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Journal of Gastroenterology Apr 2024Alterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this...
BACKGROUND/AIM
Alterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate gut microbiota composition and functionality in patients with morbid obesity with different degrees of MAFLD, as assessed by biopsy.
SUBJECTS/METHODS
110 patients with morbid obesity were evaluated by biopsy obtained during bariatric surgery for MAFLD. Stool samples were collected prior to surgery for microbiota analysis.
RESULTS
Gut microbiota from patients with steatosis and non-alcoholic steatohepatitis (NASH) were characterized by an enrichment in Enterobacteriaceae (an ethanol-producing bacteria), Acidaminococcus and Megasphaera and the depletion of Eggerthellaceae and Ruminococcaceae (SCFA-producing bacteria). MAFLD was also associated with enrichment of pathways related to proteinogenic amino acid degradation, succinate production, menaquinol-7 (K2-vitamin) biosynthesis, and saccharolytic and proteolytic fermentation. Basic histological hepatic alterations (steatosis, necroinflammatory activity, or fibrosis) were associated with specific changes in microbiota patterns. Overall, the core microbiome related to basic histological alterations in MAFLD showed an increase in Enterobacteriaceae and a decrease in Ruminococcaceae. Specifically, Escherichia coli was associated with steatosis and necroinflammatory activity, whilst Escherichia-shigella was associated with fibrosis and necroinflammatory activity.
CONCLUSIONS
We established a link between gut microbiota alterations and histological injury in liver diagnosis using biopsy. Harmful products such as ethanol or succinate may be involved in the pathogenesis and progression of MAFLD. Thus, these alterations in gut microbiota patterns and their possible metabolic pathways could add information to the classical predictors of MAFLD severity and suggest novel metabolic targets.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Obesity, Morbid; Ethanol; Fibrosis; Succinates
PubMed: 38265508
DOI: 10.1007/s00535-023-02075-7 -
Nutrients Aug 2021Ultra-processed foods (UPFs) consumption could affect gut microbiota diversity and profile. We aimed to evaluate the effects of UPFs on microbiota, considering the role... (Comparative Study)
Comparative Study
Ultra-processed foods (UPFs) consumption could affect gut microbiota diversity and profile. We aimed to evaluate the effects of UPFs on microbiota, considering the role of sex. The consumption of UPFs (using NOVA criteria) was assessed with a validated 137-item food-frequency questionnaire. Participants ( = 359) were classified into less than three servings per day ( = 96) of UPFs and more than five ( = 90). Women and men were subclassified following the same criteria. 16S rRNA sequencing was performed from DNA fecal samples, and differences in microbiota were analyzed using EdgeR. The relationship between UPFs and bacteria was assessed by Spearman correlation and comparison of tertiles of consumption. Women who consumed more than five servings/day of UPFs presented an increase in , Enterobacteriales, Bifidobacteriales and Actinobacteria and a decrease in and . , Bifidobacteriales and Actinobacteria was positively associated with pizza and Actinobacteria with industrially processed dairy in women. Men who consumed more than five servings/day presented an increase of Carnobacteriaceae, Bacteroidaceae, Peptostreptococcaceae, Bacteroidia and Bacteroidetes and a decrease of and Clostridiaceae. Bacteroidia and Bacteroidetes correlated positively with industrially processed meat. This study suggests that UPFs may affect microbiota composition differently in women and men.
Topics: Adult; Bacteria; Dairy Products; Diet; Dysbiosis; Fast Foods; Feces; Female; Food Handling; Gastrointestinal Microbiome; Humans; Intestines; Male; Middle Aged; Nutritive Value; Risk Assessment; Risk Factors; Sex Factors; Spain
PubMed: 34444870
DOI: 10.3390/nu13082710 -
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 -
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 -
Hepatology (Baltimore, Md.) Mar 2021Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), caused by autoimmune regulator (AIRE) mutations, manifests with chronic mucocutaneous...
BACKGROUND AND AIMS
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), caused by autoimmune regulator (AIRE) mutations, manifests with chronic mucocutaneous candidiasis (CMC) and multisystem autoimmunity, most often hypoparathyroidism (HP) and adrenal insufficiency (AI). European cohorts previously reported a ~10% prevalence of APECED-associated hepatitis (APAH) with presentations ranging from asymptomatic laboratory derangements to fatal fulminant hepatic failure. Herein, we characterized APAH in a large APECED cohort from the Americas.
