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The Science of the Total Environment Feb 2016
PubMed: 26796740
DOI: 10.1016/j.scitotenv.2015.12.024 -
Scientific Reports Jun 2023Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations...
Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations in the gut microbiota have been shown to correlate with the development and progression of MAFLD. However, little is known regarding differences in the gut microbiomes of MAFLD patients and healthy cohorts, and subgroups at the abnormal activity of hepatic enzymes in China. In this study, we enrolled 81 MAFLD patients and 25 healthy volunteers. The fecal microbiota was assessed using 16S rRNA gene sequencing and metagenomic sequencing. The results suggested that Ruminococcus obeum and Alistipes were most enriched in healthy individuals when compared with MAFLD patients. Microbe-set Enrichment Analysis (MSEA) results showed Dorea, Lactobacillus and Megasphaera are enriched in MAFLD group. We also found that Alistipes has negatively related to serum glucose (GLU), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT). Moreover, the abundance of Dorea was found to be significantly overrepresented in the MAFLD patients and the degree of enrichment increased with the increasing abnormal liver enzyme. An increase in Dorea, combined with decreases in Alistipes appears to be characteristic of MAFLD patients. Further study of microbiota may provide a novel insight into the pathogenesis of MAFLD as well as a novel treatment strategy.
Topics: Humans; Gastrointestinal Microbiome; Carcinoma, Hepatocellular; RNA, Ribosomal, 16S; Liver Neoplasms; Microbiota; Non-alcoholic Fatty Liver Disease; Bacteroidetes; Clostridiaceae
PubMed: 37340081
DOI: 10.1038/s41598-023-37163-4 -
Journal of Agricultural and Food... Jun 2018d-Allulose is a low-calorie sweetener and has broad applications in the food, cosmetics, and pharmaceutical industries. Recently, most studies focus on d-allulose...
d-Allulose is a low-calorie sweetener and has broad applications in the food, cosmetics, and pharmaceutical industries. Recently, most studies focus on d-allulose production from d-fructose by d-allulose 3-epimerase (DAEase). However, the major blocker of industrial production of d-allulose is the poor thermostability. In this study, site-directed mutagenesis at the interface regions of Dorea sp. DAEase was carried out, and the F154Y/E191D/I193F mutation was obtained. The mutant protein displayed much higher thermostability, with a t value of 20.47 h (50 °C) and a T value of 74.18 °C. Compared with the wild-type DAEase, the t value at 50 °C increased by 5.4-fold, and the T value increased by 17.54 °C. In the d-allulose production from 500 g/L d-fructose, 148.2 g/L d-allulose could be obtained by F154Y/E191D/I193F mutant protein. The results suggest that site-directed mutagenesis at the interface regions is an efficient approach for improving the thermostability of DAEase.
Topics: Bacterial Proteins; Enzyme Stability; Firmicutes; Fructose; Hot Temperature; Hydrogen-Ion Concentration; Kinetics; Mutagenesis, Site-Directed; Racemases and Epimerases
PubMed: 29762031
DOI: 10.1021/acs.jafc.8b01200 -
Aging Sep 2023Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with...
BACKGROUND
Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation.
METHODS
We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.
RESULTS
The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of , , , , and with GH, of (), (), , , and with PE, and of and with eclampsia, respectively.
CONCLUSIONS
This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.
Topics: Female; Pregnancy; Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Hypertension, Pregnancy-Induced; Mendelian Randomization Analysis
PubMed: 37698537
DOI: 10.18632/aging.205019 -
Journal of Autoimmunity May 2023A number of public metagenomic studies reveal an association between the gut microbiome and various immune-mediated diseases including Behcet's uveitis (BU) and...
BACKGROUND
A number of public metagenomic studies reveal an association between the gut microbiome and various immune-mediated diseases including Behcet's uveitis (BU) and Vogt-Koyanagi-Harada disease (VKH). Integrated-analysis and subsequent validation of these results could be a potentially powerful way to understand the microbial signatures and their functions in these two uveitis entities.
METHODS
We integrated the sequencing data of our previous metagenomic studies on two major uveitis entities, BU and VKH as well as four other publicly available immune-mediated diseases datasets, including Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Crohn's disease (CD) and Ulcerative Colitis (UC). Alpha-diversity and beta-diversity analysis were used to compare the gut microbiome signatures between both uveitis entities and other immune-mediated diseases and healthy controls. Amino acid homology between microbial proteins and a uveitogenic peptide of the interphotoreceptor retinoid-binding protein (IRBP) was investigated using a similarity search in the NCBI protein BLAST program (BLASTP). Enzyme-linked Immunosorbent Assay (ELISA) was performed to evaluate the cross-reactive responses of experimental autoimmune uveitis (EAU)-derived lymphocytes and BU patients-derived peripheral blood mononuclear cells (PBMCs) against homologous peptides. The area under the curve (AUC) analysis was used to test the sensitivity and specificity of gut microbial biomarkers.
