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Frontiers in Psychiatry 2024Schizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect...
INTRODUCTION
Schizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect brain function via the complex gut-brain axis, which may be a potential contributor to schizophrenia. However, the alteration of gut microbiota showed high heterogeneity across different studies. Therefore, this study aims to identify the consistently altered gut microbial taxa associated with schizophrenia.
METHODS
We conducted a systematic search and synthesis of the up-to-date human gut microbiome studies on schizophrenia, and performed vote counting analyses to identify consistently changed microbiota. Further, we investigated the effects of potential confounders on the alteration of gut microbiota.
RESULTS
We obtained 30 available clinical studies, and found that there was no strong evidence to support significant differences in α-diversity and β-diversity between schizophrenic patients and healthy controls. Among 428 differential gut microbial taxa collected from original studies, we found that 8 gut microbial taxa were consistently up-regulated in schizophrenic patients, including Proteobacteria, Gammaproteobacteria, , , , , and . While 5 taxa were consistently down-regulated in schizophrenia, including , , , and .
DISCUSSION
These findings suggested that gut microbial changes in patients with schizophrenia were characterized by the depletion of anti-inflammatory butyrate-producing genera, and the enrichment of certain opportunistic bacteria genera and probiotics. This study contributes to further understanding the role of gut microbiota in schizophrenia, and developing microbiota-based diagnosis and therapy for schizophrenia.
PubMed: 38596637
DOI: 10.3389/fpsyt.2024.1366311 -
Liver International : Official Journal... Feb 2023Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We...
BACKGROUND AND AIMS
Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut-liver axis and systemic inflammation.
METHODS
Thirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow-mediated dilation, quantification of circulating cytokines and vasoactive mediators and characterization of the gut microbiota.
RESULTS
PBC patients had a higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p = .01). Factors associated with LEAD at univariate analysis were VCAM-1 (p = .002), ICAM-1 (p = .003), and TNF-alpha (p = .04) serum levels, but only VCAM-1 (OR 1.1, 95% CI 1.0-1.1; p = .04) and TNF-alpha (OR 1.12, 95% CI 0.99-1.26; p = .04) were confirmed as independent predictors in the multivariate model. Gut microbiota analysis revealed that Acidaminococcus (FDR = 0.0008), Bifidobacterium (FDR = 0.001) and Oscillospira (FDR = 0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha serum levels. Down-regulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism and branched-chain amino acids degradation was found in the functional gut metagenome of PBC women.
CONCLUSIONS
LEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut-liver axis.
Topics: Humans; Female; Liver Cirrhosis, Biliary; Non-alcoholic Fatty Liver Disease; Tumor Necrosis Factor-alpha; Hypercholesterolemia; Prevalence; Vascular Cell Adhesion Molecule-1; Atherosclerosis; Lower Extremity
PubMed: 36287108
DOI: 10.1111/liv.15463 -
Frontiers in Microbiology 2023Growing evidence supports the role of gut microbiota in obesity, yet exact associations remain largely unknown. Specifically, very little is known about this association...
BACKGROUND
Growing evidence supports the role of gut microbiota in obesity, yet exact associations remain largely unknown. Specifically, very little is known about this association in the Emirati population.
METHODS
We explored differences in gut microbiota composition, particularly the Firmicutes/Bacteroidetes (F/B) ratio, between 43 obese and 31 lean adult Emirate counterparts, and its association with obesity markers, by using V3-V4 regions of 16 S ribosomal RNA gene sequencing data. Furthermore, we collected anthropometric and biochemical data.
RESULTS
The two major phyla in obese and lean groups were Firmicutes and Bacteroidetes. We observed a significantly lower alpha diversity (Shannon index) in obese subjects and a significant difference in beta diversity and phylum and genus levels between the two groups. The obese group had higher abundances of Verrucomicrobia and Saccharibacteira and lower abundances of Lentisphaerae. and were more abundant in obese subjects and positively correlated with adiposity markers. No correlations were found between the gut microbiota and biochemical variables, such as fasting blood sugar, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.
CONCLUSION
We reveal significant differences in the gut microbiota between obese and lean adult Emiratis and an association between certain microbial genera of the gut microbiota and obesity. A better understanding of the interactions between gut microbes, diet, lifestyle, and health is warranted.
PubMed: 37680528
DOI: 10.3389/fmicb.2023.1182460 -
BioRxiv : the Preprint Server For... Feb 2024Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting,...
Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting 1-3 genomic sites per cell. To develop a tool for higher-order ( > 3) combinatorial targeting of genomic sites with CRISPRi in functional genomics screens, we engineered an Cas12a variant -- referred to as mul tiplexed transcriptional interference AsCas12a (multiAsCas12a). multiAsCas12a incorporates a key mutation, R1226A, motivated by the hypothesis of nicking-induced stabilization of the ribonucleoprotein:DNA complex for improving CRISPRi activity. multiAsCas12a significantly outperforms prior state-of-the-art Cas12a variants in combinatorial CRISPRi targeting using high-order multiplexed arrays of lentivirally transduced CRISPR RNAs (crRNA), including in high-throughput pooled screens using 6-plex crRNA array libraries. Using multiAsCas12a CRISPRi, we discover new enhancer elements and dissect the combinatorial function of cis-regulatory elements. These results instantiate a group testing framework for efficiently surveying potentially numerous combinations of chromatin perturbations for biological discovery and engineering.
