ (25 mM). with an IC50=0.45 ± 0.02 mg/ml. The inhibitory effect of AEJO on low K+ induced contractions was significantly diminished in the presence of glibenclamide (GB) (0.3 µM) and 4-aminopyrimidine (4-AP) (100 µM), with IC50 values of 1.84 ± 0.09 mg/ml. and 1.63 ± 0.16 mg/ml, respectively). The demonstrated inhibitory effect was similar to that produced by a non-competitive antagonist acting on cholinergic receptors and calcium channels. In castor oil-induced diarrhea in mice, AEJO (100, 200, and 400 mg/kg) caused an extension of the latency time, a reduced defecation frequency, and a decrease in the amount of wet feces compared to the untreated group (distilled water). Moreover, it showed a significant anti-motility effect and reduced the amount of fluid accumulated in the intestinal lumen at all tested doses. These findings support the conventional use of Juniperus oxycedrus L. as a remedy for gastrointestinal diseases.

Immune checkpoint inhibitor associated diarrhoea.

A man in his 80s was undergoing immunotherapy with pembrolizumab, an anti-PD-1 monoclonal antibody, following his diagnosis of adenocarcinoma of primary lung origin. 24 weeks into treatment, the patient reported experiencing loose stools associated with malaise and poor appetite but no further symptoms. This progressed in frequency and a clinical diagnosis of grade 2 immune checkpoint inhibitor colitis was made. Management with oral prednisolone was commenced but symptoms persisted. Common enteric infections had been ruled out, as were coeliac disease and hyperthyroidism. Flexible sigmoidoscopy and colonoscopy results were not in keeping with colitis, having revealed normal looking mucosa. Following this, a faecal elastase level was found to be low. A diagnosis of pembrolizumab-induced pancreatic exocrine insufficiency was made, and stool frequency and consistency swiftly improved following the use of pancreatic enzyme replacement therapy.

Efficacy and safety of Chinese herbal medicine in treating postcholecystectomy diarrhea: A systematic review and meta-analysis.

BACKGROUND: Postcholecystectomy diarrhea (PCD) is among the most distressing and well-known clinical complications of cholecystectomy. Despite various available treatment options, clinical outcomes are greatly limited by unclear pathophysiological mechanisms. Chinese herbal medicine (CHM) is widely used as a complementary and alternative therapy for the treatment of functional diarrhea. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of CHM for the treatment of PCD. METHODS: Electronic database searches were conducted using the Cochrane Library, PubMed, Web of Science, Embase, Wanfang Data, China National Knowledge Infrastructure, and the Chinese Scientific Journal Database. All RCTs on CHMs for managing patients with PCD were included. The meta-analysis was performed using RevMan 5.4 software. RESULTS: The present meta-analysis included 14 RCTs published between 2009 and 2021 in China. The primary findings indicated that CHM had a higher total efficacy and cure rate as a monotherapy for PCD (P < .00001). Two trials reported the scores of the main symptoms with statistically significant differences in stool nature (P < .00001), defecation frequency (P = .002), and abdominal pain and bloating (P < .00001). In addition, CHM reduced CD3+ and CD4+ levels more effectively in terms of T lymphocyte subset determination (P < .00001). The main symptoms of PCD in traditional Chinese medicine (TCM) are splenic deficiency and liver stagnation. All treatments were used to strengthen the spleen and (or) soothing the liver. CONCLUSION: CHM had a favorable effect on PCD. No adverse events were observed. Larger, high-quality RCTs are warranted to draw definitive conclusions and standardize treatment protocols.

