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Frontiers in Microbiology 2022Treatments targeted for gut microbial regulation are newly developed strategies in constipation management. In this study, the alleviating effects of gut...
Treatments targeted for gut microbial regulation are newly developed strategies in constipation management. In this study, the alleviating effects of gut micro-ecologically regulatory treatments on constipation in mice were investigated. Male BALB/c mice were treated with loperamide to induce constipation, and then the corresponding intervention was administered in each group, respectively. The results showed that administration of mixed probiotics (MP), a 5-fold dose of postbiotics (P5), both synbiotics (S and S2), as well as mixed probiotics and postbiotics (MPP) blend for 8 days shortened the time to the first black stool, raised fecal water content, promoted intestinal motility, and increased serum motilin level in loperamide-treated mice. Furthermore, these treatments altered gut microbial composition and metabolism of short-chain fatty acids (SCFA). Based on linear regression analysis, SCFA was positively correlated with serum motilin except for isobutyrate. It suggested gut microbial metabolites affected secretion of motilin to increase gastrointestinal movement and transportation function and thus improved pathological symptoms of mice with constipation. In conclusion, the alteration of gut micro-ecology is closely associated with gastrointestinal function, and it is an effective way to improve constipation probiotic, prebiotic, and postbiotic treatment.
PubMed: 36016793
DOI: 10.3389/fmicb.2022.956438 -
RSC Advances Mar 2020KFY02 (KFY02), isolated from naturally fermented milk yoghurt in Korla, Xinjiang, Northwest of China, showed gardenoside action for the intestinal regulation of...
KFY02 (KFY02), isolated from naturally fermented milk yoghurt in Korla, Xinjiang, Northwest of China, showed gardenoside action for the intestinal regulation of constipated mice. Comparatively, the effects of KFY02 (0.5 × 10 CFU kg, by body weight (BW)), gardenoside (50 mg kg, BW), and KFY02 (0.5 × 10 CFU kg, BW) + gardenoside (50 mg kg, BW) on intestinal regulation in mice with montmorillonite-induced constipation were also studied. Enzyme linked immunoassay, hemotoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) assay and high performance liquid chromatography (HPLC) analysis were used for the study. Compared with the model group, KFY02 + genipin (combined group) increased the propelling rate of activated carbon in the small intestines of mice and accelerated the discharge of the first black stool in mice. At the same time, the combination group reduced the levels of motilin (MTL), substance P (SP) and endothelin-1 (ET-1) in the serum, and increased the somatostatin (SS), vasoactive intestinal peptide (VIP), acetylcholinesterase (AchE) and gastrin (Gastrin) levels in the serum, which made these parameters close to those of the normal group. Using qPCR analysis, it was observed that the combined group up-regulated the mRNA expression of endothelial nitric oxide synthase (eNOS), stem cell factor (SCF), stem cell factor receptor (c-Kit), glutathione (GSH), catalase and manganese-superoxide dismutase (Mn-SOD) and down-regulated the expression of inducible nitric oxide synthase (iNOS) and transient receptor potential vanilloid receptor 1 (TRPV1). The combination increased the and abundances and decreased the abundance in the feces of the constipated mice and decreased the / ratio. The expression of the above genes was similar to that of the normal group. The results indicate that KFY02 produced β-glucosidase to hydrolyze the gardenoside glycosidic bond to produce genipin and can effectively promote the regulation of gastrointestinal hormones and intestinal peristalsis and reduce oxidative tissue damage in constipated mice. This study also confirmed that KFY02 has similar relieving effects to gardenoside for constipation in mice.
PubMed: 35498605
DOI: 10.1039/c9ra10446a -
Journal of Traditional Chinese Medicine... Jun 2023To observe and explore the effect of Fuling () in alleviating the spleen deficiency symptom pattern (SDSP).
OBJECTIVE
To observe and explore the effect of Fuling () in alleviating the spleen deficiency symptom pattern (SDSP).
METHODS
We established an animal model of SDS in Sprague-Dawley () rats by treating them with deficiency-inducing factors, including irregular feeding and tail clamping. Mice were administered Fuling () and its extracts (raw/cooked powder, aqueous/alcohol extract) by gavage once a day for 21 d. The body weight, rectal temperature, and spleen and thymus organ coefficients were calculated. The levels of motilin (MTL), gastrin (GAS), aquaporin 2 (AQP2), interleukin 2 (IL-2), IL-4, and 5-hydroxytryptamine (5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay.
