Colonic mast cells in controls and slow transit constipation patients.
Bassotti G,Villanacci V,Nascimbeni R,Cadei M,Manenti S,Sabatino G,Maurer C A,Cathomas G,Salerni B
Alimentary pharmacology & therapeutics
BACKGROUND:There is recent evidence that mast cells may play important roles in the gut, especially concerning visceral hypersensitivity and motor activity. However, most data are only available for clinical conditions characterised by diarrhoea, where MC have chiefly investigated in the mucosal layer of the colon and there is almost no information concerning constipation. AIM:To investigate mast cells distribution in all colonic layers in controls and severely constipated patients. METHODS:Full-thickness specimens from colons of patients undergoing surgery for slow transit constipation (n=29), compared with controls, were obtained and the number of mast cells (evaluated by specific monoclonal antibodies) counted as a whole and in single colonic segments (caecum, ascending, transverse, descending and sigmoid). RESULTS:Compared with controls, constipated patients revealed significantly higher number of mast cells, both as overall number and in single colonic segments. The distribution of mast cells resulted fairly homogeneous in the various segment of the large bowel, in both controls and patients, and no significant difference in the percentage of degranulated cells was found between groups. CONCLUSIONS:Colonic mast cells display a homogeneous distribution within the viscus. This cell population is shown to increase in severely constipated patients, which might represent a mechanism trying to compensate for the impaired propulsive activity of these patients.
10.1111/j.1365-2036.2011.04684.x
The combination of Cassia obtusifolia L. and Foeniculum vulgare M. exhibits a laxative effect on loperamide-induced constipation of rats.
Jang Seung Hee,Yang Dong Kwon
PloS one
Chronic constipation is a functional gastrointestinal disease that is detrimental to the quality of patient life. Cassia obtusifolia L. (CO) and Foeniculum vulgare M. (FV) are commonly used as medicinal foods in many countries. We aimed to examine the laxative effect and their underlying mechanism of CO and FV mixture on loperamide (lop)-induced constipated rats. To determine the laxative effects of these compounds, Sprague-Dawley rats were divided into six groups: the control, lop-induced constipated (2mg/kg), and three doses (100, 300, and 500mg/kg) of CO and FV mixture-, and Bisacodyl (bis, 3.3mg/kg)-treated groups. The mixture of CO and FV and bis were orally administered once a day for 4 weeks. For induction of constipation, the lop were treated with a dose of 2 mg/kg twice a day on the 3rd week after treatments of CO and FV extracts and bis. The results were revealed that the CO and FV mixture has the laxative effects more than those in CO and FV-alone treatments on constipated rats by determining the stool parameters, including stool number and weight. Indeed, stool parameters, such as, stool number, weight, and water contents and colonic peristalsis from the intestinal transit length and ratio were dramatically improved by CO and FV mixture treatment. Histological study also revealed that CO and FV mixture enhanced the thicknesses of mucosa and muscular layers of the colon in constipated rats. For their underlying mechanism, the mRNAs and proteins expression of muscarinic acetylcholine receptors (mAchR) M2 and M3 and their downstream signaling were preserved by CO and FV mixture treatment in constipated rats. Therefore, this study suggests that treatment with CO and FV mixture has beneficial effects against constipation. We further suggest that CO and FV mixture may be utilized as an alternative therapeutic strategy for constipation.
10.1371/journal.pone.0195624
Comparative study of the laxative effects of konjac oligosaccharides and konjac glucomannan on loperamide-induced constipation in rats.
