Konjac glucomannan with probiotics acts as a combination laxative to relieve constipation in mice by increasing short-chain fatty acid metabolism and 5-hydroxytryptamine hormone release.
Lu Youyou,Zhang Junxue,Zhang Zhe,Liang Xi,Liu Tongjie,Yi Huaxi,Gong Pimin,Wang Lingli,Yang Wenjun,Zhang Xinyi,Zhang Lanwei,Yang Liuqing,Shi Hanping
Nutrition (Burbank, Los Angeles County, Calif.)
OBJECTIVES:Various probiotics and natural products can help to relieve constipation. This study aimed to explore the constipation-relieving effects and potential mechanism of a combination laxative of konjac glucomannan and probiotics. METHODS:This study evaluated the gastrointestinal-tract viability of probiotics in vitro. A constipation model was constructed in BALB/c mice, and the efficacies of the combinations verified in terms of their bowel movement-promoting effects, including the first black-stool defecation time and gastrointestinal transit rates of mice. Colonization by the probiotics was determined by quantitative real-time polymerase chain reaction. Hematoxylin-eosin staining, gas chromatography, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blot were also used for analysis. RESULTS:Lactobacillus paracasei X11 (X11) and L. casei YRL577 (YRL577) had outstanding gastrointestinal-tract viability. Konjac glucomannan (KGM) + X11, Prunus persica + X11, and Prunus persica + YRL577 significantly relieved constipation. In addition, KGM promoted the colonization of X11. Meanwhile, KGM + X11 effectively promoted the metabolism of short-chain fatty acids in mice better than other combinations, and the 5-hydroxytryptamine (5-HT) content in the KGM + X11 group was the highest among all the groups. Therefore, KGM + X11 was selected for further research. The combination laxative promoted the secretion of 5-HT, up-regulated mRNA and protein levels of 5-HT receptor 4 and serotonin transporter via the 5-HT pathway, and effectively relieved constipation. CONCLUSIONS:The combination laxative konjac glucomannan-probiotic (KGM + X11) promoted defecation in constipated mice, possibly by increasing short-chain fatty acid metabolism and 5-HT hormone release.
10.1016/j.nut.2020.111112
Fenchone Ameliorates Constipation-Predominant Irritable Bowel Syndrome via Modulation of SCF/c-Kit Pathway and Gut Microbiota.
Journal of microbiology and biotechnology
In this study we sought to elucidate the therapeutic effects of fenchone on constipation-predominant irritable bowel syndrome (IBS-C) and the underlying mechanisms. An IBS-C model was established in rats by administration of ice water by gavage for 14 days. Fenchone increased the reduced body weight, number of fecal pellets, fecal moisture, and intestinal transit rate, and decreased the enhanced visceral hypersensitivity in the rat model of IBS-C. In addition, fenchone increased the serum content of excitatory neurotransmitters and decreased the serum content of inhibitory neurotransmitters in the IBS-C rat model. Meanwhile, western blot and immunofluorescence experiments indicated that fenchone increased the expressions of SCF and c-Kit. Furthermore, compared with the IBS-C model group, fenchone increased the relative abundance of , , , , and , and reduced the relative abundance of , , , and on the genus level. Overall, fenchone ameliorates IBS-C via modulation of the SCF/c-Kit pathway and gut microbiota, and could therefore serve as a novel drug candidate against IBS-C.
10.4014/jmb.2308.08011
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
Dietary synbiotic ameliorates constipation through the modulation of gut microbiota and its metabolic function.
Yang Zhandong,Ye Simin,Xu Zengmei,Su Huihui,Tian Xing,Han Bo,Shen Baochun,Liao Qiongfeng,Xie Zhiyong,Hong Yanjun
Food research international (Ottawa, Ont.)
