Relief Of Constipation Research Articles

Probiotic SYNBIO® Blend’s Impact on Constipation in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aims: Research on probiotics for constipation management is still growing, and plays a crucial role in the definition of a management strategy for bowel wellbeing, constipation, and related outcomes. The present systematic review and meta-analysis of the beneficial effects of the SYNBIO® blend, to consolidate the data from various clinical trials, was conducted. Methods: A literature search using PubMed, Web of Science, and Google Scholar databases was conducted. The search was limited to clinical trials that used the SYNBIO® blend, either as dietary supplements or probiotic-enriched foods. Independently, two reviewers evaluated the trial’s quality and extracted all data. A 95% confidence interval (CI) of a weighted mean difference (MD) was used to pool continuous data. For the analysis, Review Manager version 5.4 was used. Results: Seven clinical trials involving a total of 1095 subjects were included in the analysis. Overall, the SYNBIO® blend significantly improved constipation relief by 0.75 (95% CI: 0.31 to 1.19; p = 0.0008) in 52% of the subjects, and significantly increased intestinal regularity by 1.90 compared to the placebo (95% CI: 1.02 to 2.78; p < 0.0001) in more than 60% of individuals. No adverse events were reported. Conclusions: The SYNBIO® blend was found to significantly improve overall constipation, intestinal regularity, abdominal pain, and intestinal cramping. This suggests that people with these specific symptoms could benefit from this probiotic combination.

Real World Evidence of User Experience with Microenemas for Relief of Constipation.

Constipation is a commonly reported gastrointestinal complaint. Research on this widespread condition focuses mainly on clinical trials for chronic constipation with less emphasis on patient experience and nonchronic situations. Sufferers report that constipation interferes with daily activities and quality of life. It is likely that this is common among all sufferers of constipation, regardless of how often the condition is experienced. This work explored attitudes and perceptions of people who experience occasional constipation and self-treat with over the counter products, particularly Microlax® microenemas. In this retrospective study, real-world data were collected from 1635 respondents from France and Russia who experienced occasional constipation. Participants completed a questionnaire about their experiences with occasional (not chronic) constipation and perceptions of over the counter treatments of oral laxatives, suppositories, and Microlax microenemas. Questions focused on comfort, quality of life, ease of use, and reliability of these treatments. Participants had used the microenema for treatment of occasional constipation within 3 months of study participation. Occasional constipation was based on the Rome IV diagnostic criteria for adults and babies. Data were analyzed across the total population of all groups, then by subgroup. Success criteria were defined as of at least 70% agreement with the statements scoring ≥ 7 on the scale of 0-10. The proportion of respondents agreeing with the individual statements was calculated using the denominator for the total sample within each group. This study shows that experiencing even occasional bouts of constipation negatively affect quality of life and well-being. Participants (women aged 25-54 years, older men, and women aged 60-80 years) reported that it severely limited daily life and activities and caused negative emotions and embarrassment. Pregnant women and mothers with babies showed great concern that constipation indicated a serious and painful condition and was bad for their babies. Participants agreed that using Microlax microenema provided greater ease of use, comfort, reliability, and safety than oral laxatives and rectal suppositories. Sufferers of occasional constipation report that these bouts interfere with their daily lives and reduce quality of life, similar to what is reported for those with chronic constipation based on existing literature. The microenema, Microlax, showed benefits in the relief of occasional constipation compared with oral laxatives and rectal suppositories. Trepidation about using the microenema, experienced before using it, was greatly reduced after the first and subsequent uses. Microlax microenema enabled users to regain the feeling of control and provided positive impacts on quality of life and well-being.

Formulation and Evaluation of Herbal Churna for Constipation

Formulation and evaluation of herbal churna for constipation. • Churna is a very famous ayurvedic medicine for constipation. It is a traditional ayurvedic medicine. • The goal of treatment relives the cause of constipation and to promote regular and predictable bowel movement. • Regulates bowel movement. • Relieves frequent and chronic constipation. • Helps to pass stool more smoothly. • churna is a very famous Ayurvedic medicine for constipation. It is not a traditional Ayurvedic medicine. • It is a proprietary Ayurvedic medicine. It means that the formula of Kayam churna is not mentioned in any Traditional Ayurvedic text books. • The manufacturer of Churna, Sheth Brothers, formulated a combination of few Ayurvedic herbs that benefit in constipation, blended them into powder form and labelled it as churna. • As the standardization of herbal formulation is great concern for its safety and efficacy for that reason this work is aimed to formulation comparative evaluation of churna with marketed product. Churna, a traditional Ayurvedic formulation, has been used for centuries to treat constipation. The powder, composed of a blend of natural herbs and ingredients, stimulates bowel movements, softens stools, and relieves straining during defecation. With its natural and safe composition, Churna offers a cost-effective and minimally invasive solution for managing constipation. These abstract reviews the ingredients, preparation, and pharmacological properties of Churna, highlighting its potential as a natural remedy for constipation relief..