Deciphering the pharmacological mechanisms of Shenlingbaizhu formula in antibiotic-associated diarrhea treatment: Network pharmacological analysis and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenlingbaizhu (SLBZ) formula, a classical traditional Chinese medicinal (TCM) formula, has been widely used for treating antibiotic-associated diarrhea (AAD). However, the underlying pharmacological mechanisms have not yet been investigated thoroughly. AIM OF THE STUDY: To explore the remission mechanism of SLBZ in the treatment of AAD, we conducted network pharmacological analysis and experimental validation in vitro and in vivo. MATERIALS AND METHODS: In this study, the main compounds of SLBZ were identified by ultra-high-performance liquid chromatography-mass spectroscopy (UHPLC-MS) and online databases. The targets of the active components and AAD-related targets were predicted by network pharmacology, and the potential targets of SLBZ against AAD were obtained. Then the core targets were recognized after Protein-Protein Interaction (PPI) analysis. Based on these, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were conducted, and the key pathway was screened. Subsequently, molecular docking was performed using Auto Dock Vina to find the key components that played a crucial role in that pathway. Molecular dynamics simulation was performed by Gromacs software to detect the binding mode. Finally, the results were confirmed by in vitro and in vivo experiments. RESULTS: A total of 66 active ingredients of SLBZ were detected by UHPLC-MS, and 128 active ingredients were screened out by network pharmacological analysis. Additionally, 935 drug targets and 1686 AAD-related targets were obtained. Seventy-eight intersected genes were selected as potential therapeutic targets and 19 genes were excavated as core targets. Enrichment analysis revealed PI3K-AKT signaling pathway was the key pathway in SLBZ against AAD. Topological analysis further revealed that JAK2, MTOR, TLR4, and SYK were the key targets affected by SLBZ on the PI3K-AKT pathway, and 52 components of SLBZ were associated with them. Molecular docking and dynamics simulation revealed strong binding affinities between MTOR and diosgenin. Subsequently, after SLBZ treatment, the expression levels of JAK2, MTOR, TLR4, and SYK were found significantly upregulated in the AAD model rats (p < 0.05). The cell experiment further validated the good binding ability between MTOR and diosgenin. CONCLUSION: We demonstrate that the therapeutic effect of SLBZ on AAD was achieved in part by inhibiting the PI3K-AKT pathway.

Development and Validation of a High-Performance Liquid Chromatography Method to Quantify Marker Compounds in Lysimachia vulgaris var. davurica and Its Effects in Diarrhea-Predominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS), a common gastrointestinal disorder worldwide, is characterized by chronic abdominal pain, bloating, and disordered defecation. IBS is associated with several factors, including visceral hypersensitivity, gut motility, and gut-brain interaction disorders. Because currently available pharmacological treatments cannot adequately improve symptoms and may cause adverse effects, the use of herbal therapies for managing IBS is increasing. Lysimachia vulgaris var. davurica (LV) is a medicinal plant used in traditional medicine to treat diarrhea. However, information on whether LV can effectively improve diarrhea-predominant IBS (IBS-D) remains limited. In this study, using an experimental mouse model of IBS-D, we elucidated the effects of the LV extract. The methanol extract of LV decreased fecal pellet output in the restraint stress- or 5-hydroxytryptamine (5-HT)-induced IBS mouse model and inhibited 5-HT-mediated [Ca2+]i increase in a dose-dependent manner. Furthermore, we developed and validated a high-performance liquid chromatography method using two marker compounds, namely, chlorogenic acid and rutin, for quality control analysis. Our study results suggest the feasibility of the methanol extract of LV for developing therapeutic agents to treat IBS-D by acting as a 5-HT3 receptor antagonist.

Impact of Limosilactobacillus fermentum probiotic treatment on gut microbiota composition in sahiwal calves with rotavirus diarrhea: A 16S metagenomic analysis study".

BACKGROUND: Diarrhea poses a major threat to bovine calves leading to mortality and economic losses. Among the causes of calf diarrhea, bovine rotavirus is a major etiological agent and may result in dysbiosis of gut microbiota. The current study was designed to investigate the effect of probiotic Limosilactobacillus fermentum (Accession No.OR504458) on the microbial composition of rotavirus-infected calves using 16S metagenomic analysis technique. Screening of rotavirus infection in calves below one month of age was done through clinical signs and Reverse Transcriptase PCR. The healthy calves (n = 10) were taken as control while the infected calves (n = 10) before treatment was designated as diarrheal group were treated with Probiotic for 5 days. All the calves were screened for the presence of rotavirus infection on each day and fecal scoring was done to assess the fecal consistency. Infected calves after treatment were designated as recovered group. Fecal samples from healthy, recovered and diarrheal (infected calves before sampling) were processed for DNA extraction while four samples from each group were processed for 16S metagenomic analysis using Illumina sequencing technique and analyzed via QIIME 2. RESULTS: The results show that Firmicutes were more abundant in the healthy and recovered group than in the diarrheal group. At the same time Proteobacteria was higher in abundance in the diarrheal group. Order Oscillospirales dominated healthy and recovered calves and Enterobacterials dominated the diarrheal group. Alpha diversity indices show that diversity indices based on richness were higher in the healthy group and lower in the diarrheal group while a mixed pattern of clustering between diarrheal and recovered groups samples in PCA plots based on beta diversity indices was observed. CONCLUSION: It is concluded that probiotic Limosilactobacillus Fermentum N-30 ameliorate the dysbiosis caused by rotavirus diarrhea and may be used to prevent diarrhea in pre-weaned calves after further exploration.

