-
Frontiers in Microbiology 2024Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, with its etiology attributed to a complex interplay of genetic, dietary, environmental...
BACKGROUND
Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, with its etiology attributed to a complex interplay of genetic, dietary, environmental factors, and infections such as . Despite the known risk factors, the role of gut microbiota in the development of gastric cancer remains insufficiently explored. This study aims to elucidate the causal relationship between gut microbiota and gastric cancer using a two-sample Mendelian Randomization (MR) approach.
METHODS
Utilizing genome-wide association study (GWAS) summary data from the MiBioGen consortium and gastric cancer datasets, we selected instrumental variables for MR analysis based on their association with specific microbiota. We employed several MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and others, to estimate the causal effects of gut microbiota diversity on the risk of developing gastric cancer.
RESULTS
Our analysis identified significant associations between certain gut microbiota and gastric cancer risk. Specifically, taxa such as (OR = 0.540, 95%CI: 0.354-0.823, = 0.004), (OR = 0.756, 95%CI: 0.613-0.932, = 0.009), (OR = 0.816, 95%CI: 0.666-1.000, < 0.05), (OR = 0.816, 95%CI: 0.666-1.000, < 0.05), (OR = 0.863, 95%CI: 0.746-0.999, = 0.048) were found to have a protective effect against gastric cancer. Conversely, an increased risk of gastric cancer was associated with the abundance of (OR = 1.342, 95%CI: 1.071-1.681, = 0.011), (OR = 1.132, 95%CI: 1.012-1.267, = 0.030), and (OR = 1.207, 95%CI: 1.074-1.355, = 0.002). The findings were robust across various MR methods and were not driven by any single SNP, indicating a genuine causal relationship.
CONCLUSION
Our studies have shown that there is a causal relationship between intestinal flora and gastric cancer at the genetic level. , , , , , and as having a protective role against GC, while , , and were associated with an increased risk.
PubMed: 38628871
DOI: 10.3389/fmicb.2024.1383530 -
Molecules (Basel, Switzerland) Apr 2023α-Glucosidase (AGS) inhibitors have been regarded as an ideal target for the management of type 2 diabetes mellitus (T2DM) since they can maintain an acceptable blood...
α-Glucosidase (AGS) inhibitors have been regarded as an ideal target for the management of type 2 diabetes mellitus (T2DM) since they can maintain an acceptable blood glucose level by delaying the digestion of carbohydrates and diminishing the absorption of monosaccharides. In the process of our endeavor in mining AGS inhibitors from natural sources, the culture broth of two mangrove-derived actinomycetes sp. WHUA03267 and sp. WHUA03072 exhibited an apparent inhibitory activity against AGS. A subsequent chemical investigation into the two extracts furnished 28 secondary metabolites that were identified by spectroscopic methods as two previously undescribed linear polyketides -, four benzenoid ansamycins -, fourteen cyclodipeptides -, one prenylated indole derivative , two fusicoccane-type diterpenoids -, two hydroxamate siderophore -, and five others -. Among all of the isolates, and were obtained from actinomycetes for the first time, while - had never been reported to occur in a marine-derived microorganism previously. In the in vitro AGS inhibitory assay, compounds , , , , , , and exhibited potent to moderate activity with IC values ranging from 35.76 ± 0.40 to 164.5 ± 15.5 μM, as compared with acarbose (IC = 422.3 ± 8.4 μM). The AGS inhibitory activity of , , , , and was reported for the first time. In particular, autolytimycin () represented the first ansamycin derivative reported to possess the AGS inhibitory activity. Kinetics analysis and molecular docking were performed to determine the inhibition types and binding modes of these inhibitors, respectively. In the MTT assay, , , , , , , and exhibited no apparent cytotoxicity to the human normal hepatocyte (LO2) cells, suggesting satisfactory safety of these AGS inhibitors.