Uses of Fecal Microbiota Transplantation in Neurodegenerative Disease: A Scoping Review.

Fecal microbiota transplantation (FMT) is the administration of fecal bacteria from a healthy donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition and confer a health benefit. The relationship between the gut microbiome and the central nervous system, termed the gut-brain axis, has been a frequent topic of gut microbiome studies. Commensal gut bacteria communicate with the central nervous system through various hormones, cytokines, and neural pathways. Therefore, influencing the gut microbiome via FMT may have the potential in treating symptoms of neurodegenerative conditions. This study aims to identify current uses of FMT in treating neurodegenerative diseases and highlight areas of future investigation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, a literature search was conducted of peer-reviewed sources on September 27, 2022, from Embase, MEDLINE, Web of Science, and Cochrane Central. Searchterms were utilized that were related to the application of FMT and neurodegenerative disorders and limited those human studies, those that were published in English, and those that were published between 2017 and 2022. The initial search yielded 450 unique articles, and after the assessment of the title and abstract for inclusion and exclusion criteria, six articles were identified for full-text review. Studies that focused on either Parkinson's disease (PD) or multiple sclerosis (MS) demonstrated improvements in both motor symptoms and non-motor symptoms. FMT was also shown to provide significant relief of constipation and general gastrointestinal (GI) symptoms in all conditions studied. The studies related to MS showed the most mixed results with regard to symptomatic improvement. The data on the use of FMT as a treatment for neurodegenerative disorders is limited; however, studies have shown not only improvement in GI symptoms but also improvement in the cognitive symptoms of PD and dementia. The data on FMT as a treatment to improve the motor symptoms of PD is both more complete and more compelling than the data on the motor symptoms of MS. The studies that were reviewed showed no major adverse effects of FMT and generally promising results. There is a strong case to be made for larger, more well-controlled studies to be done on FMT and its potential use as a treatment not only for GI symptoms but for the motor and cognitive symptoms of neurodegenerative diseases.

Effects of garlic-derived fructan and oligofructose mixtures on intestinal health and constipation relief in mice.

Garlic polysaccharides (GPs) constitute over 75% of the dry weight of garlic. They are characterized by fructan with a 2,1-β-d-Fruf backbone and 2,6-β-d-Fruf branches. Studies have suggested a role for GPs in regulating gut microbiota but whether they possess a comprehensive function in maintaining intestinal well-being and can serve as effective prebiotics remains unknown. To explore this, varied doses of GPs (1.25-5.0 g kg-1 body weight) and inulin (as a positive control) were administered to Kunming mice via gavage, and their effects on the intestinal epithelial, chemical, and biological barriers were assessed. A constipation model was also established using loperamide to investigate the potential effects of GPs on the relief of constipation. Administration of GPs significantly upregulated expression of tight-junction proteins and mucins in Kunming mouse small-intestine tissue. Garlic polysaccharides elevated cecal butyric acid content, reduced the abundance of Desulfobacterota, and decreased the ratio of Firmicutes to Bacteroidetes (the F/B ratio). Garlic polysaccharides also promoted the growth of Bacteroides acidifaciens and Clostridium saccharogumia. Tax4Fun functional predictions suggested the potential of GPs to prevent human diseases, reducing the risk of insulin resistance, infectious diseases, and drug resistance. Garlic polysaccharides also exhibited a beneficial effect in alleviating loperamide-induced constipation symptoms by enhancing small intestinal transit, softening stool consistency, accelerating bowel movements, and promoting the release of excitatory neurotransmitters. These findings highlight the important role of GPs in maintaining gut fitness by enhancing intestinal barrier function and peristalsis. Garlic polysaccharides are promising prebiotics, potentially contributing to overall intestinal well-being and health. © 2024 Society of Chemical Industry.

