Mucosal-Associated Microbiota Other Than Luminal Microbiota Has a Close Relationship With Diarrhea-Predominant Irritable Bowel Syndrome.
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ABSTRACT:
SUBMITTER: Yang M
PROVIDER: S-EPMC7667041 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Mucosal-Associated Microbiota Other Than Luminal Microbiota Has a Close Relationship With Diarrhea-Predominant Irritable Bowel Syndrome.
Yang Min M Hong Gaichao G Jin Yu Y Li Ying Y Li Gangping G Hou Xiaohua X
Frontiers in cellular and infection microbiology 20201102
Studies have linked dysbiosis of gut microbiota to irritable bowel syndrome (IBS). However, dysbiosis only referring to structural changes without functional alteration or focusing on luminal microbiota are incomplete. To fully investigate the relationship between gut microbiota and clinical symptoms of Irritable Bowel Syndrome with Diarrhea (IBS-D), fecal samples, and rectal mucosal biopsies were collected from 69 IBS-D patients and 20 healthy controls (HCs) before and during endoscopy without ...[more]
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Project description:Altered gut microbiota are assumed to be involved in the pathogenesis of irritable bowel syndrome (IBS). However, gut microbiota alterations reported in different studies are divergent and sometimes even contradictory. To better elucidate the relationship between altered gut microbiota and IBS, we characterized fecal microbiota of diarrhea-predominant IBS (IBS-D) patients and further explored the effect of rifaximin on gut microbiota using bacterial 16S rRNA gene-targeted pyrosequencing. In our study, IBS-D patients defined by Rome III criteria and age-and-gender matched healthy controls (HC) were enrolled to investigate the fecal microbiota alterations. These IBS-D patients were then treated with rifaximin for 2 weeks and followed up for 10 weeks. Fecal microbiota alterations, small intestine bacterial overgrowth (SIBO) and gastrointestinal (GI) symptoms of IBS-D patients were analyzed before and after treatment. Our results showed fecal microbiota richness but not diversity was decreased in IBS-D patients as compared to HC and there were alterations of fecal microbiota at different taxonomy levels. The abundant phyla Firmicutes was significantly decreased and Bacteroidetes was increased in IBS-D patients. Moreover, the alterations of predominant fermenting bacteria such as Bacteroidales and Clostridiales might be involved in the pathophysiology of IBS-D. In addition, rifaximin was effective in terms of SIBO eradication and even GI symptoms of IBS-D patients achieved at least 10-week improvement after treatment. Furthermore, rifaximin induced alterations of some special bacteria rather than affected the overall composition of microbiota in IBS-D patients. Meanwhile, a potential decrease in propanoate and butanoate metabolism was found in these IBS-D patients after rifaximin treatment. Taken together, there were alterations of gut microbiota in IBS-D patients as compared to HC. Rifaximin could relieve GI symptoms, modify gut microbiota in IBS-D patients and eradicate SIBO in those patients with SIBO, suggesting an additional therapeutic mechanism of rifaximin in the treatment of IBS-D. Our findings of compositional gut microbiota alterations in IBS-D and the effect of rifaximin on the gut microbiota implied that altered gut microbiota were associated with the pathogenesis of IBS.
| S-EPMC6068233 | biostudies-literature
Project description:BackgroundIrritable bowel syndrome (IBS) is common and difficult to treat and its pathogenesis is closely related to gut microbiota. However, differences in gut microbiota of patients in different regions make it more difficult to elucidate the mechanism of IBS. We performed an analysis of gut microbiota composition and functional prediction in Chinese patients with diarrhea-predominant IBS (IBS-D).MethodsFecal samples were obtained from 30 IBS-D patients and 30 healthy controls (HCs) in Nanchang, China. Using 16S gene sequence profiles, we analyzed the abundance of dominant microbiota at different taxonomy levels. Based on 16S information, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predicting the function of gut microbiota.ResultsCompared to HCs, gut microbiota richness but not diversity was decreased in IBS-D patients. The abundant phyla Firmicutes, Fusobacteria and Actinobacteria decreased significantly, and Proteobacteria increased significantly in IBS-D patients. PICRUSt indicated that function expression of gut microbiota in IBS-D patients was up-regulated in metabolism of cofactors and vitamins, xenobiotics biodegradation and metabolism, and down-regulated in environmental adaptation, cell growth and death.ConclusionsCompared with the normal population in China, IBS-D patients are characterized by complex and unstable gut microbiota, which may influence inflammation and metabolism of the host.
