Chronic alcohol-induced dysbiosis of the gut microbiota and gut metabolites impairs sperm quality
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE192522 | GEO | 2022/12/21
REPOSITORIES: GEO
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Project description:Studies have indicated that the ethanol exposure impairs the gut microbiota, At the same time, high levels of alcohol exposure damage sperm in mice. However, whether the gut microbiota is involved in mediating the effects of alcohol on sperm quality remains unclear. This study aimed to assess the effect of chronic alcohol consumption on intestinal microbiota in mice and analyze the potential pathophysiological effect of altered intestinal microbiota on sperm quality. We established a mouse model of chronic alcohol consumption by allowing male C57 mice to freely ingest 10% ethanol for 10 weeks, and collected the fecal microbiota of the male mice in the chronic drinking group (alcohol) and the control group (control) and transplanted the specimens into the transplant groups (the alcohol-fecal microbiota transplantation [FMT] group and the control-FMT group). Sperm quality was significantly decreased in the alcohol-FMT group compared with the control-FMT group. Gut microbiota analysis revealed that the abundance of 11 operational taxonomic units (OTUs) was altered in the alcohol-FMT group. Nontargeted metabolomics identified 105 differentially altered metabolites, which were mainly annotated to amino acids, lipids, glycerophosphoethanolamine, organic oxygenic compounds, organic acids and their derivatives, steroids, and flavonoids. In particular, the oxidative phosphorylation pathway, which is the key to spermatogenesis, was significantly enriched in the alcohol-FMT group. Moreover, compared with the control-FMT group, the alcohol-FMT group presented significantly higher serum endotoxin and inflammatory cytokine levels, with more pronounced T cell and macrophage infiltration in the intestinal lamina propria and elevated levels of testicular inflammatory cytokines. In addition, RNA sequencing showed significant differences in the expression of testis-related genes between the alcohol-FMT group and the control-FMT group. In particular, the expression of genes involved in gamete meiosis, testicular mitochondrial function, and the cell division cycle was significantly reduced in alcohol-FMT mice. In conclusion, these findings indicated that intestinal dysbiosis induced by chronic alcohol consumption may be an important factor contributing to impaired sperm quality. Chronic alcohol consumption induces intestinal dysbiosis, which then leads to metabolic disorders, elevated serum endotoxin and inflammatory cytokine levels, testicular inflammation, abnormal expression of related genes, and ultimately, impaired sperm quality. These findings are potentially useful for the treatment of male infertility.
| S-EPMC9751024 | biostudies-literature
Project description:Chronic alcohol-induced dysbiosis of the gut microbiota and gut metabolites impairs sperm quality
| PRJNA791810 | ENA
Project description:Alcohol is among the most widely consumed dietary substances. While excessive alcohol consumption damages the liver, heart and brain, clinical observations also suggest that alcohol has strong immunoregulatory properties. However, little is known about the mechanistic effects of alcohol on the immune system. T cell functions such as migration, immune synapse formation and activation depend on the reorganization of the cytoskeleton. In this study, we show that acetate, the metabolite of alcohol, effectively inhibits the migratory capacity of T cells through increased tissue acetate levels that lead to acetylation of cortactin, a protein that binds filamentous actin and facilitates branching. Current knowledge of cortactin’s role in T cells is limited. Here we demonstrate and confirm that primary mouse and human T cells express cortactin and acetylation of cortactin inhibits actin filament binding leading to reduced filament branching, lamellipodia formation and T cell migration. Mutated acetylation-resistant cortactin rescued the acetate-induced inhibition of T cell migration. Primary mouse cortactin knock-out T cells exhibited severely reduced T cell migration. Furthermore, acetate-induced cytoskeletal changes effectively inhibited activation, proliferation, and immune synapse formation in T cells exposed to acetate at tissue concentrations reached by alcohol consumption. In summary, these data show that acetate, the key metabolite of alcohol, is inhibiting T cell mediated immune responses by modulating the biomechanics of T cells through their cytoskeletal function.
2023-10-24 | PXD037723 | Pride
Project description:Alginate oligosaccharides (AOS), natural polymers from brown seaweeds (such as Laminaria japonica, Undaria pinnatifida, and Sargassum fusiforme), have been reported to possess many beneficial advantages for health. In the current study, after 9 weeks of dietary supplementation, AOS 10 mg/kg group (AOS 10) group increased boar sperm motility from 87.8% to 93.5%, p < 0.05. Moreover, AOS10 increased the relative abundances of Bifidobacterium, Coprococcus, Butyricicoccus (1.3-2.3-fold; p < 0.05) to increase the beneficial blood and sperm metabolites (1.2-1.6-fold; p < 0.05), and important sperm proteins such as gelsolin, Zn-alpha2 glycoprotein, Cation Channel Sperm-Associated Protein, outer dense fiber of sperm tails, etc. (1.5-2.2-fold; p < 0.05). AOS had a long-term beneficial advantage on boar semen quality by the increase in semen volume (175 vs. 160 ml/ejaculation, p < 0.05). AOS may be used as dietary additives for improving semen quality.
