Dataset Information

Gut microflora alleviate immune response during E.coli-induced bladder cystits via AhR/MANF activation

ABSTRACT:

In recent years, with the deepening of research on intestinal microbiota, we found intestinal microbiota plays an important role in host immune regulation and barrier maintenance through cross-talk between the microbiota and the host. New evidence suggests that disruption of the fragile balance within the intestinal microbiota, termed as dysbiosis, may cause tremendous inflammation in both intestine proximal and distant organ. Our previous studies have shown that Bacterial infections of the liver and lungs are accompanied by changes in intestinal flora diversity, and the depletion of intestinal bacteria can aggravate bacterial infection. Though, fecal microbiota transplantation (FMT) from a healthy population has already been associated with the reduction of urinary tract infections which caused by C. difficile. However, the mechanisms by which the intestinal microbiota affects the immune responses in bacterial cystitis (BC) remain poorly characterized.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase, Gas Chromatography MS - positive

SUBMITTER: yi yang

PROVIDER: MTBLS5572 | MetaboLights | 2023-07-11

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MTBLS5572	Other
	FILES	Other
	a_MTBLS5572_GC-MS_positive_metabolite_profiling.txt	Txt
	a_MTBLS5572_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS5572_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt

Items per page:

1 - 5 of 11

Similar Datasets

Project description:Purpose: To determine whether previously observed behavioral differences in alcoholic human patients after fecal microbiota transplantation (FMT) could be transferred to mice. Methods: Fecal microbiota samples from a previously published phase 1, double-blind, randomized clinical trial of AUD-related cirrhosis patients were used to colonize germ-free mice. Fecal material was transferred to 10-15-week-old GF C57BL/6 male mice by daily gavage for 3 day. The mice were housed in sterile individually filtered cages for 15 days after which stool was collected and then they underwent the alcohol preference experiment using 2-bottle choice drinking (water and 20% ethanol v/v). Microbial DNA was isolated from stool samples by sequencing the V1 and V2 variable regions of the bacterial 16S rRNA gene were sequenced using Multitag fusion primers and sequenced on an Ion Torrent PGM next-generation sequencer. Intestinal mucosa, liver, and prefrontal cortex tissue was collected from mice at time of sacrifice. RNAseq was used to measure gene expression in pre-FMT and post-FMT samples. RNAseq data were aligned to the mouse genome (GRCm39) using STAR (version 2.7.9a) and counts were generated with HTSeq (version 0.13.5). Genes with very low counts across the study (defined as fewer than 10 counts in more than 2 samples) were eliminated before differential expression analysis. Low count genes were determined separately for each tissue type. The DESeq2 package for R was then used to measure differential expression between pre-FMT and post-FMT mice in the intestine, liver, and PFC. Benjamini and Hochberg False Discovery Rate (FDR) was used to correct for multiple testing with FDR ≤ 0.2 considered significant. Results: Mice colonized with post-FMT stool significantly reduced ethanol acceptance, intake and preference versus pre-FMT colonized mice. Microbial taxa that were higher in post-FMT humans were also associated with lower alcohol intake and preference in mice. RNAseq further showed that differential gene expression, post-FMT, occurred in the intestine rather than the liver and prefrontal cortex. Conclusions: FMT leads to significant change in gut microbiome population, which in turn alters gene expression in the intestine. FMT also significantly affects alcohol consumption. The microbiotal-intestinal interface may alter gut-liver-brain axis and reduce alcohol consumption in humans.

Project description:Chorioamnionitis (CA), resulting from intra-amniotic inflammation, is a frequent cause of preterm birth and exposes the immature intestine to bacterial toxins and/or inflammatory mediators before birth via fetal swallowing. This may affect intestinal immune development, interacting with the effects of enteral feeding and gut microbiota colonization just after birth. Using preterm pigs as model for preterm infants, we hypothesized that prenatal exposure to gram-negative endotoxin influences postnatal bacterial colonization and gut immune development. Pig fetuses were given intra-amniotic lipopolysaccharide (LPS) 3 d before preterm delivery by cesarean section, and were compared with litter-mate controls (CON) at birth and after 5 d of formula feeding and spontaneous bacterial colonization. Amniotic fluid was collected for analysis of leukocyte counts and cytokines, and the distal small intestine was analyzed for endotoxin level, morphology and immune cell counts. Intestinal gene expression and microbiota were analyzed by transcriptomics and metagenomics, respectively. At birth, LPS-exposed pigs showed higher intestinal endotoxin, neutrophil/macrophage density and shorter villi. About 1.0% of intestinal genes were affected at birth and DMBT1, a regulator of mucosal immune defense, was identified as the hub gene in the co-expression network. Genes related to innate immune response (TLR2, LBP, CD14, C3, SFTPD), neutrophil chemotaxis (C5AR1, CSF3R, CCL5) and antigen processing (MHC II, CD4) were also affected and expression levels correlated with intestinal neutrophil/macrophage density and amniotic fluid cytokine levels. On day 5, LPS and CON pigs showed similar necrotizing enterocolitis (NEC) lesions, endotoxin levels, morphology, immune cell counts, gene expressions and microbiota (except for difference in some low-abundant species). Our results show that CA markedly affects intestinal genes at preterm birth, including genes related to immune cell infiltration. However, a few days later, following the physiological adaptations to preterm birth, CA had limited effects on intestinal structure, function, gene expression, bacterial colonization and NEC sensitivity. We conclude that short-term, prenatal intra-amniotic inflammation is unlikely to exert marked effects on intestinal immune development in preterm neonates beyond the immediate neonatal period.

Dataset Information

Gut microflora alleviate immune response during E.coli-induced bladder cystits via AhR/MANF activation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets