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Frontiers in Microbiology 2022Hypertension is a major threat to human health. Oliv. (EU) is a small tree and EU extract is widely used to improve hypertension in East Asia. However, its major...
bark extract reduces blood pressure and inflammation by regulating the gut microbiota and enriching the strain in high-salt diet and N(omega)-nitro-L-arginine methyl ester induced mice.
Hypertension is a major threat to human health. Oliv. (EU) is a small tree and EU extract is widely used to improve hypertension in East Asia. However, its major constituents have poor absorption and stay in the gut for a long time. The role of the gut microbiota in the anti-hypertensive effects of EU is unclear. Here, we examined the anti-hypertensive effects of EU in high-salt diet and N(omega)-nitro-L-arginine methyl ester (L-NAME) induced mice. After receiving EU for 6 weeks, the blood pressure was significantly reduced and the kidney injury was improved. Additionally, EU restored the levels of inflammatory cytokines, such as serum interleukin (IL)-6 and IL-17A, and renal IL-17A. The diversity and composition of the gut microbiota were influenced by administration of EU; 40 significantly upregulated and 107 significantly downregulated amplicon sequence variants (ASVs) were identified after administration of EU. ASV403 () was selected as a potential anti-hypertensive ASV. Its closest strain XGB65 was isolated. Furthermore, animal studies confirmed that strain XGB65 exerted anti-hypertensive effects, possibly by reducing levels of inflammatory cytokines, such as renal IL-17A. Our study is the first to report that EU reduces blood pressure by regulating the gut microbiota, and it enriches the strain, which exerts anti-hypertensive effects. These findings provide directions for developing novel anti-hypertensive treatments by combining probiotics and prebiotics.
PubMed: 36060766
DOI: 10.3389/fmicb.2022.967649 -
Microbial Biotechnology Mar 2022Endothermic mammals have a high energy cost to maintain a stable and high body temperature (T , around 37°C). Thyroid hormones are a major regulator for energy...
Endothermic mammals have a high energy cost to maintain a stable and high body temperature (T , around 37°C). Thyroid hormones are a major regulator for energy metabolism and T . The gut microbiota is involved in modulating host energy metabolism. However, whether the interaction between the gut microbiota and thyroid hormones is involved in metabolic and thermal regulations is unclear. We hypothesized that thyroid hormones via an interaction with gut microbiota orchestrate host thermogenesis and T . l-thyroxine-induced hyperthyroid Mongolian gerbils (Meriones unguiculatus) increased resting metabolic rate (RMR) and T , whereas Methimazole-induced hypothyroid animals decreased RMR. Both hypothyroid and hyperthyroid animals differed significantly in faecal bacterial community. Hyperthyroidism increased the relative abundance of pathogenic bacteria, such as Helicobacter and Rikenella, and decreased abundance of beneficial bacteria Butyricimonas and Parabacteroides, accompanied by reduced total bile acids and short-chain fatty acids. Furthermore, the hyperthyroid gerbils transplanted with the microbiota from control donors increased type 2 deiodinase (DIO2) expression in the liver and showed a greater rate of decline of both serum T3 and T4 levels and, consequently, a more rapid recovery of normal RMR and T . These findings indicate that thyroid hormones regulate thermogenesis depending on gut microbiota and colonization with normal microbiota by caecal microbial transplantation attenuates hyperthyroid-induced thermogenesis. This work reveals the functional consequences of the gut microbiota-thyroid axis in controlling host metabolic physiology and T in endotherms.
Topics: Animals; Cecum; Gerbillinae; Hyperthyroidism; Thermogenesis; Thyroid Hormones
PubMed: 33729663
DOI: 10.1111/1751-7915.13793 -
Gut Microbes 2022() is the type species for the new genus, and a gut commensal of the phylum. Emerging reports (primarily based on reference strain/ATCC-8503) concerningly propose...
() is the type species for the new genus, and a gut commensal of the phylum. Emerging reports (primarily based on reference strain/ATCC-8503) concerningly propose that long-known opportunistic pathogen is a probiotic. We posit there is an urgent need to characterize the pathogenicity of strain-strain variability. Unfortunately, no methods/insights exist to classify for this purpose. Herein, we developed a virulence gene-based classification system for and to facilitate pathogenic-vs-probiotic characterization. We used DNA methods to develop a system based on the virulence (lipopolysaccharide/bacterial wall) ' O-antigen-synthesis gene'. We then performed phylogenetic analysis of from fourteen complete genomes (21 genes), other , and ; and proposed a PCR-based Restriction-Fragment Length Polymorphism method. Cluster analysis revealed that can be classified into four lineages (based on gene gaps/insertions) which we designated -Types I, II, III, and IV. In context, we found 14 additional -types (I-XVIII) interspersed with numerous and pathogenic forming three major "-superclusters." For laboratory -Typing implementation, we developed a PCR-primer strategy to amplify genes (100%-specificity) to conduct MboII-RFLP and sub-classify primers for other are proposed/discussed. Comparative analysis of lipopolysaccharide/lipid-A gene confirmed as highly discriminant. In conclusion, -Typing classifies into unique clusters/superclusters given copy/sequence variability. Analysis revealed that most pathogenic strains are single-copy -Type I . The relevance of the strain variability in disease might depend on their hypothetical modulatory interactions with other O-antigens/lipopolysaccharides and TLR4 lipopolysaccharide-receptors in human/animal cells.
