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Frontiers in Microbiology 2020Several studies based on 16SrDNA analysis have revealed certain unique characteristics of gut microbiome in centenarians. We established a prospective cohort of fecal...
Several studies based on 16SrDNA analysis have revealed certain unique characteristics of gut microbiome in centenarians. We established a prospective cohort of fecal microbiota and conducted the first metagenomics-based study among centenarians. The objective was to explore the dynamic changes of gut microbiota in healthy centenarians and centenarians approaching end of life and to unravel the characteristics of aging-associated microbiome. Seventy-five healthy centenarians residing in three regions of Hainan participated in follow-up surveys and collection of fecal samples at intervals of 3 months. Data pertaining to dietary status, health status scores, cause of disease and death, and fecal specimens were collected for 15 months. Twenty participants died within 20 months during the follow-up period. The median survival time was 8-9 months (range, 1-17) and the mortality rate was 14.7% per year. The health status scores before death were significantly lower than those at 3 months before the end of the follow-up period [median score: 3 (range, 1-5), < 0.05]. At this time, the participants mainly exhibited symptoms of anorexia and reduced dietary intake and physical activity. Metagenomics sequencing and analysis were carried out to characterize the gut microbiota changes in the centenarians during their transition from healthy status to death. Anosim analysis showed a significant change in gut microbiota from 7 months prior to death ( = 0.10, = 0.02). All participants were grouped with 7 months before death as cut-off; no significant difference in α diversity was found between the two groups ( = 0.45). Semi-supervised monitoring and log rank sum analysis revealed significant changes in the abundance of ten bacterial species before death; of these, eight species were significantly reduced (, , , , , , , and ) while two were significantly increased before death ( and ). Compared to centenarians in northern Italy, Hainan centenarians exhibited unique characteristics of gut microbiome. The abundance of ten bacterial species showed significant changes starting from 7 months before death. We speculate that these changes might occur before the clinical symptoms of deterioration in health status.
PubMed: 32714309
DOI: 10.3389/fmicb.2020.01474 -
Cancers Apr 2024The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies...
The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder ( = 28) and non-responder ( = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of and was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.
PubMed: 38730627
DOI: 10.3390/cancers16091675 -
European Journal of Biochemistry Aug 2003Salt-active acharan sulfate lyase (no EC number) has been purified from Bacteroides stercoris HJ-15, which was isolated from human intestinal bacteria with GAG degrading...
Salt-active acharan sulfate lyase (no EC number) has been purified from Bacteroides stercoris HJ-15, which was isolated from human intestinal bacteria with GAG degrading enzymes. The enzyme was purified to apparent homogeneity by a combination of QAE-cellulose, diethylaminoethyl (DEAE)-cellulose, CM-Sephadex C-50, HA ultrogel and phosphocellulose column chromatography with the final specific activity of 81.33 micro mol x min-1 x mg-1. The purified salt-active acharan sulfate lyase was activated to 5.3-fold by salts (KCl and NaCl). The molecular weight of salt-active acharan sulfate lyase was 94 kDa by SDS/PAGE and gel filtration. The salt-active acharan sulfate lyase showed optimal activity at pH 7.2 and 40 degrees C. Salt-active acharan sulfate lyase activity was potently inhibited by Cu2+, Ni2+ and Zn2+. This enzyme was inhibited by some agents, butanediol and p-chloromercuric sulfonic acid, which modify arginine and cysteine residues. The purified Bacteroidal salt-active acharan sulfate lyase acted to the greatest extent on acharan sulfate, to a lesser extent on heparan sulfate and heparin. The biochemical properties of the purified salt-active acharan sulfate lyase are different from those of the previously purified heparin lyases. However, these findings suggest that the purified salt-active acharan sulfate lyase may belong to heparin lyase II.
Topics: Amino Acid Sequence; Bacteroides; Heparin Lyase; Hydrogen-Ion Concentration; Kinetics; Potassium Chloride; Sodium Chloride; Substrate Specificity; Temperature
PubMed: 12869191
DOI: 10.1046/j.1432-1033.2003.03696.x -
Frontiers in Microbiology 2021COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota...
COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut-lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 ( = 47) and compared it to healthy controls ( = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely , , , and . The abundances of , , , , , 5163FAA, , 6145, and 2244A were enriched in COVID-19 patients, whereas the abundances of , , , , , and were decreased ( < 0.05). The relative abundance of butyrate-producing is evidently depleted in COVID-19 patients, while the relative abundances of sp. and the probiotic were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman's correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of and decreased abundance of were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.