Hu Mengmeng,Fang Changqian,Liu Youqian,Gao Meng,Zhang Dongjian,Shi Gaofeng,Yin Zhiqi,Zheng Rendong,Zhang Jian
Food & function
Dietary fiber is the basic therapeutic method to relieve the symptoms of chronic constipation. The aim of this study was to compare the laxative effect of konjac glucomannan (KGM) and konjac oligosaccharides (KOS) on constipated rats. KGM and KOS were administered to loperamide-induced constipated rats at dosages of 100 mg per kg bw and 400 mg per kg bw for 15 days. Feces were collected to evaluate the defecation function. X-ray imaging and an electrophysiological system were used to determine gastrointestinal (GI) motility. Immunohistochemistry and western blotting were used to measure the protein levels. Magnetic resonance imaging (MRI) was performed to assess flatulence. Our results demonstrated that low-dose KOS (L-KOS) exerted the best laxative effect. Compared to the normal control (NC) group, the fecal number in the L-KOS group increased by 39.4%, and the fecal weight significantly increased by 31.9% which was higher than those in the low-dose KGM (L-KGM) and high-dose KGM (H-KGM) groups. The fecal moisture content and transit scores were significantly increased only in the L-KOS group. Meanwhile, less GI gas was produced by KOS. Additionally, further investigations suggested that KOS could upregulate the protein expression of stem cell factors (SCF)/c-kit, and significantly promoted the secretion of mucus. In conclusion, compared to KGM, KOS had a conspicuous laxative effect especially at a low dosage. The potential laxative mechanisms of KOS probably are regulating the SCF/c-kit signalling pathway and increasing mucus secretion. These findings indicated that as a kind of functional oligosaccharide, KOS is more conducive to alleviating constipation compared to polysaccharides.
10.1039/d1fo01237a
Synbiotic yogurt containing konjac mannan oligosaccharides and Bifidobacterium animalis ssp. lactis BB12 alleviates constipation in mice by modulating the stem cell factor (SCF)/c-Kit pathway and gut microbiota.
Li Tao,Yan Qiaojuan,Wen Yongping,Liu Jun,Sun Jian,Jiang Zhengqiang
Journal of dairy science
Synbiotic dietary supplements, as an effective means of regulating the gut microbiota, may have a beneficial effect on constipation. This study evaluated the effects of synbiotic yogurt containing konjac mannan oligosaccharides (KMOS) and Bifidobacterium animalis ssp. lactis BB12 (BB12) on constipated Kunming mice (the model group). Following administration of yogurt containing 2.0% KMOS and BB12 (YBK2.0), black fecal weight and number and gastrointestinal transit rate increased by 97.5, 106.3, and 55.7%, respectively, compared with the model group. Serum levels of excitability neurotransmitters (motilin, substance P, and acetylcholine) in the YBK2.0 group were increased by 139.7, 120.4, and 91.8%, respectively, and serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide, nitric oxide, and acetylcholine) were decreased. Moreover, synbiotic yogurt supplementation significantly downregulated the expression of vasoactive intestinal peptide receptor 1 (VIPR1) and upregulated the expression of serotonin receptor 4 (5-HT4) in the colon, and enhanced the expression of the stem cell factor (SCF)/c-Kit pathway. Additionally, YBK2.0 treatment significantly regulated the community composition and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of gut microbiota, which were positively correlated with physiological parameters of constipation. Thus, supplementation with synbiotic yogurt composed of KMOS and BB12 could facilitate fecal excretion by regulating related pathways and the gut microbiota. These findings demonstrated that the synbiotic yogurt can be considered a functional food for alleviating constipation.
10.3168/jds.2020-19449
A Potential Use of Vidarabine: Alleviation of Functional Constipation Through Modulation of the Adenosine A2A Receptor-MLC Signaling Pathway and the Gut Microbiota.
International journal of molecular sciences
Vidarabine (VID) is an antiviral medication that is commonly utilized to treat conditions such as hand, foot, and mouth disease and herpes. Constipation is a prevalent complication of these diseases. Could VID treat these diseases by influencing defecation behavior? To date, no studies have been conducted on the potential of VID to relieve constipation. Therefore, a systematic investigation was conducted into the laxative effects and mechanisms of VID using loperamide-induced functional constipated mice. The findings indicate that the oral administration of VID promoted gastrointestinal peristalsis, improved fecal properties, facilitated defecation, and demonstrated a significant laxative effect on functional constipated mice. It has been demonstrated that VID may increase the water content of feces by regulating the expression of aquaporins (AQP3, AQP4, and ) in the colon and promote intestinal motility by regulating the expression of neurotransmitters (AChE and VIP) and the adenosine A2A receptor-myosin light chain (A2AR-MLC) signaling pathway in constipated mice. Concurrently, VID may also reduce colonic inflammation in constipated mice, reinforce the gut barrier function, and alter the composition and structure of the gut microbial community. Some microbial taxa, including Firmicutes and , were found to be associated with the alleviation of constipation, while other taxa, including Bacteroidetes, Proteobacteria, Muribaculaceae, , , and , were found to be associated with constipation. These results indicate that the gut microbiota may play a significant role in the alleviation of constipation by VID. These findings confirm the efficacy of VID in a constipated animal model, which justifies further investigation into its potential clinical applications.