Topics: Animals; Bacterial Proteins; Bacterial Typing Techniques; Bacteroidetes; DNA Primers; Glycosyltransferases; Gram-Negative Bacterial Infections; Humans; O Antigens; Phylogeny; Polymorphism, Restriction Fragment Length; Probiotics; Virulence
PubMed: 35090379
DOI: 10.1080/19490976.2021.1997293 -
Gut Sep 2023
Topics: Humans; Colitis; Bacteroidetes; Probiotics
PubMed: 36788013
DOI: 10.1136/gutjnl-2022-329386 -
Frontiers in Microbiology 2018Adverse fluctuations in the distribution of the intestinal microbiome cohort has been associated with the onset of intra- and extra-intestinal inflammatory conditions,... (Review)
Review
Adverse fluctuations in the distribution of the intestinal microbiome cohort has been associated with the onset of intra- and extra-intestinal inflammatory conditions, like the metabolic syndrome (MetS) and it's hepatic manifestation, non-alcoholic fatty liver disease (NAFLD). The intestinal microbial community of obese compared to lean subjects has been shown to undergo configurational shifts in various genera, including but not limited to increased abundances of , and and decreased levels of , and genera. At the phylum level, decreased and increased have been reported. The intestinal microbiota therefore presents an important target for designing novel therapeutic modalities that target extra-intestinal inflammatory disorders, such as NAFLD. This review hypothesizes that disruption of the intestinal-mucosal macrophage interface is a key factor in intestinal-liver axis disturbances. Intestinal immune responses implicated in the manifestation, maintenance and progression of NAFLD provide insights into the dialogue between the intestinal microbiome, the epithelia and mucosal immunity. The pro-inflammatory activity and immune imbalances implicated in NAFLD pathophysiology are reported to stem from dysbiosis of the intestinal epithelia which can serve as a source of hepatoxic effects. We posit that the hepatotoxic consequences of intestinal dysbiosis are compounded through intestinal microbiota-mediated inflammation of the local mucosa that encourages mucosal immune dysfunction, thus contributing important plausible insight in NAFLD pathogenesis. The administration of probiotics and prebiotics as a cure-all remedy for all chronic diseases is not advocated, instead, the incorporation of evidence based probiotic/prebiotic formulations as adjunctive modalities may enhance lifestyle modification management strategies for the amelioration of NAFLD.
PubMed: 29441049
DOI: 10.3389/fmicb.2018.00061 -
Proceedings of the National Academy of... Aug 2022Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is the development of...
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells. One of the earliest aspects of this process is the development of autoantibodies and T cells directed at an epitope in the B-chain of insulin (insB:9-23). Analysis of microbial protein sequences with homology to the insB:9-23 sequence revealed 17 peptides showing >50% identity to insB:9-23. Of these 17 peptides, the peptide, found in the normal human gut commensal , activated both human T cell clones from T1D patients and T cell hybridomas from nonobese diabetic (NOD) mice specific to insB:9-23. Immunization of NOD mice with insB:9-23 peptide mimic or insB:9-23 peptide verified immune cross-reactivity. Colonization of female NOD mice with accelerated the development of T1D, increasing macrophages, dendritic cells, and destructive CD8 T cells, while decreasing FoxP3 regulatory T cells. Western blot analysis identified -reacting antibodies in sera of NOD mice colonized with and human T1D patients. Furthermore, adoptive transfer of splenocytes from -treated mice to NOD/SCID mice enhanced disease phenotype in the recipients. Finally, analysis of human children gut microbiome data from a longitudinal DIABIMMUNE study revealed that seroconversion rates (i.e., the proportion of individuals developing two or more autoantibodies) were consistently higher in children whose microbiome harbored sequences capable of producing the peptide compared to individuals who did not harbor it. Taken together, these data demonstrate the potential role of a gut microbiota-derived insB:9-23-mimic peptide as a molecular trigger of T1D pathogenesis.
Topics: Animals; Autoantibodies; Bacteroidetes; CD8-Positive T-Lymphocytes; Child; Diabetes Mellitus, Type 1; Female; Gastrointestinal Microbiome; Humans; Insulin; Mice; Mice, Inbred NOD; Mice, SCID; Molecular Mimicry; Peptides
PubMed: 35878027
DOI: 10.1073/pnas.2120028119 -
Microbial Drug Resistance (Larchmont,... Dec 2020The aim of this study was to analyze the susceptibility of and spp. strains, isolated from patients hospitalized in the clinical hospital in Poland to penicillin,...
