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Microbiome Jan 2017Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and... (Clinical Trial)
Clinical Trial
BACKGROUND
Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.
RESULTS
MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).
CONCLUSIONS
This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.
TRIAL REGISTRATION
This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554.
Topics: Abdominal Pain; Adolescent; Anti-Bacterial Agents; Autism Spectrum Disorder; Bacteriophages; Bifidobacterium; Child; Constipation; DNA, Viral; Desulfovibrio; Diarrhea; Fecal Microbiota Transplantation; Female; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Tract; High-Throughput Nucleotide Sequencing; Humans; Infant; Male; Prevotella; Probiotics
PubMed: 28122648
DOI: 10.1186/s40168-016-0225-7 -
Science (New York, N.Y.) Jul 2019The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the...
The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the development of age-associated metabolic syndrome (MetS). Expansion of and loss of Clostridia were key features associated with obesity in this model and are present in humans with MetS. T cell-dependent events were required to prevent disease, and replacement of Clostridia rescued obesity. Inappropriate immunoglobulin A targeting of Clostridia and increased antagonized the colonization of beneficial Clostridia. Transcriptional and metabolic analysis revealed enhanced lipid absorption in the obese host. Colonization of germ-free mice with Clostridia, but not , down-regulated genes that control lipid absorption and reduced adiposity. Thus, immune control of the microbiota maintains beneficial microbial populations that constrain lipid metabolism to prevent MetS.
Topics: Animals; Antibiosis; Clostridium; Desulfovibrio; Host Microbial Interactions; Intestinal Absorption; Lipid Metabolism; Metabolic Syndrome; Mice; Mice, Mutant Strains; Microbiota; Myeloid Differentiation Factor 88; Obesity; T-Lymphocytes, Regulatory
PubMed: 31346040
DOI: 10.1126/science.aat9351 -
Gut Microbes 2021The emerging evidence supports the use of prebiotics like herb-derived polysaccharides for treating nonalcoholic fatty liver disease (NAFLD) by modulating gut...
The emerging evidence supports the use of prebiotics like herb-derived polysaccharides for treating nonalcoholic fatty liver disease (NAFLD) by modulating gut microbiome. The present study was initiated on the microbiota-dependent anti-NAFLD effect of polysaccharides (APS) extracted from Bunge in high-fat diet (HFD)-fed mice. However, the exact mechanisms underlying the beneficial effects of APS on NAFLD formation remain poorly understood.Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS. Then, targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids (SCFAs) and bacteria that were specifically enriched by APS. Further experiment was carried out to test the capacity of SCFAs-producing of identified bacterium. Finally, the anti-NAFLD efficacy of identified bacterium was tested in HFD-fed mice.Our results first demonstrated the anti-NAFLD effect of APS in HFD-fed mice and the contribution of gut microbiota. Moreover, our results indicated that SCFAs, predominantly acetic acid were elevated in APS-supplemented mice and experiment. Metagenomics revealed that from genus was not only enriched by APS, but also a potent generator of acetic acid, which showed significant anti-NAFLD effects in HFD-fed mice. In addition, modulated the hepatic gene expression pattern of lipids metabolism, particularly suppressed hepatic fatty acid synthase (FASN) and CD36 protein expression.Our results demonstrate that APS enriched is effective on attenuating hepatic steatosis possibly through producing acetic acid, and modulation on hepatic lipids metabolism in mice. Further studies are warranted to explore the long-term impacts of on host metabolism and the underlying mechanism.
Topics: Acetic Acid; Animals; Bacteria; CD36 Antigens; Desulfovibrio vulgaris; Diet, High-Fat; Fatty Acid Synthases; Fatty Acids, Volatile; Gastrointestinal Microbiome; Humans; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Probiotics
PubMed: 34125646
DOI: 10.1080/19490976.2021.1930874 -
Journal of Advanced Research Oct 2023The perturbations of gut microbiota could interact with excessively activated immune responses and play key roles in the etiopathogenesis of ulcerative colitis (UC)....
