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

doi:10.3168/jds.2020-19449

Cited by 21 publications

(9 citation statements)

References 48 publications

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“…Since the 7th day, we found the weight in the STC group was slightly lower than normal ( p < 0.01), but the PTE treatment group was relieved ( p < 0.05) ( Figure 1A ). According to previous studies, the time of the first black stool was used to access the whole gut transit ability ( Li T. et al, 2021 ). Compared with the CON group, the whole gut transit time was longer in the STC group ( p < 0.05), the number of defecation particles and the water content was reduced ( p < 0.05); In addition, the above indicators after PTE administration could be restored to the level of the CON group ( p < 0.05) ( Figures 1C–E ).…”

Section: Resultsmentioning

confidence: 99%

Based on Network Pharmacology and Gut Microbiota Analysis to Investigate the Mechanism of the Laxative Effect of Pterostilbene on Loperamide-Induced Slow Transit Constipation in Mice

Yao

Ren

et al. 2022

Front. Pharmacol.

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Background: Pterostilbene (PTE) is a natural polyphenol compound that has been proven to improve intestinal inflammation, but its laxative effect on slow transit constipation (STC) has never been studied. This study aims to investigate the laxative effect of PTE on loperamide (LOP)-induced STC mice and its influence on intestinal microbes through a combination of network pharmacological analysis and experimental verification.Material and Methods: PTE was used to treat LOP-exposed mice, and the laxative effect of PTE was evaluated by the total intestinal transit time and stool parameters. The apoptosis of Cajal interstitial cells (ICCs) was detected by immunofluorescence. The mechanism of PTE’s laxative effect was predicted by network pharmacology analysis. We used western blot technology to verify the predicted hub genes and pathways. Malondialdehyde (MDA) and GSH-Px were tested to reflect oxidative stress levels and the changes of gut microbiota were detected by 16S rDNA high-throughput sequencing.Results: PTE treatment could significantly improve the intestinal motility disorder caused by LOP. Apoptosis of ICCs increased in the STC group, but decreased significantly in the PTE intervention group. Through network pharmacological analysis, PTE might reduce the apoptosis of ICCs by enhancing PI3K/AKT and Nrf2/HO-1 signaling, and improve constipation caused by LOP. In colon tissues, PTE improved the Nrf2/HO-1 pathway and upregulated the phosphorylation of AKT. The level of MDA increased and GSH-Px decreased in the STC group, while the level of oxidative stress was significantly reduced in the PTE treatment groups. PTE also promoted the secretion of intestinal hormone and restored the microbial diversity caused by LOP.Conclusion: Pterostilbene ameliorated the intestinal motility disorder induced by LOP, this effect might be achieved by inhibiting oxidative stress-induced apoptosis of ICCs through the PI3K/AKT/Nrf2 signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Based on Network Pharmacology and Gut Microbiota Analysis to Investigate the Mechanism of the Laxative Effect of Pterostilbene on Loperamide-Induced Slow Transit Constipation in Mice

Yao

Ren

et al. 2022

Front. Pharmacol.

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“…The decrease in the number and viability of ICC cells is related to the pathogenesis of many human diseases, such as chronic unexplained nausea and vomiting, small intestinal obstruction, streptozotocin-induced diabetes, and gastric dysrhythmia in STC (Li et al, 2021;Mawani et al, 2019;Kawahara et al, 2021;Kim et al, 2020;Yu et al, 2020;Cangemi et al, 2019). ICC plays an important role in regulating intestinal movement by acting as a pacemaker for gastrointestinal muscles (De Pablo-Fernandez et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Effect of miR-129-3p on autophagy of interstitial cells of Cajal in slow transit constipation through SCF C-kit signaling pathway

