RESUMO
The gut microbiota significantly contributes to human health and well-being. The aim of this study was to evaluate the stability and resilience of a consortium composed of three next-generation probiotics (NGPs) candidates originally found in the human gut. The growth patterns of Akkermansia muciniphila, Bacteroides thetaiotaomicron, and Faecalibacterium prausnitzii were studied both individually and consortium. The growth kinetics of Akkermansia muciniphila (A. muciniphila), Bacteroides thetaiotaomicron (B. thetaiotaomicron), and Faecalibacterium prausnitzii (F. prausnitzii) were characterized both individually and in consortium using isothermal microcalorimetry and 16S ribosomal RNA next-generation sequencing. The consortium reached stability after three passages and demonstrated resilience to changes in its initial composition. The concentration of butyrate produced was nearly twice as high in the consortium compared to the monoculture of F. prausnitzii. The experimental conditions and methodologies used in this article are a solid foundation for developing further complex consortia.
Assuntos
Calorimetria , Microbioma Gastrointestinal , RNA Ribossômico 16S , Humanos , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S/genética , Faecalibacterium prausnitzii/genética , Akkermansia/crescimento & desenvolvimento , Akkermansia/fisiologia , Consórcios Microbianos/fisiologia , Consórcios Microbianos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Butiratos/metabolismo , Probióticos , Verrucomicrobia/genética , Verrucomicrobia/crescimento & desenvolvimento , Bacteroides/genética , Bacteroides/crescimento & desenvolvimento , DNA Bacteriano/genéticaRESUMO
Akkermansia muciniphila (A. muciniphila) is a 'star strain' that has attracted much attention in recent years. A. muciniphila can effectively regulate host metabolism, significantly affect host immune function, and play an important role in balancing host health and disease. As one of the organs most closely related to the gut (the two can communicate through the hepatic portal vein and bile duct system), liver is widely affected by intestinal microorganisms. A growing body of evidence suggests that A. muciniphila may alleviate liver-related diseases by improving the intestinal barrier, energy metabolism and regulating inflammation through its protein components and metabolites. This paper systematically reviews the key roles of A. muciniphila and its derivatives in maintaining liver health and improving liver disease.
[Box: see text].
Assuntos
Akkermansia , Microbioma Gastrointestinal , Fígado , Humanos , Akkermansia/fisiologia , Fígado/microbiologia , Fígado/metabolismo , Microbioma Gastrointestinal/fisiologia , Animais , Hepatopatias/microbiologia , Verrucomicrobia/fisiologia , ProbióticosRESUMO
The gut microbiome has been reported to be associated with nighttime light (NTL) exposure and temperament. However, the specific role of infant gut microbiome plays in NTL exposure and temperament is unclear. This study investigated the potential mediating role of infants' gut microbiome in correlations between NTL exposure and temperament. Demographic information, stool samples, and temperament scores were collected from 40 infants. Temperament was evaluated using the Infants Behavior Questionnaire-Revised (IBQ-R). The gut microbiota was analyzed using 16S rRNA sequencing. Cumulative and lagged effects of NTL exposure were calculated based on residential address (NTLpoint) and a concentric 1 km radius buffer zone around the address (NTL1000m), respectively. Mediation models were utilized for assessing the mediating effects of the gut microbiome. The gut microbiome of infants with higher fear scores was characterized by a higher abundance of Akkermansia and Clostridium_sensu_stricto_1 and a lower abundance of Bacteroides. Mediation models indicated Akkermansia played a full mediating role in associations between NTLpoint, NTL1000m and fear in specific time periods. Genus Akkermansia explained 24.46% and 33.50% of associations between fear and cumulative exposure to NTLpoint and NTL1000m, respectively. This study provides evidence for the mediating role of Akkermansia between NTL exposure and fear. However, further experimental is required to elucidate the mechanisms through which the gut microbiome mediates between NTL exposure and temperament in infants.
