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Journal of Personalized Medicine Oct 2022Previous studies have explored the role of the microbiome in attention-deficit/hyperactivity disorder (ADHD). However, whether the microbiome is correlated with...
Previous studies have explored the role of the microbiome in attention-deficit/hyperactivity disorder (ADHD). However, whether the microbiome is correlated with emotional-behavioral disturbances, the most common comorbid symptom of ADHD, remains unclear. We established a cross-sectional study in which 6- to 18-year-old children with ADHD who were receiving no medication and a healthy control group of children without ADHD were recruited to analyze their microbiome composition. Microbiota of fecal samples were collected and analyzed using a 16s rRNA gene sequencing approach. In comparison with the healthy control group, the gut microbiota in children with ADHD exhibited significantly lower beta diversity. The abundance of the phylum Proteobacteria and the genera , , , , , and group was increased in the ADHD group compared with the healthy group. Linear discriminant effect size (LEfSe) analysis was used to highlight specific bacteria phylotypes that were differentially altered between the ADHD and control groups. A regression analysis was performed to investigate the association between microbiota and emotional-behavioral symptoms in children with ADHD. A significant association was noted between withdrawal and depression symptoms and ( = 0.044), and between rule-breaking behavior and the group ( = 0.046) after adjusting for sex, age, and the ADHD core symptoms score. This study advances the knowledge of how gut microbiota composition may contribute to emotional-behavioral symptoms in children with ADHD. The detailed mechanisms underlying the role of the gut microbiota in ADHD pathophysiology still require further investigation.
PubMed: 36294773
DOI: 10.3390/jpm12101634 -
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 -
The Science of the Total Environment Jan 2023Hydrogen (H) assisted ex-situ biogas upgrading and liquid chemicals production can augment the fossil fuel-dominated energy market, and alleviate CO-induced global...
Hydrogen (H) assisted ex-situ biogas upgrading and liquid chemicals production can augment the fossil fuel-dominated energy market, and alleviate CO-induced global warming. Recent investigations confirmed that nanoscale zero-valent iron (nZVI) enabled the enhancement of anaerobic digestion for biogas production. However, little is known about the effect of nZVI on the downstream ex-situ biogas upgrading. Herein, different levels (0 mg L, 100 mg L, 200 mg L, 500 mg L, 1000 mg L, 2000 mg L) of nZVI were added for H-assisted ex-situ biogas upgrading, to study whether nZVI could impact the biomethane purity and acetate yield for the first time. Results showed that all tested nZVI levels were favorable for biogas upgrading in the presence of H, the highest biomethane content (94.1 %, v/v), the CO utilization ratio (95.9 %), and acetate yield (19.4 mmol L) were achieved at 500 mg L nZVI, respectively. Further analysis indicated that increased biogas upgrading efficiency was related to an increase in extracellular polymeric substances, which ensures the microbial activity and stability of the ex-situ biogas upgrading. Microbial community characterization showed that the Petrimonas, Romboutsia, Acidaminococcus, and Clostridium predominated the microbiome during biogas upgrading at 500 mg L nZVI with H supply. These results suggested that nZVI and H contributed jointly to promoting the bioconversion of CO in biogas to acetate. The findings could be helpful for paving a new way for efficient simultaneous ex-situ biogas upgrading and liquid chemicals recovery.
Topics: Biofuels; Hydrogen; Methane; Iron; Carbon Dioxide; Acetates
PubMed: 36174700
DOI: 10.1016/j.scitotenv.2022.159100 -
Microorganisms Sep 2022Rheumatoid arthritis (RA) is a chronic inflammatory disabling autoimmune disorder. Little is known regarding the association between the gut microbiome and...