Topics: Humans; Glycoside Hydrolase Inhibitors; Actinobacteria; Diabetes Mellitus, Type 2; Actinomyces; Molecular Docking Simulation; Streptomyces; alpha-Glucosidases; Molecular Structure
PubMed: 37175232
DOI: 10.3390/molecules28093822 -
Medical Principles and Practice :... 2022Hepatic actinomycosis (HA) is a rare infection with an indolent course, atypical clinical manifestations, nonspecific laboratory and imaging findings, and challenging... (Review)
Review
Hepatic actinomycosis (HA) is a rare infection with an indolent course, atypical clinical manifestations, nonspecific laboratory and imaging findings, and challenging diagnosis. We describe a case of a 35-year-old female who developed HA 2 weeks after gastrectomy. In addition, we analyzed clinical characteristics and outcome of 157 additional cases of HA identified in a 60-year literature review. Patients with HA were predominantly male (57%) and more than one-half were between 40 and 70 years of age. The infection was cryptogenic in 80.8% of cases. Risk factors for HA were identified in 63.1% of the patients. Clinical presentation included fever (57.7%), abdominal pain (52.1%), weight loss (45.1%), anorexia (27.5%), fatigue and chills (12.7% each), and malaise (12%) over a 2.35 ± 3.5 months period. Leukocytosis, elevated alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein were the most frequent laboratory findings. Radiologic imaging revealed that the right lobe was more frequently affected (62.5%) with a single lesion found in two-thirds of cases. Diagnosis was achieved by histopathologic examination in 70.6% of cases. Cultures yielded Actinomyces in 45 instances, with A. israelii being the most frequent species. Less than one-half of the patients were treated only with antibiotics, while the others received combined medical and surgical treatment. The median duration of antibiotic therapy was 135 days. The presence of multiple lesions or solid tumor-like lesions (without liquefaction) was significantly associated with medical therapy alone. The outcome was favorable in most cases (94%). Although rarely encountered, HA should be considered in patients with a chronic or subacute inflammatory process of the liver to promptly diagnose and treat.
Topics: Actinomyces; Actinomycosis; Adult; Anti-Bacterial Agents; Female; Humans; Liver Abscess; Male
PubMed: 35038716
DOI: 10.1159/000521990 -
Microbiology (Reading, England) Sep 2021Last year ActinoBase, a Wiki-style initiative supported by the UK Microbiology Society, published a review highlighting the research of particular interest to the... (Review)
Review
Last year ActinoBase, a Wiki-style initiative supported by the UK Microbiology Society, published a review highlighting the research of particular interest to the actinomycete community. Here, we present the second ActinoBase review showcasing selected reports published in 2020 and early 2021, integrating perspectives in the actinomycete field. Actinomycetes are well-known for their unsurpassed ability to produce specialised metabolites, of which many are used as therapeutic agents with antibacterial, antifungal, or immunosuppressive activities. Much research is carried out to understand the purpose of these metabolites in the environment, either within communities or in host interactions. Moreover, many efforts have been placed in developing computational tools to handle big data, simplify experimental design, and find new biosynthetic gene cluster prioritisation strategies. Alongside, synthetic biology has provided advances in tools to elucidate the biosynthesis of these metabolites. Additionally, there are still mysteries to be uncovered in understanding the fundamentals of filamentous actinomycetes' developmental cycle and regulation of their metabolism. This review focuses on research using integrative methodologies and approaches to understand the bigger picture of actinomycete biology, covering four research areas: ) technology and methodology; ) specialised metabolites; ) development and regulation; and ) ecology and host interactions.
Topics: Actinobacteria; Actinomyces; Anti-Bacterial Agents; Multigene Family; Synthetic Biology
PubMed: 34515628
DOI: 10.1099/mic.0.001084 -
Molecules (Basel, Switzerland) Jun 2023Marine natural products have been recognized as the most promising source of bioactive substances for drug discovery research. This review illustrates the diversity of... (Review)
Review
Marine natural products have been recognized as the most promising source of bioactive substances for drug discovery research. This review illustrates the diversity of culturable actinobacteria associated with marine algae, their bioactivity and metabolites, and approaches to their isolation and determination of their biological properties. Furthermore, actinobacteria associated with marine algae are presented as a new subject for an extensive investigation to find novel and active natural products, which make them a potentially rich and innovative source for new drug development deserving more attention and exploration.