INTRODUCTION
The perturbations of gut microbiota could interact with excessively activated immune responses and play key roles in the etiopathogenesis of ulcerative colitis (UC). Desulfovibrio, the most predominant sulfate reducing bacteria (SRB) resided in the human gut, was observed to overgrow in patients with UC. The interactions between specific gut microbiota and drugs and their impacts on UC treatment have not been demonstrated well.
OBJECTIVES
This study aimed to elucidate whether Desulfovibrio vulgaris (D. vulgaris, DSV) and its flagellin could activate nucleotide-binding oligomerization domain-like receptors (NLR) family of apoptosis inhibitory proteins (NAIP) / NLR family caspase activation and recruitment domain-containing protein 4 (NLRC4) inflammasome and promote colitis, and further evaluate the efficacy of eugeniin targeting the interaction interface of D. vulgaris flagellin (DVF) and NAIP to attenuate UC.
METHODS
The abundance of DSV and the occurrence of macrophage pyroptosis in human UC tissues were investigated. Colitis in mice was established by dextran sulfate sodium (DSS) and gavaged with DSV or its purified flagellin. NAIP/NLRC4 inflammasome activation and macrophage pyroptosis were evaluated in vivo and in vitro. The effects of eugeniin on blocking the interaction of DVF and NAIP/NLRC4 and relieving colitis were also assessed.
RESULTS
The abundance of DSV increased in the feces of patients with UC and was found to be associated with disease activity. DSV and its flagellin facilitated DSS-induced colitis in mice. Mechanistically, RNA sequencing showed that gene expression associated with inflammasome complex and pyroptosis was upregulated after DVF treatment in macrophages. DVF was further demonstrated to induce significant macrophage pyroptosis in vitro, depending on NAIP/NLRC4 inflammasome activation. Furthermore, eugeniin was screened as an inhibitor of the interface between DVF and NAIP and successfully alleviated the proinflammatory effect of DVF in colitis.
CONCLUSION
Targeting DVF-induced NAIP/NLRC4 inflammasome activation and macrophage pyroptosis ameliorates UC. This finding is of great significance for exploring the gut microbiota-host interactions in UC development and providing new insights for precise treatment.
Topics: Humans; Mice; Animals; Inflammasomes; Flagellin; Desulfovibrio vulgaris; Colitis, Ulcerative; Macrophages; Calcium-Binding Proteins; CARD Signaling Adaptor Proteins; Neuronal Apoptosis-Inhibitory Protein
PubMed: 37586642
DOI: 10.1016/j.jare.2023.08.008 -
Nature Reviews. Microbiology Dec 2020Advances in imaging technologies have revealed that many bacteria possess organelles with a proteomically defined lumen and a macromolecular boundary. Some are bound by... (Review)
Review
Advances in imaging technologies have revealed that many bacteria possess organelles with a proteomically defined lumen and a macromolecular boundary. Some are bound by a lipid bilayer (such as thylakoids, magnetosomes and anammoxosomes), whereas others are defined by a lipid monolayer (such as lipid bodies), a proteinaceous coat (such as carboxysomes) or have a phase-defined boundary (such as nucleolus-like compartments). These diverse organelles have various metabolic and physiological functions, facilitating adaptation to different environments and driving the evolution of cellular complexity. This Review highlights that, despite the diversity of reported organelles, some unifying concepts underlie their formation, structure and function. Bacteria have fundamental mechanisms of organelle formation, through which conserved processes can form distinct organelles in different species depending on the proteins recruited to the luminal space and the boundary of the organelle. These complex subcellular compartments provide evolutionary advantages as well as enabling metabolic specialization, biogeochemical processes and biotechnological advances. Growing evidence suggests that the presence of organelles is the rule, rather than the exception, in bacterial cells.
