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Toxics Dec 2023Metabolism underlies the pathogenesis of acute myeloid leukemia (AML) and can be influenced by gut microbiota. However, the specific metabolic changes in different...
Metabolism underlies the pathogenesis of acute myeloid leukemia (AML) and can be influenced by gut microbiota. However, the specific metabolic changes in different tissues and the role of gut microbiota in AML remain unclear. In this study, we analyzed the metabolome differences in blood samples from patients with AML and healthy controls using UPLC-Q-Exactive. Additionally, we examined the serum, liver, and fecal metabolome of AML model mice and control mice using UPLC-Q-Exactive. The gut microbiota of the mice were analyzed using 16S rRNA sequencing. Our UPLC-MS analysis revealed significant differences in metabolites between the AML and control groups in multiple tissue samples. Through cross-species validation in humans and animals, as well as reverse validation of Celastrol, we discovered that the Carnosine-Histidine metabolic pathway may play a potential role in the occurrence and progression of AML. Furthermore, our analysis of gut microbiota showed no significant diversity changes, but we observed a significant negative correlation between the key metabolite Carnosine and and . In conclusion, the Carnosine-Histidine metabolic pathway influences the occurrence and progression of AML, while the gut microbiota might play a role in this process.
PubMed: 38250970
DOI: 10.3390/toxics12010014 -
Frontiers in Microbiology 2019() functions as a probiotic in animals, but the underlying mechanisms remain unclear. We aim to evaluate the protective effects and definite mechanism by which orally...
() functions as a probiotic in animals, but the underlying mechanisms remain unclear. We aim to evaluate the protective effects and definite mechanism by which orally administered prevents D-galactosamine (D-GalN)-induced liver injury in rats. Twenty-one Sprague-Dawley rats were equally assigned into three groups ( = 7 animals per group). ATCC11778 (2 × 10 colony-forming units/ml) was administered to the group via gavage, and phosphate-buffered saline was administered to the positive control (PC) and negative control (NC) groups for 2 weeks. The PC and groups received 1.1 g/kg D-GalN via an intraperitoneal injection to induce liver injury. The blood, terminal ileum, liver, kidney and mesenteric lymph nodes (MLNs) were collected for histological examinations and to evaluate bacterial translocation. Liver function was also determined. Fecal samples were collected for deep sequencing of the 16S rRNA on an Illumina MiSeq platform. significantly attenuated D-GalN-induced liver injury and improved serum alanine aminotransferase (ALT) and serum cholinesterase levels ( < 0.05 and < 0.01, respectively). modulated cytokine secretion, as indicated by the elevated levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in both the liver and plasma ( < 0.05 and < 0.01, respectively) and the substantially decreased levels of the cytokine IL-13 in the liver ( < 0.05). Pretreatment with attenuated anoxygenic bacterial translocation in the veins ( < 0.05) and liver ( < 0.05) and upregulated the expression of the tight junction protein 1. The gut microbiota from the group clustered separately from that of the PC group, with an increase in species of the and families and a decrease in those of the , , and families. The potential probiotic attenuated liver injury by restoring the gut flora balance and enhancing the intestinal barrier function.
PubMed: 31417535
DOI: 10.3389/fmicb.2019.01751 -
Communications Biology May 2021A key question in microbial ecology is what the driving forces behind the persistence of large biodiversity in natural environments are. We studied a microbial community...
A key question in microbial ecology is what the driving forces behind the persistence of large biodiversity in natural environments are. We studied a microbial community with more than 100 different types of species which evolved in a 15-years old bioreactor with benzene as the main carbon and energy source and nitrate as the electron acceptor. Using genome-centric metagenomics plus metatranscriptomics, we demonstrate that most of the community members likely feed on metabolic left-overs or on necromass while only a few of them, from families Rhodocyclaceae and Peptococcaceae, are candidates to degrade benzene. We verify with an additional succession experiment using metabolomics and metabarcoding that these few community members are the actual drivers of benzene degradation. As such, we hypothesize that high species richness is maintained and the complexity of a natural community is stabilized in a controlled environment by the interdependencies between the few benzene degraders and the rest of the community members, ultimately resulting in a food web with different trophic levels.
Topics: Bacteria; Benzene; Biodegradation, Environmental; Biodiversity; Metagenome; Nitrates
PubMed: 33953314
DOI: 10.1038/s42003-021-01948-y -
Applied and Environmental Microbiology Feb 2022Chloroform (CF) and dichloromethane (DCM) are among the more commonly identified chlorinated aliphatic compounds found in contaminated soil and groundwater. Complete...
