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Nature Metabolism Oct 2022Obesity, dyslipidemia and gut dysbiosis are all linked to cardiovascular diseases. A Ganoderma meroterpene derivative (GMD) has been shown to alleviate obesity and...
Obesity, dyslipidemia and gut dysbiosis are all linked to cardiovascular diseases. A Ganoderma meroterpene derivative (GMD) has been shown to alleviate obesity and hyperlipidemia through modulating the gut microbiota in obese mice. Here we show that GMD protects against obesity-associated atherosclerosis by increasing the abundance of Parabacteroides merdae in the gut and enhancing branched-chain amino acid (BCAA) catabolism. Administration of live P. merdae to high-fat-diet-fed ApoE-null male mice reduces atherosclerotic lesions and enhances intestinal BCAA degradation. The degradation of BCAAs is mediated by the porA gene expressed in P. merdae. Deletion of porA from P. merdae blunts its capacity to degrade BCAAs and leads to inefficacy in fighting against atherosclerosis. We further show that P. merdae inhibits the mTORC1 pathway in atherosclerotic plaques. In support of our preclinical findings, an in silico analysis of human gut metagenomic studies indicates that P. merdae and porA genes are depleted in the gut microbiomes of individuals with atherosclerosis. Our results provide mechanistic insights into the therapeutic potential of GMD through P. merdae in treating obesity-associated cardiovascular diseases.
Topics: Humans; Mice; Animals; Male; Cardiovascular Diseases; Amino Acids, Branched-Chain; Bacteroides; Obesity; Mice, Obese; Mechanistic Target of Rapamycin Complex 1; Atherosclerosis; Apolipoproteins E
PubMed: 36253620
DOI: 10.1038/s42255-022-00649-y -
FEMS Microbiology Letters Aug 2022The stability of gut microbiota is essential for the host's health. Parabacteroides spp., core members of the human gut microbiota, have an average abundance of 1.27% in... (Review)
Review
The stability of gut microbiota is essential for the host's health. Parabacteroides spp., core members of the human gut microbiota, have an average abundance of 1.27% in humans of 12 populations. Parabacteroides have recently been reported to have a close relationship with host health (e.g. metabolic syndrome, inflammatory bowel disease and obesity). Parabacteroides have the physiological characteristics of carbohydrate metabolism and secreting short chain fatty acids. However, antimicrobial resistance of Parabacteroides to antibiotics (such as clindamycin, moxifloxacin and cefoxitin) should not be ignored. In this review, we primarily focus on Parabacteroides distasonis, Parabacteroides goldsteinii, Parabacteroides johnsonii and Parabacteroides merdae and discuss their relationships with host disease, diet and the prevention or induction of diseases. Pa. distasonis and Pa. goldsteinii may be viewed as potential next generation probiotic candidates due to their protective effects on inflammation and obesity in mice. We also discuss the potential therapeutic application of Parabacteroides spp. in maintaining host-intestine homeostasis.
Topics: Animals; Bacteroides; Gastrointestinal Microbiome; Humans; Intestines; Mice; Obesity; Probiotics
PubMed: 35945336
DOI: 10.1093/femsle/fnac072 -
Immunity Feb 2023The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations...
The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.
Topics: Pregnancy; Female; Humans; Animals; Mice; Gastrointestinal Microbiome; Pyroptosis; NLR Family, Pyrin Domain-Containing 3 Protein; Macrophages; Sepsis; Inflammation
PubMed: 36792573
DOI: 10.1016/j.immuni.2023.01.015 -
Nature Metabolism Jan 2023
PubMed: 36653667
DOI: 10.1038/s42255-023-00740-y -
International Journal of Systematic and... Jul 2006The characteristics of three Bacteroides species, Bacteroides distasonis, Bacteroides goldsteinii and Bacteroides merdae, were examined. 16S rRNA gene sequence analysis...
Reclassification of Bacteroides distasonis, Bacteroides goldsteinii and Bacteroides merdae as Parabacteroides distasonis gen. nov., comb. nov., Parabacteroides goldsteinii comb. nov. and Parabacteroides merdae comb. nov.
