scholarly journals Melatonin-Mediated Colonic Microbiota Metabolite Butyrate Prevents Acute Sleep Deprivation-Induced Colitis in Mice

2021 ◽  
Vol 22 (21) ◽  
pp. 11894
Author(s):  
Ting Gao ◽  
Zixu Wang ◽  
Yulan Dong ◽  
Jing Cao ◽  
Yaoxing Chen
Keyword(s):  
Gut Microbiota ◽  
Sleep Deprivation ◽  
High Throughput Sequencing ◽  
Fecal Microbiota Transplantation ◽  
In Vitro Tests ◽  
Melatonin Level ◽  
Radical Cure ◽  
Plasma Melatonin ◽  
Gsk 3Β

Radical cure colitis is a severe public health threat worldwide. Our previous studies have confirmed that melatonin can effectively improve gut microbiota disorder and mucosal injury caused by sleep deprivation (SD). The present study further explored the mechanism whereby exogenous melatonin prevented SD-induced colitis. 16S rRNA high-throughput sequencing and metabolomics analysis were used to explore the correlation between SD-induced colitis and intestinal microbiota and metabolite composition in mice. Fecal microbiota transplantation (FMT) and melatonin or butyrate supplementation tests verified the core role of gut microbiota in melatonin-alleviating SD-induced colitis. Further, in vitro tests studied the modulatory mechanism of metabolite butyrate. The results demonstrated that SD leads to reductions in plasma melatonin levels and colonic Card9 expression and consequent occurrence of colitis and gut microbiota disorder, especially the downregulation of Faecalibacterium and butyrate levels. The FMT from SD-mice to normal mice could restore SD-like colitis, while butyrate supplementation to SD-mice inhibited the occurrence of colitis, but with no change in the plasma melatonin level in both treatments. However, melatonin supplementation reversed all inductions in SD-mice. In intestinal epithelial cells, the inflammatory ameliorative effect of butyrate was blocked with pretreatments of HDAC3 agonist and HIF-1α antagonist but was mimicked by GSK-3β and p-P65 antagonists. Therefore, the administration of MLT may be a better therapy for SD-induced colitis relative to butyrate. A feasible mechanism would involve that melatonin up-regulated the Faecalibacterium population and production of its metabolite butyrate and MCT1 expression and inhibited HDAC3 in the colon, which would allow p-GSK-3β/β-catenin/HIF-1α activation and NF-κB/NLRP3 suppression to up-regulate Card9 expression and suppress inflammation response.

scholarly journals Inhibitory Effects of Apigenin on Tumor Carcinogenesis by Altering the Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Shichang Bian ◽  
Hongjuan Wan ◽  
Xinyan Liao ◽  
Weisheng Wang
Keyword(s):  
Colon Cancer ◽  
Treatment Group ◽  
16S Rrna ◽  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Potential Mechanism ◽  
Inhibitory Effects ◽  
Antitumor Effects

The flavonoid apigenin is common to many plants. Although the responsible mechanisms have yet to be elucidated, apigenin demonstrates tumor suppression in vitro and in vivo. This study uses an azoxymethane (AOM)/dextran sodium sulfate- (DSS-) induced colon cancer mouse model to investigate apigenin’s potential mechanism of action exerted through its effects upon gut microbiota. The size and quantity of tumors were reduced significantly in the apigenin treatment group. Using 16S rRNA high-throughput sequencing of fecal samples, the composition of gut microbiota was significantly affected by apigenin. Further experiments in which gut microbiota were reduced and feces were transplanted provided further evidence of apigenin-modulated gut microbiota exerting antitumor effects. Apigenin was unable to reduce the number or size of tumors when gut microbiota were depleted. Moreover, tumor inhibition effects were initiated following the transplant of feces from mice treated with apigenin. Our findings suggest that the effect of apigenin on the composition of gut microbiota can suppress tumors.

scholarly journals A118 GUT MICROBIOTA TRANSPLANTATION FROM A PATIENT WITH SEVERE CONSTIPATION INDUCED CHANGES IN COLONIC FUNCTION AND STRUCTUR OF GNOTOBIOTIC MICE

