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Frontiers in Microbiology 2023A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut...
BACKGROUND
A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study.
METHODS
The largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen consortium. Summary-level dataset for COPD were obtained from the FinnGen consortium. The main analysis method for determining the causal link between gut microbiota and COPD was inverse variance weighted (IVW). Subsequently, pleiotropy and heterogeneity tests were performed to determine the reliability of the results.
RESULTS
IVW method identified 9 bacterial taxa nominally associated with the risk of COPD. Class Actinobacteria ( = 0.020), genus ( = 0.024), genus ( = 0.002) and genus ( = 0.018) were protective against COPD. In addition, order Desulfovibrionales ( = 0.011), family Desulfovibrionaceae ( = 0.039), family Peptococcaceae ( = 0.020), family Victivallaceae ( = 0.012) and genus ( = 0.017) were associated with a higher risk of COPD. No pleiotropy or heterogeneity were found.
CONCLUSION
According to the findings of this MR analysis, a causal relationship exists between certain gut microbiota and COPD. New insights into the mechanisms of COPD mediated by gut microbiota are provided.
PubMed: 37405157
DOI: 10.3389/fmicb.2023.1196751 -
Microbiome Oct 2020Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal...
BACKGROUND
Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear.
RESULTS
This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features.
CONCLUSIONS
These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans. Video Abstract.
Topics: Adult; Aged; Animals; Case-Control Studies; Disease; Female; Gastrointestinal Microbiome; Genome-Wide Association Study; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lupus Erythematosus, Systemic; Male; Middle Aged
PubMed: 33032658
DOI: 10.1186/s40168-020-00923-9 -
Nutrients Oct 2020A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have... (Comparative Study)
Comparative Study
A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have drawn inconsistent results. In this study, the unexpected results showed that the refined HFD increased gut microbiota diversity and short-chain fatty acids (SCFAs), causing an increase in energy metabolism. Further analysis revealed these changes were caused by the different fiber content in these two diets. Male C57BL/6J mice (4-5 weeks old) were fed either HFD or refined low-fat diet (LFD) for 14 weeks. The metabolic rates, thermogenesis, gut microbiome, and intestinal SCFAs were tested. The HFD triggered obesity and disturbed glucose homeostasis. Mice fed HFD ingested more fiber than mice fed LFD ( < 0.0001), causing higher intestinal SCFA concentrations related to the increased abundances of specific bacteria in the HFD group. Also, the HFD increased metabolic heat and up-regulated thermogenesis genes uncoupling protein 1(), peroxisome proliferator-activated receptor-γ coactivator-1α () expression in the brown adipose tissue (BAT). It was revealed by 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Desulfovibrionaceae, , and , meanwhile, reduced the abundance of , , , , and . The predicted metabolic pathways indicated HFD increased the gene expression of non-absorbed carbohydrate metabolism pathways, as well as the risks of colonization of intestinal pathogens and inflammation. In conclusion, the HFD was obesogenic in male C57BL/6J mice, and increased fiber intake from the HFD drove an increase in gut microbiota diversity, SCFAs, and energy expenditure. Meanwhile, the differences in specific nutrient intake can dissociate broad changes in energy expenditure, gut microbiota, and its metabolites from obesity, raising doubts in the previous studies. Therefore, it is necessary to consider whether differences in specific nutrient intake will interfere with the results of the experiments.
Topics: Animals; Bacteria; Biodiversity; Blood Glucose; Diet, Fat-Restricted; Diet, High-Fat; Dietary Carbohydrates; Dietary Fiber; Energy Metabolism; Fatty Acids, Volatile; Gastrointestinal Microbiome; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Nutrients; Obesity
PubMed: 33092019
DOI: 10.3390/nu12103197 -
Journal of Neuroinflammation Jun 2022Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain...
BACKGROUND
Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain elusive.
METHODS
Neuropathic pain was produced by different forms of injury or diseases, the chronic constriction injury (CCI) of the sciatic nerves, oxaliplatin (OXA) chemotherapy, and streptozocin (STZ)-induced diabetes in mice. Continuous feeding of antibiotics (ABX) cocktail was used to cause major depletion of the gut microbiota. Fecal microbiota, biochemical changes in the spinal cord and dorsal root ganglion (DRG), and the behaviorally expressed painful syndromes were assessed.
RESULTS
Under condition of gut microbiota depletion, CCI, OXA, or STZ treatment-induced thermal hyperalgesia or mechanical allodynia were prevented or completely suppressed. Gut microbiota depletion also prevented CCI or STZ treatment-induced glial cell activation in the spinal cord and inhibited cytokine production in DRG in OXA model. Interestingly, STZ treatment failed to induce the diabetic high blood glucose and painful hypersensitivity in animals with the gut microbiota depletion. ABX feeding starting simultaneously with CCI, OXA, or STZ treatment resulted in instant analgesia in all the animals. ABX feeding starting after establishment of the neuropathic pain in CCI- and STZ-, but not OXA-treated animals produced significant alleviation of the thermal hyeralgesia or mechanical allodynia. Transplantation of fecal bacteria from SPF mice to ABX-treated mice partially restored the gut microbiota and fully rescued the behaviorally expressed neuropathic pain, of which, Akkermansia, Bacteroides, and Desulfovibrionaceae phylus may play a key role.