Chloroform (CF) and dichloromethane (DCM) are among the more commonly identified chlorinated aliphatic compounds found in contaminated soil and groundwater. Complete dechlorination of CF has been reported under anaerobic conditions by microbes that respire CF to DCM and others that biodegrade DCM. The objectives of this study were to ascertain if a commercially available bioaugmentation enrichment culture (KB-1 Plus CF) uses an oxidative or fermentative pathway for biodegradation of DCM and to determine if the products from DCM biodegradation can support organohalide respiration of CF to DCM in the absence of an exogenous electron donor. In various treatments with the KB-1 Plus CF culture to which C-CF was added, the predominant product was CO, indicating that oxidation is the predominant pathway for DCM. Recovery of C-DCM when biodegradation was still in progress confirmed that CF first undergoes reductive dechlorination to DCM. C-labeled organic acids, including acetate and propionate, were also recovered, suggesting that synthesis of organic acids provides a sink for the electron equivalents from oxidation of DCM. When the biomass was washed to remove organic acids from prior additions of exogenous electron donor and only CF and DCM were added, the culture completely dechlorinated CF. The total amount of DCM added was not sufficient to provide the electron equivalents needed to reduce CF to DCM. Thus, the additional reducing power came via the DCM generated from CF reduction. Nevertheless, the rate of CF consumption was considerably lower compared to that of treatments that received an exogenous electron donor. Chloroform (CF) and dichloromethane (DCM) are among the more commonly identified chlorinated aliphatic compounds found in contaminated soil and groundwater. One way to address this problem is to add microbes to the subsurface that can biodegrade these compounds. While microbes are known that can accomplish this task, less is known about the pathways used under anaerobic conditions. Some use an oxidative pathway, resulting mainly in carbon dioxide. Others use a fermentative pathway, resulting in formation of organic acids. In this study, a commercially available bioaugmentation enrichment culture (KB-1 Plus CF) was evaluated using carbon-14 labeled chloroform. The main product formed was carbon dioxide, indicating the use of an oxidative pathway. The reducing power gained from oxidation was shown to support reductive dechlorination of CF to DCM. The results demonstrate the potential to achieve full dechlorination of CF and DCM to nonhazardous products that are difficult to identify in the field.
Topics: Anaerobiosis; Biodegradation, Environmental; Carbon Radioisotopes; Chloroform; Methylene Chloride; Peptococcaceae
PubMed: 34936839
DOI: 10.1128/AEM.01970-21 -
Frontiers in Pharmacology 2021Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota...
Diabetic kidney disease (DKD) has become the major cause of end-stage renal disease (ESRD) associated with the progression of renal fibrosis. As gut microbiota dysbiosis is closely related to renal damage and fibrosis, we investigated the role of gut microbiota and microbiota-related serum metabolites in DKD progression in this study. Fecal and serum samples obtained from predialysis DKD patients from January 2017 to December 2019 were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Forty-one predialysis patients were divided into two groups according to their estimated glomerular filtration rate (eGFR): the DKD non-ESRD group (eGFR ≥ 15 ml/min/1.73 m) (n = 22), and the DKD ESRD group (eGFR < 15 ml/min/1.73 m) (n = 19). The metabolic pathways related to differential serum metabolites were obtained by the KEGG pathway analysis. Differences between the two groups relative to gut microbiota profiles and serum metabolites were investigated, and associations between gut microbiota and metabolite concentrations were assessed. Correlations between clinical indicators and both microbiota-related metabolites and gut microbiota were calculated by Spearman rank correlation coefficient and visualized by heatmap. Eleven different intestinal floras and 239 different serum metabolites were identified between the two groups. Of 239 serum metabolites, 192 related to the 11 different intestinal flora were mainly enriched in six metabolic pathways, among which, phenylalanine and tryptophan metabolic pathways were most associated with DKD progression. Four microbiota-related metabolites in the phenylalanine metabolic pathway [hippuric acid (HA), L-(-)-3-phenylactic acid, -3-hydroxy-cinnamate, and dihydro-3-coumaric acid] and indole-3 acetic acid (IAA) in the tryptophan metabolic pathway positively correlated with DKD progression, whereas L-tryptophan in the tryptophan metabolic pathway had a negative correlation. Intestinal flora and were positively correlated with the increase in renal function indicators and serum metabolite HA. was negatively correlated with the increase in renal function indicators and serum metabolites [L-(-)-3-phenyllactic acid and IAA]. This study highlights the interaction among gut microbiota, serum metabolites, and clinical indicators in predialysis DKD patients, and provides new insights into the role of gut microbiota and microbiota-related serum metabolites that were enriched in the phenylalanine and tryptophan metabolic pathways, which correlated with the progression of DKD.
