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Nature Jun 2022Cellular iron homeostasis is vital and maintained through tight regulation of iron import, efflux, storage and detoxification. The most common modes of iron storage use...
Cellular iron homeostasis is vital and maintained through tight regulation of iron import, efflux, storage and detoxification. The most common modes of iron storage use proteinaceous compartments, such as ferritins and related proteins. Although lipid-bounded iron compartments have also been described, the basis for their formation and function remains unknown. Here we focus on one such compartment, herein named the 'ferrosome', that was previously observed in the anaerobic bacterium Desulfovibrio magneticus. Using a proteomic approach, we identify three ferrosome-associated (Fez) proteins that are responsible for forming ferrosomes in D. magneticus. Fez proteins are encoded in a putative operon and include FezB, a P-ATPase found in phylogenetically and metabolically diverse species of bacteria and archaea. We show that two other bacterial species, Rhodopseudomonas palustris and Shewanella putrefaciens, make ferrosomes through the action of their six-gene fez operon. Additionally, we find that fez operons are sufficient for ferrosome formation in foreign hosts. Using S. putrefaciens as a model, we show that ferrosomes probably have a role in the anaerobic adaptation to iron starvation. Overall, this work establishes ferrosomes as a new class of iron storage organelles and sets the stage for studying their formation and structure in diverse microorganisms.
Topics: Bacterial Proteins; Desulfovibrio; Ferric Compounds; Gram-Negative Bacteria; Multigene Family; Organelles; Phylogeny; Proteomics; Rhodopseudomonas; Shewanella putrefaciens
PubMed: 35585231
DOI: 10.1038/s41586-022-04741-x -
Microorganisms Mar 2023The balance of microbial communities in the gut is extremely important for normal physiological function. Disruption of the balance is often associated with various...
The balance of microbial communities in the gut is extremely important for normal physiological function. Disruption of the balance is often associated with various disorders and diseases. Both HIV infection and cocaine use are known to change the gut microbiota and the epithelial barrier integrity, which contribute to inflammation and immune activation. Our recent study shows that Tat expression and cocaine exposure result in changes of genome-wide DNA methylation and gene expression and lead to worsen the learning and memory impairments. In the current study, we extended the study to determine effects of Tat and cocaine on the gut microbiota composition. We found that both Tat expression and cocaine exposure increased Alteromonadaceae in 6-month-old female/male mice. In addition, we found that Tat, cocaine, or both increased Alteromonadaceae, Bacteroidaceae, Cyanobiaceae, Erysipelotrichaceae, and Muribaculaceae but decreased Clostridiales_vadinBB60_group, Desulfovibrionaceae, Helicobacteraceae, Lachnospiraceae, and Ruminococcaceae in 12-month-old female mice. Lastly, we analyzed changes of metabolic pathways and found that Tat decreased energy metabolism and nucleotide metabolism, and increased lipid metabolism and metabolism of other amino acids while cocaine increased lipid metabolism in 12-month-old female mice. These results demonstrated that Tat expression and cocaine exposure resulted in significant changes of the gut microbiota in an age- and sex-dependent manner and provide additional evidence to support the bidirectional gut-brain axis hypothesis.
PubMed: 36985373
DOI: 10.3390/microorganisms11030799 -
Ecotoxicology and Environmental Safety Dec 2021Long-term consumption of arsenic-contaminated rice has become a public health issue that urgently needs to be addressed. In this study, mice were exposed to arsenic in...
Long-term consumption of arsenic-contaminated rice has become a public health issue that urgently needs to be addressed. In this study, mice were exposed to arsenic in rice (low dose, 0.91 mg/kg; medium dose, 9.1 mg/kg) for 30 days and 60 days, respectively, and the effects on pathological structures of spleen and skin, as well as the structure of the fecal microbiome were examined. The findings revealed dose/time cumulative effects on pathological changes, with even a low dose exposure for 30 days causing destruction of splenic follicular structure and thickening of dermal keratinized and epidermal layers. The Firmicutes/Bacteroidetes ratio in the community and the positive/negative ratio in network links were higher in arsenic groups, suggesting that arsenic resulted in a less healthy and unstable microbiome for the host. Thus lifetime consumption of arsenic in rice may have potential health effects on humans and must be carefully assessed to safeguard human health. Furthermore, in arsenic groups, arsenic-resistant bacteria or arsenic hazards remediation bacteria changed to be the dominant bacteria and acted as the core bacteria in the network modules. Some microbial arsenic transforming genes (arsC, arsR, arsA, ACR3, and aoxB) differed, indicating that the gut microbiome changed to withstand arsenic stress. Furthermore, Faecalibaculum, Lachnospiraceae_NK4A136_group, Angelakisella, Ruminiclostridium, and Desulfovibrionaceae are positively associated with arsenic dosage and may be useful in the early detection of arsenicals.