10.3390/ijms252312810
subsp. relieves loperamide hydrochloride-induced constipation in mice by enhancing bile acid dissociation.
Food & function
species are known for their efficacy in alleviating constipation. This study aimed to compare the constipation-relieving effects of different species ( subsp. , , , , subsp. , and ) and to explore the underlying mechanisms from both the bacterial and host perspectives. We evaluated six species for their physiological properties, including growth rate, oligosaccharide utilization, osmotic pressure resistance, cell adhesion, and bile acid dissociation capability. Mice with severe constipation induced by loperamide hydrochloride were treated with these bacteria at a density of 10 CFU per mL for 17 days. Gastrointestinal indices such as fecal water content, time to first black stool defecation, and small intestine propulsion rate were measured to assess constipation relief. Microbiome and metabolome (bile acid and tryptophan) analyses were conducted to elucidate the differences in constipation relief among the species. Our results demonstrated that subsp. exhibited superior physiological traits, including rapid growth, extensive oligosaccharide utilization, and high bile salt dissociation capacity. Notably, only subsp. significantly ameliorated constipation symptoms in the mouse model. Furthermore, this strain markedly restored bile acid and short-chain fatty acid levels in the intestines of constipated mice and altered the composition of the intestinal microbiota. These findings suggest that the enhanced efficacy of subsp. in relieving constipation is associated with its ability to modulate intestinal physiology and microbiota structure and metabolism.
10.1039/d4fo04660a
Plasma metabolomic profiles reveal regulatory effect of chitosan oligosaccharides on loperamide-induced constipation in mice.
Zhang Xiaoyu,Hu Baifei,Sun Guangjun,Zheng Junping,Hu Haiming,Yang Huabing,Cheng Xue,Lin Aizhen,Liu Hongtao
Journal of pharmaceutical and biomedical analysis
Chitosan oligosaccharides (COS) can improve the symptoms of constipation. In this study, we further explored the regulator effect of COS on aberrant plasma metabolomics in constipated mice. Using untargeted metabolomic analysis by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS), we identified several most significantly changed metabolic pathways in plasma of constipated mice induced by loperamide, including those correlated with the metabolisms of sphingolipid, glycerophospholipid, tryptophan, bile acids, unsaturated fatty acids, and amino acids. The changes in these metabolic pathways were reversed by COS treatment largely. Furthermore, the mRNA levels of some key target genes related to the above metabolic pathways in colon samples were detected by reverse transcription-polymerase chain reaction analysis. We showed that COS significantly suppressed the abnormal expression of these genes, including ceramide glucosyltransferase (CGT), sphingolipid 4-desaturase (DEGS2), alkaline ceramidase (ACER1), sphingosine kinase 2 (SPHK2), lysophosphatidylcholine acyltransferase (LPCAT1), and aromatic-L-amino-acid (DDC). These data provide insight into the mechanisms by which COS ameliorates loperamide-induced constipation in mice.
10.1016/j.jpba.2022.114590
Polysaccharide from Spirulina platensis ameliorates diphenoxylate-induced constipation symptoms in mice.
Ma Haotian,Xiong Huaye,Zhu Xiaoli,Ji Chunli,Xue Jinai,Li Runzhi,Ge Baosheng,Cui Hongli
International journal of biological macromolecules
The aim of this study is to probe new functions of a polysaccharide from Spirulina platensis (PSP) on constipation and intestinal microbiota in mice. Diphenoxylate-induced constipation in mice was treated with different doses of PSP, followed by examining the defecation patterns, levels of acetyl cholinesterase (AchE), nitric oxide (NO), and tissue section histopathology. The composition of intestinal microbiota was determined by genome sequencing analysis of the 16S rDNA. This study found that the average molecular weight of PSP was 29, 600 Da, and mainly monosaccharides of PSP were rhamnose (24.7%), glucose (16.15%) and galactose (13.32%). The beneficial effects of PSP treatment include defecation improvement, increase of AchE activity, reduction of NO concentration, renovation of the damaged intestinal villus and affection on the expression of some related genes in the constipated mice. In addition, PSP had significant effects on the gut microbiota, showing the enhancement in abundance of beneficial bacteria including Akkermansia, Lactobacillus, Butyricimonas, Candidatus Arthromitus and Prevotella, and the reduction in abundance of harmful bacteria such as Clostridium and Dorea. The present s uncovered a new function of PSP, indicating that PSP could be used in constipation therapies.
