RESUMEN
Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.
Asunto(s)
Adhesión Bacteriana , Citrobacter rodentium/fisiología , Infecciones por Enterobacteriaceae/inmunología , Infecciones por Escherichia coli/inmunología , Escherichia coli O157/fisiología , Mucosa Intestinal/inmunología , Células Th17/inmunología , Animales , Infecciones Bacterianas/inmunología , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Células Epiteliales/ultraestructura , Heces/microbiología , Humanos , Inmunoglobulina A/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Microscopía Electrónica de Rastreo , Ratas , Ratas Endogámicas F344 , Especificidad de la EspecieRESUMEN
Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes1,2. Previous metagenomic studies have described the characteristics of gut microbiota and their roles in metabolizing major nutrients in insulin resistance3-9. In particular, carbohydrate metabolism of commensals has been proposed to contribute up to 10% of the host's overall energy extraction10, thereby playing a role in the pathogenesis of obesity and prediabetes3,4,6. Nevertheless, the underlying mechanism remains unclear. Here we investigate this relationship using a comprehensive multi-omics strategy in humans. We combine unbiased faecal metabolomics with metagenomics, host metabolomics and transcriptomics data to profile the involvement of the microbiome in insulin resistance. These data reveal that faecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolisms and host inflammatory cytokines. We identify gut bacteria associated with insulin resistance and insulin sensitivity that show a distinct pattern of carbohydrate metabolism, and demonstrate that insulin-sensitivity-associated bacteria ameliorate host phenotypes of insulin resistance in a mouse model. Our study, which provides a comprehensive view of the host-microorganism relationships in insulin resistance, reveals the impact of carbohydrate metabolism by microbiota, suggesting a potential therapeutic target for ameliorating insulin resistance.
Asunto(s)
Metabolismo de los Hidratos de Carbono , Microbioma Gastrointestinal , Resistencia a la Insulina , Animales , Humanos , Ratones , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal/fisiología , Resistencia a la Insulina/fisiología , Monosacáridos/metabolismo , Insulina/metabolismo , Síndrome Metabólico/metabolismo , Heces/química , Heces/microbiología , MetabolómicaRESUMEN
Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1-3. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells4,5. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.
Asunto(s)
Microbioma Gastrointestinal , Intestino Grueso , Simbiosis , Tripsina , Administración Oral , Animales , Sistemas de Secreción Bacterianos , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Bacteroidetes/aislamiento & purificación , Bacteroidetes/metabolismo , COVID-19/complicaciones , Citrobacter rodentium/inmunología , Diarrea/complicaciones , Heces/microbiología , Microbioma Gastrointestinal/genética , Humanos , Inmunoglobulina A/metabolismo , Intestino Grueso/metabolismo , Intestino Grueso/microbiología , Ratones , Virus de la Hepatitis Murina/metabolismo , Virus de la Hepatitis Murina/patogenicidad , Proteolisis , SARS-CoV-2/patogenicidad , Tripsina/metabolismo , Internalización del VirusRESUMEN
Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases1-3. Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3ß-hydroxysteroid dehydrogenase (3ß-HSDH) were responsible for the production of isoalloLCA. IsoalloLCA exerted potent antimicrobial effects against Gram-positive (but not Gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis.
Asunto(s)
Bacterias/metabolismo , Vías Biosintéticas , Centenarios , Microbioma Gastrointestinal , Ácido Litocólico/análogos & derivados , Ácido Litocólico/biosíntesis , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Anciano de 80 o más Años , Animales , Antibacterianos/biosíntesis , Antibacterianos/metabolismo , Bacterias/clasificación , Bacterias/enzimología , Bacterias/aislamiento & purificación , Colestenona 5 alfa-Reductasa/metabolismo , Heces/química , Heces/microbiología , Femenino , Bacterias Grampositivas/metabolismo , Humanos , Ácido Litocólico/metabolismo , Masculino , Ratones , SimbiosisRESUMEN
Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis1. Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis)2,3, as well as human studies4-6, have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4+ T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease.
