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Cell Host & Microbe Mar 2023The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune...
The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune surveillance remains poorly understood. Here, we analyzed the intratissue bacteria from CRC patient colon tissues. We found that the commensal bacteria belonging to the Lachnospiraceae family, including Ruminococcus gnavus (Rg), Blautia producta (Bp), and Dorea formicigenerans (Df), were enriched in normal tissues, while Fusobacterium nucleatum (Fn) and Peptostreptococcus anaerobius (Pa) were abundant in tumor tissues. Tissue-resident Rg and Bp reduced colon tumor growth and promoted the activation of CD8 T cells in immunocompetent mice. Mechanistically, intratissue Rg and Bp degraded lyso-glycerophospholipids that inhibited CD8 T cell activity and maintained the immune surveillance function of CD8 T cells. Lyso-glycerophospholipids alone promoted tumor growth that was abrogated with Rg and Bp injection. Collectively, intratissue Lachnospiraceae family bacteria facilitate the immune surveillance function of CD8 T cells and control colorectal cancer progression.
Topics: Animals; Mice; Colorectal Neoplasms; CD8-Positive T-Lymphocytes; Carcinogenesis; Colonic Neoplasms; Fusobacterium nucleatum
PubMed: 36893736
DOI: 10.1016/j.chom.2023.01.013 -
Probiotics and Antimicrobial Proteins Jun 2023Blautia is a genus of anaerobic microbe extensively present in the intestine and feces of mammals. This study aims to investigate the influence of Blautia producta to...
Blautia is a genus of anaerobic microbe extensively present in the intestine and feces of mammals. This study aims to investigate the influence of Blautia producta to prevent lipopolysaccharide (LPS)-induced acute liver injury (ALI) and elaborate on its hepatoprotective mechanisms. B. producta D4 and DSM2950 pretreatment decreased the activities of serum aspartate transferase (AST), and alanine transaminase (ALT) in mice with LPS treatment significantly decreased the levels of inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and increased the activities of antioxidative superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Compared with the model group, B. producta D4 and B. producta DSM2950 pretreatment slightly increased the levels of cecal propionic acid, isobutyric acid, butyric acid, valeric acid, and isovaleric acid (p > 0.05). Metagenomic analysis showed that B. producta D4 and DSM2950 pretreatment remarkably increased the relative abundance of [Eubacterium] xylanophilum group, Lachnospira, Ruminiclostridium, Ruminiclostridium 9, Coprococcus 2, Odoribacter, Roseburia, Alistipes, and Desulfovibrio in ALI mice, and their abundance is negatively related to the levels of inflammatory TNF-α, IL-1β, and IL-6 as revealed by Spearman's correlation analysis. Moreover, transcription and immunohistochemistry analysis revealed that B. producta D4 and B. producta DSM2950 intervention remarkably suppressed the transcription and expression levels of hepatic Tlr4, MyD88, and caspase-3 (p < 0.05). These data indicated that B. producta may be a good candidate for probiotics in the prevention of ALI.
Topics: Mice; Animals; Lipopolysaccharides; Interleukin-6; Tumor Necrosis Factor-alpha; Chemical and Drug Induced Liver Injury; Probiotics; Mammals
PubMed: 36790661
DOI: 10.1007/s12602-023-10044-y -
Biomedicine & Pharmacotherapy =... Nov 2022Berberine (BBR) is an effective cholesterol-lowering drug. Although gut microbiota has been implicated in the pharmacological activities of BBR, little evidence exists...
Berberine (BBR) is an effective cholesterol-lowering drug. Although gut microbiota has been implicated in the pharmacological activities of BBR, little evidence exists on the specific species of gut microbiota involved in its therapeutic effects, nor on linking gut bacteria to its recognized hypercholesterolemia-alleviating mechanism-upregulation of the low-density lipoprotein receptor (LDLR) in the liver. The present study was performed to identify the specific species of gut microbiota involved in the anti-hyperlipdemic effect of BBR, and interpret its mechanism through linking the gut microbiota and LDLR. The BBR-enriched gut bacterial species were identified by whole genome shotgun sequencing. Pure cultured B. producta was orally administered to C57BL/6 mice to evaluate its anti-hyperlipdemic effect. The LDLR-upregulating effect of B. producta was evaluated both in vitro and in vivo. Orally administration of BBR (200 mg/kg) decreased serum and liver lipid levels in HFD-induced hyperlipidemic mice. Microbiome analysis indicated that Blautia was closely associated with BBR's lipid-modulating activities. Further analysis revealed that BBR selectively promoted the growth of Blautia producta. Orally treatment of HFD mice with live B. producta reduced obesity and alleviated hyperlipidemia. Notably, the B. producta significantly increased LDLR expression in the liver, and its spent culture supernatant upregulated the LDLR level and promoted LDL uptake by HepG2 cells. Simultaneously, B. producta also linked butyrate-producing and bile salt hydrolase (BSH)-inhibiting effect of BBR. The gut microbiota, especially B. producta, may confers the hypercholesterolemia-alleviating effects of berberine. B. producta represents a novel probiotic that may be used for the treatment of dyslipidemia.
