Loperamide-induced Constipation Research Articles

Bifidobacterium longum S3 alleviates loperamide-induced constipation by modulating intestinal acetic acid and stearic acid levels in mice.

Constipation is a major gastrointestinal (GI) symptom worldwide, with diverse causes of formation, and requires effective and safe therapeutic measures. In the present study, we used loperamide hydrochloride to establish a constipation model and assessed the effect of Bifidobacterium on constipation and its possible mechanism of relief. The results showed that B. longum S3 exerted a constipation-relieving effect primarily by improving the gut microbiota, enriching genera including Lactobacillus, Alistipes, and Ruminococcaceae UCG-007, and decreasing the bacteria Lachnospiraceae NK4B4 group. These changes may thereby increase acetic acid and stearic acid (C18:0) levels, which significantly increase the expression levels of ZO-1 and MUC-2, repair intestinal barrier damage and reduce inflammation (IL-6). Furthermore, it also inhibited oxidative stress levels (SOD and CAT), decreased the expression of water channel proteins (AQP4 and AQP8), significantly elevated the Gas, 5-HT, PGE2, and Ach levels, and reduced nNOS and VIP levels to improve the intestinal luminal transit time and fecal water content. Collectively, these changes resulted in the alleviation of constipation.

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.

Preventive effect of kiwi berry (Actinidia arguta) on loperamide-induced constipation

Constipation is a common intestinal disease. Kiwi berries can effectively prevent constipation. However, studies have yet to be done to determine how kiwi berries prevent constipation. For 2 weeks, mice in this study were continually orally gavaged with kiwi berry, loperamide, or a combination of the two. This study found that the kiwi group's feces had more water than the constipated mice. In addition, kiwi berries can speed up gastrointestinal transit (GI), shorten the time it takes to pass the first dark stool, and dramatically enhance body weight gain. In the interstitial cells of Cajal (ICC) cells and colon tissues, alterations in the protein expression of vasoactive intestinal peptide (VIP), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and aquaporin-3 (AQP3) were found. At 3, 6, and 12 h of ICC cells and mouse colon, the kiwi group’s VIP, cAMP, PKA, and AQP3 protein expression levels were lower than those of the constipated mice. The kiwi berry can decrease the Firmicutes to Bacteroidetes ratio and boost the diversity and quantity of gut microbiota. By influencing the gut microbiota and VIP-cAMP-PKA-AQP3 signaling pathway, kiwi berries prevent constipation.

Different microbial ecological agents change the composition of intestinal microbiota and the levels of SCFAs in mice to alleviate loperamide-induced constipation.

Probiotics exert beneficial effects by regulating the intestinal microbiota, metabolism, immune function and other ways of their host. Patients with constipation, a common gastrointestinal disorder, experience disturbances in their intestinal microbiota. In the present study, we investigated the effectiveness of two microbial ecological agents (postbiotic extract PE0401 and a combination of postbiotic extract PE0401 and Lacticaseibacillus paracasei CCFM 2711) in regulating the makeup of the intestinal microbiota and alleviating loperamide hydrochloride-induced constipation in mice. We also preliminarily explored the mechanism underlying their effects. Both microbial ecological agents increased the abundance of the beneficial bacteria Lactobacilli and Bifidobacterium after administration and were able to relieve constipation. However, the degree of improvement in constipation symptoms varied depending on the makeup of the supplement. The postbiotic extract PE0401 increased peristalsis time and improved faecal properties throughout the intestinal tract of the host. PE0401 relieved constipation, possibly by modulating the levels of the constipation-related gastrointestinal regulatory transmitters mouse motilin, mouse vasoactive intestinal peptide, and 5-hydoxytryptamine in the intestinal tract of the host and by increasing the levels of the short-chain fatty acids (SCFAs) acetic acid, propionic acid, and isovaleric acid. It also increased the relative abundance of Lactobacillus and Bifidobacterium and reduced that of Faecalibaculum, Mucispirillum, Staphylococcus, and Lachnoclostridium, which are among the beneficial microbiota in the host intestine. Furthermore, PE0401 decreased the levels of constipation-induced host inflammatory factors. Therefore, the two microbial ecological agents can regulate the intestinal microbiota of constipation mice, and PE0401 has a stronger ability to relieve constipation.