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 137-138
Author(s):  
X Bai ◽  
G De Palma ◽  
J Lu ◽  
S M Collins ◽  
P Bercik
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Colonic Transit ◽  
Slow Transit Constipation ◽  
Antibiotic Exposure ◽  
Ach Release ◽  
Germ Free ◽  
Gi Transit

Abstract Background Increasing evidence suggests that gut microbiota play a key role in gastrointestinal (GI) tract function. We have previously shown that fecal microbiota transplantation diarrhea predominant IBS patients into germ-free mice induces faster GI transit, increased permeability and innate immune activation. However, it is unknown whether gut dysfunction is induced by microbiota from patients with chronic constipation. Aims Here, we investigated the role of the intestinal microbiota in the expression of severe slow transit constipation in a patient with previous C difficile infection and extensive antibiotic exposure. Methods Germ-free (GF) mice (14 weeks old) were gavaged with diluted fecal content from the patient with constipation (PA) or a sex and age-matched healthy control (HC). 12 weeks later, we assessed gut motility and GI transit using videofluoroscopy and a bead expulsion test.. We then investigated intestinal and colonic smooth muscle isometric contraction in vitro using electric field stimulation (EFS), and acetylcholine (Ach) release was assessed by superfusion using [3H] choline. Histological changes were evaluated by H&E and immunohistochemistry. Results Mice with PA microbiota had faster whole GI transit (score 18.9 ± 0.9 (N=9) than mice with HC microbiota (15.4 ± 1.0, N=10, p=0.032), with markers located mainly in the distal small bowel and cecum. However, bead expulsion from the colon was significantly longer in PA mice (420.8 s ± 124.6 s, N=9) than in HC mice (82.6 s ± 20.0 s, N=10, p=0.026). This delayed colonic transit was likely due to colonic retroperistalsis visualized videofluoroscopically by retrograde flow of barium in the right colon of PA mice. There was no difference between the two groups in small intestinal or colonic tissues in Ach release or contractility induced by carbachol or KCl,. EFS caused transient biphasic relaxation and contraction in small intestine and colon, with the colonic contraction being stronger in the PA group. Microscopic tissue analysis showed disruption of the interstitial cells of Cajal (ICC) network and increased lymphocyte infiltration in colonic mucosa and submucosa in PA mice. Conclusions These results indicate that the microbiota is a driver of delayed colonic transit in a patient whose constipation started following extensive antibiotic exposure for C. difficile infection. The observed dysmotility pattern was not due to lower muscle contractility but likely caused by immune mediated changes in the ICC network. Funding Agencies CIHR

Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases

2016 ◽  
Vol 34 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Giovanni Cammarota ◽  
Silvia Pecere ◽  
Gianluca Ianiro ◽  
Luca Masucci ◽  
Diego Currò
Keyword(s):  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Causative Role ◽  
Gastrointestinal Microbiota ◽  
Treatment Protocols ◽  
Irritable Bowel ◽  
Cure Rates

Fecal microbiota transplantation (FMT), a process by which the normal gastrointestinal microbiota is restored, has demonstrated extraordinary cure rates for Clostridium difficile infection and low recurrence. The community of microorganisms within the human gut (or microbiota) is critical to health status and functions; therefore, together with the rise of FMT, the gastrointestinal microbiota has emerged as a ‘virtual' organ with a level of complexity comparable to that of any other organ system and capable to compete with powerful known antibiotics for the treatment of several disorders. Although treatment protocols, donor selection, stool preparation and delivery methods varied widely, with a few reports following an identical protocol, FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). FMT can be relatively simple to perform, but a number of challenges need to be overcome before this procedure is widely accepted in clinical practice, and currently, there is no consensus between the various gastrointestinal organizations and societies regarding the FMT procedure. In this article, we describe the modern high-throughput sequencing techniques to characterize the composition of gut microbiota and the potential for therapeutics by manipulating microbiota with FMT in several gastrointestinal disorders (C. difficile-associated diarrhea, IBD and IBS), with a look on the potential future directions of FMT.

scholarly journals Effects of Sleep Deprivation on Weight Loss and Gut Microbiota Diversity in Obese Patients on a Calorie Restrict Diet