Topics: Animals; Arsenic; Arsenicals; Gastrointestinal Microbiome; Mice; Microbiota; Oryza
PubMed: 34755630
DOI: 10.1016/j.ecoenv.2021.112934 -
Frontiers in Microbiology 2022In the present study, the synergistic effects of quercetin (Q) and vitamin E (E) on cecal microbiota composition and function, as well as the microbial metabolic profile...
In the present study, the synergistic effects of quercetin (Q) and vitamin E (E) on cecal microbiota composition and function, as well as the microbial metabolic profile in aged breeder hens were investigated. A total of 400 (65 weeks old) Tianfu breeder hens were randomly allotted to four experimental groups (four replicates per group). The birds were fed diets containing quercetin at 0.4 g/kg, vitamin E (0.2 g/kg), quercetin and vitamin E (QE; 0.4 g/kg and 0.2 g/kg), and a basal diet for a period of 10 wks. After the 10 week experimental period, the cecal contents of 8 aged breeder hens per group were sampled aseptically and subjected to high-throughput 16S rRNA gene sequencing and untargeted metabolomic analysis. The results showed that the relative abundances of phyla , and were the most prominent among all the dietary groups. Compared to the control group, the relative abundance of the families , , and were enriched in the QE group; and and were enriched in the Q group, whereas those of and were enriched in the E group compared to the control group. Untargeted metabolomics analyses revealed that Q, E, and QE modified the abundance of several metabolites in prominent pathways including ubiquinone and other terpenoid-quinone biosynthesis, regulation of actin cytoskeleton, insulin secretion, pancreatic secretion, nicotine addiction, and metabolism of xenobiotics by cytochrome P450. Furthermore, key cecal microbiota, significantly correlated with important metabolites, ()-equol positively correlated with and in E_vs_C, and negatively correlated with , and but, a contrary trend was observed with in QE_vs_C. This study establishes that the synergy of quercetin and vitamin E alters the cecal microbial composition and metabolite profile in aged breeder hens, which lays a foundation for chicken improvement programs.
PubMed: 35656004
DOI: 10.3389/fmicb.2022.851459 -
Frontiers in Pharmacology 2022Increasing evidence suggested that gut microbiota played critical roles in developing autoimmune diseases. This study investigated the correlation between gut microbiota...
Increasing evidence suggested that gut microbiota played critical roles in developing autoimmune diseases. This study investigated the correlation between gut microbiota and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with kidney injury. We analyzed the fecal samples of 23 AAV patients with kidney injury using a 16s RNA microbial profiling approach. The alpha-diversity indexes were significantly lower in AAV patients with kidney injury than healthy controls (Sobs < 0.001, Shannon < 0.001, Chao < 0.001). The beta-diversity difference demonstrated a significant difference among AAV patients with kidney injury, patients with lupus nephritis (LN), and health controls (ANOSIM, = 0.001). Among these AAV patients, the Prevotellaceae Desulfovibrionaceae , and Lachnospiraceae were correlated negatively with serum creatinine, and the proportion of Desulfovibrionaceae Lachnospiraceae had a positive correlation with eGFR. In conclusion, the richness and diversity of gut microbiota were reduced in AAV patients with kidney injury, and the alteration of gut microbiota might be related with the severity of kidney injury of AAV patients. Targeted regulation of gut microbiota disorder might be a potential treatment for AAV patients with kidney injury.
PubMed: 35140612
DOI: 10.3389/fphar.2022.783679 -
Frontiers in Cellular and Infection... 2021Sulfate Reducing Bacteria (SRB), usually rare residents of the gut, are often found in increased numbers (called a SRB bloom) in inflammatory conditions such as...