The preparation of synbiotic AHY relieving loperamide-induced constipation and its modulation mechanism in vivo

Constipation is a common intestinal disorder linked to an imbalance in the gut microbiota, which can be alleviated by synbiotics as a blend of probiotics and prebiotics. In this study, three strains of Lactiplantibacillus plantarum AHQ-14, HM22 and Y12, which have shown to have constipation-relieving ability, and four prebiotics including stachyose, galactooligosaccharides, isomaltooligosaccharide and fructooligosaccharides, were selected to design a synbiotic named AHY. Its intervention in vivo experiment using loperamide-induced constipated mice was performed. Relevant biochemical indexes, histological morphology, metabolites, constipation-related gene expression and intestinal flora of loperamide-induced constipated mice were investigated to elucidate the potential mechanism for AHY relieving constipation. The results showed that AHY increased the abundance of the flora associated to short-chain fatty acids (SCFAs) and water pathway protein, such as Muribaculaceae and Prevotellaceae, thereby the content of propionic acid and isovaleric acid were increased by 56.8% and 20%, respectively, and the expression of water pathway protein genes was significantly down-regulated. It was also found that AHY significantly increased the serum levels of excitatory gastrointestinal regulatory peptides GAS and MTL, and decreased the levels of inhibitory gastrointestinal regulatory peptide VIP and oxidative stress indicators MDA and NO in constipated mice. Furthermore, it significantly increased the fecal water content and gastrointestinal motility, and restored the colonic damage, thus alleviating the symptoms of constipation. These findings suggest AHY has the potential used as a promising functional synbiotic for constipation relief.

A quality improvement program for managing clozapine-induced constipation in a long-term structured residential setting for persons with serious mental illness

ObjectivesThe goal of this quality improvement project (QIP) was to increase awareness of the serious medical consequences of clozapine-associated constipation to front line nursing staff and patients with schizophrenia. MethodsThe QIP was developed iteratively by psychiatric nurses, psychiatrists and pharmacists with input from patients. The processes involved a literature review, development of educational materials for staff and patients, and the creation of a daily bowel movements log (BML). Implementation involved review of the BML at treatment team meetings, and deployment of pharmacological and non-pharmacological interventions to resolve constipation and increase awareness and knowledge of this clinical concern. OutcomesThe initial pilot screened for symptoms of constipation in patients receiving clozapine and non-clozapine antipsychotic agents and intervening as necessary during multidisciplinary team meetings. Patients benefited from relief of constipation and improved bowel habits. Staff benefited from improved knowledge and making requisite changes in workflow and practice. Feedback allowed refinements to be made to the educational materials for patients and staff. Since full implementation, bowel habits are routinely monitored, and interventions are reviewed for effectiveness. Staff satisfaction with this QIP is reflected in answers to a structured questionnaire and in patient reports (n = 50). ConclusionsClozapine, the only approved and efficacious medication for treatment-resistant schizophrenia is significantly underutilized. Medically consequential constipation can be a serious barrier to retention of patients benefiting from clozapine.Increased awareness and use of educational materials for patients and staff, routine monitoring of bowel habits combined with pharmacological and non-pharmacological interventions can successfully address this clinical problem.

Evaluating the Efficacy and Safety Profile of Good Morning™ Constipation Drops in a Loperamide-Induced Rat Model

Introduction: Constipation is a prevalent gastrointestinal condition globally, often managed with conventional laxatives that may cause side effects and dependency. Homeopathy, offering a holistic approach through diluted natural substances, aims to stimulate the body's self-healing mechanism. This study evaluates Good Morning™ drops, an innovative homeopathic formulation designed to safely and effectively manage constipation. Using a rat model of Loperamide-induced constipation, we evaluated its safety and efficacy, unveiling promising results.Materials and Methods: A rat model of Loperamide induced constipation was utilized to assess the efficacy and safety of Good Morning™ Constipation Drops. 3 unique formulations were prepared and employed to the animal model in 3 different doses. 72 rats were randomly assigned to 12 groups (3 control groups plus 3 formulations in 3 different doses totalling 9 groups), receiving specific variants or control treatments over the period of 21 days. Parameters including body weight, water intake, stool count, intestinal function, haematology, bleeding and clotting time, blood biochemistry, and organ weight were evaluated. Results and discussion: The results showed that all homeopathic formulations, particularly Variant 2, exhibited significant effects in Loperamide induced constipated rats. Across various parameters, Variant 2 consistently influenced food intake, stool characteristics, and small intestine motility. Safety assessments indicated overall well-being, withVariant 2 demonstrating superior survival outcomes. These findings position Variant 2 as a promising candidate for constipation management, emphasizing its consistent efficacy and safety in the rat model. Conclusion: In conclusion, Good Morning™ Constipation Drops exhibited a promising blend of safety, efficacy, and a multifaceted mechanism of action. The formulation, rich in botanical ingredients, demonstrates high safety with favorable survival rates. Efficacy is evident in improved stool counts, stool weights, Small Intestine Transition percentages, and impacts on lipid profiles and liver enzymes, highlighting its potential as a comprehensive solution for constipation relief.