PubMed: 34707577
DOI: 10.3389/fmicb.2021.712081 -
Antimicrobial Agents and Chemotherapy Sep 1999Gemifloxacin mesylate (SB 265805), a new fluoronaphthyridone, was tested against 359 recent clinical anaerobic isolates by the National Committee for Clinical Laboratory... (Comparative Study)
Comparative Study
Gemifloxacin mesylate (SB 265805), a new fluoronaphthyridone, was tested against 359 recent clinical anaerobic isolates by the National Committee for Clinical Laboratory Standards reference agar dilution method with supplemented brucella blood agar and an inoculum of 10(5) CFU/spot. Comparative antimicrobials tested included trovafloxacin, levofloxacin, grepafloxacin, sparfloxacin, sitafloxacin (DU-6859a), penicillin G, amoxicillin clavulanate, imipenem, cefoxitin, clindamycin, and metronidazole. The MIC(50) and MIC(90) (MICs at which 50 and 90% of the isolates were inhibited) of gemifloxacin against various organisms (with the number of strains tested in parentheses) were as follows (in micrograms per milliliter): for Bacteroides fragilis (28), 0.5 and 2; for Bacteroides thetaiotaomicron (24), 1 and 16; for Bacteroides caccae (12), 1 and 16; for Bacteroides distasonis (12), 8 and >16; for Bacteroides ovatus (12), 4 and >16; for Bacteroides stercoris (12), 0.5 and 0.5; for Bacteroides uniformis (12), 1 and 4; for Bacteroides vulgatus (11), 4 and 4; for Clostridium clostridioforme (15), 0.5 and 0.5; for Clostridium difficile (15), 1 and >16; for Clostridium innocuum (13), 0.125 and 2; for Clostridium perfringens (13), 0.06 and 0.06; for Clostridium ramosum (14), 0.25 and 8; for Fusobacterium nucleatum (12), 0.125 and 0.25; for Fusobacterium necrophorum (11), 0.25 and 0.5; for Fusobacterium varium (13), 0.5 and 1; for Fusobacterium spp. (12), 1 and 2; for Peptostreptococcus anaerobius (13), 0.06 and 0.06; for Peptostreptococcus asaccharolyticus (13), 0.125 and 0.125; for Peptostreptococcus magnus (14), 0.03 and 0.03; for Peptostreptococcus micros (12), 0.06 and 0.06; for Peptostreptococcus prevotii (14), 0.06 and 0.25; for Porphyromonas asaccharolytica (11), 0.125 and 0.125; for Prevotella bivia (10), 8 and 16; for Prevotella buccae (10), 2 and 2; for Prevotella intermedia (10), 0.5 and 0.5; and for Prevotella melaninogenica (11), 1 and 1. Gemifloxacin mesylate (SB 265805) was 1 to 4 dilutions more active than trovafloxacin against fusobacteria and peptostreptococci, and the two drugs were equivalent against clostridia and P. asaccharolytica. Gemifloxacin was equivalent to sitafloxacin (DU 6859a) against peptostreptococci, C. perfringens, and C. ramosum, and sitafloxacin was 2 to 3 dilutions more active against fusobacteria. Sparfloxacin, grepafloxacin, and levofloxacin were generally less active than gemifloxacin against all anaerobes.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria, Anaerobic; Fluoroquinolones; Gemifloxacin; Microbial Sensitivity Tests; Naphthyridines; Therapeutic Equivalency
PubMed: 10471570
DOI: 10.1128/AAC.43.9.2231 -
BioRxiv : the Preprint Server For... Mar 2024The prototypic crAssphage () is one of the most abundant, prevalent, and persistent gut bacteriophages, yet it remains uncultured and its lifestyle uncharacterized. For...
The prototypic crAssphage () is one of the most abundant, prevalent, and persistent gut bacteriophages, yet it remains uncultured and its lifestyle uncharacterized. For the last decade, crAssphage has escaped plaque-dependent culturing efforts, leading us to investigate alternative lifestyles that might explain its widespread success. Through genomic analyses and culturing, we find that crAssphage uses a phage-plasmid lifestyle to persist extrachromosomally. Plasmid-related genes are more highly expressed than those implicated in phage maintenance. Leveraging this finding, we use a plaque-free culturing approach to measure crAssphage replication in culture with and , revealing a broad host range. We demonstrate that crAssphage persists with its hosts in culture without causing major cell lysis events or integrating into host chromosomes. The ability to switch between phage and plasmid lifestyles within a wide range of hosts contributes to the prolific nature of crAssphage in the human gut microbiome.
PubMed: 38562748
DOI: 10.1101/2024.03.20.585998 -
BMC Microbiology Sep 2018Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may...
BACKGROUND
Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults.
RESULTS
The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients.
CONCLUSION
In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.
Topics: Adult; Asthma; Bacteria; Fatty Acids, Volatile; Feces; Female; Gastrointestinal Microbiome; Humans; Intestines; Male; Metagenome; United Kingdom
PubMed: 30208875
DOI: 10.1186/s12866-018-1257-x -
Pharmaceutics Aug 2023The pharmacokinetic variability of nifedipine widely observed in the clinic cannot be fully explained by pharmacogenomics. As a new factor affecting drug metabolism, how...