10.1016/j.ijbiomac.2019.04.209
Chinese patent medicine shouhui tongbian capsule attenuated loperamide-induced constipation through modulating the gut microbiota in rat.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Shouhui tongbian capsule (SHTC) is a commercial Chinese patent medicine used in the treatment of constipation. However, its mechanism of action remains unclear. AIM OF THE STUDY:The present study was undertaken to assess SHTC relieved effects on the clinical symptoms of loperamide (LOP) induced constipation in Sprague Dawley (SD) rat model and to clarify the relationship between the protective effect of SHTC on constipation and the gut microbiota. MATERIALS AND METHODS:Constipation male SD rats models were induced with solution of LOP (1.5 mg/kg bw), and rats were treated with an oral dose of SHTC (35, 70 mg/kg bw) three times a day after successful modeling. All rats were assessed weekly by change in body weight, gastric emptying rate, fecal moisture content and wet/dry weight. Hematoxylin and eosin (H&E) were used to observe parts of the rats small intestine. The gut microbiota in colonic contents was analyzed using 16SrRNA gene sequencing. Contents of short-chain fatty acids (SCFAs) were analyzed by gas chromatography-mass spectrometer (GCMS). RESULTS:The results confirmed the therapeutic effects of SHTC on constipation. Specifically, SHTC could alleviate the decrease in body weight, gastric emptying rate and fecal moisture content caused by LOP-induced constipation. The pathological damage of small intestine was significantly improved by H&E staining. Notably, SHTC increased the relative abundances of Lactobacillus and the ratio of Firmicutes to Bacteroides (F/B). In addition, the content of acetic acid and propionic acid was significantly increased in constipated rats fed with SHTC. CONCLUSION:SHTC could ameliorate the development of LOP-induced constipation in rats by remodeling the structure of gut microbial community and regulating production of intestinal metabolites.
10.1016/j.jep.2022.115575
Xylooligosaccharides from corn cobs alleviate loperamide-induced constipation in mice modulation of gut microbiota and SCFA metabolism.
Food & function
This study aimed to optimize the structure and efficacy of xylooligosaccharides (XOSs) from corn cobs in constipated mice. Structural analysis revealed that XOSs from corn cobs were composed of β-Xyl-(1 →4)-[β-Xyl-(1→4)]-α/β-Xyl ( = 0-5) without any other substituents. XOS administration significantly reduced the defecation time, increased the gastrointestinal transit rate, restored the gastrointestinal neurotransmitter imbalance, protected against oxidative stress, and reversed constipation-induced colonic inflammation. Fecal metabolite and microbiota analysis showed that XOS supplementation significantly increased short chain fatty acid (SCFA) levels and improved the gut microbial environment. These findings highlighted the potential of XOSs from corn cobs as an active ingredient for functional foods or as a therapeutic agent in constipation therapy.
10.1039/d3fo02688d
Laxative Effects of Taurine on Loperamide-Induced Constipation in Rats.
Lee Dong-Sung,Jo Hee Geun,Kim Min Ji,Lee Hwan,Cheong Sun Hee
Advances in experimental medicine and biology
In the present study, we investigated the laxative effects of taurine in a rat model of loperamide-induced constipation. Rats were divided into six groups of six animals each: normal (NOR), control (CON), loperamide + Dulcolax (5.5 mg/kg, p.o.), and loperamide + various doses of taurine (7.5, 15, and 30 mg/kg, p.o.). Laxative activity was determined based on body weight, feeding characteristics, fecal properties, gastrointestinal transit (GIT) ratio, and the levels of serum gastrointestinal hormones. Taurine supplementation significantly increased the number, wet weight, and water content of fecal pellets in rats with loperamide-induced constipation. GIT ratio and loperamide-induced serum metabolic parameters, such as gastrin (GAS), motilin (MTL), and somatostatin (SS) significantly changed after supplementation with taurine in loperamide-induced constipated rats. We suggest that taurine had a potent effect against loperamide-induced constipation in part by increasing gastrointestinal motility.
10.1007/978-981-13-8023-5_25
Exploring the Dose-Effect Relationship of in Relieving Loperamide Hydrochloride-Induced Constipation in Rats through Colon-Released Capsules.