PubMed: 34899312
DOI: 10.3389/fphar.2021.757508 -
Frontiers in Medicine 2021Intestinal microbial colonization in early life plays a crucial role in immune development and mucosal homeostasis in later years. Antibiotic exposure in early life...
Intestinal microbial colonization in early life plays a crucial role in immune development and mucosal homeostasis in later years. Antibiotic exposure in early life increases the risk of inflammatory bowel disease (IBD). Ginger acts like a prebiotic and has been used in traditional Chinese medicine for colitis. We investigated the protective effect of ginger against dextran sulfate sodium (DSS)-induced colitis in mice exposed to antibiotic in their early years. A weaned mouse model exposed to azithromycin (AZT) for 2 weeks was used to mimic antibiotic exposure in childhood among humans. A diet containing ginger extract was administered to mice for 4 weeks after antibiotic exposure. The susceptibility to DSS-induced colitis was evaluated in terms of weight loss, disease activity index (DAI) score, colon length, colitis biomarkers, and intestinal barrier function. The gut microbiota was analyzed in terms of 16S rRNA levels. Ginger extract prevented weight loss, colon shortening, inflammation, and intestinal barrier dysfunction in mice exposed to antibiotics in early life. Ginger increased the bacterial diversity and changed the abundance of bacterial belonging to family and species to modulate microbiota structure and composition adversely affected by early antibiotic exposure. Ginger has a protective effect in potentially decreasing the susceptibility to colitis in mice exposed to antibiotics early in life.
PubMed: 35071260
DOI: 10.3389/fmed.2021.755969 -
Diagnostics (Basel, Switzerland) Apr 2022Through a multitude of studies, the gut microbiota has been recognized as a significant influencer of both homeostasis and pathophysiology. Certain microbial taxa can...
Through a multitude of studies, the gut microbiota has been recognized as a significant influencer of both homeostasis and pathophysiology. Certain microbial taxa can even affect treatments such as cancer immunotherapies, including the immune checkpoint blockade. These taxa can impact such processes both individually as well as collectively through mechanisms from quorum sensing to metabolite production. Due to this overarching presence of the gut microbiota in many physiological processes distal to the GI tract, we hypothesized that mice bearing tumors at extraintestinal sites would display a distinct intestinal microbial signature from non-tumor-bearing mice, and that such a signature would involve taxa that collectively shift with tumor presence. Microbial OTUs were determined from 16S rRNA genes isolated from the fecal samples of C57BL/6 mice challenged with either B16-F10 melanoma cells or PBS control and analyzed using QIIME. Relative proportions of bacteria were determined for each mouse and, using machine-learning approaches, significantly altered taxa and co-occurrence patterns between tumor- and non-tumor-bearing mice were found. Mice with a tumor had elevated proportions of , .g_rc4.4, and as well as significant information gains and ReliefF weights for , , , and . , , and were also implicated through shifting co-occurrences and PCA values. Using these seven taxa as a melanoma signature, a neural network reached an 80% tumor detection accuracy in a 10-fold stratified random sampling validation. These results indicated gut microbial proportions as a biosensor for tumor detection, and that shifting co-occurrences could be used to reveal relevant taxa.
PubMed: 35454006
DOI: 10.3390/diagnostics12040958 -
MicrobiologyOpen Mar 2019Recent studies have shown that interspecies electron transfer between chemoheterotrophic bacteria and methanogenic archaea can be mediated by electric currents flowing...