Ligilactobacillus acidipiscis YJ5 modulates the gut microbiota and produces beneficial metabolites to relieve constipation by enhancing the mucosal barrier.

Constipation is a prevalent gastrointestinal (GI) problem affecting a large number of individuals. This study aimed to investigate peristalsis-promoting potential characteristics of Ligilactobacillus acidipiscis YJ5 and the underlying molecular mechanism. The study demonstrated the relieving effect of L. acidipiscis YJ5 on constipation in both zebrafish and mouse models. L. acidipiscis YJ5 intervention significantly increased intestinal peristalsis by reducing the peak time and increasing the fluorescence disappearance rate in the zebrafish model. In the mouse model, the symptoms of constipation relief induced by L. acidipiscis YJ5 included a shortened first black stool time, an increased number of defecation particles, an accelerated propulsion rate of the small intestine, and an increase in fecal water content. L. acidipiscis YJ5 was found to reduce the expression of colonic aquaporins to normalize the colonic water transport system of constipated mice. Additionally, L. acidipiscis YJ5 reversed loperamide-induced morphological damage in the ileum and colon and increased the colonic mucosal barrier. The results of the 16S rRNA gene analysis indicated that L. acidipiscis YJ5 could reverse the structure of gut microbiota to a near-normal group, including levels of β-diversity, phylum, family, and genus. Furthermore, the fermentation supernatant of L. acidipiscis YJ5 was shown to relieve constipation, and metabolomics analysis revealed that these positive effects were related to its metabolites like malic acid and heliangin.

Clinical impact of a multifaceted intervention aimed at decreasing distress in people living with dementia: evaluating the Reconnect program.

To better meet the needs of people living with advanced dementia, Orchard Care Homes, United Kingdom have established an enhanced person focused program, namely the Reconnect program, which provides an enriched psycho-social care to enhance peoples' quality of life and well-being. Here we aimed to review the impact of this program on people living with dementia. In this study the implementation of the Reconnect program was evaluated for two six-month periods (April-September 2020 and April-September 2021). The focus of this evaluation was on three key interventions: increasing meaningful occupation and engagement; improving pain identification and management, and reducing constipation. The Reconnect program was conducted in a single for-profit care home. It involved residents with complex dementia needs who previously not responded to support in alternative settings or found previous care ineffective in relieving their distress and reducing risks they pose to themselves or others. A total of 24 people participated in the program during this evaluation. We observed a substantial increase in engagement in meaningful activity per person, including an increase of outdoor access to fresh air. Pain management improved as evidenced by more standardized pain assessments using the PainChek system and coverage of people with either regular and/or "when required" pain management. Constipation relief also improved. For the two comparison periods, distress responses per resident reduced from 14.5 to 10.6 events and use of regular pain relief increased from 21.7 to 48.1%. Use of "when required" benzodiazepine halved from 6 months average of 46 to 23.2 doses given. Benzodiazepine dose reductions increased from 13.3 to 31.8%, while cessations increased from 20 to 50%. We also observed a reduction from 76.3 to 56.3% in antipsychotic use. Their dose reductions increased from 8.3 to 40% and drug cessation was made in 30% of people using antipsychotics (compared to the first period in which no medication cessation was observed). A 91.7% reduction (i.e., from 36 to 3 events) in safeguarding events related to behaviors was also observed. Introduction of the Reconnect program, through its interventions focused on meaningful activity engagement, pain management and constipation relief resulted in substantial improvements related to people's distress, safeguarding and psychotropic use.