International journal of molecular sciences
Constipation is a common disease affecting humans. is reportedly effective in relieving constipation. Current studies generally focus on the dose-response relationship of oral doses; however, the dose-effect relationship of in the colon, which is the primary site where exerts constipation-relieving effects, to treat constipation has not been studied. Herein, three strains of (FGSZY6M4, FJSWXJ10M2, and FSDJN6M3) were packaged in colon-released capsules to explore the dose-effect relationship in the colon. For each strain, three groups of capsules (10, 10, and 10 CFU/capsule, respectively) and one group of free probiotics (10 CFU/mL) were used to explore the colonic dose effect of . The results showed that the three strains of improved fecal water content and promoted intestinal motility by regulating gastrointestinal peptide (MTL, GAS, and VIP), aquaporin-3, and 5-hydroxytryptamine levels while promoting gastrointestinal motility and relieving constipation by regulating the intestinal flora composition of constipated rats and changing their metabolite content (short-chain fatty acids). Among the three free bacterial solution groups (10 CFU/mL), FGSZY6M4 was the most effective in relieving constipation caused by loperamide hydrochloride in rats. The optimal effective dose of each strain was 6M4 (10 CFU/day), 10M2 (10 CFU/day), and S3 (10 CFU/day) of the colon-released capsules. Therefore, for some effective strains, the dose of oral probiotics can be reduced by colon-released capsules, and constipation can be relieved without administering a great number of bacterial solutions. Therefore, investigating the most effective dose of at the colon site can help to improve the efficiency of relieving constipation.
10.3390/ijms24076585
Prevention of loperamide induced constipation in mice by KGM and the mechanisms of different gastrointestinal tract microbiota regulation.
Zhang Qi,Zhong Dian,Sun Rui,Zhang Yang,Pegg Ronald B,Zhong Geng
Carbohydrate polymers
Constipation is one of the most prevalent gastrointestinal tract diseases. Konjac glucomannan (KGM) dietotherapy can effectively relieve the clinical symptoms of patients with constipation. However, the causal relationship among KGM, constipation and different gastrointestinal microbiome (i.e., the stomach {St}, small intestine {S}, and large intestine {L}) remains poorly understood. In this study, constipated mice were treated with KGM (75, 150, 300 mg/kg bw). Results showed that KGM treatment improved the general physiological state, fecal character, small intestinal propulsive rate, gastric emptying rate, MTL and AchE activities, ET-1, 5-HT, and NO levels, and SCFA concentrations. KGM in the diets of constipated mice reduced the diversity of St and S microbiota, while increased those in the L. The KGM intervention regulated the microbiota profile, which afterwards was closer to the normal mouse group: confirmation was provided by different changes of bacteria like Lactobacillus, Bifidobacterium and Allobaculum spp et al.
10.1016/j.carbpol.2020.117418
YJ5 modulates the gut microbiota and produces beneficial metabolites to relieve constipation by enhancing the mucosal barrier.
Food & function
Constipation is a prevalent gastrointestinal (GI) problem affecting a large number of individuals. This study aimed to investigate peristalsis-promoting potential characteristics of YJ5 and the underlying molecular mechanism. The study demonstrated the relieving effect of YJ5 on constipation in both zebrafish and mouse models. 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 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. YJ5 was found to reduce the expression of colonic aquaporins to normalize the colonic water transport system of constipated mice. Additionally, 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 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 YJ5 was shown to relieve constipation, and metabolomics analysis revealed that these positive effects were related to its metabolites like malic acid and heliangin.
10.1039/d3fo03259k
[Guidelines for diagnosis and treatment of constipation in Mexico. A) Epidemiology (meta-analysis of the prevalence), pathophysiology and classification].