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.

Hemp seeds attenuate loperamide-induced constipation in mice.

Constipation is a common gastrointestinal disease that seriously affects human physical and mental health. Studies have reported that hemp seeds can improve constipation, however the specific mechanism is still unclear. This study investigates that hemp seed (HS) and its water-ethanol extract (HSE) attenuates loperamide-induced constipation in mice. The research results show that: the fecal water content and small intestinal transit rate of mice in the hemp seed group and hemp seed hydroalcoholic extract group were significantly increased compared with MC group, and the first red feces defecation time was significantly shortened; HS and HSE significantly influence serum levels of Gastrin (Gas), motilin (MTL), substance P (SP), and endothelin (ET), potentially mediating their effects on gastrointestinal motility. HS and HSE can improve colon inflammation in constipated mice with H&E staining. Compared with the model of constipation group, the content of short-chain fatty acids in the HS group and HSE group increased significantly. Gut microbiome studies have shown that the structure and abundance of intestinal flora are altered. HS and HSE changed the abundance of Odoribacter, Bacteroide, Lactobacillus and Prevotella. Together, these results suggest that HS have the potential to stimulate the proliferation of beneficial gut microbes and promote intestinal motility, thereby improving gut health and relieving symptoms of constipation.

Blending Three Probiotics Alleviates Loperamide-Induced Constipation in Sprague-Dawley (SD)-Rats.

BIOVITA 3 bacterial species (BIOVITA 3), a probiotic blend powder containing Clostridium butyricum IDCC 1301, Weizmannia coagulans IDCC 1201 and Bacillus subtilis IDCC 1101, has been used as a food ingredient for gut health. However, its efficacy in improving constipation has not been reported. Therefore, we aimed to investigate the functional effects of oral administration of BIOVITA 3 as well as its component strains alone (at 1.0×109 CFU/day) in Sprague-Dawley (SD) rats with loperamide-induced constipation. The study included fecal analysis, gastrointestinal transit ratio, histopathological analysis, short chain fatty acids (SCFAs), and metagenome analysis. As results, the BIOVITA 3 group showed significant improvements in fecal number, water content, gastrointestinal transit ratio, and thickening of the mucosal layer. In the SCFAs analysis, all probiotic-treated groups showed an increase in total SCFAs compared to the loperamide-constipated group. Changes in microbial abundance and the diversity index of three groups (normal, constipated, and BIOVITA 3) were also defined. Of these, the BIOVITA 3 showed a significant improvement in loperamide-constipated SD-rats. This study suggests the possibility that BIOVITA 3 can be applied as an ingredient in functional foods to relieve constipation.

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.

Coadministration of Lactulose with Probiotics Ameliorates Loperamide-Induced Constipation in Mice.

We evaluated the efficacy of mixtures of lactulose with probiotic strains to ameliorate constipation and to identify suitable probiotic strains. Constipation was induced in Institute of Cancer Research mice (6-week-old, male) by the administering loperamide (5 mg/kg, twice a day) orally for 5 days, whereas the control group was not treated. To evaluate the laxative effects of the lactulose-probiotic and lactulose-magnesium hydroxide mixtures, fecal parameters, the gastrointestinal (GI) transit ratio, and fecal short-chain fatty acid (SCFA) content were analyzed. The administration of lactulose and Bacillus licheniformis or Saccharomyces boulardii significantly improved stool number and water content, which were reduced by loperamide. The GI transit ratio was significantly increased compared with that of the control group. The combined administration of lactulose and probiotics (B. licheniformis or S. boulardii) increased total SCFA content, including that of acetate, more effectively compared with lactulose alone. Similarly, coadministration of lactulose and magnesium hydroxide improved the loperamide-induced changes in fecal parameters and GI transit as well as increased total SCFA content. Overall, the combination of lactulose and probiotics relieves the symptoms of constipation by increasing SCFA content and is more effective compared with lactulose alone.