The purpose of this study is to investigate the mitigatory effect of a novel synbiotic (SBT) on constipation from the perspective of gut microbiome and metabolome. Here, intake of SBT effectively attenuated diphenoxylate-induced constipation, recuperated colonic epithelial integrity and increased serum levels of gastrointestinal excitatory neurotransmitters (P substance, vasoactive intestinal peptide, motilin, gastrin and serotonin). 16S rRNA sequencing showed that SBT intake rehabilitated the composition and functionality of gut microbiota. Relative abundances of short-chain fatty acids (SCFAs)-producing bacteria including Lactobacillus, Faecalibaculum and Bifidobacterium were elevated by administration of SBT. The gas chromatography-mass spectrometry analysis confirmed that fecal concentrations of propionate and butyrate were significantly increased in the rats intervened with SBT. In addition, SBT ingestion reduced the relative levels of opportunistic pathogens, such as Oscillibacter, Parasutterella and Parabacteroides. Microbial functional prediction showed that the relative abundances of lipopolysaccharide (LPS) biosynthesis and arachidonic acid metabolism were downregulated with SBT administration, which were in accordance with the serum metabolomics results. Furthermore, serum levels of LPS, tumour necrosis factor alpha and interleukin 6 were significantly decreased, indicating that SBT supplementation suppressed inflammatory responses. Therefore, this study demonstrated that consumption of SBT ameliorated constipation possibly by regulating gut microbiota, promoting the SCFAs production and inhibiting inflammatory responses in rats. Our study also indicated that SBT may provide a novel alternative strategy for the treatment of constipation clinically in future.
10.1016/j.foodres.2021.110569
Multi-omics analysis of fecal microbiota transplantation's impact on functional constipation and comorbid depression and anxiety.
BMC microbiology
BACKGROUND:Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted. METHODS:We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro. RESULTS:Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells. CONCLUSION:FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.
10.1186/s12866-023-03123-1
Enteric nervous system damage caused by abnormal intestinal butyrate metabolism may lead to functional constipation.
Frontiers in microbiology
Functional constipation (FC) is a high morbidity gastrointestinal disease for which dysfunction in the enteric nervous system is a major pathogenesis mechanism. To enhance our understanding of the involvement of intestinal microbiota and its metabolites in the pathogenesis of FC, we conducted a shotgun metagenomic sequencing analysis of gut microbiota and serum short-chain fatty acids (SCFAs) analysis in 460 Chinese women with different defecation frequencies. We observed that the abundance of, a butyric acid-producing bacterium, was positively correlated ( = 0.0096) with the frequency of defecation; however, the concentrations of serum butyric acid was negatively correlated ( = 3.51E-05) with defecation frequency. These results were verified in an independent cohort (6 patients with FC and 6 controls). To further study the effects of butyric acid on intestinal nerve cells, we treated mouse intestinal neurons with various concentrations of butyrate (0.1, 0.5, 1, and 2.5 mM). We found that intestinal neurons treated with 0.5 mM butyrate proliferated better than those in the other treatment groups, with significant differences in cell cycle and oxidative phosphorylation signal pathways. We suggest that the decreased butyrate production resulting from the reduced abundance of in gut microbiota affects the proliferation of intestinal neurons and the energy supply of intestinal cells. However, with FC disease advancing, the consumption and excretion of butyric acid reduce, leading to its accumulation in the intestine. Moreover, the accumulation of an excessively high amount of butyric acid inhibits the proliferation of nerve cells and subsequently exacerbates the disease.
10.3389/fmicb.2023.1117905
CCFM1163 Alleviated Cathartic Colon by Regulating the Intestinal Barrier and Restoring Enteric Nerves.
Nutrients
Cathartic colon (CC), a type of slow-transit constipation caused by the long-term use of stimulant laxatives, does not have a precise and effective treatment. This study aimed to evaluate the ability of CCFM1163 to relieve CC and to investigate its underlying mechanism. Male C57BL/6J mice were treated with senna extract for 8 weeks, followed by a 2-week treatment with CCFM1163. The results revealed that CCFM1163 effectively alleviated CC symptoms. The possible mechanism of CCFM1163 in relieving CC was analyzed by measuring the intestinal barrier and enteric nervous system (ENS)-related indices and establishing a correlation between each index and gut microbiota. The results indicated that CCFM1163 changed the gut microbiota by significantly increasing the relative abundance of and as well as the content of short-chain fatty acids, especially propionic acid, in the feces. This increased the expression of tight junction proteins and aquaporin 8, decreased intestinal transit time, increased fecal water content, and relieved CC. In addition, CCFM1163 also increased the relative abundance of in feces and the expression of enteric nerve marker proteins to repair the ENS, promote intestinal motility, and relieve constipation.
10.3390/nu15051146