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Nutrients Feb 2023Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods:...
Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods: Mendelian randomization (MR) is a type of instrumental variables (IVs) analysis; MR follows the Mendelian genetic rule of "parental alleles are randomly assigned to offspring" and takes genetic variation as IVs to infer the causal association between exposure factors and study outcome in observational studies. Genome-wide association study (GWAS) summary data of AS were from the FinnGen consortium, and the gut microbiota (Bacteroides, Streptococcus, Proteobacteria, Lachnospiraceae) were from the MiBioGen consortium. The TwoSampleMR and MRPRESSO packages of the R were used to perform a two-sample MR study. Random-effects inverse variance weighted (IVW) was the main analysis method, and MR Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We examined heterogeneity and horizontal pleiotropy, and examined whether the analysis results were influenced by a single SNP. We applied radial variants of the IVW and MR-Egger model for the improved visualization of the causal estimate. We further examined the causal relationship between AS and gut microbiota, and the robustness of the analysis results. Finally, we performed maximum likelihood, penalized weighted median, and IVW (fixed effects) to further identify the potential causal association. The random-effects IVW results showed that Bacteroides ( = 0.965, OR 95% confidence interval [CI] = 0.990 [0.621-1.579]), Streptococcus ( = 0.591, OR 95% CI = 1.120 [0.741-1.692]), Proteobacteria ( = 0.522, OR 95% CI = 1.160 [0.737-1.826]), and Lachnospiraceae ( = 0.717, OR 95% CI = 1.073 [0.732-1.574]) have no genetic causal relationship with AS. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. This study showed that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae, four common gut microbiotas associated with AS, had no causal relationship with AS at the genetic level. This study makes a positive contribution to the genetics of AS, but the insufficient number of gut microbiota included is a limitation.
Topics: Humans; Bacteroides; Clostridiales; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Proteobacteria; Spondylitis, Ankylosing
PubMed: 36839415
DOI: 10.3390/nu15041057 -
Cell Host & Microbe Nov 2022Gut-microbiota membership is associated with diverse neuropsychological outcomes, including substance use disorders (SUDs). Here, we use mice colonized with Citrobacter...
Gut-microbiota membership is associated with diverse neuropsychological outcomes, including substance use disorders (SUDs). Here, we use mice colonized with Citrobacter rodentium or the human γ-Proteobacteria commensal Escherichia coli HS as a model to examine the mechanistic interactions between gut microbes and host responses to cocaine. We find that cocaine exposure increases intestinal norepinephrine levels that are sensed through the bacterial adrenergic receptor QseC to promote intestinal colonization of γ-Proteobacteria. Colonized mice show enhanced host cocaine-induced behaviors. The neuroactive metabolite glycine, a bacterial nitrogen source, is depleted in the gut and cerebrospinal fluid of colonized mice. Systemic glycine repletion reversed, and γ-Proteobacteria mutated for glycine uptake did not alter the host response to cocaine. γ-Proteobacteria modulated glycine levels are linked to cocaine-induced transcriptional plasticity in the nucleus accumbens through glutamatergic transmission. The mechanism outline here could potentially be exploited to modulate reward-related brain circuits that contribute to SUDs.
Topics: Mice; Humans; Animals; Cocaine; Proteobacteria; Citrobacter rodentium; Gastrointestinal Microbiome; Bacteria; Escherichia coli; Glycine
PubMed: 36323315
DOI: 10.1016/j.chom.2022.09.014 -
Microbiome Jun 2022The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts...
BACKGROUND
The gut microbiota is reportedly involved in the progression and chemoresistance of various human malignancies. However, the underlying mechanisms behind how it exerts some effect on prostate cancer, as an extra-intestinal tumor, in a contact-independent way remain elusive and deserve exploration. Antibiotic exposure, one of the various factors affecting the gut microbiota community and capable of causing gut dysbiosis, is associated with multiple disorders. This study aims to preliminarily clarify the link between gut dysbiosis and prostate cancer.