Asunto(s)
Encefalomielitis Autoinmune Experimental/microbiología , Microbioma Gastrointestinal/inmunología , Inflamación/patología , Médula Espinal/patología , Linfocitos T/inmunología , Linfocitos T/patología , Animales , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/prevención & control , Femenino , Vida Libre de Gérmenes , Inflamación/inmunología , Intestino Delgado/inmunología , Intestino Delgado/microbiología , Intestino Delgado/patología , Limosilactobacillus reuteri/química , Limosilactobacillus reuteri/inmunología , Limosilactobacillus reuteri/patogenicidad , Masculino , Ratones , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/microbiología , Esclerosis Múltiple/patología , Glicoproteína Mielina-Oligodendrócito/química , Glicoproteína Mielina-Oligodendrócito/inmunología , Médula Espinal/inmunología , Células Th17/inmunología , Células Th17/patologíaRESUMEN
Recent clinical and experimental evidence has evoked the concept of the gut-brain axis to explain mutual interactions between the central nervous system and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel disease and central nervous system disorders1-4. Despite recent advances in our understanding of neuroimmune interactions, it remains unclear how the gut and brain communicate to maintain gut immune homeostasis, including in the induction and maintenance of peripheral regulatory T cells (pTreg cells), and what environmental cues prompt the host to protect itself from development of inflammatory bowel diseases. Here we report a liver-brain-gut neural arc that ensures the proper differentiation and maintenance of pTreg cells in the gut. The hepatic vagal sensory afferent nerves are responsible for indirectly sensing the gut microenvironment and relaying the sensory inputs to the nucleus tractus solitarius of the brainstem, and ultimately to the vagal parasympathetic nerves and enteric neurons. Surgical and chemical perturbation of the vagal sensory afferents at the hepatic afferent level reduced the abundance of colonic pTreg cells; this was attributed to decreased aldehyde dehydrogenase (ALDH) expression and retinoic acid synthesis by intestinal antigen-presenting cells. Activation of muscarinic acetylcholine receptors directly induced ALDH gene expression in both human and mouse colonic antigen-presenting cells, whereas genetic ablation of these receptors abolished the stimulation of antigen-presenting cells in vitro. Disruption of left vagal sensory afferents from the liver to the brainstem in mouse models of colitis reduced the colonic pTreg cell pool, resulting in increased susceptibility to colitis. These results demonstrate that the novel vago-vagal liver-brain-gut reflex arc controls the number of pTreg cells and maintains gut homeostasis. Intervention in this autonomic feedback feedforward system could help in the development of therapeutic strategies to treat or prevent immunological disorders of the gut.
Asunto(s)
Encéfalo/citología , Intestinos/citología , Intestinos/inervación , Hígado/citología , Hígado/inervación , Neuronas/fisiología , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Vías Aferentes , Animales , Células Presentadoras de Antígenos/inmunología , Colitis/inmunología , Colitis/metabolismo , Colitis/patología , Homeostasis , Humanos , Intestinos/inmunología , Masculino , Ratones , Ratas , Receptores Muscarínicos/metabolismo , Bazo/citología , Bazo/inmunología , Nervio Vago/fisiologíaRESUMEN
There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
Asunto(s)
Adenocarcinoma/inmunología , Adenocarcinoma/terapia , Bacterias/clasificación , Linfocitos T CD8-positivos/inmunología , Microbioma Gastrointestinal/inmunología , Listeriosis/prevención & control , Simbiosis/inmunología , Adenocarcinoma/patología , Animales , Antígenos CD/metabolismo , Bacterias/inmunología , Bacterias/aislamiento & purificación , Linfocitos T CD8-positivos/citología , Línea Celular Tumoral , Células Dendríticas/inmunología , Heces/microbiología , Femenino , Voluntarios Sanos , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Cadenas alfa de Integrinas/metabolismo , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Listeria monocytogenes/inmunología , Listeriosis/inmunología , Listeriosis/microbiología , Masculino , Ratones , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationshipãbetween the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples. METHODS: We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC). RESULTS: We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively). CONCLUSIONS: The gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018.