Assuntos
Akkermansia , Microbioma Gastrointestinal , Temperamento , Humanos , Temperamento/fisiologia , Microbioma Gastrointestinal/fisiologia , Lactente , Feminino , Masculino , Akkermansia/fisiologia , Comportamento do Lactente/fisiologia , Comportamento do Lactente/psicologia , Fezes/microbiologia , Medo/psicologia , Medo/fisiologia , LuzRESUMO
Heat stress (HS) poses a substantial challenge to livestock. Studies have demonstrated that HS reduces fertility and leads to gut microbiota dysbiosis in bulls. However, the impact of the gut microbiota on fertility in bulls during HS is still unclear. Our research revealed that HS exposure decreased semen quality in bulls, and fecal microbiota transplantation (FMT) from heat-stressed bulls to recipient mice resulted in a significant decrease in number of testicular germ cells and epididymal sperm. Untargeted metabolomics methodology and 16S rDNA sequencing conjoint analysis revealed that Akkermansia muciniphila (A. muciniphila) seemed to be a key bacterial regulator of spermatogenesis after HS exposure. Moreover, the research indicated that A. muciniphila regulated secondary bile acid metabolism by promoting the colonization of bile salt hydrolase (BSH)-metabolizing bacteria, leading to increase of retinol absorption in the host gut and subsequently elevation of testicular retinoic acid level, thereby improving spermatogenesis. This study sheds light on the relationship between HS-induced microbiota dysbiosis and spermatogenesis, offering a potential therapeutic approach for addressing bull spermatogenic dysfunction triggered by HS exposure.
Assuntos
Ácidos e Sais Biliares , Disbiose , Microbioma Gastrointestinal , Espermatogênese , Animais , Microbioma Gastrointestinal/fisiologia , Espermatogênese/fisiologia , Masculino , Ácidos e Sais Biliares/metabolismo , Camundongos , Bovinos , Resposta ao Choque Térmico/fisiologia , Akkermansia/fisiologia , Transplante de Microbiota Fecal , Testículo/metabolismoRESUMO
An accumulating body of evidence suggests that the bacterium Akkermansia muciniphila exhibits positive systemic effects on host health, mainly by improving immunological and metabolic functions, and it is therefore regarded as a promising potential probiotic. Recent clinical and preclinical studies have shown that A. muciniphila plays a vital role in a variety of neuropsychiatric disorders by influencing the host brain through the microbiota-gut-brain axis (MGBA). Numerous studies observed that A. muciniphila and its metabolic substances can effectively improve the symptoms of neuropsychiatric disorders by restoring the gut microbiota, reestablishing the integrity of the gut mucosal barrier, regulating host immunity, and modulating gut and neuroinflammation. However, A. muciniphila was also reported to participate in the development of neuropsychiatric disorders by aggravating inflammation and influencing mucus production. Therefore, the exact mechanism of action of A. muciniphila remains much controversial. This review summarizes the proposed roles and mechanisms of A. muciniphila in various neurological and psychiatric disorders such as depression, anxiety, Parkinson's disease, Alzheimer's disease, multiple sclerosis, strokes, and autism spectrum disorders, and provides insights into the potential therapeutic application of A. muciniphila for the treatment of these conditions.
Assuntos
Akkermansia , Transtornos Mentais , Doenças do Sistema Nervoso , Akkermansia/fisiologia , Humanos , Animais , Doenças Neurodegenerativas/microbiologia , Doenças Neurodegenerativas/patologia , Transtornos Mentais/microbiologia , Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Inflamação/patologia , Doenças do Sistema Nervoso/microbiologia , Doenças do Sistema Nervoso/patologiaRESUMO
Acute kidney injury (AKI) is a global public health hazard with high morbidity and mortality. Sepsis accounts for nearly half of all causes of AKI. Scientists have made a great effort to explore effective therapeutic agents with limited side effects in the treatment of AKI, but have had little success. With the development of gut flora study, Akkermansia muciniphila (A. muciniphila) has been proven to prevent different organs by regulating the inflammatory response. However, the reno-protective function is still unknown. Here, the AKI model was induced using lipopolysaccharide (LPS) in mice with or without pretreatment of A. muciniphila. Renal function and histological change were measured. Inflammatory factors were detected by ELISA and rt-PCR. TLR4/NF-κB signaling factors and NLRP3 inflammasome were tested by western blot and immunohistochemistry. Pretreatment of A. muciniphila markedly inhibited inflammatory response and ameliorated kidney histopathological changes. Furthermore, the TLR4, p-NF-κB p65, and downstream IκBα were notably activated in the model group and inhibited by A. muciniphila. A similar effect was found in the regulation of NLRP3 inflammasome. In conclusion, pretreatment with A. muciniphila could protect against LPS-induced AKI by inhibition of the TLR4/NF-κB pathway and NLRP3 inflammasome activation. It may be a new therapeutic strategy for AKI prevention and treatment in the future.