The rhizomes of Atractylodes macrocephala relieve loperamide-induced constipation in rats by regulation of tryptophan metabolism

Ethnopharmacological relevanceConstipation is one of the most prevalent gastrointestinal tract diseases that seriously affects health-related quality of human life and requires effective treatments without side effect. The rhizome of Atractylodes macrocephala Koidz. (Compositae), called Atractylodes Macrocephala Rhizome (AMR), a commonly used traditional Chinese medicine, has been used to relieve the clinical symptoms of patients with constipation. Aim of the studyTo reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. Materials and methodsLoperamide-induced constipation rat model was established and the dose-dependent laxative effect of AMR was investigated. Untargeted metabolomics based on an UPLC-Q/TOF-MS technique combined with western blot analysis was used to explain the potential mechanism of AMR relieve loperamide-induced constipation in rats. ResultsThe results showed that medium dose of AMR (AMR-M, 4.32 g raw herb/kg) and high dose of AMR (AMR-H, 8.64 g raw herb/kg) treatments significantly increased the fecal water content, Bristol score, gastrointestinal transit rate, and recovered the damaged colon tissues of constipated rats, but low dose of AMR (AMR-L, 2.16 g raw herb/kg) did not show laxative effect. Both AMR-M and AMR-H treatments also remarkably reduced the serum levels of vasoactive intestinal peptide (VIP), somatostatin (SS) and dopamine (DA), and increased the levels of motilin (MTL), gastrin (GAS) and 5-hydroxytryptamine (5-HT). Urine metabolomics revealed that constipation development was mainly ascribed to the perturbed tryptophan metabolism, and AMR-M and AMR-H markedly corrected the abnormal levels of five urine tryptophan metabolites, namely 4,6-dihydroxyquinoline, indole, 4,8-dihydroxyquinoline, 5-hydroxytryptamine, and kynurenic acid. Additionally, western blot analysis confirmed that the abnormal expression of rate-limiting enzyme involving in tryptophan metabolism, including tryptophan hydroxylase (TPH), monoamine oxidase (MAO) and indoleamine-2,3-dioxygenase (IDO) in the colon of constipated rats, were mediated by AMR-M and AMR-H. Conclusions: The findings provide insight into the mechanisms of STC and AMR could be developed as new therapeutic agent for prevention or healing of constipation.

Barley Vinegar Relieves Loperamide-Induced Constipation in Mice via the Modulation of the Gut Microbiota and Serum Metabolism

This study investigated the effect of barley vinegar on constipation by regulating the structure of intestinal microbiota and the level of short-chain fatty acids (SCFAs). BALB/c mice with loperamide-induced constipation were treated with barley vinegar in the intervention. After treatment, constipation-related factors were identified. The effect of barley vinegar on the composition of the intestinal microbiota was evaluated by means of 16S rDNA gene sequencing, and the content of SCFAs in enteral feces was determined via the GC-MS method. Treating constipated mice with barley vinegar accelerated gastrointestinal peristalsis, inhibited the inflammatory response, protected the intestinal barrier, upregulated the production of beneficial intestinal bacteria, and downregulated the production of harmful intestinal bacteria. These therapeutic effects are attributed to reversed gut microbiota dysfunction, which favors the production of intestinal metabolites such as SCFAs. The purgative function of highland barley vinegar may improve the intestinal environment by regulating the balance of intestinal flora and the concentration of SCFAs. In addition, LC-MS metabolomics was used to analyze the effect of barley vinegar on intestinal metabolites in mice with constipation. The results show that the treatment of barley vinegar inhibited the decrease in aspartate, L-threonine, L-serine, L-proline, 3,4-dihydroxymandelic acid, epinephrine, glyceric acid, and 3,4-dihydroxymandelic acid content in intestinal metabolites caused by constipation. 4-2 hydroxy benzene acetic acid and fumaric acid content increased. KEGG pathway analysis showed that digestive system, amino acid and lipid metabolism pathways were important pathways for highland barley vinegar relieving constipation. This study proves that highland barley vinegar mainly regulates lipid metabolism, the digestive system and amino acid metabolism to maintain a steady state, prevent intestinal injury, and improve constipation. In short, this study demonstrates that highland barley vinegar can alleviate constipation in mice and repair colitis damage.

