Comparison of the laxative effects of Korean containing different microbiota on loperamide-induced constipation in ICR mice.
Food & function
The prevalence of constipation, one of the common gastrointestinal (GI) diseases, has been gradually increasing. , a traditional Korean fermented paste, has various microbiota and exerts diverse health beneficial effects. However, the ameliorative effect of on constipation is unexplored. Seven-week-old ICR mice were divided into five groups: the normal group, the loperamide (LOP) group, the LOP + mosapride citrate (3 mg per kg BW, MOSA) treated group, the LOP + BMG (2 g per kg BW) group, and the LOP + VMG (2 g per kg BW) group. alleviated constipation by increasing defecation frequency and water content in feces by reducing AQP3 mRNA expression. Additionally, increased GI transit time and excitatory neurotransmitter levels and decreased inhibitory neurotransmitter levels. Moreover, reduced mitogen-activated protein kinase (MAPK) activation and increased the c-Kit/SCF signaling pathway, suggesting that regulates the enteric nervous system (ENS). Interestingly, BMG and VMG differently influenced the gut microbiota composition. Both groups significantly decreased the and ratio compared to the LOP group. However, among genera, was only reduced in BMG, and VMG only decreased and . In summary, effectively alleviated LOP-induced constipation outcomes regardless of their different microbial communities by ameliorating GI motility and changing the gut microbiota composition.
10.1039/d2fo04111a
Effects of Bifidobacterium breve 207-1 on regulating lifestyle behaviors and mental wellness in healthy adults based on the microbiome-gut-brain axis: a randomized, double-blind, placebo-controlled trial.
European journal of nutrition
PURPOSE:Our study aimed to explore the efficacy of Bifidobacterium breve 207-1 on specific neurotransmitters and hormones and the ability to regulate lifestyle behaviors in healthy adults. METHODS:In total, 120 healthy adults with high mental stress, overweight, insomnia, and constipation were randomly assigned to receive low-dose B. breve 207-1 (LD, n = 40), high-dose B. breve 207-1 (HD, n = 40), or placebo (n = 40) for 28 days. Fecal and blood samples were collected and questionnaires were answered before and after the trial. Neurotransmitters and serum hormones were detected using enzyme-linked immunosorbent assay. The gut microbiota composition was assessed using 16 S rRNA sequencing. Short-chain fatty acids (SCFAs) concentrations were determined via gas chromatography-mass spectrometry (GC-MS). RESULTS:The primary outcome of our study was changes in mental wellness, including neurotransmitters, the hypothalamic-pituitary-adrena (HPA) axis hormones, and the psychological scales. The results showed that γ-aminobutyric acid (GABA) increased significantly and the HPA axis hormones were suppressed overall in the probiotic groups while 5-hydroxytryptamine (5-HT) did not change significantly. However, there was no significant change in mood scale scores. The secondary outcome focused on the ability of 207-1 to regulate the body and lifestyle of healthy adults (e.g., sleep, diet, exercise, etc.). The PSQI scores in the probiotics groups significantly decreased, indicating improved sleep quality. Meanwhile, the probiotic groups had a slight increase in exercise consumption while dietary intake stabilized. By physical examination, the participants showed weight loss although no statistically significant difference was observed between the groups. Then, validated by gut microbiota, changes in the gut microbiota were observed under the effective intervention of 207-1 while short-chain fatty acids (SCFAs) increased in the LD group, particularly acetic and propionic acids. There was a slight decrease in alpha-diversity in the HD group. CONCLUSION:Bifidobacterium breve 207-1 entered the organism and affected neurotransmitter and the HPA axis hormone levels via the microbiome-gut-brain axis. Meanwhile, 207-1 supplementation improved daily lifestyle behaviors in healthy adults, which may in turn lead to changes in their bodies (e.g. weight and lipid metabolism). However, this study did not find significant mood-modulating efficacy. The mechanism of the overall study is unclear, but we hypothesize that SCFAs may be the key pathway, and more experiments are needed for validation in the future. TRIAL REGISTRATION:This trial was retrospectively registered in the Chinese Clinical Trial Registry under the accession number ChiCTR2300069453 on March 16, 2023.
10.1007/s00394-024-03447-2
Total Flavonoids of Aurantii Fructus Immaturus Regulate miR-5100 to Improve Constipation by Targeting Fzd2 to Alleviate Calcium Balance and Autophagy in Interstitial Cells of Cajal.
Molecular neurobiology
Aurantii Fructus Immaturus total flavonoids (AFIF) is the main effective fraction extracted from AFI, which has a good effect on promoting gastrointestinal motility. This study aimed to investigate AFIF which regulates miR-5100 to improve constipation symptoms in mice by targeting Frizzled-2 (Fzd2) to alleviate interstitial cells of Cajal (ICCs) calcium ion balance and autophagy apoptosis. The constipated mouse model was induced by an antibiotic suspension, and then treated with AFIF. RNA-seq sequencing, luciferase assay, immunofluorescence staining, transmission electron microscopy, ELISA, flow cytometry, quantitative polymerase chain reaction (PCR), and Western blot were applied in this study. The results showed that AFIF improved constipation symptoms in antibiotic-induced constipated mice, and decreased the autophagy-related protein Beclin1 levels and the LC3-II/I ratio in ICCs. miR-5100 and its target gene Fzd2 were screened as key miRNAs and regulator associated with autophagy. Downregulation of miR-5100 caused increased expression of Fzd2, decreased proliferation activity of ICCs, increased apoptotic cells, and enhanced calcium ion release and autophagy signals. After AFIF treatment, miR-5100 expression was upregulated and Fzd2 was downregulated, while autophagy-related protein levels and calcium ion concentration decreased. Furthermore, AFIF increased the levels of SP, 5-HT, and VIP, and increased the expression of PGP9.5, Sy, and Cx43, which alleviated constipation by improving the integrity of the enteric nervous system network. In conclusion, AFIF could attenuate constipation symptoms by upregulating the expression of miR-5100 and targeting inhibition of Fzd2, alleviating calcium overload and autophagic death of ICCs, regulating the content of neurotransmitters, and enhancing the integrity of the enteric nervous system network.