| S-EPMC7934555 | biostudies-literature
Project description:ObjectiveGut microbiota might play a crucial role in the pathogenesis of irritable bowel syndrome (IBS), and probiotics supplement may be an effective treatment option. This study aims to explore the therapeutic effects of Golden bifid on the diarrhea-predominant IBS (IBS-D).MethodsTwenty-one consecutive IBS-D patients were recruited based on Rome IV criteria. All patients took 2000 mg Golden bifid triple daily for 4 weeks. Gastrointestinal (GI) symptoms, psychological symptoms, small intestine bacterial overgrowth (SIBO) and fecal microbiota characteristics were evaluated in IBS-D patients before and after treatment.ResultsAfter 4-week treatment of Golden bifid, the GI symptoms such as abdominal pain (2.90 ± 1.04 vs. 1.90 ± 1.26, P = 0.002), abdominal distension (2.00 ± 1.34 vs. 1.29 ± 1.31, P = 0.007), diarrhea (3.24 ± 1.37 vs. 1.81 ± 1.21, P = 0.001), defecatory urgency (3.48 ± 1.03 vs. 2.33 ± 1.35, P = 0.000) and incomplete evacuation (2.71 ± 1.15 vs. 1.76 ± 1.26, P = 0.003) were significantly alleviated in IBS-D patients. The Self-Rating Depression Scale (SDS) decreased significantly (46.19 ± 11.36 vs. 43.33 ± 9.65, P = 0.041), and SIBO could be eradicated in 25% (4/16) of IBS-D patients with SIBO. Meanwhile, the abundance of Unclassified Lachnospiraceae and Dorea in genus level and Unclassified Lachnospiraceae, Bacterium Dorea, Bacterium Butyricicoccus and Dorea formicigenerans ATCC 27755 in species level were increased in fecal microbiota (P < 0.05).ConclusionsGolden bifid could improve most of GI symptoms and depressive symptoms in IBS-D patients and eradicate a small proportion of SIBO in those IBS-D patients with SIBO. What's more, Golden bifid could also modulate the fecal microbiota in IBS-D patients, which implied that the Golden bifid might improve IBS-D via microbiota modulation.
| S-EPMC9109320 | biostudies-literature
Project description:Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT(3) receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT(3) receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder.
| S-EPMC3385976 | biostudies-other
Project description:BackgroundIrritable bowel syndrome (IBS) is one of the most common functional intestinal diseases, but its pathogenesis is still unknown. The present study aimed to screen the differentially expressed proteins in the mucosa of colon between IBS with diarrhea (IBS-D) patients and the healthy controls.MethodsForty-two IBS-D patients meeting the Rome III diagnostic criteria and 40 control subjects from July 2007 to June 2009 in Chinese PLA General Hospital were enrolled in the present study. We examined the protein expression profiles in mucosa of colon corresponding to IBS-D patients (n = 5) and controls (n = 5) using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Secondly, Western blot and immunohistochemical analysis were carried out to validate the screened proteins in 27 IBS-D patients and 27 controls. Thirdly, high-performance liquid chromatography (HPLC) was further carried out to determine ATP concentration in the mucosa of colon between 10 IBS-D patients and 8 controls. Comparisons between 2 groups were performed by Student's t-test or Mann-Whitney U-test.ResultsTwelve differentially expressed proteins were screened out. The α-enolase (ENOA) in the sigmoid colon (0.917 ± 0.007 vs. 1.310 ± 0.100, t = 2.643, P = 0.017) and caecum (0.765 ± 0.060 vs. 1.212 ± 0.122, t = 2.225, P = 0.023), Isobutyryl-CoA dehydrogenase (ACAD8) in the sigmoid colon (1.127 ± 0.201 vs. 1.497 ± 0.392, t = 7.093, P = 0.008) of the IBS-D group were significantly lower while acetyl-CoA acetyltransferase (CT) in the caecum (2.453 ± 0.422 vs. 0.931 ± 0.652, t = 8.363, P = 0.015) and ATP synthase subunit d (ATP5H) in the sigmoid (0.843 ± 0.042 vs. 0.631 ± 0.042, t = 8.613,P = 0.007) of the IBS-D group was significantly higher, compared with the controls. The ATP concentration in the mucosa of the sigmoid colon in IBS-D group was significantly lower than that of control group (0.470 [0.180, 1.360] vs. 5.350 [2.230, 7.900], U = 55, P < 0.001).ConclusionsMany proteins related to energy metabolism presented differential expression patterns in the mucosa of colon of the IBS-D patients. The abnormalities in energy metabolism may be involved in the pathogenesis of IBS which deserves more studies to elucidate.