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.

Croton tiglium L. seeds ameliorate loperamide-induced constipation via regulating gastrointestinal hormones and gut microbiota before and after processing

Ethnopharmacological relevanceCrotonis Fructus (CF), the seeds of Croton tiglium L., have been commonly used in the treatment of constipation for more than two thousand years in traditional Chinese medicine (TCM). CF needs to be processed before clinical use and Crotonis Semen Pulveratum (CP) is the processed cream of CF, which could reduce the drastic purgative action and gastrointestinal damages. However, the mechanism of CF and CP in the treatment of constipation is still unclear. Aim of the studyThis study was to evaluate the effects of CF and CP on loperamide-induced constipation and the underlying mechanism. Materials and methodsThe chemical compositions of CF and CP were analyzed by UPLC-Q-TOF-MS. Constipated mouse model was established by loperamide (9.6 mg/kg, b.w., i.g.) for two weeks. After successful modeling, the mice were treated with CF or CP (45.5 and 136.5 mg/kg, b.w., i.g.) once a day for seven days. The physiological status, defecation indices, defecation time, and intestinal propulsion rate in mice were measured. Histopathologic examination and serum biochemical parameters were further estimated. 16S rDNA gene sequencing was carried out to characterize the effects of CF and CP on intestinal microbiome structure. Spearman correlation analysis was also performed to explore the association between gut microbiotic abundance and serum indices. ResultsThe results verified the therapeutic effects of CF and CP on loperamide-induced constipation. CF and CP could significantly ameliorate the reduction of fecal number, fecal weight, fecal water content, and intestinal propulsion rate in mice with constipation, and the first stool defecation time was also obviously reduced. Moreover, CF and CP could regulate the secretion of gastrointestinal hormones and inflammatory factors induced by constipation. Histopathologic examination showed that CP was superior to CF in relieving pathological injury and inflammatory cell infiltration. According to 16S rDNA sequencing, CF and CP treatment could improve gut microbiota disturbance in mice with constipation and the abundance of opportunistic pathogens such as Parabacteroides, Parasutterella and Bacillus remarkably declined, while the levels of beneficial bacterial such as Candidatus_Arthromitus significantly increased. Besides, CP may play a better role in correcting the intestinal flora disorder than CF, which was more obvious in the high-dose group. In addition, phytochemical analysis revealed the presence of diterpenoids and alkaloids in CF and CP. ConclusionsCF and CP could ameliorate loperamide-induced constipation by regulating gastrointestinal hormones secretion, reducing the levels of inflammatory cytokines and improving the disturbance of gut microbiota. Moreover, CP was superior to CF in the enrichment of beneficial bacteria and reduction of harmful bacteria and histopathological damage induced by constipation, which may be related to the changes in the species and content of diterpenoids after processing. The study provides new evidence for the processing mechanism and clinical application of CF and CP.

Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites.

Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.

Broccoli-Derived Exosome-like Nanoparticles Alleviate Loperamide-Induced Constipation, in Correlation with Regulation on Gut Microbiota and Tryptophan Metabolism.

Constipation, a common gastrointestinal dysfunction, damages patients' life quality and predisposes them to other serious diseases. Current strategies against constipation often cause drug dependency and side effects. Here, we demonstrated that broccoli-derived exosome-like nanoparticles (BENs), a natural product with high gastrointestinal stability, ameliorated LOP-induced constipation in mice. Specifically, orally administered BENs (17.5 mg/kg/d) effectively shortened defecation time, sped up intestinal propulsion rate, and increased feces amount in constipated mice. BENs also raised excitatory neurotransmitters SP and MTL and reduced inhibitory neurotransmitters VIP and ET-1. Mechanistically, BENs were taken up by gut microbes, restored LOP-disordered gut microbiota, and altered microbial metabolism of SCFAs and tryptophan, as evidenced by the results of fluorescence microscopy, 16S rRNA gene sequencing, and nontargeted metabolomics. Thereinto, BEN-enriched SCFA-producing microorganisms are closely associated with the feces amount and SP and VIP levels and BEN-elevated indole-3-pyruvic acid and 3-indoleacetic acid are highly linked to ET-1, SP, and MTL levels. Conclusively, BENs, mitigating constipation by regulating gut microbiota and microbial tryptophan metabolism, showed high potential to be developed as alternative regimens for constipation.