Asunto(s)
Microbioma Gastrointestinal , Sensibilidad Química Múltiple , Humanos , Femenino , Japón , Heces/microbiología , AminoácidosRESUMEN
BACKGROUND: Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. METHODS: We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. RESULTS: During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kUA/L increments, 0.67 and 0.66; 95%CI, 0.41-0.93 and 0.42-0.90; Bifidobacterium-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10-2.03), and these associations were observed until the end of OIT. CONCLUSIONS: In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.
Asunto(s)
Microbioma Gastrointestinal , Hipersensibilidad a la Leche , Niño , Animales , Bovinos , Femenino , Humanos , Lactante , Hipersensibilidad a la Leche/terapia , Caseínas , Estudios de Cohortes , Inmunoglobulina E , Inmunoterapia , LecheRESUMEN
BACKGROUND & AIMS: Medication is a major determinant of human gut microbiome structure, and its overuse increases the risks of morbidity and mortality. However, effects of certain commonly prescribed drugs and multiple medications on the gut microbiome are still underinvestigated. METHODS: We performed shotgun metagenomic analysis of fecal samples from 4198 individuals in the Japanese 4D (Disease, Drug, Diet, Daily life) microbiome project. A total of 759 drugs were profiled, and other metadata, such as anthropometrics, lifestyles, diets, physical activities, and diseases, were prospectively collected. Second fecal samples were collected from 243 individuals to assess the effects of drug initiation and discontinuation on the microbiome. RESULTS: We found that numerous drugs across different treatment categories influence the microbiome; more than 70% of the drugs we profiled had not been examined before. Individuals exposed to multiple drugs, polypharmacy, showed distinct gut microbiome structures harboring significantly more abundant upper gastrointestinal species and several nosocomial pathobionts due to additive drug effects. Polypharmacy was also associated with microbial functions, including the reduction of short-chain fatty acid metabolism and increased bacterial stress responses. Even nonantibiotic drugs were significantly correlated with an increased antimicrobial resistance potential through polypharmacy. Notably, a 2-time points dataset revealed the alteration and recovery of the microbiome in response to drug initiation and cessation, corroborating the observed drug-microbe associations in the cross-sectional cohort. CONCLUSION: Our large-scale metagenomics unravels extensive and disruptive impacts of individual and multiple drug exposures on the human gut microbiome, providing a drug-microbe catalog as a basis for a deeper understanding of the role of the microbiome in drug efficacy and toxicity.
Asunto(s)
Antiinfecciosos , Microbioma Gastrointestinal , Microbiota , Estudios Transversales , Ácidos Grasos Volátiles/farmacología , Heces/microbiología , Microbioma Gastrointestinal/fisiología , Humanos , MetagenómicaRESUMEN
Foxp3(+) T cells play a critical role for the maintenance of immune tolerance. Here we show that in mice, Foxp3(+) T cells contributed to diversification of gut microbiota, particularly of species belonging to Firmicutes. The control of indigenous bacteria by Foxp3(+) T cells involved regulatory functions both outside and inside germinal centers (GCs), consisting of suppression of inflammation and regulation of immunoglobulin A (IgA) selection in Peyer's patches, respectively. Diversified and selected IgAs contributed to maintenance of diversified and balanced microbiota, which in turn facilitated the expansion of Foxp3(+) T cells, induction of GCs, and IgA responses in the gut through a symbiotic regulatory loop. Thus, the adaptive immune system, through cellular and molecular components that are required for immune tolerance and through the diversification as well as selection of antibody repertoire, mediates host-microbial symbiosis by controlling the richness and balance of bacterial communities required for homeostasis.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Inmunoglobulina A/inmunología , Microbiota/inmunología , Inmunidad Adaptativa , Animales , Factores de Transcripción Forkhead/inmunología , Vida Libre de Gérmenes , Centro Germinal/inmunología , Proteínas de Homeodominio/genética , Homeostasis/inmunología , Tolerancia Inmunológica/inmunología , Inflamación/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones SCID/microbiología , Ganglios Linfáticos Agregados/inmunología , Simbiosis/inmunologíaRESUMEN