10.1007/s12035-024-03958-3
Engineered 5-HT producing gut probiotic improves gastrointestinal motility and behavior disorder.
Frontiers in cellular and infection microbiology
Slow transit constipation is an intractable constipation with unknown aetiology and uncertain pathogenesis. The gut microbiota maintains a symbiotic relationship with the host and has an impact on host metabolism. Previous studies have reported that some gut microbes have the ability to produce 5-hydroxytryptamine (5-HT), an important neurotransmitter. However, there are scarce data exploiting the effects of gut microbiota-derived 5-HT in constipation-related disease. We genetically engineered the probiotic Nissle 1917 (EcN-5-HT) for synthesizing 5-HT in situ. The ability of EcN-5-HT to secrete 5-HT and was confirmed. Then, we examined the effects of EcN-5-HT on intestinal motility in a loperamide-induced constipation mouse model. After two weeks of EcN-5-HT oral gavage, the constipation-related symptoms were relieved and gastrointestinal motility were enhanced. Meanwhile, administration of EcN-5-HT alleviated the constipation related depressive-like behaviors. We also observed improved microbiota composition during EcN-5-HT treatment. This work suggests that gut microbiota-derived 5-HT might promise a potential therapeutic strategy for constipation and related behavioral disorders.
10.3389/fcimb.2022.1013952
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
Soluble dietary fiber and cellulose from Saccharina japonica by-product ameliorate Loperamide-induced constipation via modulating enteric neurotransmitters, short-chain fatty acids and gut microbiota.
International journal of biological macromolecules
The effects of soluble dietary fiber (SDF) and cellulose (IDF) from Saccharina japonica by-product and their differences in improving constipation were further clarified in the present study. We demonstrated that SDF was mainly made up of d-mannuronic acid and d-mannose while IDF consisted of d-glucose , which is different from other reported dietary fibers of terrestrial plants. In this research, both SDF and IDF improved fecal-related indicators, gastrointestinal transit rate and histological morphology in Lop-induced mice. Moreover, they could increase the level of antioxidant enzymes (SOD and GSH-Px), restore the expression of enteric neurotransmitters, and maintain the function of ZO-1, JAM-1 as well as Occludin. Interestingly, SDF and IDF had a significant up-regulated effect on the proportion of Muribaculacea, Prevotellaceaen and Lachnospiraceae, which are critical to preserving intestinal immune homeostasis. Besides, they promoted the biosynthesis of short-chain fatty acids (SCFAs). The overall index showed that SDF is more effective for constipation due to its better water retention capacity. Thus, they can be used as a safe dietary supplement for the treatment of chronic or occasional constipation in humans.
10.1016/j.ijbiomac.2022.11.243
The probiotic fermented milk of Lacticaseibacillus paracasei JY062 and Lactobacillus gasseri JM1 alleviates constipation via improving gastrointestinal motility and gut microbiota.
Journal of dairy science
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.
10.3168/jds.2023-24154
Yunpi Tongbian Fang alleviates slow transit constipation induced by loperamide by regulating intestinal microbiota and short-chain fatty acids in rats.
Cellular and molecular biology (Noisy-le-Grand, France)
Slow transit constipation (STC) is a prevalent chronic colonic dysfunction disease that significantly impairs the quality of life for affected individuals. Yunpi Tongbian Fang (YPTBF), a traditional Chinese medicine compound, has demonstrated promising clinical efficacy; however, its underlying mechanism remains elusive. In order to assess the laxative properties of YPTBF, which encompasses the influence on gut microbiota, gut metabolites, gut neurotransmitters, and colon histology, an oral administration of YPTBF was conducted for a duration of two consecutive weeks on STC rats induced by loperamide hydrochloride. The results showed that YPTBF improved the symptoms of STC, alleviated the decrease in total fecal volume and fecal water content caused by loperamide-induced constipation, restored intestinal transport function, and HE staining showed the recovery of pathological damage to the colon mucosa. In addition, YPTBF increased the concentrations of 5-HT and ACHE, while reducing the concentrations of VIP and NO. YPTBF adjusted the diversity and abundance of gut microbiota in STC rats, enabling the recovery of beneficial bacteria and promoting the production of acetic acid, propionic acid, and butyric acid. We found that YPTBF can improve constipation in STC rats, possibly by regulating the intestinal microbiota structure and improving SCFAs metabolism.
10.14715/cmb/2023.69.10.4
Surgical Interventions for Functional Constipation: An Update.
Vilanova-Sanchez Alejandra,Levitt Marc A
European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie
Chronic idiopathic constipation, also known as functional constipation, is defined as difficult and infrequent defecation without an identifiable organic cause. Medical management with laxatives is effective for the majority of constipated children. However there is a subset of patients who may need evaluation by a surgeon. As constipation progresses, it can lead to fecal retention and rectal and sigmoid distension, which impairs normal colorectal motility. Surgical interventions are influenced by the results of: a rectal biopsy, transit studies, the presence of megacolon/megarectum on contrast enema, the degree of soiling/incontinence, anorectal manometry findings, and colonic motility evaluation. In this review, we describe the different surgical options available (intestinal diversion, antegrade enemas, sacral nerve stimulation, colonic resections, and Botulinum toxin injection) and provide guidance on how to choose the best procedure for a given patient.
10.1055/s-0040-1716729