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ABSTRACT:
PROVIDER: PRJNA751889 | ENA |
REPOSITORIES: ENA
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Project description:Chronic diseases arise when pathophysiological processes achieve a steady state by self-reinforcing. Here, we explored the possibility of a self-reinforcement state in a common condition, chronic constipation, where alterations of the gut microbiota have been reported. The functional impact of the microbiota shifts on host physiology remains unclear, however we hypothesized that microbial communities adapted to slow gastrointestinal transit affect host functions in a way that reinforces altered transit, thereby maintaining the advantage for microbial self-selection. To test this, we examined the impact of pharmacologically (loperamide)-induced constipation (PIC) on the structural and functional profile of altered gut microbiota. PIC promoted changes in the gut microbiome, characterized by decreased representation of butyrate-producing Clostridiales, decreased cecal butyrate concentration and altered metabolic profiles of gut microbiota. PIC-associated gut microbiota also impacted colonic gene expression, suggesting this might be a basis for decreased gastrointestinal (GI) motor function. Introduction of PIC-associated cecal microbiota into germ-free (GF) mice significantly decreased GI transit time. Our findings therefore support the concept that chronic diseases like constipation are caused by disease-associated steady states, in this case, caused by reciprocating reinforcement of pathophysiological factors in host-microbe interactions. We used microarrays to detail the global gene expression profile in the proximal colon smooth muscle tissues of germ-free, conventionalized, or specific pathogen free mouse
2014-07-12 | GSE59320 | GEO
Project description:Chronic diseases arise when pathophysiological processes achieve a steady state by self-reinforcing. Here, we explored the possibility of a self-reinforcement state in a common condition, chronic constipation, where alterations of the gut microbiota have been reported. The functional impact of the microbiota shifts on host physiology remains unclear, however we hypothesized that microbial communities adapted to slow gastrointestinal transit affect host functions in a way that reinforces altered transit, thereby maintaining the advantage for microbial self-selection. To test this, we examined the impact of pharmacologically (loperamide)-induced constipation (PIC) on the structural and functional profile of altered gut microbiota. PIC promoted changes in the gut microbiome, characterized by decreased representation of butyrate-producing Clostridiales, decreased cecal butyrate concentration and altered metabolic profiles of gut microbiota. PIC-associated gut microbiota also impacted colonic gene expression, suggesting this might be a basis for decreased gastrointestinal (GI) motor function. Introduction of PIC-associated cecal microbiota into germ-free (GF) mice significantly decreased GI transit time. Our findings therefore support the concept that chronic diseases like constipation are caused by disease-associated steady states, in this case, caused by reciprocating reinforcement of pathophysiological factors in host-microbe interactions. We used microarrays to detail the global gene expression profile in the proximal colon smooth muscle tissues of germ-free, conventionalized, or specific pathogen free mouse C57Bl/6 female and male specific pathogen free (SPF) mice were bred and housed in the animal care facility at the University of Chicago. Mice of 8–10 weeks of age were treated with 0.1% loperamide in the drinking water for 7 days. Age matched, germ-free (GF) C57Bl/6 mice were gavaged orally with cecal luminal contents harvested from control or loperamide-treated C57Bl/6 donor mice. Recipient mice were sacrificed 4 weeks post-colonization.
2014-07-12 | E-GEOD-59320 | biostudies-arrayexpress
Project description:To investigate the pathogenesis of slow transit constipation (STC), we have employed microarray-based miRNA analysis as a discovery platform to identify miRNAs potentially related with STC pathogenesis.Full-thickness specimens were obtained from colons of STC patients undergoing total colectomy and ileorectal anastomosis or subtotal colectomy with antiperistaltic cecoproctostomy. And patients undergoing radical surgery for non-obstructing colon cancer (left colon cancer) as control. These patients were not constipated and had no colonic dilatation. The control specimens were obtained at least 5 cm from the resection margin in tumor free areas. Expression of five miRNAs (miRNA-128, miRNA-129-3p, miRNA-20b,miRNA-27b and miRNA-30b) from this signature was identified by arbitrarily setting the threshold at a fold change of 1.3 or above combined with p < 0.05 in the same RNA samples. Expression of miRNAs in the colon may be involved in STC pathogenesis.
2014-05-27 | GSE57969 | GEO
Project description:To investigate the pathogenesis of slow transit constipation (STC), we have employed microarray-based miRNA analysis as a discovery platform to identify miRNAs potentially related with STC pathogenesis.Full-thickness specimens were obtained from colons of STC patients undergoing total colectomy and ileorectal anastomosis or subtotal colectomy with antiperistaltic cecoproctostomy. And patients undergoing radical surgery for non-obstructing colon cancer (left colon cancer) as control. These patients were not constipated and had no colonic dilatation. The control specimens were obtained at least 5 cm from the resection margin in tumor free areas. Expression of five miRNAs (miRNA-128, miRNA-129-3p, miRNA-20b,miRNA-27b and miRNA-30b) from this signature was identified by arbitrarily setting the threshold at a fold change of 1.3 or above combined with p < 0.05 in the same RNA samples. Expression of miRNAs in the colon may be involved in STC pathogenesis. The samples were obtained and washed with cold PBS, transported in liquid nitrogen and immediately stored in liquid nitrogen after removal. Total RNA was isolated from frozen histologic specimens using a mirVana™ RNA isolation Kit.
2014-05-27 | E-GEOD-57969 | biostudies-arrayexpress
Project description:In order to characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects induced by aqueous extract of Liriope platyphylla (AEtLP) including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays.Overall, 581 genes were up-regulated and 216 genes were down-regulated by constipation induced by loperamide, while 67 genes were up-regulated and 421 genes were down-regulated by AEtLP treatment in constipated rats compared to controls. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 20 were recovered to normal levels by AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15 and Alpi, while the major genes in the recovered categories were Cyp2b2, Ace, G6pc and Setbp1. However, nine of these genes that were down-regulated by constipation were significantly up-regulated and four were recovered to normal levels by AEtLP treatment. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a81, while the major genes in the recovered categories were Tmem45a, Rerg and Rgc32.
2014-10-04 | GSE62041 | GEO
Project description:In order to characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects induced by aqueous extract of Liriope platyphylla (AEtLP) including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays.Overall, 581 genes were up-regulated and 216 genes were down-regulated by constipation induced by loperamide, while 67 genes were up-regulated and 421 genes were down-regulated by AEtLP treatment in constipated rats compared to controls. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 20 were recovered to normal levels by AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15 and Alpi, while the major genes in the recovered categories were Cyp2b2, Ace, G6pc and Setbp1. However, nine of these genes that were down-regulated by constipation were significantly up-regulated and four were recovered to normal levels by AEtLP treatment. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a81, while the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. Constipation was induced in SD rats by subcutaneous injection of loperamide for 3 days. At 15 hr after the final treatment of loperamide, each animal were received a consistent volume of water or 15 uL/g body weight of AEtLP (1,000 mg/kg weight) via oral administration for once at 9 AM.
2014-10-04 | E-GEOD-62041 | biostudies-arrayexpress