Topics: Bacterial Proteins; Caulobacter crescentus; Cell Compartmentation; Cell Engineering; Desulfovibrio; Escherichia coli; Macromolecular Substances; Magnetosomes; Magnetospirillum; Organelle Biogenesis; Organelles; Shewanella putrefaciens; Species Specificity
PubMed: 32710089
DOI: 10.1038/s41579-020-0413-0 -
Accounts of Chemical Research Nov 2015The development of technology for the inexpensive generation of the renewable energy vector H2 through water splitting is of immediate economic, ecological, and...
The development of technology for the inexpensive generation of the renewable energy vector H2 through water splitting is of immediate economic, ecological, and humanitarian interest. Recent interest in hydrogenases has been fueled by their exceptionally high catalytic rates for H2 production at a marginal overpotential, which is presently only matched by the nonscalable noble metal platinum. The mechanistic understanding of hydrogenase function guides the design of synthetic catalysts, and selection of a suitable hydrogenase enables direct applications in electro- and photocatalysis. [FeFe]-hydrogenases display excellent H2 evolution activity, but they are irreversibly damaged upon exposure to O2, which currently prevents their use in full water splitting systems. O2-tolerant [NiFe]-hydrogenases are known, but they are typically strongly biased toward H2 oxidation, while H2 production by [NiFe]-hydrogenases is often product (H2) inhibited. [NiFeSe]-hydrogenases are a subclass of [NiFe]-hydrogenases with a selenocysteine residue coordinated to the active site nickel center in place of a cysteine. They exhibit a combination of unique properties that are highly advantageous for applications in water splitting compared with other hydrogenases. They display a high H2 evolution rate with marginal inhibition by H2 and tolerance to O2. [NiFeSe]-hydrogenases are therefore one of the most active molecular H2 evolution catalysts applicable in water splitting. Herein, we summarize our recent progress in exploring the unique chemistry of [NiFeSe]-hydrogenases through biomimetic model chemistry and the chemistry with [NiFeSe]-hydrogenases in semiartificial photosynthetic systems. We gain perspective from the structural, spectroscopic, and electrochemical properties of the [NiFeSe]-hydrogenases and compare them with the chemistry of synthetic models of this hydrogenase active site. Our synthetic models give insight into the effects on the electronic properties and reactivity of the active site upon the introduction of selenium. We have utilized the exceptional properties of the [NiFeSe]-hydrogenase from Desulfomicrobium baculatum in a number of photocatalytic H2 production schemes, which are benchmark systems in terms of single site activity, tolerance toward O2, and in vitro water splitting with biological molecules. Each system comprises a light-harvesting component, which allows for light-driven electron transfer to the hydrogenase in order for it to catalyze H2 production. A system with [NiFeSe]-hydrogenase on a dye-sensitized TiO2 nanoparticle gives an enzyme-semiconductor hybrid for visible light-driven generation of H2 with an enzyme-based turnover frequency of 50 s(-1). A stable and inexpensive polymeric carbon nitride as a photosensitizer in combination with the [NiFeSe]-hydrogenase shows good activity for more than 2 days. Light-driven H2 evolution with the enzyme and an organic dye under high O2 levels demonstrates the excellent robustness and feasibility of water splitting with a hydrogenase-based scheme. This has led, most recently, to the development of a light-driven full water splitting system with a [NiFeSe]-hydrogenase wired to the water oxidation enzyme photosystem II in a photoelectrochemical cell. In contrast to the other systems, this photoelectrochemical system does not rely on a sacrificial electron donor and allowed us to establish the long sought after light-driven water splitting with an isolated hydrogenase.