2021 ◽  
Author(s):  
Surong Wen ◽  
Yaojun Ni ◽  
Ziyu Liu ◽  
Xiaoqing Wang ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gut Microbiota ◽  
Sleep Deprivation ◽  
High Throughput Sequencing ◽  
Resistance Index ◽  
The Body ◽  
Obese Patients ◽  
Anthropometric Parameters ◽  
Deprivation Group ◽  
Microbiota Diversity

Abstract Objective: This study aimed to investigate the effects of sleep deprivation (SD) on the weight loss and gut microbiota diversity in obese patients on a calorie restrict diet (CRD). Methods: Twenty obese patients who were divided into two groups: sleep deprivation group(SD group,n=10) and non-sleep deprivation group(NSD group ,n=10). All the patients received CRD for twelve weeks. Measurement of anthropometric parameters, biochemical examinations and gut microbiota detection were done at baseline and the end of week 12. MI Bands were used to monitor the sleep and exercise. Body shape parameters were measured by using the JAWON ioi353. The gut microbiota was examined by PCR in the v3-v5 region of 16S rDNA gene, and high-throughput sequencing was carried out on the Illumina Miseq platform. The operational taxonomic units (OTUs) was used for analysis. Results: 1. CRD improved the body weight (BW) , waist circumference(WC), blood pressure (BP),basal metabolic rate (BMR) ,body fat content(BFC),and Insulin resistance index (HOMA-IR) in all obese patients. 2. In the NSD group, the BW, BFC, VFA, BMR and total cholesterol (TC) reduced significantly when compared with the NSD group after CRD intervention (P<0.05). 3. The Alpha diversity of gut microbiota remained unchanged after the intervention in two groups after CRD intervention. 4. There was a negative correlation between Mollicutes and BMR in the NSD group. Conclusion: The effects of CRD may be weaken by SD in weight loss and the metabolism of blood lipid. Mollicutes bacteria may be related to the weight loss after CRD intervention in obese patients.

scholarly journals Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao-Ming Xu ◽  
Hong-Li Huang ◽  
Jing Xu ◽  
Jie He ◽  
Chong Zhao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Butyric Acid ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
16S Sequencing ◽  
Α Diversity ◽  
The Impact

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

scholarly journals Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Xuelian Tang ◽  
Weijun Wang ◽  
Gaichao Hong ◽  
Caihan Duan ◽  
Siran Zhu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Epithelium ◽  
Intestinal Inflammation ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Epithelial Barrier ◽  
16S Rrna Analysis ◽  
New Strategy

Abstract Background and aims Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. Methods Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. Results The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria—Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. Conclusion Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

scholarly journals Alteration of Gut Microbiota in Carbapenem-Resistant Enterobacteriaceae Carriers during Fecal Microbiota Transplantation According to Decolonization Periods

2021 ◽  
Vol 9 (2) ◽  
pp. 352
Author(s):  
Jin-Jae Lee ◽  
Dongeun Yong ◽  
Ki Tae Suk ◽  
Dong Joon Kim ◽  
Heung-Jeong Woo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Throughput Sequencing ◽  
Rectal Swab ◽  
Fecal Microbiota Transplantation ◽  
Therapeutic Option ◽  
Fecal Microbiota ◽  
Carbapenem Resistant ◽  
Before And After ◽  
Serial Samples ◽  
Carbapenem Resistant Enterobacteriaceae

Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.

scholarly journals Effects of Antibiotic Pretreatment of an Ulcerative Colitis-Derived Fecal Microbial Community on the Integration of Therapeutic Bacteria In Vitro

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Kaitlyn Oliphant ◽  
Kyla Cochrane ◽  
Kathleen Schroeter ◽  
Michelle C. Daigneault ◽  
Sandi Yen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Microbial Community ◽  
Side Effects ◽  
Antimicrobial Resistance ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Clinical Success ◽  
Distinct Species ◽  
Fecal Microbiota