Topics: Actinobacteria; Actinomyces; Biological Products; Drug Discovery; Bacteria
PubMed: 37446800
DOI: 10.3390/molecules28135138 -
Diagnostics (Basel, Switzerland) Mar 2024A hypothesis-forming exploratory cross-sectional assessment was conducted to assess the occurrence and relevance of Gram-positive rod-shaped bacteria like spp. and...
Preanalytical, Analytical and Postanalytical Analyses on spp. and Actinomycetaceae in Urine Samples of Patients with Suspected Urinary Tract Infection-A Hypothesis-Forming Observational Study.
A hypothesis-forming exploratory cross-sectional assessment was conducted to assess the occurrence and relevance of Gram-positive rod-shaped bacteria like spp. and Actinomycetaceae in human urine samples. In total, 1170 urine samples from 1031 inpatients with suspected urinary tract infection were assessed for culture-based growth of Gram-positive rod-shaped bacteria applying API Coryne assays, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and in-house 16S rRNA gene sequencing. Overall, 502 different bacterial colonies from 346 urine samples taken from 324 inpatients were observed. The three quantitatively most abundant genera or genus clusters were (254 isolates, 62%), / (79 isolates, 19%), and / (29 isolates, 7%). Compared to sequencing, the diagnostic accuracy of all assessed competitor assays from the diagnostic routine was <80% for differentiation on the genus level and <30% for differentiation on the species level. Prolongated incubation for 4 days compared to 2 days resulted in additional detection of 15% of the totally recorded Gram-positive rod-shaped bacteria. An approximately 5-fold increased detection rate in mid-stream urine compared to urine acquired applying alternative sampling strategies was observed. In conclusion, in the rare event of the suspected clinical relevance of such findings, confirmatory testing with invasively sampled urine should be considered due to the high contamination rate observed in mid-stream urine. Confirmatory testing by DNA-sequencing methods should be considered if an exact identification of genus or species is regarded as relevant for the individual choice of the therapeutic strategy.
PubMed: 38611658
DOI: 10.3390/diagnostics14070746 -
Journal of Alzheimer's Disease : JAD 2022Despite decades of research, our understanding of Alzheimer's disease (AD) etiology remains incomplete. In recent years, appreciation has grown for potential roles for...
BACKGROUND
Despite decades of research, our understanding of Alzheimer's disease (AD) etiology remains incomplete. In recent years, appreciation has grown for potential roles for the microbiota in shaping neurological health.
OBJECTIVE
This study aimed to examine associations between the microbiota and AD in a human cross-sectional cohort.
METHODS
Forty-five AD patients and 54 matched controls were recruited in Vancouver, Canada. Fecal and oral samples underwent 16S microbiota sequencing. A wide array of demographic and clinical data were collected. Differences between participant groups were assessed, and associations between microbes and clinical variables were examined within the AD population.
RESULTS
The gut microbiota of AD patients displayed lower diversity relative to controls, although taxonomic differences were sparse. In contrast, the AD oral microbiota displayed higher diversity, with several taxonomic differences relative to controls, including a lower abundance of the families Streptococcaceae and Actinomycetaceae, and a higher abundance of Weeksellaceae, among others. The periodontitis-associated oral microbe Porphyromonas gingivalis was 5 times more prevalent among patients. No significant associations between gut or oral microbes and cognition were detected, but several correlations existed between microbes and mood disorders and BMI among patients, including a strong positive correlation between Alphaproteobacteria and depression score.
CONCLUSION
The gut microbiota of AD patients was not overtly different from controls, although it displayed lower diversity, an overall marker of microbiota health. The oral microbiota did display marked differences. Cognition was not associated with a microbial signature, but other relevant AD factors including mood and BMI did demonstrate an association.