Gastrointestinal Fermentable Polysaccharide Is Beneficial in Alleviating Loperamide-Induced Constipation in Mice.

To investigate the role of gastrointestinal (GI) polysaccharide fermentation in alleviating constipation, two polysaccharide fractions were isolated from a soluble fiber extract with determined anti-constipation activity: a 2.04 kDa neutral fraction (SSP-1) contained 99.29% glucose, and a 41.66 kDa acidic fraction (SSP-2) contained 63.85% uronic acid. After mice were given loperamide for 14 d to induce constipation, the GI transit rate increased significantly in the SSP-1 group (p < 0.05) but not in the SSP-2 group. The stool weight in the SSP-2 group was significantly higher than that in SSP-1 (383.60 mg vs. 226.23 mg) (p < 0.05). Both SSP-1 and SSP-2 groups had significantly increased serum gastrin and motilin levels (p < 0.05) and changes in their fecal short-chain fatty acid (SCFA) profiles, while SSP-1 showed better fermentation properties than SSP-2 in terms of statistically higher fecal contents of acetic acid and total SCFAs (p < 0.05). Bioinformatic analysis indicated that SSP-1 upregulated bacteria such as Oscillibacter to improve SCFA metabolism and stimulate GI hormone secretion, while SSP-2 had less influence on the gut microbiota. These results suggest that the neutral polysaccharide with superior GI fermentation properties exerted beneficial effects on constipation, while the less fermentable pectic fraction might act as a stool-bulking agent.

Lychee Pulp-Derived Dietary Fiber-Bound Phenolic Complex Upregulates the SCFAs-GPRs-ENS Pathway and Aquaporins in Loperamide-Induced Constipated Mice by Reshaping Gut Microbiome.

This study aimed to investigate the effects of the lychee pulp-derived dietary fiber-bound phenolic complex (DF-BPC) on a murine model of loperamide-induced constipation and its molecular mechanism associated with gut microbiota modification. DF-BPC supplementation mitigated loperamide-induced dyschezia, intestinal hypomotility, and colonic impairment, as evidenced by the increased gastro-intestinal transit rate and mucus cell counts. By comparison, short-chain fatty acids (SCFAs) contents and relative abundances of associated genera (Butyricimonas, Clostridium, and Lactobacillus) were effectively upregulated following DF-BPC supplementation. Notably, DF-BPC significantly enhanced expressions of G protein-coupled receptor (GPR) 41 and 43, reaching 1.43- and 1.62-fold increase, respectively. Neurotransmitter secretions were simultaneously altered in DF-BPC-treated mice, suggesting upregulation of the SCFAs-GPRs-enteric nervous system pathway. The overexpression of aquaporins (AQP3, 8, and 9) was stimulated partly through GPRs activation. Mild inflammation associated with constipation was inhibited by suppressing LBP-TLR4-NF-κB signaling translocation. These findings suggest that DF-BPC from lychee pulp has the potential to alleviate constipation in mice through modifying the gut microbiome.

Hetong decoction relieves loperamide-induced constipation in rats by regulating expression of aquaporins.