Multiple sclerosis (MS), an autoimmune disease of the central nervous system, generally starts as the relapsing remitting form (RRMS), but often shifts into secondary progressive MS (SPMS). SPMS represents a more advanced stage of MS, characterized by accumulating disabilities and refractoriness to medications. The aim of this study was to clarify the microbial and functional differences in gut microbiomes of the different stages of MS. Here, we compared gut microbiomes of patients with RRMS, SPMS, and two closely related disorders with healthy controls (HCs) by 16S rRNA gene and whole metagenomic sequencing data from fecal samples and by fecal metabolites. Each patient group had a number of species having significant changes in abundance in comparison with HCs, including short-chain fatty acid (SCFA)-producing bacteria reduced in MS. Changes in some species had close association with clinical severity of the patients. A marked reduction in butyrate and propionate biosynthesis and corresponding metabolic changes were confirmed in RRMS compared with HCs. Although bacterial composition analysis showed limited differences between the patient groups, metagenomic functional data disclosed an increase in microbial genes involved in DNA mismatch repair in SPMS as compared to RRMS. Together with an increased ratio of cysteine persulfide to cysteine in SPMS revealed by sulfur metabolomics, we postulate that excessive DNA oxidation could take place in the gut of SPMS. Thus, gut ecological and functional microenvironments were significantly altered in the different stages of MS. In particular, reduced SCFA biosynthesis in RRMS and elevated oxidative level in SPMS were characteristic.
Asunto(s)
Microbioma Gastrointestinal , Esclerosis Múltiple Crónica Progresiva/microbiología , Esclerosis Múltiple Recurrente-Remitente/microbiología , Adulto , Estudios de Casos y Controles , Cisteína/metabolismo , Ácidos Grasos Volátiles/metabolismo , Heces/microbiología , Femenino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiología , Humanos , Masculino , Metagenoma/genética , Esclerosis Múltiple Crónica Progresiva/epidemiología , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Estrés Oxidativo/fisiología , Azufre/metabolismoRESUMEN
Changes in the gut ecosystem, including the microbiome and the metabolome, and the host immune system after fructo-oligosaccharide (FOS) supplementation were evaluated. The supplementation of FOS showed large inter-individual variability in the absolute numbers of fecal bacteria and an increase in Bifidobacterium. The fecal metabolome analysis revealed individual variability in fructose utilization in response to FOS supplementation. In addition, immunoglobulin A(IgA) tended to increase upon FOS intake, and peripheral blood monocytes significantly decreased upon FOS intake and kept decreasing in the post-FOS phase. Further analysis using a metagenomic approach showed that the differences could be at least in part due to the differences in gene expressions of enzymes that are involved in the fructose metabolism pathway. While the study showed individual differences in the expected health benefits of FOS supplementation, the accumulation of "personalized" knowledge of the gut ecosystem with its genetic expression may enable effective instructions on prebiotic consumption to optimize health benefits for individuals in the future.