CONCLUSION
This study demonstrates distinct roles of gut microbiota in the pathogenesis of chronic painful conditions with nerve injury, chemotherapy and diabetic neuropathy and supports the clinical significance of fecal bacteria transplantation.
Topics: Animals; Anti-Bacterial Agents; Chronic Pain; Diabetes Mellitus; Gastrointestinal Microbiome; Hyperalgesia; Mice; Neuralgia; Rats; Rats, Sprague-Dawley
PubMed: 35764988
DOI: 10.1186/s12974-022-02523-w -
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 -
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 -
Cells Jun 2023Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been... (Review)
Review
Multiple sclerosis (MS) is a chronic, progressive neuroinflammatory disease with a complex pathophysiological background. A variety of diverse factors have been attributed to the propagation of inflammation and neurodegeneration in MS, mainly genetic, immunological, and environmental factors such as vitamin D deficiency, infections, or hormonal disbalance. Recently, the importance of the gut-brain axis for the development of many neurological conditions, including stroke, movement disorders, and neuroinflammatory disorders, has been postulated. The purpose of our paper was to summarize current evidence confirming the role of the gut microbiome in the pathophysiology of MS and related disorders, such as neuromyelitis optica spectrum disorder (NMO-SD). For this aim, we conducted a systematic review of the literature listed in the following databases: Medline, Pubmed, and Scopus, and were able to identify several studies demonstrating the involvement of the gut microbiome in the pathophysiology of MS and NMO-SD. It seems that the most relevant bacteria for the pathophysiology of MS are those belonging to , , , , , , , and , while and have been demonstrated to play a role in the pathophysiology of NMO-SD. Following this line of evidence, there is also some preliminary data supporting the use of probiotics or other agents affecting the microbiome that could potentially have a beneficial effect on MS/NMO-SD symptoms and prognosis. The topic of the gut microbiome in the pathophysiology of MS is therefore relevant since it could be used as a biomarker of disease development and progression as well as a potential disease-modifying therapy.
Topics: Humans; Multiple Sclerosis; Gastrointestinal Microbiome; Neuromyelitis Optica; Vitamin D Deficiency; Inflammation
PubMed: 37443793
DOI: 10.3390/cells12131760 -
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 -
Cells Mar 2022Several bacterial species can generate hydrogen sulfide (HS). Study evidence favors the view that the microbiome of the colon harbors increased amounts of HS producing... (Review)
Review
Several bacterial species can generate hydrogen sulfide (HS). Study evidence favors the view that the microbiome of the colon harbors increased amounts of HS producing bacteria in Parkinson's disease. Additionally, HS can easily penetrate cell membranes and enter the cell interior. In the cells, excessive amounts of HS can potentially release cytochrome c protein from the mitochondria, increase the iron content of the cytosolic iron pool, and increase the amount of reactive oxygen species. These events can lead to the formation of alpha-synuclein oligomers and fibrils in cells containing the alpha-synuclein protein. In addition, bacterially produced HS can interfere with the body urate metabolism and affect the blood erythrocytes and lymphocytes. Gut bacteria responsible for increased HS production, especially the mucus-associated species of the bacterial genera belonging to the Desulfovibrionaceae and Enterobacteriaceae families, are likely play a role in the pathogenesis of Parkinson's disease. Special attention should be devoted to changes not only in the colonic but also in the duodenal microbiome composition with regard to the pathogenesis of Parkinson's disease. Influenza infections may increase the risk of Parkinson's disease by causing the overgrowth of HS-producing bacteria both in the colon and duodenum.
Topics: Bacteria; Humans; Hydrogen Sulfide; Iron; Parkinson Disease; alpha-Synuclein
PubMed: 35326429
DOI: 10.3390/cells11060978 -
Microorganisms Mar 2022The gut microbiome is a large and complex organic assemblage with subtle and close relationships with the host. This symbiotic mechanism is important for the health and...
BACKGROUND
The gut microbiome is a large and complex organic assemblage with subtle and close relationships with the host. This symbiotic mechanism is important for the health and adaptability of the host to the environment. Compared with other ruminants, there are few studies on yak intestinal microbes. The study of the gut microbiota of the yak will help us better understand the correlation between the microbiota and the environmental adaptability of the host. In this study, we adapted 16S rDNA sequencing technology to investigate the diversity and composition of the intestinal microbial community in free-range yaks and captive yaks living on the Qinghai-Tibet Plateau (QTP).
RESULTS
Sequencing results showed that the intestinal microbial community diversity was significantly different between free-range yaks and captive yaks. and were the dominant bacteria in both free-range and captive yaks. However, there were differences between the microbes of the two analyzed feeding styles in different classification levels. Compared with the captive type, free-range yaks had a higher abundance of , , , , and , while the abundance of , , , , , and was relatively low. The feeding method may be the key factor for the formation of intestinal flora differences in yaks, while altitude did not significantly affect Qinghai yak.
CONCLUSIONS
In this study, we used 16S rDNA sequencing technology to investigate the composition of intestinal flora in free-range and captive yaks living on the QTP. The exploration of dietary factors can provide a theoretical basis for scientifically and rationally breeding yaks and provides a new direction for the development of prebiotics and microecological agents.
PubMed: 35456805
DOI: 10.3390/microorganisms10040754