Remes Troche José María,Remes Troche José María,Tamayo de la Cuesta José Luis,Raña Garibay Ricardo,Huerta Iga Francisco,Suarez Morán Edgardo,Schmulson Max,
Revista de gastroenterologia de Mexico
BACKGROUND:Constipation is a common problem in the general population and its prevalence is based on the diagnostic criteria, the study population and the research methodology for collecting the data. OBJECTIVES AND METHODS:To establish the clinical gudelines for diagnosis and treatment of chronic constipation in Mexico we have reviewed the epidemiological factors of constipation and have conducted meta-analysis according to the 3 available community-based studies from our country. In addition, evidence-based recommendations have been provided. RESULTS:The estimated prevalence of functional constipation in Mexico is 14.4% (95% CI: 12.6-16.6%) according to Rome II and Rome III criteria. Although constipation is present in both genders and all age groups, it is more common among young women with a female to male ratio of 3:1. In our population, 43.6% report using laxatives, teas for stimulating bowel movements or fiber supplements, but only 18.0% did so because they considered themselves as constipated. Also, data from a tertiary referral center in Mexico City suggests that patients with prolonged colonic transit time have lower scores in the physical component of the SF-36 compared to those with chronic constipation and a normal colonic transit time. CONCLUSIONS:Functional constipation is a very common problem in Mexico affecting mainly young women. Laxatives and other related agents are frequently used and this disorder seems to have a negative impact on quality of life.
Fu Brick Tea Alleviates Constipation via Regulating the Aquaporins-Mediated Water Transport System in Association with Gut Microbiota.
Journal of agricultural and food chemistry
This study aimed to investigate the amendatory effects of Fu brick tea aqueous extract (FTE) on constipation and its underlying molecular mechanism. The administration of FTE by oral gavage (100 and 400 mg/kg·bw) for 5 weeks significantly increased fecal water content, improved difficult defecation, and enhanced intestinal propulsion in loperamide (LOP)-induced constipated mice. FTE also reduced colonic inflammatory factors, maintained the intestinal tight junction structure, and inhibited colonic Aquaporins (AQPs) expression, thus normalizing the intestinal barrier and colonic water transport system of constipated mice. 16S rRNA gene sequence analysis results indicated that two doses of FTE increased the / (F/B) ratio at the phylum level and increased the relative abundance of from 5.6 ± 1.3 to 21.5 ± 3.4% and 28.5 ± 4.3% at the genus level, subsequently resulting in a significant elevation of colonic contents short-chain fatty acids levels. The metabolomic analysis demonstrated that FTE improved levels of 25 metabolites associated with constipation. These findings suggest that Fu brick tea has the potential to alleviate constipation by regulating gut microbiota and its metabolites, thereby improving the intestinal barrier and AQPs-mediated water transport system in mice.
10.1021/acs.jafc.2c07709
Modulation of gut microbiota ecosystem by a glucan-rich snail mucin heteropolysaccharide attenuates loperamide-induced constipation.
International journal of biological macromolecules
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.
10.1016/j.ijbiomac.2023.126560
Polysaccharides from Relieve Loperamide-Induced Constipation Symptoms in Mice.
International journal of molecular sciences
A vital bioactive component of marine resources is polysaccharides (HLP). This study examined whether HLP could regulate intestinal flora to treat loperamide-induced constipation. Constipated mice showed signs of prolonged defecation (up by 60.79 min) and a reduced number of bowel movements and pellet water content (decreased by 12.375 and 11.77%, respectively). The results showed that HLP treatment reduced these symptoms, reversed the changes in related protein expression levels in the colon, and regulated the levels of active peptides associated with the gastrointestinal tract in constipated mice, which significantly improved water-electrolyte metabolism and enhanced gastrointestinal motility. Meanwhile, it was found that intestinal barrier damage was reduced and the inflammatory response was inhibited through histopathology and immunohistochemistry. As a means to further relieve constipation symptoms, treatment with low, medium, and high HLP concentrations increased the total short-chain fatty acid (SCFA) content in the intestine of constipated mice by 62.60 μg/g, 138.91 μg/g, and 126.51 μg/g, respectively. Moreover, an analysis of the intestinal flora's gene for 16S rRNA suggested that the intestinal microbiota was improved through HLP treatment, which is relevant to the motivation for the production of SCFAs. In summary, it was demonstrated that HLP reduced loperamide-induced constipation in mice.
10.3390/ijms24032553
The Anti-Constipation Effects of Raffino-Oligosaccharide on Gut Function in Mice Using Neurotransmitter Analyses, 16S rRNA Sequencing and Targeted Screening.