RESULTS
Depleted Dorea, Blautia, Coprococcus, Erysipelotrichaceae and Lachnospiraceae as well as enriched Bilophila and Stenotrophomonas were identified in BU patients. An enriched Alistipes along with a lower level of Dorea were observed in VKH patients. A peptide antigen (SteTDR) encoded by BU specifically enriched Stenotrophomonas was identified to share homology with IRBP. In vitro experiments showed that lymphocytes from EAU or PBMCs from BU patients reacted to this peptide antigen as shown by the production of IFN-γ and IL-17. Addition of the SteTDR peptide to the classical IRBP immunization protocol exacerbated EAU severity. Gut microbial marker profiles consisted of 24 species and 32 species respectively differentiated BU and VKH from each other as well as from the other four immune-mediated diseases and healthy controls. Protein annotation identified 148 and 119 specific microbial proteins associated with BU and VKH, respectively. For metabolic function analysis, 108 and 178 metabolic pathways were shown to be associated with BU and VKH, respectively.
CONCLUSIONS
Our study revealed specific gut microbial signatures and their potentially functional roles in BU and VKH pathogenesis that differ significantly from other immune-mediated diseases as well as healthy controls.
Topics: Humans; Uveomeningoencephalitic Syndrome; Leukocytes, Mononuclear; Gastrointestinal Microbiome; Uveitis; Behcet Syndrome
PubMed: 37208257
DOI: 10.1016/j.jaut.2023.103055 -
Frontiers in Cellular and Infection... 2022Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial... (Review)
Review
Many individuals diagnosed with autism spectrum disorder (ASD) experience gastrointestinal (GI) dysfunction and show microbial dysbiosis. Variation in gut microbial populations is associated with increased risk for GI symptoms such as chronic constipation and diarrhoea, which decrease quality of life. Several preclinical models of autism also demonstrate microbial dysbiosis. Given that much pre-clinical research is conducted in mouse models, it is important to understand the similarities and differences between the gut microbiome in humans and these models in the context of autism. We conducted a systematic review of the literature using PubMed, ProQuest and Scopus databases to compare microbiome profiles of patients with autism and transgenic (NL3, Shank3 KO, 15q dup), phenotype-first (BTBR) and environmental (Poly I:C, Maternal Inflammation Activation (MIA), valproate) mouse models of autism. Overall, we report changes in fecal microbial communities relevant to ASD based on both clinical and preclinical studies. Here, we identify an overlapping cluster of genera that are modified in both fecal samples from individuals with ASD and mouse models of autism. Specifically, we describe an increased abundance of , , and and a decrease in genera in both humans and rodents relevant to this disorder. Studies in both humans and mice highlighted multidirectional changes in abundance (i.e. in some cases increased abundance whereas other reports showed decreases) for several genera including , , , and , suggesting that these genera may be susceptible to modification in autism. Identification of these microbial profiles may assist in characterising underlying biological mechanisms involving host-microbe interactions and provide future therapeutic targets for improving gut health in autism.
Topics: Animals; Autism Spectrum Disorder; Autistic Disorder; Disease Models, Animal; Dysbiosis; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Mice; Microfilament Proteins; Nerve Tissue Proteins; Quality of Life
PubMed: 35846755
DOI: 10.3389/fcimb.2022.905841 -
The British Journal of Nutrition Nov 2002The objective of the present review is to discuss Se nutrition during breast-feeding, encompassing environmental and maternal constitutional factors affecting... (Review)
Review
The objective of the present review is to discuss Se nutrition during breast-feeding, encompassing environmental and maternal constitutional factors affecting breast-milk-Se metabolism and secretion. A literature search of Medline and Webofscience was used to retrieve and select papers dealing with Se and breast milk. Although Se in natural foods occurs only in organic form, breast milk responds to organic and inorganic Se in supplements. Inorganic Se (selenite, selenate), which is largely used in maternal supplements, is not detectable in breast milk. The mammary-gland regulating mechanism controls the synthesis and secretion of seleno-compounds throughout lactation, with a high total Se level in colostrum that decreases as lactation progresses. Se appears in breast milk as a component of specific seleno-proteins and seleno-amino-acids in milk proteins that are well tolerated by breast-fed infants even in high amounts. Se in breast milk occurs as glutathione peroxidase (4-32 % total Se) > selenocystamine > selenocystine > selenomethionine. The wide range of breast-milk Se concentrations depends on Se consumed in natural foods, which reflects the Se content of the soils where they are grown. Se prophylaxis, either through soil Se fertilization or maternal supplements, is effective in raising breast-milk Se concentration. In spite of wide variation, the median Se concentration from studies worldwide are 26, 18, 15, and 17 microg/l in colostrum (0-5 d), transitional milk (6-21 d), mature milk (1-3 months) and late lactation (>5 months) respectively. Se recommendations for infants are presently not achieved in 30 % of the reported breast-milk Se concentrations; nevertheless Se status is greater in breast-fed than in formula-fed infants.