APPROACH AND RESULTS
Forty-five consecutive patients with APECED were evaluated (2013-2015) at the National Institutes of Health (NIH; NCT01386437). Hepatology consultation assessed hepatic and autoimmune biomarkers and liver ultrasound in all patients. Liver biopsies evaluated autoimmune features and fibrosis. The 16S ribosomal RNA (rRNA) sequencing was performed in 35 patients' stools (12 with and 23 without APAH). Among 43 evaluable patients, 18 (42%) had APAH; in 33.3% of those with APAH, APAH occurred before developing classic APECED diagnostic criteria. At APAH diagnosis, the median age was 7.8 years, and patients manifested with aminotransferase elevation and/or hyperbilirubinemia. All patients with APAH were in clinical remission during their NIH evaluation while receiving immunomodulatory treatment. We found no difference in age, sex, or prevalence of CMC, AI, or HP between patients with or without APAH. Autoantibody positivity against aromatic L-amino acid decarboxylase, cytochrome P450 family 1 subfamily A member 2, histidine decarboxylase (HDC), bactericidal/permeability-increasing fold-containing B1, tryptophan hydroxlase, and 21-hydroxylase (21-OH), and the homozygous c.967_979del13 AIRE mutation were associated with APAH development. Classical serological biomarkers of autoimmune hepatitis (AIH) were only sporadically positive. AIH-like lymphoplasmacytic inflammation with mild fibrosis was the predominant histological feature. Stool microbiome analysis found Slackia and Acidaminococcus in greater abundance in patients with APAH.
CONCLUSIONS
APAH is more common than previously described, may present early before classic APECED manifestations, and most often manifests with milder, treatment-responsive disease. Several APECED-associated autoantibodies, but not standard AIH-associated biomarkers, correlate with APAH.
Topics: Adolescent; Adult; Americas; Autoantibodies; Biomarkers; Biopsy; Female; Gene Deletion; Hepatitis, Autoimmune; Humans; Immunotherapy; Liver; Liver Cirrhosis; Male; Polyendocrinopathies, Autoimmune; Young Adult
PubMed: 32557834
DOI: 10.1002/hep.31421 -
BioMed Research International 2022Most of colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of...
BACKGROUND
Most of colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of colorectal cancer. However, there are still no absolute markers predicting the progression from adenoma to carcinoma.
AIMS
To investigate the characteristics of intestinal microbiota in colorectal adenoma and carcinoma patients and the correlations with clinical characteristics.
METHODS
Fecal samples were collected from 154 colorectal carcinoma patients (CRC group), 20 colorectal adenoma patients (AD group), and 199 healthy controls (control group). The intestinal microbiota was investigated by 16S rRNA gene sequencing.
RESULTS
Compared to the healthy controls, microbial diversity was dramatically decreased in AD/CRC. At the genus level, significantly decreased with the order of control-AD-CRC ( < 0.05). , , , , , and were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. Combination of the top 10 most important species, including , , , bacterium feline oral taxon 001, , , bacterium LD2013, , bacterium 19gly4, and , showed the best performance in distinguishing AD patients from CRC (AUC = 85.54%, 95% CI: 78.83%-92.25%). The clinicopathologic features, including age, sex, tumor location, differentiation degree, and TNM stage, were identified to be closely linked to the intestinal microbiome in CRC.
CONCLUSION
Several intestinal bacteria changed along the adenoma-carcinoma sequence and might be the potential markers for the diagnosis and treatment of colorectal adenoma/carcinoma. Intestinal microbiota characteristics in CRC should account for the host factors.
Topics: Adenoma; Animals; Bacteria; Carcinoma; Cats; Colorectal Neoplasms; Dysbiosis; Feces; Gastrointestinal Microbiome; Humans; RNA, Ribosomal, 16S
PubMed: 35937408
DOI: 10.1155/2022/3140070 -
Food & Nutrition Research 2023The relationship between fruit, whole grain, and total energy consumption and the gut microbiome in the Chinese population remains unclear.
BACKGROUND
The relationship between fruit, whole grain, and total energy consumption and the gut microbiome in the Chinese population remains unclear.
OBJECTIVE
We investigated the relationship between intakes of fruits, whole grains, and energy, and the diversity and composition of gut microbiota.
DESIGN
This cross-sectional study included 167 subjects aged 40-75 years who underwent colonoscopy at Nankai Hospital in Tianjin, China. Each of the participants completed a personal history questionnaire, a 7-day dietary record, and donated a fecal sample. The V3-V4 hypervariable region of the bacterial 16S rRNAgene was amplified and sequenced using Illumina Novaseq. The relationship between diet and gut microbiota was evaluated in terms of both the overall composition and the abundance of specific taxon.
RESULTS
Fruits intake was positively related to the abundance of Bacilli, Porphyromonadaceae, Streptococcaceae, , and Bilophila in fecal samples. Higher whole grains intake was associated with higher microbial diversity, as measured by Shannon, Simpson, and Chao1 indices. Specifically, there was a significant increase inthe relative abundance of Lachnospiraceae and a decrease in Actinobacteria with increased whole grains intake. Moreover, higher intake of total energy was associated with a lower abundance of and a higher abundance of Lactobacillales and .
CONCLUSION
Whole grains intake was positively associated with gut microbial diversity. Fruits and total energy intake were related to the abundance of specifictaxon (e.g., Bacilli and Acidaminococcus). These findings highlight the potential importance of dietary interventions for modulating gut microbiota composition and promoting overall health.
PubMed: 38084154
DOI: 10.29219/fnr.v67.9725 -
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 -
New Microbes and New Infections Jun 2024
PubMed: 38799905
DOI: 10.1016/j.nmni.2024.101246 -
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