Topics: Alzheimer Disease; Canada; Cross-Sectional Studies; Humans; Microbiota; RNA, Ribosomal, 16S
PubMed: 35275538
DOI: 10.3233/JAD-215520 -
Trends in Microbiology Dec 2020Adhesive pili in Gram-positive bacteria represent a variety of extracellular multiprotein polymers that mediate bacterial colonization of specific host tissues and... (Review)
Review
Adhesive pili in Gram-positive bacteria represent a variety of extracellular multiprotein polymers that mediate bacterial colonization of specific host tissues and associated pathogenesis. Pili are assembled in two distinct but coupled steps, an orderly crosslinking of pilin monomers and subsequent anchoring of the polymer to peptidoglycan, catalyzed by two transpeptidase enzymes - the pilus-specific sortase and the housekeeping sortase. Here, we review this biphasic assembly mechanism based on studies of two prototypical models, the heterotrimeric pili in Corynebacterium diphtheriae and the heterodimeric pili in Actinomyces oris, highlighting some newly emerged basic paradigms. The disparate mechanisms of protein ligation mediated by the pilus-specific sortase and the spatial positioning of adhesive pili on the cell surface modulated by the housekeeping sortase are among the notable highlights.
Topics: Actinobacteria; Actinomyces; Cell Wall; Corynebacterium diphtheriae; Fimbriae Proteins; Fimbriae, Bacterial; Gram-Positive Bacteria; Humans; Peptidoglycan; Virulence
PubMed: 32499101
DOI: 10.1016/j.tim.2020.05.008 -
The American Journal of Forensic... Jun 2021A 19-year-old woman in septic shock with recent computed tomography findings of a loculated hepatic abscess was transferred to an intensive care unit where she went into...
A 19-year-old woman in septic shock with recent computed tomography findings of a loculated hepatic abscess was transferred to an intensive care unit where she went into asystolic cardiac arrest. After resuscitation, surgical exploration revealed a purulent pericardial effusion with tamponade and a liver abscess. Microbiological analyses from both sites were negative. Shortly after surgical exploration, she developed multiorgan failure and died. At autopsy, pus was observed both within the pericardial cavity and around the left lobe of the liver. Green "sulfur granules" suggestive of infection with Actinomyces spp. were able to be extruded from the liver during the postmortem examination and cultures returned positive for Actinomyces israelii. This case is a rare example of primary hepatic actinomycosis infection that resulted in the death of a young woman. Nonspecific clinical manifestations may delay diagnosis; however, the finding of "sulfur granules" in areas of abscess formation at autopsy should be taken as an indication of possible underlying Actinomyces infection.
Topics: Actinomyces; Actinomycosis; Cardiac Tamponade; Fatal Outcome; Female; Humans; Liver Abscess; Multiple Organ Failure; Pericardial Effusion; Pneumonia; Shock, Septic; Young Adult
PubMed: 33346982
DOI: 10.1097/PAF.0000000000000637 -
Biotechnology Advances Nov 2019Actinomycetes are one of the most valuable sources of natural products with industrial and medicinal importance. After more than half a century of exploitation, it has... (Review)
Review
Actinomycetes are one of the most valuable sources of natural products with industrial and medicinal importance. After more than half a century of exploitation, it has become increasingly challenging to find novel natural products with useful properties as the same known compounds are often repeatedly re-discovered when using traditional approaches. Modern genome mining approaches have led to the discovery of new biosynthetic gene clusters, thus indicating that actinomycetes still harbor a huge unexploited potential to produce novel natural products. In recent years, innovative synthetic biology and metabolic engineering tools have greatly accelerated the discovery of new natural products and the engineering of actinomycetes. In the first part of this review, we outline the successful application of metabolic engineering to optimize natural product production, focusing on the use of multi-omics data, genome-scale metabolic models, rational approaches to balance precursor pools, and the engineering of regulatory genes and regulatory elements. In the second part, we summarize the recent advances of synthetic biology for actinomycetal metabolic engineering including cluster assembly, cloning and expression, CRISPR/Cas9 technologies, and chassis strain development for natural product overproduction and discovery. Finally, we describe new advances in reprogramming biosynthetic pathways through polyketide synthase and non-ribosomal peptide synthetase engineering. These new developments are expected to revitalize discovery and development of new natural products with medicinal and other industrial applications.
Topics: Actinobacteria; Actinomyces; Biological Products; Metabolic Engineering; Multigene Family; Synthetic Biology
PubMed: 30853630
DOI: 10.1016/j.biotechadv.2019.03.005