Topics: Biomimetic Materials; Deltaproteobacteria; Desulfovibrio vulgaris; Hydrogenase; Photosynthesis; Selenocysteine
PubMed: 26488197
DOI: 10.1021/acs.accounts.5b00326 -
Advances in Microbial Physiology 2019Hydrogen metabolism plays a central role in sulfate-reducing bacteria of the Desulfovibrio genus and is based on hydrogenases that catalyze the reversible conversion of... (Review)
Review
Hydrogen metabolism plays a central role in sulfate-reducing bacteria of the Desulfovibrio genus and is based on hydrogenases that catalyze the reversible conversion of protons into dihydrogen. These metabolically versatile microorganisms possess a complex hydrogenase system composed of several enzymes of both [FeFe]- and [NiFe]-type that can vary considerably from one Desulfovibrio species to another. This review covers the molecular and physiological aspects of hydrogenases and H metabolism in Desulfovibrio but focuses particularly on our model bacterium Desulfovibrio fructosovorans. The search of hydrogenase genes in more than 30 sequenced genomes provides an overview of the distribution of these enzymes in Desulfovibrio. Our discussion will consider the significance of the involvement of electron-bifurcation in H metabolism.
Topics: Bacterial Proteins; Biocatalysis; Desulfovibrio; Electrons; Gene Expression Regulation, Bacterial; Genetic Variation; Hydrogen; Hydrogenase; Models, Biological
PubMed: 31126530
DOI: 10.1016/bs.ampbs.2019.03.001 -
Nature Reviews. Microbiology Dec 2021The defining trait of obligate anaerobes is that oxygen blocks their growth, yet the underlying mechanisms are unclear. A popular hypothesis was that these... (Review)
Review
The defining trait of obligate anaerobes is that oxygen blocks their growth, yet the underlying mechanisms are unclear. A popular hypothesis was that these microorganisms failed to evolve defences to protect themselves from reactive oxygen species (ROS) such as superoxide and hydrogen peroxide, and that this failure is what prevents their expansion to oxic habitats. However, studies reveal that anaerobes actually wield most of the same defences that aerobes possess, and many of them have the capacity to tolerate substantial levels of oxygen. Therefore, to understand the structures and real-world dynamics of microbial communities, investigators have examined how anaerobes such as Bacteroides, Desulfovibrio, Pyrococcus and Clostridium spp. struggle and cope with oxygen. The hypoxic environments in which these organisms dwell - including the mammalian gut, sulfur vents and deep sediments - experience episodic oxygenation. In this Review, we explore the molecular mechanisms by which oxygen impairs anaerobes and the degree to which bacteria protect their metabolic pathways from it. The emergent view of anaerobiosis is that optimal strategies of anaerobic metabolism depend upon radical chemistry and low-potential metal centres. Such catalytic sites are intrinsically vulnerable to direct poisoning by molecular oxygen and ROS. Observations suggest that anaerobes have evolved tactics that either minimize the extent to which oxygen disrupts their metabolism or restore function shortly after the stress has dissipated.
Topics: Anaerobiosis; Bacteria, Anaerobic; Bacteroides; Clostridium; Desulfovibrio; Hydrogen Peroxide; Oxygen; Pyrococcus; Reactive Oxygen Species; Superoxides
PubMed: 34183820
DOI: 10.1038/s41579-021-00583-y -
The Journal of Contemporary Dental... Jun 2022Even with the exponential popularity of the contemporary clear aligners, the main stream of orthodontic practice still remains to be metal braces especially in...