Topics: Mice; Animals; Diet, High-Fat; Berberine; Hyperlipidemias; Hypercholesterolemia; Mice, Inbred C57BL; Liver; Bacteria; Butyrates; Cholesterol; Lipoproteins, LDL
PubMed: 36174380
DOI: 10.1016/j.biopha.2022.113749 -
Brain, Behavior, and Immunity Mar 2024Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study...
Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.
Topics: Humans; Animals; Mice; Microglia; Neuroinflammatory Diseases; NF-kappa B; Parkinson Disease; Microbiota; Butyrates; Clostridiales
PubMed: 38211635
DOI: 10.1016/j.bbi.2024.01.010 -
Gut Microbes 2023Compelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g.,...
Compelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g., hyperlipidemia). However, the regulatory profile of individual bacterial species and strain on lipid homeostasis remains largely unknown. Herein, we performed a large-scale screening of 2250 human gut bacterial strains (186 species) for the lipid-decreasing activity. Different strains in the same species usually displayed distinct lipid-modulatory actions, showing evident strain-specificity. Among the tested strains, exhibited the most potency to suppress cellular lipid accumulation and effectively ameliorated hyperlipidemia in high fat diet (HFD)-feeding mice. Taking a joint comparative approach of pharmacology, genomics and metabolomics, we identified an anteiso-fatty acid, 12-methylmyristic acid (12-MMA), as the key active metabolite of . experiment confirmed that 12-MMA could exert potent hyperlipidemia-ameliorating efficacy and improve glucose metabolism via activating G protein-coupled receptor 120 (GPR120). Altogether, our work reveals a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, emphasizes the strain-specific function of gut bacteria, and provides a possibility to develop microbial therapeutics against hyperlipidemia based on and its metabolite.
Topics: Humans; Animals; Mice; Gastrointestinal Microbiome; Fatty Acids; Hyperlipidemias; Probiotics; Ruminococcus; Diet, High-Fat
PubMed: 37408362
DOI: 10.1080/19490976.2023.2228045 -
Microbiology Resource Announcements Apr 2020We report a complete genome sequence of JCM 1471 The genome consists of a single circular chromosome of 6,197,116 bp with a G+C content of 45.7%. The genome was...
We report a complete genome sequence of JCM 1471 The genome consists of a single circular chromosome of 6,197,116 bp with a G+C content of 45.7%. The genome was annotated as containing 5 complete sets of rRNA genes, 70 tRNA genes, and 5,516 protein-coding sequences.
PubMed: 32327523
DOI: 10.1128/MRA.00141-20 -
The Journal of Biological Chemistry Jun 2023The β-glucans are structurally varied, naturally occurring components of the cell walls, and storage materials of a variety of plant and microbial species. In the human...
The β-glucans are structurally varied, naturally occurring components of the cell walls, and storage materials of a variety of plant and microbial species. In the human diet, mixed-linkage glucans [MLG - β-(1,3/4)-glucans] influence the gut microbiome and the host immune system. Although consumed daily, the molecular mechanism by which human gut Gram-positive bacteria utilize MLG largely remains unknown. In this study, we used Blautia producta ATCC 27340 as a model organism to develop an understanding of MLG utilization. B. producta encodes a gene locus comprising a multi-modular cell-anchored endo-glucanase (BpGH16), an ABC transporter, and a glycoside phosphorylase (BpGH94) for utilizing MLG, as evidenced by the upregulation of expression of the enzyme- and solute binding protein (SBP)-encoding genes in this cluster when the organism is grown on MLG. We determined that recombinant BpGH16 cleaved various types of β-glucan, generating oligosaccharides suitable for cellular uptake by B. producta. Cytoplasmic digestion of these oligosaccharides is then performed by recombinant BpGH94 and β-glucosidases (BpGH3-AR8 and BpGH3-X62). Using targeted deletion, we demonstrated BpSBP is essential for B. producta growth on barley β-glucan. Furthermore, we revealed that beneficial bacteria, such as Roseburia faecis JCM 17581, Bifidobacterium pseudocatenulatum JCM 1200T, Bifidobacterium adolescentis JCM 1275T, and Bifidobacterium bifidum JCM 1254, can also utilize oligosaccharides resulting from the action of BpGH16. Disentangling the β-glucan utilizing the capability of B. producta provides a rational basis on which to consider the probiotic potential of this class of organism.