Asunto(s)
Microbiota , Oligosacáridos , Fructosa/farmacología , Humanos , Inmunoglobulina A/metabolismo , Oligosacáridos/metabolismo , Oligosacáridos/farmacología , PrebióticosRESUMEN
A novel lactic acid-producing, Gram-stain-positive, catalase-negative and rod-shaped strain, designated as strain C06_No.73T, was isolated from a traditional Japanese fermented beverage called kôso. According to the results of phylogenetic analysis based on 16S rRNA gene sequences, strain C06_No.73T belongs to the genus Lentilactobacillus. The closest type strain was Lentilactobacillus curieae CCTCC M 2011381T, with a sequence identity of 98.1â%. The identity values with other strains were all below 97â%. The isolate propagated under the conditions of 18-39 °C (optimum, 27 °C for 48 h incubation) and pH 4.0-7.0 (optimum, pH 6.5). The G+C content of its genomic DNA was determined to be 37.9âmol%. The main fatty acids were C16â:â0, C18â:â1 ω7c, C18â:â1 ω9c and C19â:â0 cyclopropane 11,12. The major polar lipid was identified as phosphatidylglycerol. No isoprenoid quinone was detected. The predominant cell-wall amino acids were lysine, alanine, glutamic acid and aspartic acid. Neither meso-diaminopimelic acid nor ornithine were detected. On the basis of this polyphasic taxonomic study, the isolate is concluded to represent a novel species, for which the name Lentilactobacillus kosonis sp. nov. is proposed. The type strain is C06_No.73T (=NBRC 111893T=BCRC 81282T).
Asunto(s)
Alimentos Fermentados , Lactobacillaceae/clasificación , Filogenia , Verduras , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Japón , Lactobacillaceae/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfatidilgliceroles/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Gastric microbiome, other than Helicobacter pylori, plays a role in the tumorigenesis of gastric cancer (GC). Patients who undergo endoscopic submucosal dissection for early GC have a high risk of developing metachronous GC even after successful eradication of H. pylori. Thus, we investigated the microbial profiles and associated changes in such patients after the eradication of H. pylori. METHODS: A total of 19 H. pylori-infected patients with early GC who were or to be treated by endoscopic resection, with paired biopsy samples at pre- and post-eradication therapy, were retrospectively enrolled. Ten H. pylori-negative patients were enrolled as controls. Biopsy samples were analyzed using 16S rRNA sequencing. RESULTS: H. pylori-positive patients exhibited low richness and evenness of bacteria with the deletion of several genera, including Blautia, Ralstonia, Faecalibacterium, Methylobacterium, and Megamonas. H. pylori eradication partially restored microbial diversity, as assessed during a median follow-up at 13 months after eradication therapy. However, post-eradication patients had less diversity than that in the controls and possessed a lower abundance of the five genera mentioned above. The eradication of H. pylori also altered the bacterial composition, but not to the same extent as that in controls. The microbial communities could be clustered into three separate groups: H. pylori-negative, pre-eradication, and post-eradication. CONCLUSION: Changes in dysbiosis may persist long after the eradication of H. pylori in patients with a history of GC. Dysbiosis may be involved in the development of both primary and metachronous GC after the eradication of H. pylori in such patients.
Asunto(s)
Disbiosis/patología , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas/cirugía , Anciano , Resección Endoscópica de la Mucosa , Femenino , Microbioma Gastrointestinal , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Chemo-organotrophic iodide (I-)-oxidizing bacterial strains Hi-2T and Mie-1 were isolated from iodide-rich natural gas brine water in Chiba and surface seawater in Mie, Japan, respectively. Cells of strains Hi-2T and Mie-1 were aerobic, Gram-negative and rod-shaped (0.3-0.5 µm width and 1.2-4.4 µm in length). Two isolates grew optimally at 30 °C, pH 7.5 and with 3% NaCl (w/v). Iodide oxidation to form molecular iodine (I2) was a biochemically unique trait for strains Hi-2T and Mie-1. The major cellular fatty acids are C18:1ω7c, C16:1ω5c and C18:1 2-OH. A phylogenetic analysis based on the 16S rRNA gene sequence revealed that strains Hi-2T and Mie-1 were located near Iodidimonas muriae C-3T with 99.2% sequence similarity. The calculated digital DNA-DNA hybridization (dDDH) value of 65.7-65.9% between the two isolates and I. muriae C-3T was lower than the threshold of 70%, which was used for prokaryotic species delineation. Strains Hi-2T and Mie-1 differed in the hydrolysis of aesculin, the hydrolysis of gelatin and the major cellular fatty acids composition from I. muriae C-3T. Considering these biochemical properties, the major cellular fatty acids composition and dDDH value, a novel species is proposed for strains Hi-2T (= JCM 17844T = LMG 28661T) and Mie-1 (= JCM 17845 = LMG 28662), to be named Iodidimonas gelatinilytica.