et al. 2022

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Objective: To explore the mechanism by which miR-129-3p affected the autophagy of interstitial cells of Cajal (ICCs) in slow transit constipation tissues through the SCF C-kit signaling pathway. Methods: Colon samples from 20 Slow transit constipation (STC) patients who underwent total colectomy plus ileorectal anastomosis or subtotal colon resection plus anti-peristaltic rectal anastomosis were collected in our hospital. The colon of 20 non-STC patients was used as control. The control of this study was 20 patients undergoing radical surgery for colon cancer (left colon cancer) in our hospital. Fifty healthy SPF Kunming mice were purchased from Liaoning Changsheng Biotechnology Co., Ltd. Results: The mRNA expression of miR-129-3p in the STC group was lower than that in the control group (CTLR) group (P<0.05). The mRNA expression of miR-129-3p in STC group was lower than that in the NC group (P<0.05), and mRNA expression in STC+miR-129-3p group was higher than that in STC+miR-NC group (P<0.05). In the first week, the weight of dry and wet feces of the STC group was lower than that of the NC mice (P<0.05), and the weight of dry feces and wet feces of the STC group was lower than that of the NC group at the 2, 3, and 4 weeks, STC+miR-129 -3p was higher than that in the STC group (P<0.05). Conclusion: The increased expression of C-kit and SCF regulated by miR-129-3p contributed to the protection of interstitial cells. Knockdown of miR-129-3p expression could inhibit the activation of AKT/mTOR signaling pathway, reduce cell proliferation activity.

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“…Published studies indicated that the expression of SCF and c-Kit gene was decreased in STC model rats, and the effectiveness of treatment for constipation can be blocked by inhibiting SCF/c-Kit pathways [ 36 ]. To summarize, the SCF/c-Kit signaling pathway is a promising therapeutic target for STC treatment [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats

Kuang

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. The pathogenesis of slow transit constipation (STC) is associated with exosomal miR-34c-5p. Electroacupuncture (EA) improves gastrointestinal motility in gastrointestinal disorders, especially STC. Our study aimed to explore the mechanism by which EA improves intestinal motility by modulating the release of exosomes and the transmission of exosomal miR-34c-5p. Methods. Fifty rats were randomly divided into five groups. STC model rats were induced, and GW4869, the exosome release inhibitor, was used to inhibit the release of exosome. The serum exosomes were authenticated under a transmission electron microscope and nanoparticle tracking analysis. RT-qPCR detected the expression of miR-34c-5p in serum exosomes and colonic tissues. The fecal number in 24 hours, Bristol scores, and intestinal transit rates were used to assess intestinal motility. Subsequently, hematoxylin and eosin (H&E) staining was used to examine the colonic mucosal histology. Finally, the expression of stem cell factor (SCF) and receptor tyrosine kinase (c-Kit) protein was measured using immunohistochemistry staining. Results. We found that EA upregulated exosomal miR-34c-5p in serum and downregulated miR-34c-5p in colonic tissues ( P < 0.01 ). EA improved fecal numbers in 24 hours, Bristol scores, and intestinal transit rates in STC rats ( P < 0.01 ). EA recovered the colonic histological structure and enhanced the expression of SCF and c-Kit protein ( P < 0.01 ). The therapeutic effect of EA was attenuated after inhibiting the release of the exosome. Conclusion. Our results indicated that EA improves intestinal motility in STC rats by transporting of exosomal miR-34c-5p targeting the SCF/c-Kit signaling pathway.

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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

Cited by 21 publications

References 48 publications

Based on Network Pharmacology and Gut Microbiota Analysis to Investigate the Mechanism of the Laxative Effect of Pterostilbene on Loperamide-Induced Slow Transit Constipation in Mice

Based on Network Pharmacology and Gut Microbiota Analysis to Investigate the Mechanism of the Laxative Effect of Pterostilbene on Loperamide-Induced Slow Transit Constipation in Mice

Effect of miR-129-3p on autophagy of interstitial cells of Cajal in slow transit constipation through SCF C-kit signaling pathway

Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats

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