RESULTS
Fuling () and its extracts did not change the body weight, rectal temperature, and organ coefficients of the spleen and thymus. However, it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2. In addition, the levels of IL-4 and 5-HT showed no significant alteration.
CONCLUSIONS
These results suggested the crucial function of () in SDSP, especially promoting digestive function and water metabolism.
Topics: Rats; Mice; Animals; Rats, Sprague-Dawley; Spleen; Interleukin-2; Wolfiporia; Interleukin-4; Serotonin; Aquaporin 2; Body Weight; Gastrins
PubMed: 37147751
DOI: 10.19852/j.cnki.jtcm.2023.03.002 -
Frontiers in Nutrition 2022Slow transit constipation (STC) is a common disorder in the digestive system. This study aimed to evaluate the effects of stachyose (ST) and Furu 2019 () alone or...
INTRODUCTION
Slow transit constipation (STC) is a common disorder in the digestive system. This study aimed to evaluate the effects of stachyose (ST) and Furu 2019 () alone or combined on diphenoxylate-induced constipation and explore the underlying mechanisms using a mouse model.
METHODS
ICR mice were randomly divided into five groups. The normal and constipation model groups were intragastrically administrated with PBS. The ST, , and synbiotic groups were intragastrically administrated with ST (1.5 g/kg body weight), alive (3 × 10 CFU/mouse), or ST + (1.5 g/kg plus 3 × 10 CFU/mouse), respectively. After 21 days of intervention, all mice except the normal mice were intragastrically administrated with diphenoxylate (10 mg/kg body weight). Defecation indexes, constipation-related intestinal factors, serum neurotransmitters, hormone levels, short-chain fatty acids (SCFAs), and intestinal microbiota were measured.
RESULTS
Our results showed that three interventions with ST, , and synbiotic combination (ST + . sakei) all alleviated constipation, and synbiotic intervention was superior to ST or alone in some defecation indicators. The RT-PCR and immunohistochemical experiment showed that all three interventions relieved constipation by affecting aquaporins (AQP4 and AQP8), interstitial cells of Cajal (SCF and c-Kit), glial cell-derived neurotrophic factor (GDNF), and Nitric Oxide Synthase (NOS). The three interventions exhibited a different ability to increase the serum excitatory neurotransmitters and hormones (5-hydroxytryptamine, substance P, motilin), and reduce the serum inhibitory neurotransmitters (vasoactive intestinal peptide, endothelin). The result of 16S rDNA sequencing of feces showed that synbiotic intervention significantly increased the relative abundance of beneficial bacteria such as , and regulated the gut microbes of STC mice. In conclusion, oral administration of ST or alone or combined are all effective to relieve constipation and the symbiotic use may have a promising preventive effect on STC.
PubMed: 36687730
DOI: 10.3389/fnut.2022.1039403 -
Nutrients Aug 2023Slow transit constipation (STC) is a prevalent gastrointestinal condition with slow transit, and some probiotics can effectively relieve constipation, but the exact...
Slow transit constipation (STC) is a prevalent gastrointestinal condition with slow transit, and some probiotics can effectively relieve constipation, but the exact mechanisms have not been fully understood. In this study, we evaluate the impact of GUANKE (GUANKE) on diphenoxylate-induced slow transit constipation and speculate on the underlying mechanisms in a mouse model. Administration of GUANKE alleviated constipation indexes, including defecation time, fecal output and water content, and gastrointestinal transit ratio. In addition, GUANKE restored the protein expression of constipation-related intestinal factors (aquaporins (AQPs) and interstitial Cajal cells (ICCs)) in colon tissues measured using immunofluorescence staining; regulated the neurotransmitters and hormones, such as increased levels of 5-hydroxytryptamine, substance P, and motilin; and decreased levels of vasoactive intestinal peptide and nitric oxide in serum, as measured by an ELISA. 16S rRNA and correlation analysis of feces indicated that GUANKE administration effectively reduced constipation-induced enrichment and suggested a potential contribution of to diphenoxylate-induced STC in mice. GUANKE had no effect on short-chain fatty acids (SCFAs) in cecum content. This study revealed that GUANKE may alleviate constipation in mice through regulating intestinal neurotransmitter and hormone release and altering specific bacterial taxa, rather than by affecting SCFAs and the diversity of microbiota in the gut. Further research is needed to confirm if the findings observed in this study will be consistent in other animal studies or clinical trials.