Asunto(s)
Yoduros , Agua , Alphaproteobacteria , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos , Hibridación de Ácido Nucleico , Oxidación-Reducción , Filogenia , ARN Ribosómico 16S/genética , Sales (Química) , Agua de Mar , Análisis de Secuencia de ADNRESUMEN
Three groups of Gram-stain-negative, obligately anaerobic, rod or coccoid-shaped bacteria, which were phylogenetically assigned in the genus Alistipes belonging to the family Rikenellaceae in the phylum Bacteroidetes, were isolated from the faecal samples of healthy Japanese humans. Group I (strains 5CBH24T and 6CPBBH3) showed highest 16S rRNA gene sequence similarity to 'Alistipes obesi' ph8T (99.73â¯%). Group II (strain 5CPEGH6T) was related to Alistipes shahii WAL 8301T (96.82â¯%). Ten strains of group III (3BBH6T, 5CPYCFAH4, 5NYCFAH2 and others) were related to Alistipes onderdonkii DSM 19147T (98.96â%). Group I could be differentiated from other strains by the ability to hydrolyse aesculin and the lack of catalase activity. Strain 5CPEGH6T could be differentiated from A. shahii JCM 16773T by the inability to hydrolyse aesculin and the lack of catalase activity, and so on. Phenotypic characteristics of group III were similar to those of A. onderdonkii JCM 16771T. Strains 5CBH24T, 6CPBBH3 and 'A. obesi' ph8T shared 98.8-98.9â¯% average nucleotide identity (ANI) with each other. In addition, the in silico DNA-DNA hybridization (DDH) values among three strains were 86.7-89.4â%. Strain 5CPEGH6T showed relatively low values (≤ 84.4â% for ANI ; ≤26.2â% for DDH) with other strains. Three strains in the group III (3BBH6T, 5CPYCFAH4 and 5NYCFAH2) shared 97.9-99.9% ANI with each other. These three strains showed 96.9-97.3â% ANI with A. onderdonkii DSM 19147T. The DDH values of strains 3BBH6T, 5CPYCFAH4 and 5NYCFAH2 among themselves were 80.5-99.8â%, while those compared to A. onderdonkii DSM 19147T were 71.0-73.4â%. On the basis of the collected data, three novel species, Alistipes communis sp. nov. (5CBH24T=JCM 32850T=DSM 108979T), Alistipes dispar sp. nov. (5CPEGH6T=JCM 32848T=DSM 108978T) and Alistipes onderdonkii subsp. vulgaris subsp. nov. (3BBH6T=JCM 32839T=DSM 108977T), are proposed.
Asunto(s)
Bacteroidetes/clasificación , Heces/microbiología , Filogenia , Técnicas de Tipificación Bacteriana , Bacteroidetes/aislamiento & purificación , Composición de Base , ADN Bacteriano/genética , Humanos , Japón , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
The commensal microbiota within the gastrointestinal tract is essential in maintaining homeostasis. Indeed, dysregulation in the repertoire of microbiota can result in the development of intestinal immune-inflammatory diseases. Further, this immune regulation by gut microbiota is important systemically, impacting health and disease of organ systems beyond the local environment of the gut. What has not been explored is how distant organs might in turn shape the microbiota via microbe-targeted molecules. Here, we provide evidence that surfactant protein D (SP-D) synthesized in the gallbladder and delivered into intestinal lumen binds selectively to species of gut commensal bacteria. SP-D-deficient mice manifest intestinal dysbiosis and show a susceptibility to dextran sulfate sodium-induced colitis. Further, fecal transfer from SP-D-deficient mice to wild-type, germ-free mice conveyed colitis susceptibility. Interestingly, colitis caused a notable increase in Sftpd gene expression in the gallbladder, but not in the lung, via the activity of glucocorticoids produced in the liver. These findings describe a unique mechanism of interorgan regulation of intestinal immune homeostasis by SP-D with potential clinical implications such as cholecystectomy.