PubMed: 37781594
DOI: 10.1101/2023.09.18.558350 -
Journal of Dairy Science May 2024Methane is a potent greenhouse gas produced during the ruminal fermentation and is associated with a loss of feed energy. Therefore, efforts to reduce methane emissions...
Methane is a potent greenhouse gas produced during the ruminal fermentation and is associated with a loss of feed energy. Therefore, efforts to reduce methane emissions have been ongoing in the last decades. Methane production is highly influenced by factors such as the ruminal microbiome and host genetics. Previous studies have proposed to use the ruminal microbiome to reduce long-term methane emissions, as ruminal microbiome composition is a moderately heritable trait and genetic improvement accumulates over time. Lactation stage is another important factor that might influence methane production but potential associations with the ruminal microbiome have not been evaluated previously. This study sought to examine the changes in ruminal microbiome over the lactation period of primiparous Holstein cows differing in methane intensity and estimate the heritability of the abundance of relevant microorganisms. Ruminal content samples from 349 primiparous Holstein cows with 14 - 378 d in milk were collected from May 2018 to June 2019. Methane intensity (MI) of each cow was calculated as methane concentration/milk yield. Up to 64 taxonomic features (TF) from 20 phyla had a significant differential abundance between cows with low and high MI early in lactation, 16 TF during mid lactation, and none late in lactation. Taxonomical features within the Firmicutes, Proteobacteria, Melainabacteria, Cyanobacteria, Bacteroidetes and Actinobacteria phyla were associated to low MI, whereas eukaryotic TF and those within the Euryarchaeota, Verrucomicrobia, Kiritimatiellaeota, Lentisphaerae phyla were associated to high MI. Out of the 60 TF that were found to be differentially abundant between early and late lactation in cows with low MI, 56 TF were also significant when cows with low and high MI were compared in the first third of the lactation. In general, microbes associated with low MI were more abundant early in lactation (e.g., Acidaminococcus, Aeromonas and Weimeria genera) and showed low to moderate heritabilities (0.03 to 0.33). These results suggest some potential to modulate the rumen microbiome composition through selective breeding for lower MI. Differences in the ruminal microbiome of cows with extreme MI levels likely result from variations in the ruminal physiology of these cows and were more noticeable early in lactation probably due to important interactions between the host phenotype and environmental factors associated to that period. Our results suggest that the ruminal microbiome evaluated early in lactation may be more precise for MI difference, and hence, this should be considered to optimize sampling periods to establish a reference population in genomic selection scenarios.
PubMed: 38788852
DOI: 10.3168/jds.2023-24552 -
PLoS Biology Oct 2019Imaging dense and diverse microbial communities has broad applications in basic microbiology and medicine, but remains a grand challenge due to the fact that many...
Imaging dense and diverse microbial communities has broad applications in basic microbiology and medicine, but remains a grand challenge due to the fact that many species adopt similar morphologies. While prior studies have relied on techniques involving spectral labeling, we have developed an expansion microscopy method (μExM) in which bacterial cells are physically expanded prior to imaging. We find that expansion patterns depend on the structural and mechanical properties of the cell wall, which vary across species and conditions. We use this phenomenon as a quantitative and sensitive phenotypic imaging contrast orthogonal to spectral separation to resolve bacterial cells of different species or in distinct physiological states. Focusing on host-microbe interactions that are difficult to quantify through fluorescence alone, we demonstrate the ability of μExM to distinguish species through an in vitro defined community of human gut commensals and in vivo imaging of a model gut microbiota, and to sensitively detect cell-envelope damage caused by antibiotics or previously unrecognized cell-to-cell phenotypic heterogeneity among pathogenic bacteria as they infect macrophages.
Topics: Acetobacter; Acidaminococcus; Animals; Anti-Bacterial Agents; Cell Wall; Drosophila melanogaster; Escherichia coli; Gastrointestinal Microbiome; Humans; Hydrolysis; Lactobacillus plantarum; Mice; Microscopy; Muramidase; Platyhelminths; RAW 264.7 Cells; Stress, Mechanical; Symbiosis; Vancomycin
PubMed: 31622337
DOI: 10.1371/journal.pbio.3000268 -
Frontiers in Microbiology 2020The aim of the study was to investigate the effect of untreated and processed rapeseed meal (RSM) on fiber degradability by pig gut microbiota and the adaptation of the...
