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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 -
Toxins Jul 2021Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia....
Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress.
Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Sarcopenic patients had a greater abundance of the and families and of , , , and genera. They had a lower abundance of the and families and of and genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.
Topics: Aged; Bacteria; Gastrointestinal Microbiome; Humans; Indican; Inflammation; Interleukin-6; Malondialdehyde; Middle Aged; Oxidative Stress; Renal Dialysis; Renal Insufficiency, Chronic; Sarcopenia; Uremia; Uremic Toxins
PubMed: 34357944
DOI: 10.3390/toxins13070472 -
Journal of Hepatocellular Carcinoma 2021Gut microbiome has been associated with the efficacy of immune checkpoint inhibitors (ICI) in patients with various types of cancers but not yet in hepatocellular...
BACKGROUND
Gut microbiome has been associated with the efficacy of immune checkpoint inhibitors (ICI) in patients with various types of cancers but not yet in hepatocellular carcinoma (HCC).
AIMS
To investigate the association between gut microbiome and efficacy of ICI in patients with HCC.
METHODS
Patients with HCC who were scheduled to receive ICI were prospectively enrolled. Fecal samples were collected within 7 days before initiation of ICI (baseline) and 8 weeks later. Gut microbiome was assessed using 16S rRNA sequencing and shotgun whole-genome sequencing and correlated with objective response (complete or partial response), disease control (objective response or stable disease for ≥16 weeks), and overall survival.
RESULTS
Thirty-six patients with HCC were enrolled, and 20 of them provided both baseline and 8-week feces. Alpha diversity, richness, and compositions of baseline gut microbiome indicated no difference between responders and nonresponders or between disease control and nondisease control groups. For the 20 paired feces, immunotherapy did not change any of the major microbiome features. No specific taxa were enriched in patients with objective response. Three taxa-, and -were enriched in patients with disease control. However, the baseline abundance of these three taxa did not predict overall survival benefit.
CONCLUSIONS
In this exploratory study, we failed to disclose any overt association of gut microbiome with the efficacy of ICI in patients with HCC. A larger prospective study is warranted for definite conclusion.
PubMed: 34336726
DOI: 10.2147/JHC.S315696 -
Frontiers in Microbiology 2021Acute myocardial infarction (AMI) continues as the main cause of morbidity and mortality worldwide. Interestingly, emerging evidence highlights the role of gut...
Acute myocardial infarction (AMI) continues as the main cause of morbidity and mortality worldwide. Interestingly, emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease, but few studies have systematically assessed the alterations and influence of gut microbiota in AMI patients. As one approach to address this deficiency, in this study the composition of fecal microflora was determined from Chinese AMI patients and links between gut microflora and clinical features and functional pathways of AMI were assessed. Fecal samples from 30 AMI patients and 30 healthy controls were collected to identify the gut microbiota composition and the alterations using bacterial 16S rRNA gene sequencing. We found that gut microflora in AMI patients contained a lower abundance of the phylum and a slightly higher abundance of the phylum compared to the healthy controls. Chao1 ( = 0.0472) and PD-whole-tree ( = 0.0426) indices were significantly lower in the AMI versus control group. The AMI group was characterized by higher levels of the genera , , , and , and lower levels of , , , , and as compared to that in the healthy controls ( < 0.05). The common metabolites of these genera are mostly short-chain fatty acids, which reveals that the gut flora is most likely to affect the occurrence and development of AMI through the short-chain fatty acid pathway. In addition, our results provide the first evidence revealing remarkable differences in fecal microflora among subgroups of AMI patients, including the STEMI vs. NSTEMI, IRA-LAD vs. IRA-Non-LAD and Multiple (≥2 coronary stenosis) vs. Single coronary stenosis groups. Several gut microflora were also correlated with clinically significant characteristics of AMI patients, including LVEDD, LVEF, serum TnI and NT-proBNP, Syntax score, counts of leukocytes, neutrophils and monocytes, and fasting serum glucose levels. Taken together, the data generated enables the prediction of several functional pathways as based on the fecal microfloral composition of AMI patients. Such information may enhance our comprehension of AMI pathogenesis.