Rheumatoid arthritis (RA) is a chronic inflammatory disabling autoimmune disorder. Little is known regarding the association between the gut microbiome and etiopathogenesis of RA. We aimed to dissect the differences in gut microbiomes associated with RA in comparison to healthy individuals and, in addition, to identify the shifts in the bacterial community in association with disease activity; Methods: In order to identify compositional shifts in gut microbiomes of RA patients, V3-V4 hypervariable regions of 16S rRNA were sequenced using Illumina MiSeq. In total, sixty stool samples were collected from 45 patients with RA besides 15 matched healthy subjects; Results: Notably, RA microbiomes were significantly associated with diverse bacterial communities compared with healthy individuals. Likewise, a direct association between bacterial diversity and disease activity was detected in RA patients (Kruskal Wallis; = 0.00047). In general, genus-level analysis revealed a positive coexistence between RA and , , , , and . Furthermore, Spearman correlation analysis significantly stratified the most dominant genera into distinct clusters that were mainly based on disease activity ( ≥ 0.6; ≤ 0.05). The predictive metabolic profile of bacterial communities associated with RA could support the potential impact of gut microbiomes in either the development or recovery of RA; Conclusions: The overall shifts in bacterial composition at different disease statuses could confirm the cross-linking of certain genera either to causation or progression of RA.
PubMed: 36144422
DOI: 10.3390/microorganisms10091820 -
International Journal of Molecular... Aug 2022Type V Cas12a nucleases are DNA editors working in a wide temperature range and using expanded protospacer-adjacent motifs (PAMs). Though they are widely used, there is...
Type V Cas12a nucleases are DNA editors working in a wide temperature range and using expanded protospacer-adjacent motifs (PAMs). Though they are widely used, there is still a demand for discovering new ones. Here, we demonstrate a novel ortholog from sp. entitled RbCas12a, which is able to efficiently cleave target DNA templates, using the particularly high accessibility of PAM 5'-YYN and a relatively wide temperature range from 20 °C to 42 °C. In comparison to sp. (AsCas12a) nuclease, RbCas12a is capable of processing DNA more efficiently, and can be active upon being charged by spacer-only RNA at lower concentrations in vitro. We show that the human-optimized RbCas12a nuclease is also active in mammalian cells, and can be applied for efficient deletion incorporation into the human genome. Given the advantageous properties of RbCas12a, this enzyme shows potential for clinical and biotechnological applications within the field of genome editing.
Topics: Acidaminococcus; Animals; CRISPR-Cas Systems; DNA; Endonucleases; Gene Editing; Humans; Mammals; Ruminococcus
PubMed: 36012553
DOI: 10.3390/ijms23169289 -
ACS Synthetic Biology Aug 2022Pathway engineering is commonly employed to improve the production of various metabolites but may incur in bottlenecks due to the low catalytic activity of a particular...
Pathway engineering is commonly employed to improve the production of various metabolites but may incur in bottlenecks due to the low catalytic activity of a particular reaction step. The reduction of 2-oxoadipate to ()-2-hydroxyadipate is a key reaction in metabolic pathways that exploit 2-oxoadipate conversion via α-reduction to produce adipic acid, an industrially important platform chemical. Here, we engineered ()-2-hydroxyglutarate dehydrogenase from (Hgdh) with the aim of improving 2-oxoadipate reduction. Using a combination of computational analysis, saturation mutagenesis, and random mutagenesis, three mutant variants with a 100-fold higher catalytic efficiency were obtained. As revealed by rational analysis of the mutations found in the variants, this improvement could be ascribed to a general synergistic effect where mutation A206V played a key role since it boosted the enzyme's activity by 4.8-fold. The Hgdh variants with increased activity toward 2-oxoadipate generated within this study pave the way for the bio-based production of adipic acid.
Topics: Adipates; Alcohol Oxidoreductases; Mutagenesis
PubMed: 35939387
DOI: 10.1021/acssynbio.2c00162 -
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 -
Frontiers in Medicine 2022Most colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of...
BACKGROUND
Most 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. This study aimed to investigate the characteristics of intestinal microbiota in patients with colorectal adenoma and carcinoma and its correlations with clinical characteristics.
METHODS
Fecal samples were collected from 154 patients with CRC, 20 patients with colorectal adenoma (AD) and 199 healthy controls. To analyze the differences in the intestinal microbiota, 16S rRNA gene sequencing was conducted.