| S-EPMC9441641 | biostudies-literature
Project description:Purpose: Alcohol abuse induces changes in microglia morphology and immune function, but whether microglia initiate or simply amplify the harmful effects of alcohol exposure is still a matter of debate. Here we determined microglia function in acute and voluntary drinking behaviors using a colony stimulating factor 1 receptor inhibitor (PLX5622) and 3’UTR biased-sequencing. Therefore, The purpose of this study was to provide insight regarding microglia depletion and voluntary alcohol consumption. Methods: We performed 3’UTR biased transcriptome sequencing (3’Tag-seq) on total homogenate isolated from the prefrontal cortex (PFC) of C57BL6/J mice following microglia depletion and chronic every-other-day alcohol consumption. Results: Differential expression analysis and WGCNA network analysis revealed that although many immune genes have been implicated in alcohol abuse, downregulation of microglia genes does not necessitate changes in alcohol intake. Finally, we show that microglia depletion and chronic alcohol result in compensatory upregulation of ethanol-responsive, reactive astrocyte genes, indicating astrocytes may play a critical role in regulation of these alcohol behaviors. Conclusion:Taken together our behavioral and transcriptional data indicate that microglia are not the primary effector cell responsible for regulation of acute and voluntary alcohol behaviors. In addition, our data represents a novel resource for groups interested in transcriptional effects of microglia depletion after alcohol consumption.
2020-06-01 | GSE132516 | GEO
Project description:Background: Alcohol misuse, binge drinking pattern, and gender-specific effects in the middle-aged population has been clearly underestimated. In the present study, we focused on understanding gender-specific effects of alcohol exposure on the gut-liver axis and the role of gut microbiota in modulating gender-specific responses to alcohol consumption. Methods: Fifty-two-week-old female and male C57BL/6 mice were fasted for 12 h, and then administered a single oral dose of ethanol (EtOH) (6 g/kg). Controls were given a single dose of PBS. Animals were sacrificed 8 h later. Alternatively, fecal microbiota transplantation (FMT) was performed in 52-week-old male mice from female donors of the same age. Permeability of the large intestine (colon), gut microbiota, liver injury, and inflammation was thoroughly evaluated in all groups. Results: Middle-aged male mice exposed to EtOH showed a significant increase in gut permeability in the large intestine, evaluated by FITC-dextran assay and ZO-1, OCCLUDIN and MUCIN-2 immuno-staining, compared to PBS-treated animals, whilst female mice of the same age also increased their gut permeability, but displayed a partially maintained intestinal barrier integrity. Moreover, there was a significant up-regulation of TLRs and markers of hepatocellular injury, cell death (AST, TUNEL-positive cells) and lipid accumulation (ORO) in male mice after EtOH exposure. Interestingly, FMT from female donors to male mice reduced gut leakiness, modified gut microbiota composition, ameliorated liver injury and inflammation, TLR activation and the senescence phenotype of middle-aged mice. Conclusion: Our findings highlighted the relevance of gender in middle-aged individuals who are exposed to alcohol in the gut-liver axis. Moreover, our study revealed that gender-specific microbiota transplantation might be a plausible therapy in the management of alcohol-related disorders during aging.
2024-04-18 | GSE263477 | GEO
Project description:Background and purposeGut microbiota is essential for the development of the gastrointestinal system, including the enteric nervous system (ENS). Perturbations of gut microbiota in early life have the potential to alter neurodevelopment leading to functional bowel disorders later in life. We examined the hypothesis that gut dysbiosis impairs the structural and functional integrity of the ENS, leading to gut dysmotility in juvenile mice.Experimental approachTo induce gut dysbiosis, broad-spectrum antibiotics were administered by gavage to juvenile (3weeks old) male C57Bl/6 mice for 14 days. Bile acid composition in the intestinal lumen was analysed by liquid chromatography-mass spectrometry. Changes in intestinal motility were evaluated by stool frequency, transit of a fluorescent-labelled marker and isometric muscle responses of ileal full-thickness preparations to receptor and non-receptor-mediated stimuli. Alterations in ENS integrity were assessed by immunohistochemistry and Western blot analysis.Key resultsAntibiotic treatment altered gastrointestinal transit, luminal bile acid metabolism and bowel architecture. Gut dysbiosis resulted in distorted glial network, loss of myenteric plexus neurons, altered cholinergic, tachykininergic and nitrergic neurotransmission associated with reduced number of nNOS neurons and different ileal distribution of the toll-like receptor TLR2. Functional defects were partly reversed by activation of TLR2 signalling.Conclusions and implicationsGut dysbiosis caused complex morpho-functional neuromuscular rearrangements, characterized by structural defects of the ENS and increased tachykininergic neurotransmission. Altogether, our findings support the beneficial role of enteric microbiota for ENS homeostasis instrumental in ensuring proper gut neuromuscular function during critical stages of development.