RESULTS
First, we discovered that perturbing the gut microbiota by consuming broad-spectrum antibiotics in water promoted the growth of subcutaneous and orthotopic tumors in mice. Fecal microbiota transplantation could transmit the effect of antibiotic exposure on tumor growth. Then, 16S rRNA sequencing for mouse feces indicated that the relative abundance of Proteobacteria was significantly higher after antibiotic exposure. Meanwhile, intratumoral lipopolysaccharide (LPS) profoundly increased under the elevation of gut permeability. Both in vivo and in vitro experiments revealed that the NF-κB-IL6-STAT3 axis activated by intratumoral LPS facilitated prostate cancer proliferation and docetaxel chemoresistance. Finally, 16S rRNA sequencing of patients' fecal samples revealed that Proteobacteria was enriched in patients with metastatic prostate cancer and was positively correlated with plasma IL6 level, regional lymph node metastasis status, and distant metastasis status. The receiver operating characteristic (ROC) curves showed that the relative abundance of Proteobacteria had better performance than the prostate-specific antigen (PSA) level in predicting the probability of distant metastasis in prostate cancer (area under the ROC curve, 0.860; p < 0.001).
CONCLUSION
Collectively, this research demonstrated that gut dysbiosis, characterized by the enrichment of Proteobacteria due to antibiotic exposure, resulted in the elevation of gut permeability and intratumoral LPS, promoting the development of prostate cancer via the NF-κB-IL6-STAT3 axis in mice. Considering findings from human patients, Proteobacteria might act as an intestinal biomarker for progressive prostate cancer. Video Abstract.
Topics: Animals; Anti-Bacterial Agents; Docetaxel; Dysbiosis; Feces; Humans; Interleukin-6; Lipopolysaccharides; Male; Mice; NF-kappa B; Prostatic Neoplasms; Proteobacteria; RNA, Ribosomal, 16S; STAT3 Transcription Factor
PubMed: 35710492
DOI: 10.1186/s40168-022-01289-w -
Current Biology : CB Mar 2023Muñoz-Gómez and Hess introduce purple photosymbioses, which involve a heterotrophic protist host and anoxygenic photosymbionts from the phylum Proteobacteria.
Muñoz-Gómez and Hess introduce purple photosymbioses, which involve a heterotrophic protist host and anoxygenic photosymbionts from the phylum Proteobacteria.
Topics: Proteobacteria; Symbiosis; Photosynthesis
PubMed: 36917934
DOI: 10.1016/j.cub.2023.01.015 -
Microbiome Dec 2022Mounting experimental evidence has shown that the gut microbiota plays a significant role in the pathogenesis of mastitis, and clinical investigations have found that...
BACKGROUND
Mounting experimental evidence has shown that the gut microbiota plays a significant role in the pathogenesis of mastitis, and clinical investigations have found that the occurrence of mastitis is correlated with ruminal dysbiosis. However, the underlying mechanism by which the ruminal microbiota participates in the development of mastitis remains unknown.
RESULTS
In the present study, we found that cows with clinical mastitis had marked systemic inflammation, which was associated with significant ruminal dysbiosis, especially enriched Proteobacteria in the rumen. Ruminal microbiota transplantation from mastitis cows (M-RMT) to mice induced mastitis symptoms in recipient mice along with increased mammary proinflammatory signature activation of the TLR4-cGAS-STING-NF-κB/NLRP3 pathways. M-RMT also induced mucosal inflammation and impaired intestinal barrier integrity, leading to increased endotoxemia and systemic inflammation. Moreover, we showed that M-RMT mirrored ruminal microbiota disruption in the gut of recipient mice, as evidenced by enriched Proteobacteria and similar bacterial functions, which were correlated with most proinflammatory parameters and serum lipopolysaccharide (LPS) levels in mice. Recurrent low-grade LPS treatment mirrored gut dysbiosis-induced endotoxemia and caused severe mastitis in mice. Furthermore, we found that gut dysbiosis-derived LPS reduced host alkaline phosphatase activity by activating neuraminidase (Neu), which facilitates low-grade LPS exposure and E. coli-induced mastitis in mice. Conversely, treatment with calf intestinal alkaline phosphatase or the Neu inhibitor zanamivir alleviated low-grade LPS exposure and E. coli-induced mastitis in mice.