To investigate whether Hetong decoction (, HTT) alleviates constipation via regulating AQPs expression. Constipation in rats was induced by loperamide, and rats were randomly assigned into model (saline), HHT-low (95 g/kg), HTT-medium (190 g/kg), HTT-high (380 g/kg) and positive control (mosapride) groups. Then the defecation function, the concentration of serum arginine vasopressin (AVP) and cyclic adenosine monophosphate (cAMP), and the expression of AQP3 and AQP8 in colon tissues were assessed. NCM460 colon cells with AQP3 and AQP8 knockdown or overexpression were exposed to serum from rats that received low or high dose of HTT, followed by detection of AQP3 and AQP8 expression. The model group showed lower fecal weight and water content, weaker intestinal transit, higher serum concentration of AVP and cAMP, increased proximal and distal AQP8 expression, increased proximal but decreased distal AQP3 expression. However, these trends were reversed in both the HTT group (low, medium and high dose) and the positive control group. In NCM460 cells, HTT dose-dependently stabilized AQP3 and AQP8 expression under AQP3/8 plasmid interference or overexpression. HTT relieves constipation in rats through regulating AQP3 and AQP8 expression.

Arecoline alleviated loperamide induced constipation by regulating gut microbes and the expression of colonic genome

This study aimed to investigate the effects of arecoline on constipation by intervening at different times to explore its preventive and therapeutic effects. Symptoms related to constipation, gut microbes, short-chain fatty acid (SCFA) content in the cecum, and gene expression in the colon were measured to examine the effect of arecoline on relieving constipation. The results showed that arecoline intervention alleviated loperamide-induced constipation, as evidenced by significantly shortened intestinal transit time, increased fecal water content, improved small bowel propulsion, and increased defecation frequency. In addition, arecoline significantly reduced the levels of gastrointestinal regulatory peptides such as somatostatin and vasoactive intestinal peptide in the serum, thereby regulating intestinal peristalsis. Histopathological analysis showed that arecoline ameliorated intestinal injury caused by constipation. Gut microbial analysis indicated that arecoline altered the taxonomic composition and levels of its metabolite SCFAs in the gut microbiota. Furthermore, the colonic transcriptome results indicated that genes expression related to intestinal diseases were significantly down-regulated by arecoline intervention. In conclusion, the results of the correlation analysis propose a possible mechanism of arecoline in alleviating constipation by modulating the gut microbes and their metabolites and regulating the gut genome.

Modulation of gut microbiota ecosystem by a glucan-rich snail mucin heteropolysaccharide attenuates loperamide-induced constipation

The present study aimed to investigate the effect of oral administration of snail-derived mucin extract (SM) on ameliorating constipation symptoms of loperamide-induced constipated rats (n = 6). The analytical results indicated that SM mainly contains a glucan-rich snail mucin heteropolysaccharide with high molecular weights (108.5–267.9 kDa), comprising primarily of glucose (64.9 %) and galactose (22.4 %) with some deoxyhexoses (5.0 %) and hexosamines (4.9 %). Daily SM administration at doses of 10–40 mg/kg/day to the loperamide-induced constipated rats significantly (p < 0.05) ameliorated the deterioration in fecal parameters, such as numbers and weight of feces, fecal water contents, and gastrointestinal transit ratio. The histomorphometric results showed that the loperamide-induced decreases in the thickness of mucosal and muscularis mucosae layers as well as the distribution of mucin and c-KIT-positive areas were significantly (p < 0.05) improved via SM consumption at all doses tested. SM administration at all doses significantly increased the expression of genes encoding tryptophan hydroxylases (TPH1 and TPH2; p < 0.05), tight junction molecules (OCLN, CLDN1, and TJP1; p < 0.05), and mucin (MUC2 and MUC4; p < 0.05), but significantly decreased the aquaporin-encoding genes (AQP3 and AQP8; p < 0.05). Gut microbial community analysis indicated that SM administration could modulate loperamide-induced dysbiosis by increasing the phyla Actinobacteria (11.72–12.64 % at 10–40 mg/kg doses; p < 0.05) and Firmicutes (79.33 % and 74.24 % at 20 and 40 mg/kg doses; p < 0.05) and decreasing the phyla Bacteroidetes (5.98–12.47 % at 10–40 mg/kg doses; p < 0.05) and Verrucomicrobia (2.21 % and 2.78 % at 20 and 40 mg/kg doses; p < 0.05), suggesting that SM administration is effective in ameliorating constipation by controlling gut microbial communities. These findings can be utilized as fundamental data for developing novel functional materials using SM to prevent or treat constipation.