PubMed: 34295318
DOI: 10.3389/fmicb.2021.680101 -
Frontiers in Veterinary Science 2021The gut microbiome plays important roles in maintaining host health, and inappropriate use of antibiotics can cause imbalance, which may contribute to serious disease....
The gut microbiome plays important roles in maintaining host health, and inappropriate use of antibiotics can cause imbalance, which may contribute to serious disease. However, despite its promise, using metagenomic sequencing to explore the effects of colistin on gut microbiome composition in pig has not been reported. Herein, we evaluated the roles of colistin in gut microbiome modulation in pigs. Metagenomic analysis demonstrated that overall microbial diversity was higher in the colistin group compared with the control group. Antibiotic Resistance Genes Database analysis demonstrated that following colistin treatment, expression levels of , and were significantly upregulated, indicating that colistin may induce transformation of antibiotic resistance genes. Colistin also affected the microbiome distribution patterns at both genus and phylum levels. In addition, at the species level, colistin significantly reduced the abundance of , and and enhanced the abundance of and compared to the control group. Gene Ontology analysis demonstrated that following treatment with colistin, metabolic process, cellular process, and single-organism process were the dominant affected terms. Kyoto Encyclopedia of Genes and Genomes analysis showed that oxidative phosphorylation, protein processing in endoplasmic reticulum, various types of N-glycan biosynthesis, protein processing in endoplasmic reticulum, pathogenic infection, and mitogen-activated protein kinase signaling pathway-yeast were the dominant signaling pathways in the colistin group. Overall, our results suggested that colistin affects microbial diversity and may modulate gut microbiome composition in pig, potentially providing novel strategy or antibiotic rationalization pertinent to human and animal health.
PubMed: 34277753
DOI: 10.3389/fvets.2021.663820 -
Biotechnology Reports (Amsterdam,... Sep 2021Chinese hamster ovary (CHO) cells are the most widely used host for the expression of therapeutic proteins. Recently, significant progress has been made due to advances...
Chinese hamster ovary (CHO) cells are the most widely used host for the expression of therapeutic proteins. Recently, significant progress has been made due to advances in genome sequence and annotation quality to unravel the black box CHO. Nevertheless, in many cases the link between genotype and phenotype in the context of suspension cultivated production cell lines is still not fully understood. While frameshift approaches targeting coding genes are frequently used, the non-coding regions of the genome have received less attention with respect to such functional annotation. Importantly, for non-coding regions frameshift knock-out strategies are not feasible. In this study, we developed a CRISPR-mediated screening approach that performs full deletions of genomic regions to enable the functional study of both the translated and untranslated genome. An pipeline for the computational high-throughput design of paired guide RNAs (pgRNAs) directing CRISPR/AsCpf1 was established and used to generate a library tackling process-related genes and long non-coding RNAs. Next generation sequencing analysis of the plasmid library revealed a sufficient, but highly variable pgRNA composition. Recombinase-mediated cassette exchange was applied for pgRNA library integration rather than viral transduction to ensure single copy representation of pgRNAs per cell. After transient AsCpf1 expression, cells were cultivated over two sequential batches to identify pgRNAs which massively affected growth and survival. By comparing pgRNA abundance, depleted candidates were identified and individually validated to verify their effect.
PubMed: 34277363
DOI: 10.1016/j.btre.2021.e00649 -
Metabolites Jun 2021Diet-induced acidosis imposes a health risk to young calves. In this study, we aimed to investigate the host jejunum transcriptome changes, along with its microbial...
Diet-induced acidosis imposes a health risk to young calves. In this study, we aimed to investigate the host jejunum transcriptome changes, along with its microbial community variations, using our established model of feed-induced ruminal acidosis in young calves. Eight bull calves were randomly assigned to two diet treatments beginning at birth (a starch-rich diet, Aci; a control diet, Con). Whole-transcriptome RNA sequencing was performed on the jejunum tissues collected at 17 weeks of age. Ribosomal RNA reads were used for studying microbial community structure variations in the jejunum. A total of 853 differentially expressed genes were identified (402 upregulated and 451 downregulated) between the two groups. The cell cycle and the digestion and absorption of protein in jejunal tissue were affected by acidosis. Compared to the control, genera of , and significantly increased in abundance in the Aci group, while and were significantly lower in the Aci group. Expression changes in the gene were associated with the abundance variations of a high number of genera in jejunum. Our study provided a snapshot of the transcriptome changes in the jejunum and its associated meta-transcriptome changes in microbial communities in young calves with feed-induced acidosis.