Even with the exponential popularity of the contemporary clear aligners, the main stream of orthodontic practice still remains to be metal braces especially in adolescent age-group. Along with the advantages of metal braces such as lower cost, reduced friction, etc., there goes the disadvantages such as corrosion possibility, reduced esthetics, etc. Corrosion of orthodontic appliances is a widely researched topic. It is surprising to learn that microbially induced corrosion (MIC) has not been addressed in orthodontic literature till date. Microbial corrosion is an interesting arena which requires knowledge of both corrosion science and microbiology. The microorganisms capable of corrosion include various bacteria, fungi, and algae. The most common among them which has been widely indicated in MIC are the bacteria belonging to the sulfur cycle especially the sulfate-reducing bacteria (SRB). The connecting knot with orthodontics is the reported prevalence of these SRB in the oral cavity. SRB is prevalent in healthy individuals, patients associated with periodontitis and patients with gastrointestinal issues. The prevalence of SRB in the oral cavity has a greater clinical implication since the SRB have been proven to cause corrosion of stainless steel. There is literature attributing SRB as a potential cause in periodontal diseases as well as gastrointestinal diseases such as ulcerative colitis, inflammatory bowel diseases, and Crohn's disease. With its presence in the healthy oral environment already reported in the previous studies, it further emphasizes the absolute need to be researching on its corrosion possibility in the intra oral environment. The genus generally found intraorally was and which is commonly regarded as the most "opportunistic" and ubiquitous group of sulfate reducers. There is an interesting literature on the inhibition of spp. by human saliva, the reason being quoted as salivary nitrate and nitrite. The mechanism behind the antimicrobial action of nitrate and nitrite is that they increase the oxidative stress on the bacteria. However, concentrations of salivary nitrate vary depending on the food intake, endogenous production, and salivary flow rate. Despite there exist natural inhibitors, the prevalence in oral cavity is high, 22% in healthy and 86% in patients associated with periodontitis. There is a predilection for the bacteria to grow when favorable conditions exist. Biofilms is one such favorable medium for the growth of SRB. Paster et al. identified SRB in biofilms of patients associated with refractory periodontitis, periodontitis, acute necrotizing ulcerative gingivitis (ANUG), and also in healthy subjects. Biofilm is a surface film composed of organic and inorganic saliva components that are colonized with microorganisms in extracellular polymeric substances adsorbed on all surfaces in the oral cavity. The oral biofilm formation is a complex process involving interspecies aggregation, which is surrounded by a cohesive matrix, forms a complex structure which in turn facilitates anaerobic growth. It is the intrinsic nature of oral biofilms which make the survival of facultative anaerobes such as SRB in the oral cavity possible. Literatures report that there are increased biofilm formations in orthodontic patients due to increased retentive areas caused by the brackets, ligatures, wires, mini implants, force components, and archwires. Bacteria in dental plaque function as a metabolically, functionally, and physically integrated community. The study by Mystkowska et al. mentioned that biofilm play a critical role in corrosion process by forming corrosive microcells. With time-dependent association, the microbes in the biofilm, along with saliva acting as an electrolyte and components from food, causes a decreased pH in the areas immediately under the biofilms. The decreased pH along with a change of oxygenation releases metal oxides and hydroxides from the metal surface ultimately leading to the corrosion of metallic structures. The initial roughness also acts in a vicious form promoting more biofilm adherence and the process repeats causing more corrosion. With the biofilm itself serving to initiate and propagate corrosion, the increased prevalence of SRB in patients associated with orthodontics treatment all the more increases the possibility of MIC of orthodontic materials.
Topics: Humans; Adolescent; Corrosion; Stainless Steel; Steel; Nitrates; Nitrites; Caustics; Desulfovibrio; Biofilms; Sulfates; Bacteria; Sulfur; Oxides; Anti-Infective Agents
PubMed: 36259293
DOI: No ID Found -
Microorganisms Jan 2023belongs to Sulfate-reducing bacteria (SRB), which are widely present in anaerobic environments, including the human gut. has been associated with many human diseases,...
belongs to Sulfate-reducing bacteria (SRB), which are widely present in anaerobic environments, including the human gut. has been associated with many human diseases, including chronic liver disease. However, the characteristics and difference of from fecal samples of healthy volunteers (HV) and patients with liver cirrhosis (LC) have not been fully elucidated. Here, we isolated from the feces of 6 HV and 9 LC, and 88 strains were obtained. In the feces of HV, 55% of isolated strains were , followed by (15%), D. (11%), (9%), (4%), (4%) and (2%). However, only (60%) and (40%) were isolated from fecal samples of patients with LC. Our results suggest that there was a significant difference in the desulfurization ability and the HS production ability of different . . Furthermore, we found that isolated from the patients with LC generally had a higher hydrogen sulfide production capacity, gastrointestinal tolerance, and levels of antibiotic resistance than the same species isolated from HV. Our findings suggested that may be associated with the occurrence and development of liver cirrhosis.
PubMed: 36838242
DOI: 10.3390/microorganisms11020276