Sulfate Reducing Bacteria (SRB), usually rare residents of the gut, are often found in increased numbers (called a SRB bloom) in inflammatory conditions such as Inflammatory Bowel Disease (IBD), pouchitis, and periodontitis. However, the underlying mechanisms of this association remain largely unknown. Notch signaling, a conserved cell-cell communication pathway, is usually involved in tissue development and differentiation. Dysregulated Notch signaling is observed in inflammatory conditions such as IBD. Lipolysaccharide and pathogens also activate Notch pathway in macrophages. In this study, we tested whether Desulfovibrio, the most dominant SRB genus in the gut, may activate Notch signaling. RAW 264.7 macrophages were infected with (DSV) and analyzed for the expression of Notch signaling pathway-related proteins. We found that DSV induced protein expression of Notch1 receptor, Notch intracellular domain (NICD) and p21, a downstream Notch target, in a dose-and time-dependent manner. DSV also induced the expression of pro-IL1β, a precursor of IL-1β, and SOCS3, a regulator of cytokine signaling. The gamma secretase inhibitor DAPT or Notch siRNA dampened DSV-induced Notch-related protein expression as well the expression of pro-IL1β and SOCS3. Induction of Notch-related proteins by DSV was not affected by TLR4 -IN -C34(C34), a TLR4 receptor antagonist. Additionally, cell-free supernatant of DSV-infected macrophages induced NICD expression in uninfected macrophages. DSV also activated Notch pathway in the human epithelial cell line HCT116 and in mouse small intestine. Thus, our study uncovers a novel mechanism by which SRB interact with host cells by activating Notch signaling pathway. Our study lays a framework for examining whether the Notch pathway induced by SRB contributes to inflammation in conditions associated with SRB bloom and whether it can be targeted as a therapeutic approach to treat these conditions.
Topics: Animals; Bacteria; Desulfovibrio; Mice; RAW 264.7 Cells; Receptor, Notch1; Signal Transduction; Sulfates
PubMed: 34336718
DOI: 10.3389/fcimb.2021.695299 -
Drug Design, Development and Therapy 2023To study the efficacy of Qianshan Huoxue Gao (QS) in treating acute coronary syndrome (ACS) and to explore the mechanism of action from the perspective of intestinal...
PURPOSE
To study the efficacy of Qianshan Huoxue Gao (QS) in treating acute coronary syndrome (ACS) and to explore the mechanism of action from the perspective of intestinal flora regulation.
METHODS
Male Sprague-Dawley rats were divided into control, model, QS, and atorvastatin groups; except for the control group, rats underwent ligation of the left anterior descending branch of the coronary artery. Following treatment for 28 days, cardiac function was evaluated using an echocardiographic assay; ELISAs for serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α); assessment of cardiac enzymes and inflammatory response; hematoxylin and eosin (HE) staining for histopathological changes in the heart, skin, and viscera; 16S rRNA gene sequencing for intestinal flora diversity and structural differences analysis; and we further investigated intestinal contents using metabolomics.
RESULTS
Compared with controls, CK-MB and cTnI were increased (<0.01); ejection factor and fractional shortening were decreased (<0.01); left ventricular internal end-diastolic dimension and left ventricular internal end-systolic dimension were increased (<0.01); and IL-2, IL-6, TNF-α, and hs-CRP were increased in the model group. Myocardial damage and inflammation were also observed by HE staining. QS improved these indexes, similar to the atorvastatin group; therefore, QS could effectively treat ACS. QS modulates the structure and abundance of the intestinal flora in ACS model rats, among which , and are associated with cardiovascular disease. Metabolomics revealed that the intestinal metabolite content changed in ACS, with ethanolamine (EA) being the most relevant metabolite for ACS treatment by QS. EA was significantly positively correlated with , and .
CONCLUSION
QS can effectively treat ACS and can restore regulation of the intestinal flora. EA may be the primary metabolite of QS, exerting a therapeutic effect in ACS.
Topics: Male; Animals; Rats; Rats, Sprague-Dawley; Acute Coronary Syndrome; Tumor Necrosis Factor-alpha; Interleukin-2; Atorvastatin; C-Reactive Protein; Gastrointestinal Microbiome; Interleukin-6; RNA, Ribosomal, 16S; Ethanolamine; Ethanolamines
PubMed: 36855515
DOI: 10.2147/DDDT.S396649 -
European Review For Medical and... Jul 2021High-altitude pulmonary hypertension (HAPH) is one of the diseases with higher occurrence among people living in plateau areas. The possible mechanism of angiotensin II...
OBJECTIVE
High-altitude pulmonary hypertension (HAPH) is one of the diseases with higher occurrence among people living in plateau areas. The possible mechanism of angiotensin II receptor 1 inhibitor irbesartan in improving HAPH was explored from the perspective of intestinal bacterial flora in this study.
MATERIALS AND METHODS
A HAPH rat model was established under simulated high-altitude hypobaric hypoxia. The levels of oxidative stress and vasoactive substances were detected after irbesartan intervention, and intestinal flora genomics analysis was performed.