Asunto(s)
Colitis/metabolismo , Vesícula Biliar/metabolismo , Microbioma Gastrointestinal , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Animales , Colitis/microbiología , Factores de Transcripción Forkhead/metabolismo , Glucocorticoides/biosíntesis , Homeostasis , Mucosa Intestinal/inmunología , Hígado/metabolismo , Ratones Endogámicos C57BL , Simbiosis , Linfocitos T Reguladores/metabolismoRESUMEN
Beetles, representing the majority of the insect species diversity, are characterized by thick and hard cuticle, which plays important roles for their environmental adaptation and underpins their inordinate diversity and prosperity. Here, we report a bacterial endosymbiont extremely specialized for sustaining beetle's cuticle formation. Many weevils are associated with a γ-proteobacterial endosymbiont lineage Nardonella, whose evolutionary origin is estimated as older than 100 million years, but its functional aspect has been elusive. Sequencing of Nardonella genomes from diverse weevils unveiled drastic size reduction to 0.2 Mb, in which minimal complete gene sets for bacterial replication, transcription, and translation were present but almost all of the other metabolic pathway genes were missing. Notably, the only metabolic pathway retained in the Nardonella genomes was the tyrosine synthesis pathway, identifying tyrosine provisioning as Nardonella's sole biological role. Weevils are armored with hard cuticle, tyrosine is the principal precursor for cuticle formation, and experimental suppression of Nardonella resulted in emergence of reddish and soft weevils with low tyrosine titer, confirming the importance of Nardonella-mediated tyrosine production for host's cuticle formation and hardening. Notably, Nardonella's tyrosine synthesis pathway was incomplete, lacking the final step transaminase gene. RNA sequencing identified host's aminotransferase genes up-regulated in the bacteriome. RNA interference targeting the aminotransferase genes induced reddish and soft weevils with low tyrosine titer, verifying host's final step regulation of the tyrosine synthesis pathway. Our finding highlights an impressively intimate and focused aspect of the host-symbiont metabolic integrity via streamlined evolution for a single biological function of ecological relevance.
Asunto(s)
Bacterias/patogenicidad , Genoma Bacteriano , Integumento Común/fisiología , Simbiosis , Transaminasas/metabolismo , Tirosina/metabolismo , Gorgojos/genética , Animales , Fenómenos Fisiológicos Bacterianos , Evolución Molecular , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno , Gorgojos/microbiologíaRESUMEN
The present study aimed to identify and compare the microbial signatures between periodontally healthy and periodontitis subjects using 454 sequences of 16S rRNA genes. Subgingival plaque samples were collected from ten periodontally healthy subjects and ten matched chronic periodontitis patients. Bacterial DNA was extracted and next-generation sequencing of 16S rRNA genes was performed. The microbial composition differed between healthy subjects and periodontitis patients at all phylogenetic levels. Particularly, 16 species, including Lautropia mirabilis and Neisseria subflava predominated in healthy subjects, whereas nine species, including Porphyromonas gingivalis and Filifactor alocis predominated in periodontitis. UniFrac, a principal coordinate and network analysis, confirmed distinct community profiles in healthy subjects and periodontitis patients. Using predicted function profiling, pathways involved in phenylpropanoid, GPI-anchor biosynthesis, and metabolism of alanine, arginine, aspartate, butanoate, cyanoamino acid, fatty acid, glutamate, methane, proline, and vitamin B6 were significantly over-represented in periodontitis patients. These results highlight the oral microbiota alterations in microbial composition in periodontitis and suggest the genes and metabolic pathways associated with health and periodontitis. Our findings help to further elucidate microbial composition and interactions in health and periodontitis.