The characteristics of three Bacteroides species, Bacteroides distasonis, Bacteroides goldsteinii and Bacteroides merdae, were examined. 16S rRNA gene sequence analysis showed that B. distasonis, B. goldsteinii and B. merdae should not be classified as species within the genus Bacteroides. Although B. distasonis, B. goldsteinii and B. merdae were phylogenetically related to Tannerella forsythensis, the ratios of anteiso-C(15 : 0) to iso-C(15 : 0) in whole-cell methanolysates of the three species were different from that of T. forsythensis. In addition, whereas the major menaquinones of T. forsythensis were MK-10 and MK-11, the major menaquinones of B. distasonis, B. goldsteinii and B. merdae were MK-9 and MK-10. The three species were phenotypically similar to Bacteroides sensu stricto, but phylogenetically distinct. Furthermore, B. distasonis, B. goldsteinii and B. merdae could be differentiated from Bacteroides sensu stricto (predominant menaquinones: MK-10 and MK-11) by the menaquinone composition. This is an important chemotaxonomic characteristic of the three species. On the basis of these data, a novel genus, Parabacteroides gen. nov., is proposed for B. distasonis, B. goldsteinii and B. merdae, with three species, Parabacteroides distasonis gen. nov., comb. nov. (the type species), Parabacteroides goldsteinii comb. nov. and Parabacteroides merdae comb. nov. The type strains of P. distasonis, P. goldsteinii and P. merdae are JCM 5825(T) (=CCUG 4941(T)=DSM 20701(T)=ATCC 8503(T)), JCM 13446(T) (=CCUG 48944(T)) and JCM 9497(T) (=CCUG 38734(T)=ATCC 43184(T)), respectively.
Topics: Bacterial Typing Techniques; Bacteroides; Bacteroidetes; DNA, Bacterial; DNA, Ribosomal; Fatty Acids; Genes, rRNA; Molecular Sequence Data; Phylogeny; RNA, Bacterial; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Sequence Homology, Nucleic Acid; Vitamin K 2
PubMed: 16825636
DOI: 10.1099/ijs.0.64192-0 -
Theranostics 2021Prior chronic treatment with statins has been shown to be associated with more favorable outcomes in patients with acute coronary syndrome (ACS). Specific changes in...
Multi-omics study reveals that statin therapy is associated with restoration of gut microbiota homeostasis and improvement in outcomes in patients with acute coronary syndrome.
Prior chronic treatment with statins has been shown to be associated with more favorable outcomes in patients with acute coronary syndrome (ACS). Specific changes in the gut microbiota and microbial metabolites have been shown to influence the progression of coronary artery disease. However, the critical microbial and metabolomic changes associated with the cardiovascular protective effects of statins in ACS remain elusive. In the present study, we performed 16S rRNA sequencing and serum metabolomic analysis in 36 ACS patients who had received chronic statin treatment, 67 ACS patients who had not, and 30 healthy volunteers. A follow-up study was conducted. Metagenomic functional prediction of important bacterial taxa was achieved using PICRUSt2. : Statins modulated the gut microbiome of ACS patients towards a healthier status, i.e., reducing potentially pathogenic bacteria such as but increasing beneficial bacteria such as , and . Moreover, prior chronic statin therapy was associated with improved outcome in ACS patients. Multi-omics analysis revealed that specific changes in bacterial taxa were associated with disease severity or outcomes either directly or by mediating metabolites such as fatty acids and prenol lipids. Finally, we discovered that important taxa associated with statins were correlated with fatty acid- and isoprenoid-related pathways that were predicted by PICRUSt2. Our study suggests that statin treatment might benefit ACS patients by modulating the composition and function of the gut microbiome, which might result in improved circulating metabolites and reduced metabolic risk. Our findings provide new insights for understanding the heterogenic roles of statins in ACS patients through host gut microbiota metabolic interactions.