The pharmacokinetic variability of nifedipine widely observed in the clinic cannot be fully explained by pharmacogenomics. As a new factor affecting drug metabolism, how the gut microbiota affects the pharmacokinetics of nifedipine needs to be explored. Spontaneously hypertensive rats (SHRs) have been commonly used in hypertension-related research and served as the experimental groups; Wistar rats were used as control groups. In this study, the bioavailability of nifedipine decreased by 18.62% ( < 0.05) in the SHRs compared with the Wistar rats. Changes in microbiota were associated with the difference in pharmacokinetics. The relative abundance of was negatively correlated with AUC ( = -0.881, = 0.004) and ( = -0.714, = 0.047). Analysis of serum bile acid (BA) profiles indicated that glycoursodeoxycholic acid (GUDCA) and glycochenodeoxycholic acid (GCDCA) were significantly increased in the SHRs. Compared with the Wistar rats, the expressions of CYP3A1 and PXR were upregulated and the enzyme activity of CYP3A1 increased in the SHRs. Spearman's rank correlation revealed that was negatively correlated with GUDCA ( = -0.7126, = 0.0264) and GCDCA ( = -0.6878, = 0.0339). Moreover, GUDCA was negatively correlated with ( = -0.556, = 0.025). In primary rat hepatocytes, GUDCA could induce the expressions of PXR target genes and . Furthermore, antibiotic treatments in SHRs verified the impact of microbiota on the pharmacokinetics of nifedipine. Generally, gut microbiota affects the pharmacokinetics of nifedipine through microbial biotransformation or by regulating the enzyme activity of CYP3A1.
PubMed: 37631299
DOI: 10.3390/pharmaceutics15082085 -
Foods (Basel, Switzerland) Jul 2023Amaranth has been recognized as a nutraceutical food because it contains high-quality proteins due to its adequate amino acid composition that covers the recommended...
Amaranth has been recognized as a nutraceutical food because it contains high-quality proteins due to its adequate amino acid composition that covers the recommended requirements for children and adults. Since pre-Hispanic times, amaranth has been consumed as popped grain; the popping process improves its nutritive quality and improves its digestibility. Popped amaranth consumption has been associated with the recovery of malnourished children. However, there is no information on the impact that popped amaranth consumption has on gut microbiota composition. A non-randomized pilot trial was conducted to evaluate the changes in composition, structure, and function of the gut microbiota of stunted children who received four grams of popped amaranth daily for three months. Stool and serum were collected at the beginning and at the end of the trial. Short-chain fatty acids (SCFA) were quantified, and gut bacterial composition was analyzed by gene sequencing. Biometry and hematology results showed that children had no pathology other than low height-for-age. A decrease in the relative abundance of , , and bacteria related to inflammation and colitis, and an increase in the relative abundance of and bacteria associated with health and longevity, was observed. The results demonstrate that popped amaranth is a nutritious food that helps to combat childhood malnutrition through gut microbiota modulation.
PubMed: 37509852
DOI: 10.3390/foods12142760 -
Science Immunology Feb 2018The human leukocyte antigen-A2 (HLA-A2)-restricted zinc transporter 8 (ZnT8) and other islet epitopes elicit interferon-γ secretion by CD8 T cells preferentially in...
The human leukocyte antigen-A2 (HLA-A2)-restricted zinc transporter 8 (ZnT8) and other islet epitopes elicit interferon-γ secretion by CD8 T cells preferentially in type 1 diabetes (T1D) patients compared with controls. We show that clonal ZnT8-reactive CD8 T cells express private T cell receptors and display equivalent functional properties in T1D and healthy individuals. Ex vivo analyses further revealed that CD8 T cells reactive to ZnT8 and other islet epitopes circulate at similar frequencies and exhibit a predominantly naïve phenotype in age-matched T1D and healthy donors. Higher frequencies of ZnT8-reactive CD8 T cells with a more antigen-experienced phenotype were detected in children versus adults, irrespective of disease status. Moreover, some ZnT8-reactive CD8 T cell clonotypes were found to cross-recognize a mimotope. Whereas ZnT8 was poorly expressed in thymic medullary epithelial cells, variable thymic expression levels of islet antigens did not modulate the peripheral frequency of their cognate CD8 T cells. In contrast, ZnT8-reactive cells were enriched in the pancreata of T1D patients versus nondiabetic and type 2 diabetic individuals. Thus, islet-reactive CD8 T cells circulate in most individuals but home to the pancreas preferentially in T1D patients. We conclude that the activation of this common islet-reactive T cell repertoire and progression to T1D likely require defective peripheral immunoregulation and/or a proinflammatory islet microenvironment.
Topics: Adult; CD8-Positive T-Lymphocytes; Cell Line; Child; Diabetes Mellitus, Type 1; Female; HLA-A2 Antigen; Healthy Volunteers; Humans; Islets of Langerhans; Male; Pancreas
PubMed: 29429978
DOI: 10.1126/sciimmunol.aao4013