Sishen Wan enhances intestinal barrier function via regulating endoplasmic reticulum stress to improve mice with diarrheal irritable bowel syndrome.

BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D), characterized primarily by the presence of diarrhea and abdominal pain, is a clinical manifestation resulting from a multitude of causative factors. Furthermore, Sishen Wan (SSW) has demonstrated efficacy in treating IBS-D. Nevertheless, its mechanism of action remains unclear. METHODS: A model of IBS-D was induced by a diet containing 45 % lactose and chronic unpredictable mild stress. Additionally, the impact of SSW was assessed by measuring body weight, visceral sensitivity, defecation parameters, intestinal transport velocity, intestinal neurotransmitter levels, immunohistochemistry, and transmission electron microscopy analysis. Immunofluorescent staining was used to detect the expression of Mucin 2 (MUC2) and Occludin in the colon. Western blotting was used to detect changes in proteins related to tight junction (TJ), autophagy, and endoplasmic reticulum (ER) stress in the colon. Finally, 16S rRNA amplicon sequencing was used to monitor the alteration of gut microbiota after SSW treatment. RESULTS: Our study revealed that SSW administration resulted in reduced visceral sensitivity, improved defecation parameters, decreased intestinal transport velocity, and reduced intestinal permeability in IBS-D mice. Furthermore, SSW promotes the secretion of colonic mucus by enhancing autophagy and inhibiting ER stress. SSW treatment caused remodeling of the gut microbiome by increasing the abundance of Blautia, Muribaculum and Ruminococcus torques group. CONCLUSION: SSW can improve intestinal barrier function by promoting autophagy and inhibiting ER stress, thus exerting a therapeutic effect on IBS-D.

Treatment-Free Interval: A Novel Approach to Assessing Real-World Treatment Effectiveness and Economic Impact Among Patients with Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Objective assessment of treatment effectiveness using real-world claims data is challenging. This study assessed treatment-free intervals (TFI) as a proxy for treatment effectiveness, and all-cause healthcare costs among adult patients with irritable bowel syndrome with diarrhea (IBS-D) treated with rifaximin or eluxadoline in the USA. METHODS: Adult patients (18-64 years) with IBS-D and ≥ 1 rifaximin or eluxadoline prescription were identified in the IQVIA PharMetrics® Plus database (10/01/2015-12/31/2021) and classified into two mutually exclusive cohorts (i.e., rifaximin and eluxadoline). Index date was the date of rifaximin or eluxadoline initiation. Entropy-balanced baseline characteristics, TFI (periods of ≥ 30 consecutive days without IBS-D treatment), and healthcare costs were reported. Healthcare costs were compared between cohorts using mean cost differences. RESULTS: There were 7094 and 2161 patients in the rifaximin and eluxadoline cohorts, respectively. After balancing, baseline characteristics (mean age 44.1 years; female 72.4%) were similar between cohorts. A higher proportion of patients treated with rifaximin achieved a TFI of ≥ 30 days (76.2% vs. 66.7%), ≥ 60 days (67.0% vs. 47.0%), ≥ 90 days (61.0% vs. 38.7%), ≥ 180 days (51.7% vs. 31.0%), and ≥ 240 days (47.7% vs. 27.9%) compared to eluxadoline. Among patients with a TFI ≥ 30 days, mean TFI durations were 8.3 and 6.0 months for the rifaximin and eluxadoline cohorts. Mean all-cause healthcare costs were lower for rifaximin vs. eluxadoline ($18,316 vs. $23,437; p = 0.008), primarily driven by pharmacy costs ($7348 vs. $10,250; p < 0.001). In a simulated health plan of one million commercially insured lives, initiating 50% of patients on rifaximin instead of eluxadoline resulted in total cost savings of $2.1 million per year or $0.18 per-member-per-month. CONCLUSIONS: This real-world study suggests that TFI is a meaningful surrogate measure of treatment effectiveness in IBS-D. Patients treated with rifaximin had longer treatment-free periods and lower healthcare costs than patients treated with eluxadoline.

Pharmacokinetic considerations for drugs that treat diarrhea-predominant irritable bowel syndrome: what's new?