RESULTS
At the genus level, there were four significantly different genera among the three groups, namely Acidaminococcus, Alloprevotella, Mycoplasma, and Sphingobacterium, while Acidaminococcus significantly decreased with the order of Control-AD-CRC ( < 0.05). In addition, Parvimonas, Peptostreptococcus, Prevotella, Butyricimonas, Alistipes, and Odoribacter were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. The top 10 most important species, including , , , , , , , , and , showed the best performance in distinguishing AD from CRC (AUC = 85.54%, 95% CI: 78.83-92.25%). The clinicopathologic features, including age, gender, 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.
PubMed: 35935780
DOI: 10.3389/fmed.2022.888340 -
Environmental Pollution (Barking, Essex... Oct 2022The intestine is not only the main accumulation organ of microplastics (MPs), but also the intestinal environment is very conductive to the release of additives in MPs....
The intestine is not only the main accumulation organ of microplastics (MPs), but also the intestinal environment is very conductive to the release of additives in MPs. However, the kinetics of release process, influence factors, and the related effects on gut microbiota remain largely unknown. In this study, a mucosal-simulator of the human intestinal microbial ecosystem (M-SHIME) was used to investigate the influence of gut microbiota on the release of phthalates (PAEs) from MPs and the effects of MPs on the intestinal luminal microbiota and mucosal microbiota. We found that di-(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and dimethyl phthalate (DMP) were the dominant PAEs released in the gut. Gut microbiota accelerated the release of PAEs, with the time to reach the maximum release was shortened from 7 days to 2 days. Moreover, MPs induced differential effects on luminal microbiota and mucosal microbiota. Compared with mucosal microbiota, the luminal microbiota was more susceptible to the leaching of PAEs from MPs, as evidenced by more microbiota alterations. MPs also inhibited the metabolic activity of intestinal flora based on the reduced production of short chain fatty acids (SCFA). These effects were mainly contributed by the release of PAEs. Acidaminococcus and Morganella were simultaneously correlated to the release of PAEs and the inhibition of metabolic activity of intestinal microbiota and can be used as indicators for the intestinal exposure of MPs and additives.
Topics: Dibutyl Phthalate; Esters; Humans; Microbiota; Microplastics; Phthalic Acids; Plastics
PubMed: 35931388
DOI: 10.1016/j.envpol.2022.119884 -
European Journal of Clinical Nutrition Dec 2022Intrauterine environment can influence the offspring's body adiposity whose distribution affect the cardiometabolic risk. Underlying mechanisms may involve the gut...
UNLABELLED
Intrauterine environment can influence the offspring's body adiposity whose distribution affect the cardiometabolic risk. Underlying mechanisms may involve the gut microbiome. We investigated associations of gestational weight gain with the adult offspring's gut microbiota, body adiposity and related parameters in participants of the Nutritionists' Health Study.
METHODS
This cross-sectional analysis included 114 women who had early life and clinical data, body composition, and biological samples collected. The structure of fecal microbiota was analyzed targeting the V4 region of the 16 S rRNA gene. Beta diversity was calculated by PCoA and PERMANOVA used to test the impact of categorical variables into the diversity. Bacterial clusters were identified based on the Jensen-Shannon divergence matrix and Calinski-Harabasz index. Correlations were tested by Spearman coefficient.
RESULTS
Median age was 28 (IQR 24-31) years and BMI 24.5 (IQR 21.4-28.0) kg/m. Fifty-eight participants were assigned to a profile driven by Prevotella and 56 to another driven by Blautia. Visceral adipose tissue was correlated to abundance of Acidaminococcus genus considering the entire sample (r = 0.37; p < 0.001) and the profiles (Blautia: r = 0.35, p = 0.009, and Prevotella: r = 0.38, p = 0.006). In Blautia-driven profile, the same genus was also correlated to maternal gestational weight gain (r = 0.38, p = 0.006).
CONCLUSIONS
Association of Acidaminococcus with gestational weight gain could reinforce the relevance with mothers' nutritional status for gut colonization at the beginning of life. Whether Acidaminococcus abundance could be a marker for central distribution of adiposity in young women requires further investigation.
Topics: Adult; Humans; Female; Gestational Weight Gain; Adiposity; Acidaminococcus; Body Mass Index; Cross-Sectional Studies; Adult Children; Obesity, Abdominal; Obesity
PubMed: 35906333
DOI: 10.1038/s41430-022-01182-7