Topics: Adult; Biological Availability; Breast Feeding; Female; Global Health; Humans; Infant; Infant, Newborn; Maternal Nutritional Physiological Phenomena; Milk, Human; Nutrition Policy; Nutritional Status; Selenium
PubMed: 12425725
DOI: 10.1079/BJN2002692 -
Nutrients Nov 2023The objective of this study was to examine the correlation between gut microbiota and both age-related macular degeneration (AMD) and glaucoma. Mendelian randomization...
The objective of this study was to examine the correlation between gut microbiota and both age-related macular degeneration (AMD) and glaucoma. Mendelian randomization studies were conducted utilizing the data sourced from the genome-wide association study (GWAS) database for the gut microbiome, AMD, and glaucoma. Single nucleotide polymorphism (SNP) estimates were summarized through five Mendelian randomization (MR) methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables (IVs). Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Inverse variance weighted (IVW) suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggest that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggest that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Likewise, reverse MR found that glaucoma led to an increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Glaucoma; Macular Degeneration; Clostridiales; Lactobacillales
PubMed: 37960299
DOI: 10.3390/nu15214646 -
Clinica Chimica Acta; International... Apr 2015Thimerosal (or Thiomersal) is a trade name for an organomercurial compound (sodium ethyl-mercury (Hg) thiosalicylate) that is 49.55% Hg by weight, which rapidly... (Review)
Review
INTRODUCTION
Thimerosal (or Thiomersal) is a trade name for an organomercurial compound (sodium ethyl-mercury (Hg) thiosalicylate) that is 49.55% Hg by weight, which rapidly decomposes in aqueous saline solutions into ethyl-Hg hydroxide and ethyl-Hg chloride. Developed in 1927, it has been and is still being used as a preservative in some cosmetics, topical pharmaceuticals, and biological drug products, including vaccines. Concerns have been voiced about its use because it is toxic to human cells. Although it is banned in several countries, it continues to be added to some vaccines in the United States and many vaccines in the developing world.
DISCUSSION
This critical review focuses on the clinical, epidemiological, and biochemical studies of adverse effects from Thimerosal in developing humans. This review will include research that examines fetal, infant, and childhood death; birth defects; neurodevelopmental testing deficits in children; and neurodevelopmental disorders (attention deficit/hyperactivity disorder, autism spectrum disorder, tic disorder, and specific developmental delays). The review will also look at the research that examined the outcomes of acute accidental ethyl-Hg poisoning in humans. The studies that examine the underlying biochemical insights into the neuronal cellular damage will also be explored.
CONCLUSION
The culmination of the research that examines the effects of Thimerosal in humans indicates that it is a poison at minute levels with a plethora of deleterious consequences, even at the levels currently administered in vaccines.
Topics: Growth and Development; Humans; Thimerosal
PubMed: 25708367
DOI: 10.1016/j.cca.2015.02.030 -
International Journal of Systematic and... Mar 2002Two strains of a gram-positively staining, obligately anaerobic, non-spore-forming, rod-shaped bacterium, designated strains 111-13A and 111-35T, were isolated from... (Comparative Study)
Comparative Study
Reclassification of Eubacterium formicigenerans Holdeman and Moore 1974 as Dorea formicigenerans gen. nov., comb. nov., and description of Dorea longicatena sp. nov., isolated from human faeces.
Two strains of a gram-positively staining, obligately anaerobic, non-spore-forming, rod-shaped bacterium, designated strains 111-13A and 111-35T, were isolated from human faeces. Analysis of the 16S rRNA gene sequences indicated that these strains were members of the Clostridium coccoides rRNA group of organisms. The nearest relatives of the unknown bacterium were Eubacterium formicigenerans (having a sequence similarity of 94%) and an uncultured bacterium (similarity > 99%). Characterization studies indicated that the unidentified faecal bacterium was biochemically distinct from Eubacterium formicigenerans, members of the Clostridium coccoides group and all other described Eubacterium species. On the basis of the data from these studies, it is proposed that the hitherto unknown rod-shaped bacterium be designated a species of a novel genus, namely Dorea longicatena gen. nov., sp. nov., and that Eubacterium formicigenerans be transferred to this genus as Dorea formicigenerans gen. nov., comb. nov.
Topics: Eubacterium; Feces; Humans; Molecular Sequence Data; Phylogeny; RNA, Bacterial; RNA, Ribosomal, 16S; Sequence Homology, Nucleic Acid; Species Specificity
PubMed: 11931151
DOI: 10.1099/00207713-52-2-423