INTRODUCTION: Irritable bowel syndrome (IBS), which presents a significant healthcare and socioeconomic burden, is one of the main issues in the field of therapy. Hence, it is imperative to tackle this matter by evaluating the safety and efficacy of the available treatments and determining the ideal approach for each patient. AREAS COVERED: We reviewed the pharmacokinetics and safety of pharmacologic interventions administered in diarrhea-predominant IBS (IBS-D) patients. PubMed, Google Scholar and the USFDA databases were searched up to November 2023 to include all updated information on eluxadoline, alosetron, and rifaximin. EXPERT OPINION: The most effective way to treat IBS-D is to focus on managing the most common symptoms. However, healthcare providers face a challenge when it comes to identifying the right treatment for each patient, and the root cause of this is the diversity of IBS-D population. Studies have shown that there are differences in how men and women metabolize drugs, which may lead to gender-specific adverse reactions. Women tend to have higher drug concentrations in their bloodstream and take longer to eliminate them. Therefore, healthcare providers may need to reduce the dosage for female patients. Integrating IBS care into sustainable development efforts can indirectly contribute to achieving SDGs and promote health and well-being for all.

Chang-Kang-Fang alleviates diarrhea predominant irritable bowel syndrome (IBS-D) through inhibiting TLR4/NF-κB/NLRP3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Chang-Kang-Fang (CKF), originated from traditional Chinese medicine (TCM) formulas, has been utilized to treat diarrhea predominant irritable bowel syndrome (IBS-D) based on clinical experience. However, the underlying mechanism of CKF for treating IBS-D remains unclear and need further clarification. AIM OF THE STUDY: The objective of this present investigation was to validate the efficacy of CKF on IBS-D model rats and to uncover its potential mechanism for the treatment of IBS-D. MATERIALS AND METHODS: We first established the IBS-D rat model through neonatal maternal separation (NMS) in combination with restraint stress (RS) and the administration of senna decoction via gavage. To confirm the therapeutic effect of CKF on treating IBS-D, abdominal withdrawal reflex (AWR) scores, the quantity of fecal pellets, and the fecal water content (FWC) were measured to evaluate the influence of CKF on visceral hypersensitivity and the severity of diarrhea symptom after the intragastric administration of CKF for 14 days. Subsequently, enzyme linked immunosorbent assay (ELISA) was applied to assess the effect of CKF on neuropeptides substance P (SP) and 5-hydroxytryptamine (5-HT), as well as inflammatory cytokines in serum and in intestinal tissues. Further, colonic pathological changes, the amount of colonic mast cells, and the expression level of occludin in rat colon tissues, were investigated by hematoxylin-eosin (HE) staining, toluidine blue staining, and immunohistochemistry, respectively. To explore the underlying mechanisms, alterations in colonic RNA transcriptomics for the normal, model, and CKF treatment groups were assessed using RNA sequencing (RNA-Seq). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunofluorescence (IF) assays were applied to validate the effect of CKF on predicted pathways in vivo and in vitro. In addition, to elucidate the potential active compounds in CKF, 11 representative components found in CKF were selected, and their anti-inflammation potentials were evaluated using LPS-treated RAW264.7 cell models. RESULTS: CKF treatment significantly reduced the number of fecal pellets, attenuated visceral hypersensitivity, and decreased 5-HT and SP concentrations in serum and colon tissues, along with a reduction in colonic mast cell counts, correlating with improved symptoms in IBS-D rats. Meanwhile, CKF treatment reduced the colonic inflammatory cell infiltration, lowered the levels of IL-6, TNF-α, and IL-1ß in serum and colon tissues, and increased the occludin protein expression in colon tissues to improve inflammatory response and colonic barrier function. RNA-Seq, in conjugation with our previous network pharmacology analysis, indicated that CKF might mitigate the symptoms of IBS-D rats by inhibiting the Toll like receptor 4/Nuclear factor kappa-B/NLR family pyrin domain-containing protein 3 (TLR4/NF-κB/NLRP3) pathway, which was confirmed by WB, IF, and qRT-PCR experiments in vivo and in vitro. Furthermore, coptisine, berberine, hyperoside, epicatechin, and gallic acid present in CKF emerged as potential active components for treating IBS-D, as they demonstrated in vitro anti-inflammatory effects. CONCLUSION: Our findings demonstrate that CKF effectively improves the symptoms of IBS-D rats, potentially through the inhibition of the TLR4/NF-κB/NLRP3 pathway. Moreover, this study unveils the potential bioactive components in CKF that could be applied in the treatment of IBS-D.

Mechanisms and emerging strategies for irinotecan-induced diarrhea.