CONCLUSIONS
Our results suggest that ruminal dysbiosis-derived low-grade endotoxemia can cause mastitis and aggravate pathogen-induced mastitis by impairing host anti-inflammatory enzymes, which implies that regulating the ruminal or gut microbiota to prevent low-grade systemic inflammation is a potential strategy for mastitis intervention. Video Abstract.
Topics: Female; Humans; Animals; Cattle; Mice; Dysbiosis; Endotoxemia; Lipopolysaccharides; Alkaline Phosphatase; Escherichia coli; Mastitis; Anti-Inflammatory Agents; Inflammation; Proteobacteria
PubMed: 36451232
DOI: 10.1186/s40168-022-01402-z -
Cold Spring Harbor Perspectives in... Mar 2021
Review
Topics: Adenosine Triphosphate; Archaea; Calcium; Citric Acid Cycle; Glucose; Glycolysis; Homeostasis; Mitochondria; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen Consumption; Proteobacteria; Reactive Oxygen Species; Symbiosis
PubMed: 33649187
DOI: 10.1101/cshperspect.a040543 -
Microbial Physiology 2021Predatory bacteria gained interest in the last 20 years. Nevertheless, only a few species are well characterized. The endobiotic predator Bdellovibrio bacteriovorus... (Review)
Review
Predatory bacteria gained interest in the last 20 years. Nevertheless, only a few species are well characterized. The endobiotic predator Bdellovibrio bacteriovorus invades its prey to consume it from the inside, whereas Myxococcus xanthus hunts as a whole group to overcome its prey. Both species were described to prey on cyanobacteria as well. This minireview summarizes the findings of the last 20 years of predatory bacteria of cyanobacteria and is supplemented by new findings from a screening experiment for bacterial predators of the model organism Anabaena variabilis PCC 7937. Known predatory bacteria of cyanobacteria belong to the phyla Proteobacteria, Bacteroidetes, and Firmicutes and follow different hunting strategies. The underlying mechanisms are in most cases not known in much detail. Isolates from the screening experiment were clustered after predation behaviour and analyzed with respect to their size. The effect of predation in high nitrate levels and the occurrence of nitrogen-fixing cells, called heterocysts, are addressed.
Topics: Animals; Bdellovibrio bacteriovorus; Cyanobacteria; Myxococcus xanthus; Predatory Behavior
PubMed: 34010833
DOI: 10.1159/000516427 -
Journal of the American Society of... Dec 2022Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and treatment response have not been identified.
METHODS
We recruited 127 patients with IgAN who were treatment naive and 127 matched healthy controls (HCs) who were randomly divided into discovery and validation cohorts to investigate the characteristics of their gut microbiota and establish a bacterial diagnosis model for IgAN. A separate cohort of 56 patients and HCs was investigated to assess crossregional validation. A further 40 patients with primary membranous nephropathy (MN) were enrolled to probe disease-specific validation. A subgroup of 77 patients was prospectively followed to further dissect the association between alterations in gut microbiota and treatment response after 6 months of immunosuppressive therapy. Fecal microbiota samples were collected from all participants and analyzed using 16S ribosomal RNA sequencing.
RESULTS
Decreased -diversity (Shannon, =0.03), altered microbial composition (Adonis, =0.0001), and a striking expansion of the taxonomic chain ---- (all <0.001) were observed in patients with IgAN who were treatment naive, which reversed only in patients who achieved clinical remission after 6 months of immunosuppressive therapy. Importantly, seven operational taxa units, of which contributed the most, were determined to be the optimal bacterial classifier of IgAN (AUC=0.8635, 0.8551, 0.8026 in discovery, validation, and cross-regional validation sets, respectively), but did not effectively distinguish patients with IgAN versus those with MN (AUC=0.6183). Bacterial function prediction further verified enrichment of the shigellosis infection pathway in IgAN.