Topics: Acute Coronary Syndrome; Bacteria; Female; Follow-Up Studies; Gastrointestinal Microbiome; Healthy Volunteers; Homeostasis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metabolomics; Middle Aged; RNA, Ribosomal, 16S
PubMed: 33897881
DOI: 10.7150/thno.55946 -
Protein Science : a Publication of the... Dec 2018β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and...
β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs.
Topics: Bacteroidaceae; Catalytic Domain; Crystallography, X-Ray; Gastrointestinal Microbiome; Glucuronidase; Humans; Models, Molecular; Protein Conformation
PubMed: 30230652
DOI: 10.1002/pro.3507 -
Gut Microbes 2023The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and...
The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and influenced by many postnatal factors, moreover, little is known about the development of the gut metabolome. We showed that geography has an important influence on the microbiome dynamics in the first year of life based on two independent cohorts from China and Sweden. Major compositional differences since birth were the high relative abundance of in the Swedish cohort and in the Chinese cohort. We analyzed the development of the fecal metabolome in the first year of life in the Chinese cohort. Lipid metabolism, especially acylcarnitines and bile acids, was the most abundant metabolic pathway in the newborn gut. Delivery mode and feeding induced particular differences in the gut metabolome since birth. In contrast to C-section newborns, medium- and long-chain acylcarnitines were abundant at newborn age only in vaginally delivered infants, associated by the presence of bacteria such as and . Our data provide a basis for understanding the maturation of the fecal metabolome and the metabolic role of gut microbiota in infancy.
Topics: Gastrointestinal Microbiome; Humans; Infant, Newborn; Infant; China; Bile Acids and Salts; Amino Acids; Sweden; Bacteroides; Streptococcus; Feces; Lipid Metabolism; Feeding Behavior; Metabolic Networks and Pathways; Delivery, Obstetric; Female; Pregnancy; Cesarean Section; Longitudinal Studies; Male
PubMed: 37424334
DOI: 10.1080/19490976.2023.2231596 -
New Microbes and New Infections Mar 2022Strain Quantibio-BCGUT is a new species from the genus Parabacteroides that was isolated from a stool sample of a 49-year-old healthy Chinese male adult. Cells are...
Strain Quantibio-BCGUT is a new species from the genus Parabacteroides that was isolated from a stool sample of a 49-year-old healthy Chinese male adult. Cells are Gram-negative and obligate anerobic bacilli. Strain Quantibio-BCGUT exhibits 95.86% 16S rRNA gene sequence similarity to Parabacteroides merdae strain JCM 9497 (NR_041343.1), the phylogenetically closely related species with standing in nomenclature. Major fatty acids are C16:0, C18:0 and C19:0-IS. Quantibio-BCGUT exhibits a high level of resistance to aztreonam. Growth occurred at pH 5.5-9.0. Optimal growth was observed at 35 °C in YCFA medium in anerobic condition, no growth occurs at 25 °C or 50 °C. Strain grows in YCFA medium in the presence of 0.1%-2.0% (w/v) NaCl (optimum 1.0%). Based on the phenotypic and phylogenetic evidence, OrthoANI values and results of the biochemical tests, the new species is named Parabacteroides pekinense sp. nov., for which strain Quantibio-BCGU T (= CGMCC = QHBCGU) is proposed as the type strain.
PubMed: 35496671
DOI: 10.1016/j.nmni.2022.100973 -
New Microbes and New Infections Nov 2019sp. nov., strain Marseille-P2231 (= CSURP2231 = DSM 101860) is a new species within the family . It was isolated from a stool specimen of a 25-year-old healthy woman....
sp. nov., strain Marseille-P2231 (= CSURP2231 = DSM 101860) is a new species within the family . It was isolated from a stool specimen of a 25-year-old healthy woman. Its genome was 5 013 798 bp long with a 45.7 mol% G+C content. The closest species based on 16S rRNA sequence was strain JCM 9497 with 98.19% sequence similarity. Considering phenotypic features and comparative genome studies, we proposed the strain Marseille-P2231 as the type strain of sp. nov., a new species within the genus
PubMed: 31641517
DOI: 10.1016/j.nmni.2019.100602