Irinotecan (also known as CPT-11) is a topoisomerase I inhibitor first approved for clinical use as an anticancer agent in 1996. Over the past more than two decades, it has been widely used for combination regimens to treat various malignancies, especially in gastrointestinal and lung cancers. However, severe dose-limiting toxicities, especially gastrointestinal toxicity such as late-onset diarrhea, were frequently observed in irinotecan-based therapy, thus largely limiting the clinical application of this agent. Current knowledge regarding the pathogenesis of irinotecan-induced diarrhea is characterized by the complicated metabolism of irinotecan to its active metabolite SN-38 and inactive metabolite SN-38G. A series of enzymes and transporters were involved in these metabolic processes, including UGT1A1 and CYP3A4. Genetic polymorphisms of these metabolizing enzymes were significantly associated with the occurrence of irinotecan-induced diarrhea. Recent discoveries and progress made on the detailed mechanisms enable the identification of potential biomarkers for predicting diarrhea and as such guiding the proper patient selection with a better range of tolerant dosages. In this review, we introduce the metabolic process of irinotecan and describe the pathogenic mechanisms underlying irinotecan-induced diarrhea. Based on the mechanisms, we further outline the potential biomarkers for predicting the severity of diarrhea. Finally, based on the current experimental evidence in preclinical and clinical studies, we discuss and prospect the current and emerging strategies for the prevention of irinotecan-induced diarrhea.

Milk-derived Lactobacillus with high production of short-chain fatty acids relieves antibiotic-induced diarrhea in mice.

Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, and this has warranted research into alternative protocols. In this study, we investigated the potential therapeutic effects of three cohorts, Lactobacillus plantarum KLDS 1.0386, Lactobacillus acidophilus KLDS 1.0901 and a mixed strain of both, on intestinal inflammation, the intestinal mucosal barrier, and microbial community in mice with ampicillin-induced diarrhea. The results showed that Lactobacillus inhibited the activation of the TLR4/NF-κB signaling pathway, decreased the expression of pro-inflammatory cytokines, increased the expression of anti-inflammatory cytokines in the murine intestine, and alleviated the intestinal barrier damage and inflammation induced by ampicillin. In addition, Lactobacillus ameliorates intestinal epithelial barrier damage by increasing the expression of tight junction proteins and aquaporins. After Lactobacillus treatment, the diversity of gut microbiota increased significantly, and the composition and function of gut microbiota gradually recovered. In the gut microbiota, Bacteroidetes and Escherichia Shigella related to the synthesis of short-chain fatty acids (SCFAs) were significantly affected by ampicillin, while Lactobacillus regulates the cascade of the microbial-SCFA signaling pathway, which greatly promoted the generation of SCFAs. Collectively, Lactobacillus showed better results in treating AAD, especially in mixed strains.

Macleaya cordata extract improves growth performance, immune responses and anti-inflammatory capacity in neonatal piglets.

Macleaya cordata was a kind of traditional herbal medicine, which may a potential substitute for antibiotics. However, the effects of Macleaya cordata on neonatal piglets have rarely been reported. In this study, three groups were designed, including normal saline (Control group, CON), 8 mg/mL Macleaya cordata extract (MCE group, MCE) and 5 mg/mL Chlortetracycline Hydrochloride (CCH group, CCH), to investigate the effects of MCE on growth performance, blood parameters, inflammatory cytokines, regenerating islet-derived 3 gamma (REG3γ) expression and the transcriptomes of neonatal piglets. The results showed that, compared with the control group, MCE significantly increased the average daily gain (p < 0.01); spleen index (p < 0.05) contents of IL-10, TGF-ß, IgG in serum and sIgA in the ileum mucus of neonatal piglets at 7 d and 21 d (p < 0.01). The diarrhoea incidence and serum TNF-α and IFN-γ contents of neonatal piglets at 7 d and 21 d were significantly decreased (p < 0.01). In addition, MCE significantly increased the mRNA expression of TGF-ß, IL-10, and REG3γ (p < 0.01) and significantly decreased the mRNA expression of IL-33, TNF-α and IFN-γ in the ileal mucosa of neonatal piglets at 21 d (p < 0.01). The differentially expressed genes and the signal pathways, related to cytokine generation and regulation, immunoregulation and inflammation were identified. In conclusion, MCE can significantly improve growth performance, reduce diarrhoea incidence, relieve inflammation, improve immune function, and improve disease resistance in neonatal piglets. MCE can be used as a potential substitute for antibiotics in neonatal piglets.