The probiotic fermented milk of Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 alleviates constipation via improving gastrointestinal motility and gut microbiota

Constipation is directly related to the intestinal microenvironment, in which the promotion of gastrointestinal (GI) motility and improvement of gut microbiota distribution are important for alleviating symptoms. Herein, after the intervention of probiotic fermented milk (FMMIX) containing Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 for 14 d in Kunming mice with loperamide-induced constipation, the results indicated that FMMIX significantly increased the secretion of serum motilin, gastrin and 5-hydroxytryptamine, as well as decreased the secretion of peptide YY, vasoactive intestinal peptide, and nitric oxide in mice. As determined by immunohistochemical analysis, FMMIX promoted an augmentation in the quantity of Cajal interstitial cells. In addition, the mRNA and protein expression of c-kit and stem cell factor (SCF) were upregulated to facilitate intestinal motility. High-throughput sequencing and gas chromatography techniques revealed that FMMIX led to an increase in the relative abundance of beneficial bacteria (Lactobacillus, Oscillospira, Ruminococcus, Coprococcus, and Akkermansia), reduced the presence of harmful bacteria (Prevotella), and resulted in elevated levels of short-chain fatty acids (SCFA) with a superior improvement compared with unfermented milk. Untargeted metabolomics revealed significant upregulation of functional metabolites such as l-pipecolinic acid, dl-phenylalanine, and naringenin in FMMIX, presumably playing a potential role in constipation relief. Overall, our results showed that FMMIX had the potential to alleviate constipation symptoms in mice by improving the secretion of serum GI regulatory peptides and neurotransmitters, increasing the expression of c-kit and SCF proteins, and modulating the gut microbiota structure and SCFA levels, and may be associated with an increase in these functional metabolites. This suggested that FMMIX could be a promising adjunctive strategy for managing constipation symptoms and could contribute to the development of functional foods aimed at improving gut health.

Combination of galacto-oligosaccharides and wheat peptides synergistically relieved constipation via regulating water transport, gut barrier, inflammation and gut microbiota

Constipation is a common gastrointestinal problem. This study aimed to identify a combination of prebiotics and wheat peptides (WP) to promote intestinal peristalsis and explore the underlying mechanism. First, we screened four prebiotics (galacto-oligosaccharides (GOS), fructose oligosaccharides (FOS), inulin (IN), and resistant dextrin (RD)) using a zebrafish model and found that GOS was the most synergistic with WP. We then tested the GOS-WP combination in a mouse model of loperamide (Lop)-induced constipation and found that it significantly improved constipation symptoms. Specifically, GOS-WP shortened the first black stool time, increased the number of defecation particles, accelerated small intestinal propulsion rate, and increased fecal water content. GOS-WP also normalized the colonic water transport system by inhibiting colonic AQP4/8 expression. Additionally, GOS-WP reversed Lop-induced morphological damage in the ileum and colon, increased colonic barrier, and reduced inflammation in mice. Furthermore, 16S rRNA gene sequence analysis showed that GOS-WP reversed the gut microbiota structure changes induced by Lop. GOS-WP significantly increased butyric acid and decreased BCFA levels, indicating improved gut health. Our findings suggest that the GOS-WP combination has potential as a novel intervention for constipation relief. This study highlights the potential of combining prebiotics and WP as a therapeutic strategy for constipation.

Time-dependent laxative effect of sennoside A, the core functional component of rhubarb, is attributed to gut microbiota and aquaporins.

Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). Based on a mouse constipation model, 2.6mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

Experiences of persons with multiple sclerosis of a collaborative care programme: A qualitative study.

This study aimed to explain the experiences of individuals with multiple sclerosis (MS) about the collaborative care programme. This qualitative study was conducted from July 2021 to March 2022. We conducted this study with individuals with MS who participated in the collaborative care programme in Hamadan, Iran. A purposive sampling with maximum variety was applied to recruit patients until data saturation. Eventually, 18 patients consented and were interviewed using a semi-structured interview guide. The transcriptions of audio-checked interviews were analysed using a conventional content analysis approach of Graneheim and Lundman by MAXQDA 10, 2010 edition. The study identified three main categories. that emerged from the participants' experiences of collaborative care: the 'Beginning of Communication', which included two subcategories, 'Introduction and Acquaintance with Each Other' and 'Formation of Trust'; 'Mutual Interaction', which included three subcategories, 'Dialogue', 'Mutual Goal Setting' and 'Mutual Agreement of Care Solutions'; and 'Exchange of Targeted Behaviors', which included six categories, Implementation of Strategies for 'Nutritional Behaviors', 'Sleep and Rest', 'Constipation Relief', 'Promotion of Physical Activity and Exercise', 'Fatigue Reduction' and 'Stress Management'. The findings highlight the statistically significant role of collaborative care in MS management. Utilizing these research findings can update the development of interventions based on collaborative care, which can provide appropriate support to individuals with MS. Individuals with multiple sclerosis.