Assuntos
Injúria Renal Aguda , Akkermansia , NF-kappa B , Animais , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Inflamassomos/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptor 4 Toll-Like , Akkermansia/fisiologiaRESUMO
The gut microbiota drives individual sensitivity to excess acetaminophen (APAP)-mediated hepatotoxicity. It has been reported that the bacterium Akkermansia muciniphila protects hosts against liver disease via the liver-gut axis, but its therapeutic potential for drug-induced liver injury remains unclear. In this study, we aimed to investigate the effect of A. muciniphila on APAP-induced liver injury and the underlying mechanism. Administration of A. muciniphila efficiently alleviated APAP-induced hepatotoxicity and reduced the levels of serum alanine aminotransferase (ALT) and aspartate transaminase (AST). A. muciniphila significantly attenuated APAP-induced oxidative stress and the inflammatory response, as evidenced by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, enhanced superoxide dismutase (SOD) activity, reduced proinflammatory cytokine production, and alleviation of macrophage and neutrophil infiltration. Moreover, A. muciniphila maintained gut barrier function, reshaped the perturbed microbial community and promoted short-chain fatty acid (SCFA) secretion. The beneficial effects of A. muciniphila were accompanied by alterations in hepatic gene expression at the transcriptional level and activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results suggested that A. muciniphila could be a potential pretreatment for APAP-induced liver injury. IMPORTANCE Our work revealed that A. muciniphila attenuated APAP-induced liver injury by alleviating oxidative stress and inflammation in the liver, and its hepatoprotective effect was accompanied by activation of the PI3K/Akt pathway and mediated by regulation of the composition and metabolic function of the intestinal microbiota. This finding suggested that the microbial community is a non-negligible impact on drug metabolism and probiotic administration could be a potential therapy for drug-induced liver injury.
Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Akkermansia/fisiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/microbiologia , Ácidos Graxos Voláteis/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Several studies have shown that probiotics have beneficial effects on weight control and metabolic health. In addition to probiotics, recent studies have investigated the effects of paraprobiotics and postbiotics. Therefore, we evaluated the preventive effects of live and pasteurized Akkermansia muciniphila MucT (A. muciniphila) and its extracellular vesicles (EVs) on HFD-induced obesity. RESULTS: The results showed that body weight, metabolic tissues weight, food consumption, and plasma metabolic parameters were increased in the HFD group, whereas A. muciniphila preventive treatments inhibited these HFD. The effects of pasteurized A. muciniphila and its extracellular vesicles were more noticeable than its active form. The HFD led to an increase in the colonic, adipose tissue, and liver inflammations and increased the expression of genes involved in lipid metabolism and homeostasis. Nevertheless, these effects were inhibited in mice that were administered A. muciniphila and its EVs. The assessment of the gut microbiota revealed significant differences in the microbiota composition after feeding with HFD. However, all treatments restored the alterations in some bacterial genera and closely resemble the control group. Also, the correlation analysis indicated that some gut microbiota might be associated with obesity-related indices. CONCLUSIONS: Pasteurized A. muciniphila and its EVs, as paraprobiotic and postbiotic agents, were found to play a key role in the regulation of metabolic functions to prevent obesity, probably by affecting the gut-adipose-liver axis.