Topics: Humans; beta-Glucans; Diet; Oligosaccharides; Dietary Carbohydrates; Hordeum; Probiotics; Clostridiales; Bifidobacterium; Gastrointestinal Microbiome
PubMed: 37172725
DOI: 10.1016/j.jbc.2023.104806 -
Microorganisms Apr 2021In recent years, has attracted attention for its role in ameliorating host diseases. In particular, DSM 2950 has been considered a potential probiotic due to its...
In recent years, has attracted attention for its role in ameliorating host diseases. In particular, DSM 2950 has been considered a potential probiotic due to its ability to mitigate inflammation in poly(I:C) induced HT-29 cells. Thus, to promote the development of indigenous intestinal microorganisms with potential probiotic function, we conducted a comprehensive experimental analysis of DSM 2950 to determine its safety. This comprised a study of its potential virulence genes, antibiotic resistance genes, genomic islands, antibiotic resistance, and hemolytic activity and a 14-day test of its acute oral toxicity in mice. The results indicated no toxin-related virulence genes in the DSM 2950 genome. Most of the genomic islands in DSM 2950 were related to metabolism, rather than virulence expression. DSM 2950 was sensitive to most of the tested antibiotics but was tolerant of treatment with kanamycin, neomycin, clindamycin, or ciprofloxacin, probably because it possessed the corresponding antibiotic resistance genes. Oral acute toxicity tests indicated that the consumption of DSM 2950 does not cause toxic side effects in mice. Overall, the safety profile of DSM 2950 confirmed that it could be a candidate probiotic for use in food and pharmaceutical preparations.
PubMed: 33922843
DOI: 10.3390/microorganisms9050908 -
Nature Communications Jan 2023The interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis....
The interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. However, the specific microbial and metabolic mediators contributing to non-alcoholic steatohepatitis remain to be identified. Here, a choline-low high-fat and high-sugar diet, representing a typical western diet, named CL-HFS, successfully induces male mouse non-alcoholic steatohepatitis with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis. Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced non-alcoholic steatohepatitis. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice. Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation. These findings advance our understanding of non-alcoholic steatohepatitis pathogenesis and provide targets for developing microbiome/metabolite-based therapeutic strategies against non-alcoholic steatohepatitis.
Topics: Animals; Male; Mice; Diet, High-Fat; Diet, Western; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Liver; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Receptors, G-Protein-Coupled
PubMed: 36646715
DOI: 10.1038/s41467-023-35861-1 -
International Journal of Systematic and... Nov 2023Two Gram-positive, anaerobic, non-spore-forming and coccoid or oval-shaped bacterial strains, namely, DN0138 and DN0266, were isolated from faecal samples of healthy...
Two Gram-positive, anaerobic, non-spore-forming and coccoid or oval-shaped bacterial strains, namely, DN0138 and DN0266, were isolated from faecal samples of healthy Japanese people. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DN0138 clustered with a species of the genus and was closely related to JCM 1471, JCM 1395, KB1 and '' Marseille-P2377, with sequence similarities of 98.6, 98.5, 98.8 and 98.2 %, respectively. The average nucleotide identity values were 85.3 % for JCM 1471, 85.0 % for NCTC 11035, 84.3 % for KB1 and 84.3 % for '' Marseille-P2377. The major end products of glucose metabolism were acetic acid, lactic acid and succinic acid. The genome length of strain DN0138 was 6 247 046 bp with 46.7 mol% G+C content of genome sequence. Based on their phenotypic, cellular fatty acid and phylogenetic characteristics, the three isolates represent a novel species within the genus , for which the name sp. nov. is proposed. The type strain is DN0138 (=NBRC 113351=BCRC 81349).
Topics: Humans; Bacterial Typing Techniques; Base Composition; DNA, Bacterial; East Asian People; Fatty Acids; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Clostridiales; Feces
PubMed: 37971477
DOI: 10.1099/ijsem.0.005871