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Project description:Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, which impacts the quality of life, work productivity and social activities of patients. Diarrhea-predominant IBS (IBS-D) is one of several subtypes, and accounts for approximately one third of all cases. Currently available treatments are typically unable to alleviate the cardinal symptoms of IBS-D, including abdominal pain and diarrhea, and a clinical unmet need remains for an effective treatment which simultaneously relieves multiple symptoms. Patients may benefit from a multipronged, individualized approach, including dietary modifications, and psychological and pharmacological therapies. The aim of this review is to provide an update on the available and upcoming treatment options for IBS-D in Canada, with reference to the recently updated Canadian IBS consensus guidelines. Initial treatment approaches include lifestyle modifications, dietary modifications, and non-prescription therapies such as peppermint oil. While some medications such as tricyclic antidepressants are also used to treat IBS-D symptoms, eluxadoline and rifaximin are the only two pharmacological therapies approved for the treatment of IBS-D in Canada. Key clinical trial data for the currently available pharmacological options are presented to provide an overview of the efficacy and safety of these agents.
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Project description:ObjectiveFructose malabsorption is a common digestive disorder in which absorption of fructose in the small intestine is impaired. An abnormality of the main intestinal fructose transporter proteins has been proposed as a cause for fructose malabsorption. However the underlying molecular mechanism for this remains unclear. In this study, we investigated whether carbohydrate response element-binding protein (ChREBP) plays a role in intestinal fructose absorption through the regulation of genes involved in fructose transport and metabolism and ion transport.MethodsWild type (WT) and Chrebp knockout (KO) mice (6 or 8 weeks old) were fed a control diet (55% starch, 15% maltodextrin 10) or high-fructose diet (HFrD, 60% fructose, 10% starch) for 3-12 days. Body weight and food intake were measured, signs of fructose malabsorption were monitored, and the expression of genes involved in fructose transport/metabolism and ion transport was evaluated. Furthermore, transient transfection and chromatin immunoprecipitation were performed to show the direct interaction between ChREBP and carbohydrate response elements in the promoter of Slc2A5, which encodes the fructose transporter GLUT5.ResultsChrebp KO mice fed the control diet maintained a constant body weight, whereas those fed a HFrD showed significant weight loss within 3-5 days. In addition, Chrebp KO mice fed the HFrD exhibited a markedly distended cecum and proximal colon containing both fluid and gas, suggesting incomplete fructose absorption. Fructose-induced increases of genes involved in fructose transport (GLUT5), fructose metabolism (fructokinase, aldolase B, triokinase, and lactate dehydrogenase), and gluconeogenesis (glucose-6-phosphatase and fructose-1,6-bisphosphatase) were observed in the intestine of WT but not of Chrebp KO mice. Moreover the Na+/H+ exchanger NHE3, which is involved in Na+ and water absorption in the intestine, was significantly decreased in HFrD-fed Chrebp KO mice. Consistent with this finding, the high-fructose diet-fed Chrebp KO mice developed severe diarrhea. Results of chromatin immunoprecipitation assays showed a direct interaction of ChREBP with the Glut5 promoter, but not the Nhe3 promoter, in the small intestine. Ectopic co-expression of ChREBP and its heterodimer partner Max-like protein X activated the Glut5 promoter in Caco-2BBE cells.ConclusionsChREBP plays a key role in the dietary fructose transport as well as conversion into lactate and glucose through direct transcriptional control of genes involved in fructose transport, fructolysis, and gluconeogenesis. Moreover, ablation of Chrebp results in a severe diarrhea in mice fed a high-fructose diet, which is associated with the insufficient induction of GLUT5 in the intestine.