Assuntos
Tecido Adiposo/metabolismo , Vesículas Extracelulares , Obesidade/prevenção & controle , Probióticos/administração & dosagem , Akkermansia/citologia , Akkermansia/fisiologia , Animais , Homeostase/genética , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PasteurizaçãoRESUMO
Reduction of A. muciniphila relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized A. muciniphila when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of A. muciniphila administered with respect to a control group. Common responses encompassed modulation of amino acid metabolism, characterized by reduced levels of arginine and alanine, alongside several intermediates of tyrosine, phenylalanine, tryptophan, and glutathione metabolism. The global increase in levels of acylcarnitines together with specific modulation of acetoacetate also suggested induction of ketogenesis through enhanced ß-oxidation. Moreover, our data pinpointed some metabolites of interest considering their emergence as substantial compounds pertaining to health and diseases in the more recent literature.
Assuntos
Síndrome Metabólica/dietoterapia , Metaboloma/efeitos dos fármacos , Probióticos/farmacologia , Adolescente , Adulto , Idoso , Akkermansia/fisiologia , Aminoácidos/metabolismo , Carnitina/análogos & derivados , Carnitina/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Resistência à Insulina , Corpos Cetônicos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Probióticos/administração & dosagem , Adulto JovemRESUMO
In the modern world, metabolic syndrome is one of the major health problems. Heredity, overeating, and a sedentary lifestyle are believed to be the main predisposing factors for its development. However, recent data indicate that gut microbiota plays a significant role in metabolic profile formation. In 2004, Derrien et al. isolated and characterized the bacterium Akkermansia muciniphila, which lives mainly in the human intestine and has the ability to utilize intestinal mucin. It proved to be a good candidate for the role of a new-generation probiotic due to its ability to improve the laboratory and physical indicators associated with metabolic syndrome and type 2 diabetes in mice and humans. In this review, we describe the basic microbiological characteristics of this bacterium, its main habitats, clinical effects after oral administration, and different ways of influencing the digestive tract. All these data allow us to understand the mechanism of its beneficial effects, which is important for its future introduction into the treatment of the metabolic syndrome.
Assuntos
Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Akkermansia/efeitos dos fármacos , Akkermansia/fisiologia , Akkermansia/ultraestrutura , Antibacterianos/farmacologia , Permeabilidade da Membrana Celular , Suscetibilidade a Doenças , Farmacorresistência Bacteriana , Matriz Extracelular , Vesículas Extracelulares/metabolismo , Regulação Bacteriana da Expressão Gênica , Humanos , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Mucinas/metabolismo , Especificidade de Órgãos , Consumo de Oxigênio , Probióticos , SimbioseRESUMO
Alteration in the composition of the gut microbiota can lead to a number of chronic clinical diseases. Akkermansia muciniphila is an anaerobic bacteria constituting 3-5% of the gut microbial community in healthy adults. This bacterium is responsible for degenerating mucin in the gut; its scarcity leads to diverse clinical disorders. In this review, we focus on the role of A. muciniphila in diabetes, obesity and atherosclerosis, as well as the use of this bacterium as a next-generation probiotic. In regard to obesity and diabetes, human and animal trials have shown that A. muciniphila controls the essential regulatory system of glucose and energy metabolism. However, the underlying mechanisms by which A. muciniphila alleviates the complications of obesity, diabetes and atherosclerosis are unclear. At the same time, its abundance suggests improved metabolic disorders, such as metabolic endotoxemia, adiposity insulin resistance and glucose tolerance. The role of A. muciniphila is implicated in declining aortic lesions and atherosclerosis. Well-characterized virulence factors, antigens and cell wall extracts of A. muciniphila may act as effector molecules in these diseases. These molecules may provide novel mechanisms and strategies by which this bacterium could be used as a probiotic for the treatment of obesity, diabetes and atherosclerosis.
Assuntos
Aterosclerose/microbiologia , Diabetes Mellitus/microbiologia , Obesidade/microbiologia , Probióticos , Akkermansia/fisiologia , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Metabolismo Energético , Microbioma Gastrointestinal , Humanos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Probióticos/uso terapêuticoRESUMO
The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, we show that microbiota-derived stimulator of interferon genes (STING) agonists induce type I interferon (IFN-I) production by intratumoral monocytes to regulate macrophage polarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation with a high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved the efficacy of immune checkpoint blockade (ICB). We validated our findings in individuals with melanoma treated with ICB and showed that the predicted intratumoral IFN-I and immune compositional differences between responder and non-responder individuals can be transferred by fecal microbiota transplantation. Our study uncovers a mechanistic link between the microbiota and the innate TME that can be harnessed to improve cancer therapies.