| S-EPMC5610159 | biostudies-literature
Project description:The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-naïve iP and P.NP rats. Background: Selectively bred P (alcohol preferring) and NP (alcohol non-preferring) rats differ greatly in alcohol preference, in part due to a highly significant QTL on chromosome 4. Reciprocal congenic strains in which the iP chromosome 4 QTL interval was transferred to the iNP background (NP.P) and the iNP chromosome 4 QTL was transferred to the iP background (P.NP) exhibited alcohol consumption scores that correlated with the introgressed interval. The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-naïve iP and P.NP rats. Methods: RNA from the amygdala, nucleus accumbens, hippocampus, caudate putamen, and frontal cortex from each of 8 iP and 8 P.NP rats was labeled and analyzed on Affymetrix Rat Genome 230 2.0 microarrays. Expression levels were normalized using robust multi-chip average (RMA), and differential gene expression was measured in individual brain regions and in the average of the five brain regions. Differential gene expression was validated using quantitative real-time PCR. Meta-analysis was applied to compare microarray data from this experiment with data from the reciprocal congenic strains NP.P vs. iNP (Carr et al, 2007). Results: We detected between 72 (nucleus accumbens) and 89 (hippocampus) cis-regulated probe sets within the QTL that significantly differed between the strains in the five brain regions. There was significant overlap among the regions; 157 cis-regulated probe sets were detected in at least one brain region, of which 104 showed differential expression in more than one region. Fewer trans-regulated probe sets were detected, ranging from 7 in the amygdala to 54 in the caudate putamen, and most of these differed in only one region; only 10 of the 85 trans-regulated probe sets differed in more than one region. To increase the power to detect differentially expressed genes, data from the five discrete brain regions of each animal were averaged; in this analysis we detected 141 cis-regulated probe sets and 207 trans-regulated probe sets. Meta-analysis comparing the present results from iP vs. P.NP rats with an earlier experiment that used the reciprocal congenic NP.P vs. iP demonstrated that 74 cis-regulated probe sets were differentially expressed in the same direction and with a consistent magnitude of difference in both experiments. No consistent trans-regulated probe sets were identified. Conclusions: Cis-regulated candidate genes for alcohol consumption that lie within the chromosome 4 QTL were identified and confirmed by meta-analysis with the reciprocal congenic NP.P vs iNP study. These genes are strong candidates for producing the difference in alcohol preference and consumption between the iP and iNP rats. There was little evidence for consistent trans-acting effects. Keywords: comparison of gene expression profiles for strain1 (P rat) vs. strain2 (P.NP rat) 40 samples each of P and P.NP (8 animals each of P and P.NP. 5 brain regions)
2009-12-30 | E-GEOD-15415 | biostudies-arrayexpress
Project description:We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes in brain and liver among three different alcohol consumption tests and lipopolysaccharide injection. We also demonstrated distinct genomic consequences of different types of alcohol consumption.
2013-04-01 | GSE42789 | GEO
Project description:Introduction: Though heavy alcohol drinking has been well characterized as causing a variety of injuries, recent epidemiological evidence in humans suggests moderate consumption may provide beneficial effects. For example, there exists a J- or U-shaped relationship between the level of alcohol intake and cardiovascular disease risk. We investigated the underlying mechanisms of these positive consequences by identifying which genes are responsive to moderate alcohol intake in the liver, the primary site for alcohol metabolism. Methods: Twelve female, inbred, alcohol-preferring (iP10a) rats were split equally between chronic water exposure and voluntary chronic ethanol exposure. Hepatic cholesterol and triglyceride levels were analyzed both histologically and biochemically. Hepatic transcriptomes were paired-end sequenced on the Illumina HiScanSQ system. Reads were analyzed and mapped using CLCbio Genomics Workbench 4.9. We confirmed altered expression of a subset of genes using TaqMan-based qRT-PCR. To quantify DNA methylation, we first digested DNA with methylation sensitive restriction enzymes and then performed qPCR using TaqMan assays surrounding the digest sites. Calculating M-NM-^TCt between a mock digest and digest determines the percent methylation in that locus. Results: Voluntary alcohol consumption in iP10a rats modeled moderate consumption in humans. These levels did not result in intrahepatic fat accumulation. Sequencing produced ~1.2 Gb of sequence per sample, and 65% of reads mapped uniquely. Using a FDR corrected p value of 0.05 we found 250 altered transcripts. Ontology analysis of genes with a fold change M-bM-^IM-%1.3 identified many cholesterol synthesis genes and cytoskeleton subunit genes, all of which were down-regulated. Of the 28 genes reanalyzed by qRT-PCR, altered expression was confirmed in 24 genes including the majority of the cholesterol synthesis and cytoskeleton subunit genes. Lastly, we profiled methylation throughout the promoter and gene body of four genes elicited in the RNA-Seq experiment. We found that alcohol caused demethylation at all loci; however this loss happened in a site-specific, tightly regulated manner. Conclusion: Voluntary consumption in the iP10a animals models moderate consumption in humans, does not produce intrahepatic fat accumulation, and causes down-regulation of a majority of cholesterol synthesis genes. Moderate alcohol also results in a tightly-regulated demethylation effect. Our results explain, at least in part, the J- or U-shaped relationship between level of alcohol intake and cardiovascular disease risk. We sequenced 12 female iP10a rat hepatic transcriptomes providing 6 biological replicates for water control and 6 for ethanol treatment.
2013-05-07 | E-GEOD-46669 | biostudies-arrayexpress