PubMed: 34201826
DOI: 10.3390/metabo11070414 -
Nature Communications Jun 2021Though AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. Here we...
Though AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. Here we isolate an engineered variant, "AsCas12a Ultra", that increased editing efficiency to nearly 100% at all sites examined in HSPCs, iPSCs, T cells, and NK cells. We show that AsCas12a Ultra maintains high on-target specificity thereby mitigating the risk for off-target editing and making it ideal for complex therapeutic genome editing applications. We achieved simultaneous targeting of three clinically relevant genes in T cells at >90% efficiency and demonstrated transgene knock-in efficiencies of up to 60%. We demonstrate site-specific knock-in of a CAR in NK cells, which afforded enhanced anti-tumor NK cell recognition, potentially enabling the next generation of allogeneic cell-based therapies in oncology. AsCas12a Ultra is an advanced CRISPR nuclease with significant advantages in basic research and in the production of gene edited cell medicines.
Topics: Acidaminococcus; Bacterial Proteins; CRISPR-Associated Proteins; CRISPR-Cas Systems; Cells, Cultured; Endonucleases; Gene Editing; HEK293 Cells; Hematopoietic Stem Cells; Humans; Induced Pluripotent Stem Cells; Jurkat Cells; Killer Cells, Natural; Reproducibility of Results; T-Lymphocytes
PubMed: 34162850
DOI: 10.1038/s41467-021-24017-8 -
Frontiers in Physiology 2021Carotid atherosclerosis (CAS) is an important cause of stroke. Although interactions between the gut microbiome and metabolome have been widely investigated with respect...
BACKGROUND
Carotid atherosclerosis (CAS) is an important cause of stroke. Although interactions between the gut microbiome and metabolome have been widely investigated with respect to the pathogenesis of cardiovascular diseases, information regarding CAS remains limited.
MATERIALS AND METHODS
We utilized 16S ribosomal DNA sequencing and untargeted metabolomics to investigate the alterations in the gut microbiota and plasma metabolites of 32 CAS patients and 32 healthy controls. The compositions of the gut microbiota differed significantly between the two groups, and a total of 11 differentially enriched genera were identified. In the metabolomic analysis, 11 and 12 significantly changed metabolites were screened in positive (POS) and negative (NEG) modes, respectively. α-N-Phenylacetyl-L-glutamine was an upregulated metabolite in CAS patients detected in both POS and NEG modes and had the highest | log(fold change)| in POS mode. In addition, transcriptomic analysis was performed using the GSE43292 dataset.
RESULTS
A total of 132 differentially expressed genes (DEGs) were screened. Among the upregulated DEGs in CAS patients, FABP4 exhibited the highest | log(fold change)|. Furthermore, FABP4 was positively associated with and had the highest Spearman's correlation coefficient and the most significant -value among the microbiota-DEG pairs.
CONCLUSION
In this study, we investigated the potential "microbiota-metabolite-gene" regulatory axis that may act on CAS, and our results may help to establish a theoretical basis for further specialized study of this disease.
PubMed: 34108883
DOI: 10.3389/fphys.2021.645212 -
Evidence-based Complementary and... 2021To evaluate the prebiotic effects of polysaccharide (CPP) on human gut bacteria in vitro.
OBJECTIVE
To evaluate the prebiotic effects of polysaccharide (CPP) on human gut bacteria in vitro.
METHODS
Codonopsis Radix was extracted with water at 100°C, and the extract was precipitated by 80% ethanol to obtain CPP. Human fresh fecal samples were collected from three healthy adults and used to ferment CPP. The fermented samples were collected to be analyzed by 16S rRNA sequencing.
RESULTS
The results showed that CPP exhibited significantly the stimulation on the growth of genus of human gut bacteria ( < 0.05). Although CPP also exhibited regulative trends on the genera including , , , and , no significant differences were observed ( > 0.05), which was likely associated with the limited samples ( = 3).
CONCLUSION
CPP has the potential to stimulate the growth of of the human gut bacteria and to be benefit to human health.
PubMed: 33859715
DOI: 10.1155/2021/9524913