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial

ABSTRACT Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95–1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884.

Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study

Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients’ quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects’ gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.

Naloxegol (Movantik®) Provides Rapid Response and Sustained Improvement of Opioid-Induced Constipation Symptoms in Older Adults

Naloxegol (Movantik®), an oral peripherally acting mu-opioid receptor antagonist (PAMORA) has demonstrated rapid and predictable relief of OIC in patients treated with opioids for chronic non-cancer pain in two phase 3 trials (KODIAC 4/5; NCT01309841/NCT01323790). In subjects ≥65 yrs, naloxegol (25mg, 12.5mg) demonstrated significantly better response rates, clinically relevant early symptom relief, and predictable efficacy compared with PBO. Improvements in SBMs, CSBMs, straining, and stool consistency were rapid and sustained across 12 weeks. Naloxegol is effective and safe in individuals ≥65 yrs with non-cancer pain experiencing OIC.Aim: Naloxegol, an oral peripherally acting mu-opioid receptor antagonist (PAMORA) has demonstrated rapid and predictable relief of opioid-induced constipation (OIC) in patients treated with opioids for chronic non-cancer pain in two phase 3 trials (KODIAC 4/5; NCT01309841/NCT01323790). This analysis evaluates the speed and predictability of response, and the rapid and sustained impact of naloxegol on OIC symptoms in subjects aged ≥65 yrs. Methods: Data were pooled from the KODIAC 4/5 intent-to-treat populations (N=1337). Subjects ≥65 yrs treated once daily with naloxegol 25mg, 12.5mg, or placebo (PBO) were evaluated. Response definition: ≥3 SBM/wk and increase of ≥1 SBM/wk over baseline for ≥9 of 12 weeks, and ≥3 of the final 4 weeks. For each SBM, patients documented complete evacuation (CSBM) (Yes/No), degree of straining (scale 1=not at all, 5=extreme), and stool consistency via the Bristol Stool Scale (1=hard, 7=watery). Results: This analysis evaluated 148 subjects ≥65 yrs (11.1% of the overall population). In these older adults, a significantly higher response rate was achieved with naloxegol (25mg, 50.9%, p=0.037; 12.5mg, 53.3%; p=0.036) vs PBO (32.0%). Corresponding HRs (2.52, p< 0.001; 1.90, p=0.005) indicated significant, ∼two-fold reduction in time to first SBM with naloxegol vs PBO. Time to first CSBM was ∼50% shorter for naloxegol vs PBO for both regimens (Hazard Ratios: 1.66, p=0.019; 1.45, p=0.103). Rapid, statistically significant, and clinically relevant symptom improvement (straining and stool consistency) was generally sustained from weeks 1-12 for naloxegol vs PBO. The most common AEs were GI-related and similar across regimens. Conclusion: In subjects ≥65 yrs, naloxegol (25mg, 12.5mg) demonstrated significantly better response rates, clinically relevant early symptom relief, and predictable efficacy compared with PBO. Improvements in SBMs, CSBMs, straining, and stool consistency were rapid and sustained across 12 weeks. Naloxegol is effective and safe in individuals ≥65 yrs with non-cancer pain experiencing OIC.

Naloxegol (Movantik®) Provides Rapid and Sustained Improvement of Opioid-Induced Constipation Symptoms Irrespective of Opioid Dose