| S-EPMC7400734 | biostudies-literature
Project description:An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.
| S-EPMC6934182 | biostudies-literature
Project description:IntroductionPrevious studies in patients with irritable bowel syndrome (IBS) showed immune activation, secretion, and barrier dysfunction in duodenal, jejunal, or colorectal mucosa. This study aimed to measure ileal mucosal expression of genes and proteins associated with mucosal functions.MethodsWe measured by reverse transcription polymerase chain reaction messenger RNA (mRNA) expression of 78 genes (reflecting tight junction proteins, chemokines, innate immunity, ion channels, and transmitters) and 5 proteins (barrier, bile acid receptor, and ion exchanger) in terminal ileal mucosa from 11 patients with IBS-diarrhea (IBS-D), 17 patients with IBS-constipation (IBS-C), and 14 healthy controls. Fold changes in mRNA were calculated using 2(-Δ, ΔCT) formula. Group differences were measured using analysis of variance. Protein ratios relative to healthy controls were based on Western blot analysis. Nominal P values (P < 0.05) are reported.ResultsIn ileal mucosal biopsies, significant differences of mRNA expression in IBS-D relative to IBS-C were upregulation of barrier proteins (TJP1, FN1, CLDN1, and CLDN12), repair function (TFF1), and cellular functions. In ileal mucosal biopsies, mRNA expression in IBS-C relative to healthy controls was reduced GPBAR1 receptor, myosin light chain kinase (MYLK in barrier function), and innate immunity (TLR3), but increased mRNA expression of cadherin cell adhesion mechanisms (CTNNB1) and transport genes SLC9A1 (Na-H exchanger [NHE1]) and INADL (indirect effect on ion transport).DiscussionThese data support a role of ileal mucosal dysfunction in IBS, including barrier dysfunction in IBS-D and alterations in absorption/secretion mechanisms in IBS-C.
| S-EPMC8043738 | biostudies-literature
Project description:Imbalanced gut microbiota (GM) and abnormal fecal bile acid (BA) are thought to be the key factors for diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying mechanism remains unclear. Herein, we explore the influence of the GM-BA-Takeda G-protein-coupled receptor 5 (TGR5) axis on IBS-D. Twenty-five IBS-D patients and fifteen healthy controls were recruited to perform BA-related metabolic and metagenomic analyses. Further, the microbiota-humanized IBS-D rat model was established by fecal microbial transplantation (FMT) to investigate the GM-BA-TGR5 axis effects on the colonic barrier and visceral hypersensitivity (VH) in IBS-D. Finally, we used chenodeoxycholic acid (CDCA), an important BA screened out by metabolome, to evaluate whether it affected diarrhea and VH via the TGR5 pathway. Clinical research showed that GM associated with bile salt hydrolase (BSH) activity such as Bacteroides ovatus was markedly reduced in the GM of IBS-D, accompanied by elevated total and primary BA levels. Moreover, we found that CDCA not only was increased as the most important primary BA in IBS-D patients but also could induce VH through upregulating TGR5 in the colon and ileum of normal rats. TGR5 inhibitor could reverse the phenotype, depression-like behaviors, pathological change, and level of fecal BSH in a microbiota-humanized IBS-D rat model. Our findings proved that human-associated FMT could successfully induce the IBS-D rat model, and the imbalanced GM-BA-TGR5 axis may promote colonic mucosal barrier dysfunction and enhance VH in IBS-D.ImportanceVisceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.
| S-EPMC10949424 | biostudies-literature