CONCLUSION
Gut dysbiosis, characterized by a striking expansion of genus , is a hallmark of patients with IgAN and may serve as a promising diagnostic biomarker and therapeutic target for IgAN. Further studies are warranted to investigate the potential contribution of in IgAN pathogenesis.
Topics: Humans; Bacteria; Dysbiosis; Escherichia; Glomerulonephritis, IGA; Immunosuppression Therapy; Shigella
PubMed: 36041791
DOI: 10.1681/ASN.2022020189 -
Frontiers in Cellular and Infection... 2023Rickettial agents are a diverse group of alpha-proteobacteria within the order Rickettsiales, which possesses two families with human pathogens, Rickettsiaceae and... (Review)
Review
Rickettial agents are a diverse group of alpha-proteobacteria within the order Rickettsiales, which possesses two families with human pathogens, Rickettsiaceae and Anaplasmataceae. These obligate intracellular bacteria are most frequently transmitted by arthropod vectors, a first step in the pathogens' avoidance of host cell defenses. Considerable study of the immune responses to infection and those that result in protective immunity have been conducted. Less study has focused on the initial events and mechanism by which these bacteria avoid the innate immune responses of the hosts to survive within and propagate from host cells. By evaluating the major mechanisms of evading innate immunity, a range of similarities among these bacteria become apparent, including mechanisms to escape initial destruction in phagolysosomes of professional phagocytes, those that dampen the responses of innate immune cells or subvert signaling and recognition pathways related to apoptosis, autophagy, proinflammatory responses, and mechanisms by which these microbes attach to and enter cells or those molecules that trigger the host responses. To illustrate these principles, this review will focus on two common rickettsial agents that occur globally, species and .
Topics: Humans; Rickettsia Infections; Immunity, Innate; Rickettsia; Anaplasma phagocytophilum; Autophagy
PubMed: 37228668
DOI: 10.3389/fcimb.2023.1187267 -
Journal of Biological Inorganic... Feb 2022Since the characterization of cytochrome c as a multiheme nitrite reductase, research on this enzyme has gained major interest. Today, it is known as pentaheme... (Review)
Review
Since the characterization of cytochrome c as a multiheme nitrite reductase, research on this enzyme has gained major interest. Today, it is known as pentaheme cytochrome c nitrite reductase (NrfA). Part of the NH produced from NO is released as NH leading to nitrogen loss, similar to denitrification which generates NO, NO, and N. NH can also be used for assimilatory purposes, thus NrfA contributes to nitrogen retention. It catalyses the six-electron reduction of NO to NH, hosting four His/His ligated c-type hemes for electron transfer and one structurally differentiated active site heme. Catalysis occurs at the distal side of a Fe(III) heme c proximally coordinated by lysine of a unique CXXCK motif (Sulfurospirillum deleyianum, Wolinella succinogenes) or, presumably, by the canonical histidine in Campylobacter jejeuni. Replacement of Lys by His in NrfA of W. succinogenes led to a significant loss of enzyme activity. NrfA forms homodimers as shown by high resolution X-ray crystallography, and there exist at least two distinct electron transfer systems to the enzyme. In γ-proteobacteria (Escherichia coli) NrfA is linked to the menaquinol pool in the cytoplasmic membrane through a pentaheme electron carrier (NrfB), in δ- and ε-proteobacteria (S. deleyianum, W. succinogenes), the NrfA dimer interacts with a tetraheme cytochrome c (NrfH). Both form a membrane-associated respiratory complex on the extracellular side of the cytoplasmic membrane to optimize electron transfer efficiency. This minireview traces important steps in understanding the nature of pentaheme cytochrome c nitrite reductases, and discusses their structural and functional features.
Topics: Ammonia; Ferric Compounds; Nitrite Reductases; Nitrites; Wolinella
PubMed: 34865208
DOI: 10.1007/s00775-021-01921-4