AimNaloxegol (Movantik), an oral peripherally acting mu-opioid receptor antagonist has demonstrated rapid relief of opioid-induced constipation (OIC) in patients with chronic non-cancer pain in two phase 3 trials (KODIAC 4/5; NCT01309841/NCT01323790). This analysis aims to characterize the OIC symptom burden and evaluate the efficacy of naloxegol in treating symptoms of OIC based on daily opioid dosages. This is the first naloxegol analysis based on a lower opioid dose cutoff of 100 MEU/day. MethodsData were pooled from the KODIAC 4/5 intent-to-treat populations (N=1337). Subjects treated with placebo (PBO) and naloxegol (12.5mg, 25mg) QD were evaluated based on opioid dose ranges (lower dose, ≤100mg; higher dose, >100mg MEU/day). OIC symptoms assessed include number of spontaneous bowel movements (SBM/wk), complete evacuation (CSBM), straining (scale 1=not at all, 5=extreme) and stool consistency (Bristol Stool Scale: 1=hard, 7=watery). ResultsBaseline OIC symptom burden (SBM/wk, CSBM/wk, straining, stool consistency) was similar between lower (n=764) and higher (n=567) opioid dose subgroups. Naloxegol (12.5mg, 25mg) provided significant improvement vs PBO in SBMs/wk in the lower and higher opioid dose subgroups; ≤100 MEU (mean SBM/wk: 2.41, 2.91 vs 1.99, respectively; p<0.05) and ˃100 MEU (mean SBM/wk: 2.81, 3.53 vs 2.05, respectively; p< 0.05). A significant improvement in CSBMs/wk vs PBO was demonstrated in the lower dose subgroup for naloxegol 25mg (mean CSBM/wk: 1.48, 1.97 vs 1.38; p=0.54 and p<0.05, respectively) and in the higher dose subgroup for both naloxegol regimens (mean CSBM/wk: 1.90, 2.36 vs 1.20, respectively; p<0.05). In both dose subgroups, rapid symptom improvement in SBM, CSBM and stool consistency were seen within the first week with naloxegol (p<0.05). ConclusionsRegardless of opioid dose, naloxegol (12.5mg, 25mg) provided rapid and sustained improvement of clinically relevant OIC symptoms. These data suggest that all patients should routinely be assessed for OIC, as lower opioid doses often induce constipation.

The effect of kiwi berry (&lt;i&gt;Actinidia arguta&lt;/i&gt;) on preventing and alleviating loperamide-induced constipation

This research aimed to study the preventive and relieving outcomes of kiwi berry on constipation. The administration of kiwi berries to mice resulted in a significant increase in body weight gain of 148.2% compared to mice that were constipated. The number of stools and the water content of stools both increased by 138.5% and 106.5%, respectively. The gastrointestinal transit rate increased by 45.3%, and the time it took for the first dark stool to form decreased by 57.5%. The levels of the excitability neurotransmitters were found to be higher in the group that had been given kiwi berries in comparison to the group that had been given loperamide. The opposite results were produced by vasoactive intestinal peptide (VIP) and aquaporin-3 (AQP3). In addition, kiwi berry consumption may lessen epithelial cell apoptosis and promote colon health. All the results point to kiwi berries as an extremely promising food supplement for the prevention and relief of constipation in the future since they successfully prevent and alleviate constipation brought on by loperamide.

Apple juice relieves loperamide-induced constipation in rats by downregulating the intestinal apical sodium-dependent bile acid transporter ASBT.

Apples are known to exhibit various beneficial effects on human health. In the present study, we investigated the effect of continuous intake of apple juice (AJ) on constipation status. A single dose of loperamide in rats as the constipation model markedly decreased the weight and number of fecal pellets compared to saline-administered rats as a control. After the administration of AJ twice a day for seven days, recovery of defecation close to that of the control was observed in loperamide-treated rats. In addition, the total bile acid content in the feces increased from day 4 after the administration of AJ. Among hepatic and intestinal transporters and enzymes that regulate bile acids, the mRNA expression of the apical sodium-dependent bile acid transporter (Asbt, slc10a2) was decreased by AJ in rats. Furthermore, the Asbt-mediated bile acid transport activity in the rat ileum decreased after AJ administration. Moreover, in human colonic cancer-derived Caco-2 cells, AJ exposure for 24 and 48 h decreased the expressions of ASBT mRNA and protein, and the uptake activity of taurocholic acid in both 7- and 21-d cultures. Several components of AJ, such as procyanidins, decreased the expression of ASBT in Caco-2 cells. In conclusion, ASBT downregulation is a possible mechanism responsible for the constipation-relieving effect of apples, and procyanidins may play a role in downregulating ASBT, which leads to the beneficial effects of apples against constipation. Although it is generally agreed that the common dietary compositions play a role in constipation relief, the novel specific mechanism of apples found in this study would facilitate understanding food functions.