The aim of the study was to investigate the effect of untreated and processed rapeseed meal (RSM) on fiber degradability by pig gut microbiota and the adaptation of the microbiota to the substrate, by using the Swine Large Intestine Model (SLIM). A standardized swine gut microbiota was fed for 48 h with pre-digested RSM which was processed enzymatically by a cellulase (CELL), two pectinases (PECT), or chemically by an alkaline (ALK) treatment. Amplicons of the V3-V4 region of the 16S rRNA gene were sequenced to evaluate the gut microbiota composition, whereas short chain fatty acids (SCFA) were measured to assess fiber degradation. Adaptive gPCA showed that CELL and ALK had larger effects on the microbiota composition than PECT1 and PECT2, and all substrates had larger effects than CON. The relative abundance of family Prevotellaceae was significantly higher in CELL treatment compared to other treatments. Regardless of the treatments (including CON), the relative abundance of , , and (in the order of Clostridiales) were significantly increased after 24 h, and , , , , 009, , , and were significantly higher in abundance at time point 48 compared to the earlier time points. 9 had significant positive correlations with propionic and valeric acid, and positively correlated with acetic and caproic acid. There was no significant difference in SCFA production between untreated and processed RSM. Overall, degradability in the processed RSM was not improved compared to CON. However, the significantly different microbes detected among treatments, and the bacteria considerably correlating with SCFA production might be important findings to determine strategies to shorten the fiber adaptation period of the microbiota, in order to increase feed efficiency in the animal, and particularly in pig production.
PubMed: 32983078
DOI: 10.3389/fmicb.2020.570985 -
Cells Feb 2021The normal composition of the intestinal microbiota is a key factor for maintaining healthy homeostasis, and accordingly, dysbiosis is well known to be present in HIV-1...
The normal composition of the intestinal microbiota is a key factor for maintaining healthy homeostasis, and accordingly, dysbiosis is well known to be present in HIV-1 patients. This article investigates the gut microbiota profile of antiretroviral therapy-naive HIV-1 patients and healthy donors living in Latin America in a cohort of 13 HIV positive patients (six elite controllers, EC, and seven non-controllers, NC) and nine healthy donors (HD). Microbiota compositions in stool samples were determined by sequencing the V3-V4 region of the bacterial 16S rRNA, and functional prediction was inferred using PICRUSt. Several taxa were enriched in EC compared to NC or HD groups, including , , , , and . In addition, our data indicate that the route of infection is an important factor associated with changes in gut microbiome composition, and we extend these results by identifying several metabolic pathways associated with each route of infection. Importantly, we observed several bacterial taxa that might be associated with different viral subtypes, such as , which were more abundant in patients infected by HIV subtype B, and enrichment in patients infected by subtype C. In conclusion, our data brings a significant contribution to the understanding of dysbiosis-associated changes in HIV infection and describes, for the first time, differences in microbiota composition according to HIV subtypes. These results warrant further confirmation in a larger cohort of patients.
Topics: Adult; Bacteria; Discriminant Analysis; Feces; Female; Gastrointestinal Microbiome; HIV Infections; HIV-1; Humans; Metabolic Networks and Pathways; Middle Aged
PubMed: 33668457
DOI: 10.3390/cells10020385 -
Nucleic Acids Research Jan 2022CRISPR RNAs (crRNAs) that direct target DNA cleavage by Type V Cas12a nucleases consist of constant repeat-derived 5'-scaffold moiety and variable 3'-spacer moieties....
CRISPR RNAs (crRNAs) that direct target DNA cleavage by Type V Cas12a nucleases consist of constant repeat-derived 5'-scaffold moiety and variable 3'-spacer moieties. Here, we demonstrate that removal of most of the 20-nucleotide scaffold has only a slight effect on in vitro target DNA cleavage by a Cas12a ortholog from Acidaminococcus sp. (AsCas12a). In fact, residual cleavage was observed even in the presence of a 20-nucleotide crRNA spacer moiety only. crRNAs split into separate scaffold and spacer RNAs catalyzed highly specific and efficient cleavage of target DNA by AsCas12a in vitro and in lysates of human cells. In addition to dsDNA target cleavage, AsCas12a programmed with split crRNAs also catalyzed specific ssDNA target cleavage and non-specific ssDNA degradation (collateral activity). V-A effector nucleases from Francisella novicida (FnCas12a) and Lachnospiraceae bacterium (LbCas12a) were also functional with split crRNAs. Thus, the ability of V-A effectors to use split crRNAs appears to be a general property. Though higher concentrations of split crRNA components are needed to achieve efficient target cleavage, split crRNAs open new lines of inquiry into the mechanisms of target recognition and cleavage and may stimulate further development of single-tube multiplex and/or parallel diagnostic tests based on Cas12a nucleases.
Topics: Acidaminococcus; Bacterial Proteins; CRISPR-Associated Proteins; CRISPR-Cas Systems; DNA; DNA Cleavage; Endodeoxyribonucleases; Francisella; Gene Editing
PubMed: 34951459
DOI: 10.1093/nar/gkab1227 -
Applied Microbiology Jan 1974Fecal bacterial cultures from 40 normal humans yielded Megasphaera elsdenii from four individuals and Acidaminococcus fermentans from 10 individuals, with two...
Fecal bacterial cultures from 40 normal humans yielded Megasphaera elsdenii from four individuals and Acidaminococcus fermentans from 10 individuals, with two individuals having both organisms.
Topics: Anaerobiosis; Bacteria; Bacteriological Techniques; Cell Count; Feces; Humans
PubMed: 4589136
DOI: 10.1128/am.27.1.274-275.1974