ABSTRACT Fecal microbiota transplantation (FMT) is a proposedly useful strategy for the treatment of gastrointestinal (GI) disorders through remediation of the patient gut microbiota. However, its therapeutic success has been variable, necessitating research to uncover mechanisms that improve patient response. Antibiotic pretreatment has been proposed as one method to enhance the success rate by increasing niche availability for introduced species. Several limitations hinder exploring this hypothesis in clinical studies, such as deleterious side effects and the development of antimicrobial resistance in patients. Thus, the purpose of this study was to evaluate the use of an in vitro, bioreactor-based, colonic ecosystem model as a form of preclinical testing by determining how pretreatment with the antibiotic rifaximin influenced engraftment of bacterial strains sourced from a healthy donor into an ulcerative colitis-derived defined microbial community. Distinct species integrated under the pretreated and untreated conditions, with the relative rifaximin resistance of the microbial strains being an important influencer. However, both conditions resulted in the integration of taxa from Clostridium clusters IV and XIVa, a concomitant reduction of Proteobacteria, and similar decreases in metabolites associated with poor health status. Our results agree with the findings of similar research in the clinic by others, which observed no difference in primary patient outcomes whether or not patients were given rifaximin prior to FMT. We therefore conclude that our model is useful for screening for antibiotics that could improve efficacy of FMT when used as a pretreatment. IMPORTANCE Patients with gastrointestinal disorders often exhibit derangements in their gut microbiota, which can exacerbate their symptoms. Replenishing these ecosystems with beneficial bacteria through fecal microbiota transplantation is thus a proposedly useful therapeutic; however, clinical success has varied, necessitating research into strategies to improve outcomes. Antibiotic pretreatment has been suggested as one such approach, but concerns over harmful side effects have hindered testing this hypothesis clinically. Here, we evaluate the use of bioreactors supporting defined microbial communities derived from human fecal samples as models of the colonic microbiota in determining the effectiveness of antibiotic pretreatment. We found that relative antimicrobial resistance was a key determinant of successful microbial engraftment with rifaximin (broad-spectrum antibiotic) pretreatment, despite careful timing of the application of the therapeutic agents, resulting in distinct species profiles from those of the control but with similar overall outcomes. Our model had results comparable to the clinical findings and thus can be used to screen for useful antibiotics.

scholarly journals Antidiabetic Function of Lactobacillus fermentum MF423-Fermented Rice Bran and Its Effect on Gut Microbiota Structure in Type 2 Diabetic Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojuan Ai ◽  
Cuiling Wu ◽  
Tingting Yin ◽  
Olena Zhur ◽  
Congling Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Rice Bran ◽  
High Throughput Sequencing ◽  
Short Chain Fatty Acids ◽  
Lactobacillus Fermentum ◽  
Fermentation Products ◽  
Type 2 Diabetic

Rice bran is an industrial byproduct that exerts several bioactivities despite its limited bioavailability. In this study, rice bran fermented with Lactobacillus fermentum MF423 (FLRB) had enhanced antidiabetic effects both in vitro and in vivo. FLRB could increase glucose consumption and decrease lipid accumulation in insulin resistant HepG2 cells. Eight weeks of FLRB treatment significantly reduced the levels of blood glucose and lipids and elevated antioxidant activity in type 2 diabetic mellitus (T2DM) mice. H&amp;E staining revealed alleviation of overt lesions in the livers of FLRB-treated mice. Moreover, high-throughput sequencing showed notable variation in the composition of gut microbiota in FLRB-treated mice, especially for short-chain fatty acids (SCFAs)-producing bacteria such as Dubosiella and Lactobacillus. In conclusion, our results suggested that rice bran fermentation products can modulate the intestinal microbiota and improve T2DM-related biochemical abnormalities, so they can be applied as potential probiotics or dietary supplements.

scholarly journals New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianbo Lai ◽  
Peifen Zhang ◽  
Jiajun Jiang ◽  
Tingting Mou ◽  
Yifan Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Depressive Episode ◽  
Cortical Neurons ◽  
Fecal Microbiota Transplantation ◽  
Bipolar Depression ◽  
Inflammatory Factors ◽  
Mrna Levels ◽  
New Evidence ◽  
Lps Treatment

Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring ‘BD microbiota’ following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.

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