Molecules (Basel, Switzerland)
Raffino-oligosaccharide (ROS), the smallest oligosaccharide of the raffinose family, is a novel food ingredient. However, the anti-constipation effects of ROS remain obscure. This study investigates the anti-constipation effects of ROS based on the loperamide-induced mice model and reveals the underlying mechanism using constipation parameters, neurotransmitter level, 16S rRNA sequencing, and the targeted screening strategy. The prevention effects were firstly investigated by the gastro-intestinal transit rate experiment (50 mice) and defecation status experiment (50 mice), which were divided into five groups ( = 10/group): blank, model, and low-, medium- and high-dose ROS. Furthermore, the slow-transit constipation experiment (blank, model, and high-dose ROS, = 10/group) was conducted to illustrate the underlying mechanism. The results showed that ROS aided in preventing the occurrence of constipation by improving the gastro-intestinal transit rate and the defecation frequency in mice, and ROS significantly reduced the serum levels of vasoactive intestinal peptide (VIP). In addition, ROS regulated the diversity and structure of intestinal flora. Among them, one specific family and six specific genera were significantly regulated in constipated mice. The targeted screening revealed that 29 targets related to the anti-constipation effects of ROS, indicating ROS may play a role by regulating multiple targets. Furthermore, the network pharmacology analysis showed that Akt1, Stat3, Mapk8, Hsp90aa1, Cat, Alb, Icam1, Sod2, and Gsk3b can be regarded as the core anti-constipation targets. In conclusion, ROS could effectively relieve constipation, possibly by inhibiting the level of neurotransmitters and regulating the gut flora in mice. This study also provides a novel network pharmacology-based targeted screening strategy to reveal the anti-constipation effects of ROS.
10.3390/molecules27072235
The Effect of Psyllium Husk on Intestinal Microbiota in Constipated Patients and Healthy Controls.
Jalanka Jonna,Major Giles,Murray Kathryn,Singh Gulzar,Nowak Adam,Kurtz Caroline,Silos-Santiago Inmaculada,Johnston Jeffrey M,de Vos Willem M,Spiller Robin
International journal of molecular sciences
Psyllium is a widely used treatment for constipation. It traps water in the intestine increasing stool water, easing defaecation and altering the colonic environment. We aimed to assess the impact of psyllium on faecal microbiota, whose key role in gut physiology is being increasingly recognised. We performed two randomised, placebo-controlled, double-blinded trials comparing 7 days of psyllium with a placebo (maltodextrin) in 8 healthy volunteers and 16 constipated patients respectively. We measured the patients' gastrointestnal (GI) transit, faecal water content, short-chain fatty acid (SCFA) and the stool microbiota composition. While psyllium supplement had a small but significant effect on the microbial composition of healthy adults (increasing and decreasing ), in constipated subjects there were greater effects on the microbial composition (increased , , , and and decreased uncultured and ) and alterations in the levels of acetate and propionate. We found several taxa to be associated with altered GI transit, SCFAs and faecal water content in these patients. Significant increases in three genera known to produce butyrate, , and , correlated with increased faecal water. In summary, psyllium supplementation increased stool water and this was associated with significant changes in microbiota, most marked in constipated patients.
10.3390/ijms20020433
The rhizomes of Atractylodes macrocephala relieve loperamide-induced constipation in rats by regulation of tryptophan metabolism.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Constipation 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 STUDY:To reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. MATERIALS AND METHODS:Loperamide-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. RESULTS:The 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.
10.1016/j.jep.2023.117637
[Constipation in Patients with Incurable Cancer - Recommendations of the German S3 Guideline 'Palliative Medicine'].
Wirz Stefan,Simon Steffen,Frieling Thomas,Bausewein Claudia,Voltz Raymond,Pralong Anne,Mönig Stefan,Follmann Markus,Holtmann Martin,Becker Gerhild
Deutsche medizinische Wochenschrift (1946)
According to the German S3-guideline 'Palliative Medicine' which has been supported by the German Guideline Program in Oncology, constipation in palliative patients requires a consistent prophylaxis and therapy. Constipation is caused by immobilisation, poor health, exsiccosis, a low-fiber diet or a preexisting functional constipation. Further important causes are substances with constipating side effects, such as opioids or anticholinergic drugs. Pragmatically, constipation should be assessed by subjective parameters such as the feeling of incomplete evacuation, straining, or other complaints. Objective parameters are hard stool or reduced number of bowel movements. For the early detection of constipation the amount of the stool mass and the stool frequency are applicable. If constipation occurs, a standardized escalating protocol applying adequate fluid intake, a high fibre diet, and laxatives is recommended. New prokinetic agents, secretagogues, or opioid antagonists may be used as reserve drugs.
10.1055/s-0042-101899
Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites.
Nutrients
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 and , reducing the . 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.
10.3390/nu15214502