RESULTS
High-altitude hypobaric hypoxia-induced the increase in pulmonary artery pressure and left ventricular systolic dysfunction in HAPH model rats, but its effects were alleviated by irbesartan. Changes in the levels of oxidative damage in intestinal tissues, such as the increase in superoxide dismutase and glutathione peroxidase in intestinal tissues and the decrease in malondialdehyde content, were also reversed by irbesartan. The serum levels of angiotensin II, endothelin 1, interleukin-6, and C-reactive protein increased substantially whereas the level of nitric oxide decreased in HAPH model rats. The levels of these vasoconstriction and inflammatory indicators were also reversed after irbesartan intervention. The distribution of intestinal florae in rats was changed by the simulated high-altitude hypoxia environment as manifested by the increased Firmicutes-to-Bacteroidetes ratio (F/B), the increased abundance of Lactobacillaceae and Lachnospiraceae, and the decreased abundance of Prevotellaceae and Desulfovibrionaceae at the family level. However, the changes in F/B ratio and the abundance of these florae were reversed by irbesartan.
CONCLUSIONS
Irbesartan can alleviate pulmonary artery pressure and left ventricular relaxation in HAPH model rats, reduce the oxidative damage caused by high-altitude hypoxia, and lower the release of vasoconstrictor factors and inflammatory mediators. These effects might be caused by the increased abundance of Lactobacillaceae and Lachnospiraceae and the decreased abundance of Prevotellaceae and Desulfovibrionaceae in the intestines.
Topics: Altitude Sickness; Angiotensin II Type 1 Receptor Blockers; Animals; Disease Models, Animal; Gastrointestinal Microbiome; Humans; Hypertension, Pulmonary; Inflammation Mediators; Irbesartan; Male; Oxidative Stress; Rats
PubMed: 34286497
DOI: 10.26355/eurrev_202107_26247 -
Frontiers in Pharmacology 2022Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease (NAFLD). The non-absorbable antibiotic rifaximin has been used for...
Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease (NAFLD). The non-absorbable antibiotic rifaximin has been used for treatment of irritable bowel syndrome, traveling diarrhea, and hepatic encephalopathy, but the efficacy of rifaximin in NASH patients remains controversial. This study investigated the effects and underlying mechanisms of rifaximin treatment in mice with methionine and choline deficient (MCD) diet-induced NASH. We found that rifaximin greatly ameliorated hepatic steatosis, lobular inflammation, and fibrogenesis in MCD-fed mice. Bacterial 16S rRNA sequencing revealed that the gut microbiome was significantly altered in MCD-fed mice. Rifaximin treatment enriched 13 amplicon sequence variants (ASVs) belonging to the groups , , , , , , , and . However, rifaximin treatment also reduced seven ASVs in the groups , , , , , , and in MCD-fed mice. Bile acid-targeted metabolomic analysis indicated that the MCD diet resulted in accumulation of primary bile acids and deoxycholic acid (DCA) in the ileum. Rifaximin delivery reduced DCA levels in MCD-fed mice. Correlation analysis further showed that DCA levels were associated with differentially abundant ASVs modulated by rifaximin. In conclusion, rifaximin may ameliorate NASH by decreasing ileal DCA through alteration of the gut microbiome in MCD-fed mice. Rifaximin treatment may therefore be a promising approach for NASH therapy in humans.
PubMed: 35450049
DOI: 10.3389/fphar.2022.841132 -
BioMed Research International 2020Although the role of the gut microbiota in obesity has recently received considerable attention, the exact mechanism is unclear. This study was aimed at investigating...
Although the role of the gut microbiota in obesity has recently received considerable attention, the exact mechanism is unclear. This study was aimed at investigating the profiles of bacterial communities in fecal samples and differentially expressed proteins (DEPs) in the peripheral blood in mice fed a high-fat diet (HFD) and standard diet (SD) and at providing new insights into the pathogenesis of obesity. The profiles of bacterial communities in fecal samples and DEPs in the peripheral blood were characterized in mice fed HFD and SD, respectively. The levels of 3 DEPs increased in HFD mice. The alpha diversity was significantly lower after 4 and 12 weeks in HFD mice. The beta diversity was higher after 4, 8, and 12 weeks in HFD mice. A total of 16 gut bacterial clades were significantly different with the linear discriminant analysis (LDA) score higher than 4 over time. The relative abundance levels of Proteobacteria and Deferribacteres were higher, while those of Bacteroidetes and Firmicutes were lower in HFD mice at the phylum level. The relative abundance of Desulfovibrionaceae and Rikenellaceae increased in HFD mice at the family level. The relative abundance of the Bacteroidetes_S24-7_group and Lachnospiraceae was lower in HFD mice. The gut microbiota had a significant correlation with serum lipid indexes and expression of DEPs at the phylum and family levels. The changes in the gut microbiota of HFD mice and their associations with the levels of inflammatory proteins could be one of the major etiological mechanisms underlying obesity.
Topics: Animals; Body Weight; Diet, High-Fat; Gastrointestinal Microbiome; Inflammation; Lipids; Male; Mice, Inbred C57BL; Obesity; Phylogeny; Proteins
PubMed: 33029514
DOI: 10.1155/2020/5376108