Topics: Animals; Mice; Gastrointestinal Microbiome; Diphenoxylate; RNA, Ribosomal, 16S; Constipation
PubMed: 37686774
DOI: 10.3390/nu15173741 -
Frontiers in Endocrinology 2024Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the...
INTRODUCTION
Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the migratory motor complex. It is understudied at least in part due to the lack of commercially available immunoassays.
METHOD
A multiplexed liquid chromatography mass spectrometry (LC-MS/MS) method was optimised to measure motilin, insulin, C-peptide, GIP (1-42) and GIP (3-42). Corresponding active ghrelin concentrations were determined by immunoassay. Ten healthy volunteers with no prior history of gastroenterological or endocrine condition attended after overnight fast and had blood samples taken every 15 minutes for 4 hours whilst continuing to fast, and then further sampling for 2 hours following a liquid mixed meal. Hunger scores were taken at each time point using a visual analogue scale. Normal bowel habit was confirmed by 1 week stool diary.
RESULTS
Motilin levels fluctuated in the fasting state with an average period between peaks of 109.5 mins (SD:30.0), but with no evidence of a relationship with either ghrelin levels or hunger scores. The mixed meal interrupted cyclical motilin fluctuations, increased concentrations of motilin, insulin, C-peptide, GIP(1-42) and GIP(3-42), and suppressed ghrelin levels.
DISCUSSION
This study highlights the utility of LC-MS/MS for parallel measurement of motilin alongside other peptide hormones, and supports previous reports of the cyclical nature of motilin levels in the fasting state and interruption with feeding. This analytical method has utility for further clinical studies into motilin and gut hormone physiology in human volunteers.
Topics: Humans; Motilin; Ghrelin; Healthy Volunteers; C-Peptide; Chromatography, Liquid; Liquid Chromatography-Mass Spectrometry; Duodenum; Tandem Mass Spectrometry
PubMed: 38544692
DOI: 10.3389/fendo.2024.1348146 -
Biochemical and Biophysical Research... Oct 2023The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled...
The peptide hormone ghrelin (an agonist) and LEAP2 (an antagonist) play important functions in energy metabolism via their receptor GHSR, an A-class G protein-coupled receptor. Ghrelin, LEAP2, and GHSR are widely present from fishes to mammals. However, our recent study suggested that fish GHSRs have different binding properties to ghrelin: a GHSR from the lobe-finned fish Latimeria chalumnae (coelacanth) is efficiently activated by ghrelin, but GHSRs from the ray-finned fish Danio rerio (zebrafish) and Larimichthys crocea (large yellow croaker) have lost binding to ghrelin. Do fish GHSRs use another peptide as their agonist? In the present study we tested to two fish motilins from D. rerio and L. chalumnae because motilin is distantly related to ghrelin. In ligand binding and activation assays, the fish GHSRs from D. rerio and L. crocea displayed no detectable or very low binding to all tested motilins; however, the fish GHSR from L. chalumnae bound to its motilin with high affinity and was efficiently activated by it. Therefore, it seemed that motilin is not a ligand for GHSR in the ray-finned fish D. rerio and L. crocea, but is an efficient agonist for GHSR in the lobe-finned fish L. chalumnae, one of the closest fish relatives of tetrapods. The results of present study suggested that GHSR might have two efficient agonists, ghrelin and motilin, in ancient fishes; however, this feature might be only preserved in some extant fishes with ancient evolutionary origins.
PubMed: 37677979
DOI: 10.1016/j.bbrc.2023.09.002 -
Clinical and Translational... Apr 2022Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal...
INTRODUCTION
Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal pain.
METHODS
To ascertain the genetic risk factors for gastroparesis, we conducted the largest thus far whole-genome sequencing study of gastroparesis. We investigated the frequency and effect of rare loss-of-function variants in patients with both idiopathic and diabetic gastroparesis enrolled in a clinical study of gastroparesis.