The aim of this study was to analyze the susceptibility of and spp. strains, isolated from patients hospitalized in the clinical hospital in Poland to penicillin, amoxicillin with clavulanic acid, imipenem, clindamycin, and metronidazole. We analyzed susceptibility of 476 isolates to routinely use for the treatment of anaerobic bacterial infections antibiotics. test method was used to determining the minimal inhibitory concentration values. To show the trend of drug resistance, we compared data from two periods within the years 2003-2017. Research results indicate that the problem of resistance is mainly related to strains belonging to non-fragilis . In the analyzed periods, there was an increase in the percentage of clindamycin-resistant isolates (35.21% vs. 53.33%), amoxicillin/clavulanic acid (2.83% vs. 8.15%), and imipenem (1.41% vs. 3.7%). In isolates belonging to , we observed a constant high (∼50%) percentage of clindamycin-resistant strains. The overwhelming majority of strains were resistant to penicillin (>95%) and about 20% of the isolates were not susceptible to clindamycin. Clindamycin, due to the high and increasing percentage of resistant strains, may not be a good choice in the empirical therapy of infections caused by and . Our study highlighted the importance of a routine or at least periodic monitoring of antimicrobial susceptibility of anaerobic Gram-negative bacilli, providing important information for appropriate therapy. The study shows that infection caused (or suspected of being caused) by and spp. can be empirically treated with metronidazole or imipenem.
Topics: Anti-Bacterial Agents; Bacteroides; Bacteroidetes; Cross Infection; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Poland
PubMed: 32407191
DOI: 10.1089/mdr.2019.0462 -
Scientific Reports Jun 2023Hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-thyroid (HPT) axis were found in acute high altitude challenge, but the role of...
Hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-thyroid (HPT) axis were found in acute high altitude challenge, but the role of gut microbiota and metabolites is unknown. We utilized adult male Sprague-Dawley rats at a simulated altitude of 5500 m for 3 days in a hypobaric-hypoxic chamber. ELISA and metabolomic analyses of serum and 16S rRNA and metabolomic analyses of fecal samples were then performed. Compared with the normoxic group, serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and thyroxine (tT) were increased in the hypoxia group, whereas thyrotropin-releasing hormone (TRH) was decreased. Bacteroides, Lactobacillus, Parabacteroides, Butyricimonas, SMB53, Akkermansia, Phascolarctobacterium, and Aerococcus were enriched in hypoxia group, whereas [Prevotella], Prevotella, Kaistobacter, Salinibacterium, and Vogesella were enriched in normoxic group. Metabolomic analysis indicated that acute hypoxia significantly affected fecal and serum lipid metabolism. In addition, we found five fecal metabolites may mediate the cross-talk between TRH, tT, and CORT with [Prevotella], Kaistobacter, Parabacteroides, and Aerococcus, and 6 serum metabolites may mediate the effect of TRH and tT on [Prevotella] and Kaistobacter by causal mediation analysis. In conclusion, this study provides new evidence that key metabolites mediate the cross-talk between gut microbiota with HPA and HPT axis under acute hypobaric hypoxia challenge.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Gastrointestinal Microbiome; Altitude; RNA, Ribosomal, 16S; Corticotropin-Releasing Hormone; Hypothalamo-Hypophyseal System; Corticosterone; Thyrotropin-Releasing Hormone; Hypoxia; Pituitary-Adrenal System
PubMed: 37286697
DOI: 10.1038/s41598-023-35573-y -
Microbiome May 2021The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function...
BACKGROUND
The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function and underlying mechanism of heparanase in acute pancreatitis remain poorly understood. Here, we investigated the interplay between heparanase and the gut microbiota in the development of acute pancreatitis.
METHODS
Acute pancreatitis was induced in wild-type and heparanase-transgenic mice by administration of caerulein. The differences in gut microbiota were analyzed by 16S ribosomal RNA sequencing. Antibiotic cocktail experiment, fecal microbiota transplantation, and cohousing experiments were used to assess the role of gut microbiota.
RESULTS
As compared with wild-type mice, acute pancreatitis was exacerbated in heparanase-transgenic mice. Moreover, the gut microbiota differed between heparanase-transgenic and wild-type mice. Heparanase exacerbated acute pancreatitis in a gut microbiota-dependent manner. Specially, the commensal Parabacteroides contributed most to distinguish the differences between wild-type and heparanase-transgenic mice. Administration of Parabacteroides alleviated acute pancreatitis in wild-type and heparanase-transgenic mice. In addition, Parabacteroides produced acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.
CONCLUSIONS
The gut-pancreas axis played an important role in the development of acute pancreatitis and the acetate produced by Parabacteroides may be beneficial for acute pancreatitis treatment. Video abstract.
Topics: Acetates; Acute Disease; Animals; Bacteroides; Gastrointestinal Microbiome; Glucuronidase; Mice; Mice, Transgenic; Neutrophil Infiltration; Pancreatitis
PubMed: 34016163
DOI: 10.1186/s40168-021-01065-2 -
Nature Reviews. Microbiology Mar 2024
PubMed: 38279063
DOI: 10.1038/s41579-024-01016-2