Recent studies have shown that interspecies electron transfer between chemoheterotrophic bacteria and methanogenic archaea can be mediated by electric currents flowing through conductive iron oxides, a process termed electric syntrophy. In this study, we conducted enrichment experiments with methanogenic microbial communities from rice paddy soil in the presence of ferrihydrite and/or sulfate to determine whether electric syntrophy could be enabled by biogenic iron sulfides. Although supplementation with either ferrihydrite or sulfate alone suppressed methanogenesis, supplementation with both ferrihydrite and sulfate enhanced methanogenesis. In the presence of sulfate, ferrihydrite was transformed into black precipitates consisting mainly of poorly crystalline iron sulfides. Microbial community analysis revealed that a methanogenic archaeon and iron- and sulfate-reducing bacteria (Methanosarcina, Geobacter, and Desulfotomaculum, respectively) predominated in the enrichment culture supplemented with both ferrihydrite and sulfate. Addition of an inhibitor specific for methanogenic archaea decreased the abundance of Geobacter, but not Desulfotomaculum, indicating that Geobacter acquired energy via syntrophic interaction with methanogenic archaea. Although electron acceptor compounds such as sulfate and iron oxides have been thought to suppress methanogenesis, this study revealed that coexistence of sulfate and iron oxide can promote methanogenesis by biomineralization of (semi)conductive iron sulfides that enable methanogenesis via electric syntrophy.
Topics: Desulfotomaculum; Ferrous Compounds; Geobacter; Methane; Methanosarcina; Microbial Consortia; Microbial Interactions; Minerals; Oryza; Water Microbiology
PubMed: 29877051
DOI: 10.1002/mbo3.647 -
PLoS Computational Biology Nov 2021The study of microbial communities and their interactions has attracted the interest of the scientific community, because of their potential for applications in...
The study of microbial communities and their interactions has attracted the interest of the scientific community, because of their potential for applications in biotechnology, ecology and medicine. The complexity of interspecies interactions, which are key for the macroscopic behavior of microbial communities, cannot be studied easily experimentally. For this reason, the modeling of microbial communities has begun to leverage the knowledge of established constraint-based methods, which have long been used for studying and analyzing the microbial metabolism of individual species based on genome-scale metabolic reconstructions of microorganisms. A main problem of genome-scale metabolic reconstructions is that they usually contain metabolic gaps due to genome misannotations and unknown enzyme functions. This problem is traditionally solved by using gap-filling algorithms that add biochemical reactions from external databases to the metabolic reconstruction, in order to restore model growth. However, gap-filling algorithms could evolve by taking into account metabolic interactions among species that coexist in microbial communities. In this work, a gap-filling method that resolves metabolic gaps at the community level was developed. The efficacy of the algorithm was tested by analyzing its ability to resolve metabolic gaps on a synthetic community of auxotrophic Escherichia coli strains. Subsequently, the algorithm was applied to resolve metabolic gaps and predict metabolic interactions in a community of Bifidobacterium adolescentis and Faecalibacterium prausnitzii, two species present in the human gut microbiota, and in an experimentally studied community of Dehalobacter and Bacteroidales species of the ACT-3 community. The community gap-filling method can facilitate the improvement of metabolic models and the identification of metabolic interactions that are difficult to identify experimentally in microbial communities.
Topics: Algorithms; Bacteroidetes; Bifidobacterium adolescentis; Computational Biology; Computer Simulation; Databases, Factual; Escherichia coli; Faecalibacterium prausnitzii; Gastrointestinal Microbiome; Humans; Metabolic Networks and Pathways; Microbiota; Models, Biological; Peptococcaceae; Synthetic Biology
PubMed: 34723959
DOI: 10.1371/journal.pcbi.1009060 -
GeroScience Apr 2022Recently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the...
Recently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell α-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81 years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age > 70 years old) was significantly lower than the middle-aged group (age ≤ 70 years old). Furthermore, individual age was negatively correlated with HD5 concentration (r = - 0.307, p < 0.001). In β-diversity, the intestinal microbiota of the elderly showed a significantly different composition compared to the middle-aged. At the genus level, relative abundance of Collinsella, Alistipes, Peptococcaceae; unassigned, Lactobacillus, Lactococcus, Weissella, Christensenellaceae R-7 group, Megasphaera, and [Eubacterium] eligens group was significantly higher, and Lachnospiraceae; unassigned, Blautia, Anaerostipes, Fusicatenibacter, Dorea, and Faecalibacterium was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with Alistipes, Peptococcaceae; unassigned, and Christensenellaceae R-7 group and positively correlated with Lachnospiraceae; unassigned and Dorea. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.
Topics: Adult; Aged; Aged, 80 and over; Defensins; Feces; Gastrointestinal Microbiome; Humans; Japan; Middle Aged; alpha-Defensins
PubMed: 34105106
DOI: 10.1007/s11357-021-00398-y