RESULTS
Among rare loss-of-function variants, we reported an increased frequency of a frameshift mutation p.Leu202ArgfsTer105, within the motilin receptor gene, variant rs562138828 (odds ratio 4.9). We currently replicated this finding in an independent large cohort of gastroparesis samples obtained from patients participating in the ongoing phase III gastroparesis clinical study.
DISCUSSION
Motilin receptor is an important therapeutic target for the treatment of hypomotility disorders. The identified genetic variants may be important risk factors for disease as well as may inform treatments, especially those targeting motilin receptor.
Topics: Gastroparesis; Humans; Nausea; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Vomiting
PubMed: 35297797
DOI: 10.14309/ctg.0000000000000474 -
Experimental and Therapeutic Medicine May 2023Functional constipation (FC), a common symptom that is primarily associated with intestinal motility dysfunction, is a common problem worldwide. Arctiin (Arc) is a...
Functional constipation (FC), a common symptom that is primarily associated with intestinal motility dysfunction, is a common problem worldwide. Arctiin (Arc) is a lignan glycoside isolated from the Chinese herbal medicine , which is a health food in China. The present study aimed to evaluate the laxative effects of Arc against FC in mice. A model of FC induced by loperamide (5 mg/kg) was established in male Institute of Cancer Research (ICR) mice. Arc was administered at a dose of 100 mg/kg as a protective agent. The faecal status, intestinal motility and histological analyses were evaluated. Furthermore, the levels of gastrointestinal motility-associated neurotransmitters, such as motilin (MTL), nitric oxide (NO), and brain-derived neurotrophic factor (BDNF) and the protective effect of Arc on interstitial cells of Cajal (ICC) were assessed. Arc treatment reversed the loperamide-induced reduction in faecal number and water content and the intestinal transit ratio in ICR mice. Histological analysis confirmed that Arc administration mitigated colonic injury. Moreover, Arc treatment increased levels of motilin and brain-derived neurotrophic factor while decreasing nitric oxide levels and ICC injury in the colon of FC mice. Arc decreased inflammation induction and aquaporin expression levels. Owing to its pro-intestinal motility property, Arc was shown to have a protective effect against FC and may thus serve as a promising therapeutic strategy for the management of FC.
PubMed: 37090075
DOI: 10.3892/etm.2023.11898 -
Frontiers in Pharmacology 2023Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the...
Motilin (MLN) is a gastrointestinal (GI) hormone produced in the upper small intestine. Its most well understood function is to participate in Phase III of the migrating myoelectric complex component of GI motility. Changes in MLN availability are associated with GI diseases such as gastroesophageal reflux disease and functional dyspepsia. Furthermore, herbal medicines have been used for several years to treat various GI disorders. We systematically reviewed clinical and animal studies on how herbal medicine affects the modulation of MLN and subsequently brings the therapeutic effects mainly focused on GI function. We searched the PubMed, Embase, Cochrane, and Web of Science databases to collect all articles published until 30 July 2023, that reported the measurement of plasma MLN levels in human randomized controlled trials and herbal medicine studies. The collected characteristics of the articles included the name and ingredients of the herbal medicine, physiological and symptomatic changes after administering the herbal medicine, changes in plasma MLN levels, key findings, and mechanisms of action. The frequency patterns (FPs) of botanical drug use and their correlations were investigated using an FP growth algorithm. Nine clinical studies with 1,308 participants and 20 animal studies were included in the final analyses. Herbal medicines in clinical studies have shown therapeutic effects in association with increased levels of MLN, including GI motility regulation and symptom improvement. Herbal medicines have also shown anti-stress, anti-tumor, and anti-inflammatory effects . Various biochemical markers may correlate with MLN levels. Markers may have a positive correlation with plasma MLN levels included ghrelin, acetylcholine, and secretin, whereas a negative correlation included triglycerides and prostaglandin E. Markers, such as gastrin and somatostatin, did not show any correlation with plasma MLN levels. Based on the FP growth algorithm, and were the most frequently used species. Herbal medicine may have therapeutic effects mainly on GI symptoms with involvement of MLN regulation and may be considered as an alternative option for the treatment of GI diseases. Further studies with more solid evidence are needed to confirm the efficacy and mechanisms of action of herbal medicines. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=443244, identifier CRD42023443244.
PubMed: 38161695
DOI: 10.3389/fphar.2023.1286333