Assuntos
Interferon Tipo I/metabolismo , Proteínas de Membrana/metabolismo , Microbiota , Monócitos/metabolismo , Microambiente Tumoral , Akkermansia/efeitos dos fármacos , Akkermansia/fisiologia , Animais , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Fibras na Dieta/farmacologia , Fosfatos de Dinucleosídeos/administração & dosagem , Fosfatos de Dinucleosídeos/farmacologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunomodulação/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Melanoma/imunologia , Melanoma/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microbiota/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Fagócitos/efeitos dos fármacos , Fagócitos/metabolismo , Transcrição Gênica/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacosRESUMO
The increasing prevalence of metabolic diseases has become a severe public health problem. Gut microbiota play important roles in maintaining human health by modulating the host's metabolism. Recent evidences demonstrate that Akkermansia muciniphila is effective in improving metabolic disorders and is thus considered as a promising "next-generation beneficial microbe". In addition to the live A. muciniphila, similar or even stronger beneficial effects have been observed in pasteurized A. muciniphila and its components, including the outer membrane protein Amuc_1100, A. muciniphila-derived extracellular vesicles (AmEVs), and secreted protein P9. Hence, this paper presents a systemic review of recent progress in the effects and mechanisms of A. muciniphila and its components in the treatment of metabolic diseases, including obesity, type 2 diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease, as well as perspectives on its future study.
Assuntos
Doenças Metabólicas/tratamento farmacológico , Probióticos/administração & dosagem , Akkermansia/fisiologia , Animais , Microbioma Gastrointestinal , Humanos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/microbiologiaRESUMO
Akkermansia muciniphila, as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease. In this study, we aimed to determine the beneficial effects of live and pasteurized A. muciniphila and its extracellular vesicles (EVs) on the prevention of liver fibrosis. The response of hepatic stellate cells (HSCs) to live and pasteurized A. muciniphila and its EVs was examined in quiescent, lipopolysaccharide (LPS)-activated LX-2 cells. Liver fibrosis was induced in 8-week-old C57BL/6 mice, using a high-fat diet (HFD) and carbon tetrachloride (CCl4) administration for 4 weeks. The mice were concomitantly treated via oral gavage with three forms of bacteria. The relative expression of different fibrosis and inflammatory markers was assessed in the tissues. Histological markers, serum biochemical parameters, and cytokine production were also analyzed, and their correlations with the relative abundance of targeted fecal bacteria were examined. All A. muciniphila preparations exhibited protective effects against HSC activation; however, EVs showed the greatest activity in HSC regression. Oral gavage with A. muciniphila ameliorated the serum biochemical and inflammatory cytokines and improved liver and colon histopathological damages. The relative expression of fibrosis and inflammatory biomarkers was substantially attenuated in the tissues of all treated mice. The composition of targeted stool bacteria in the live A. muciniphila group was clearly different from that in the fibrosis group. This study indicated that A. muciniphila and its derivatives could successfully protect against HFD/CCl4-induced liver injury. However, further studies are needed to prove the beneficial effects of A. muciniphila on the liver. IMPORTANCE Akkermansia muciniphila, as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease. In this study, we aimed to determine the beneficial effects of live and pasteurized A. muciniphila and its extracellular vesicles (EVs) on the prevention of liver fibrosis. The results of the present study indicated that oral administration of live and pasteurized A. muciniphila and its EVs could normalize the fecal targeted bacteria composition, improve the intestinal permeability, modulate inflammatory responses, and subsequently prevent liver injury in HFD/CCl4-administered mice. Following the improvement of intestinal and liver histopathology, HFD/CCl4-induced kidney damage and adipose tissue inflammation were also ameliorated by different A. muciniphila treatments.
Assuntos
Cirrose Hepática/prevenção & controle , Probióticos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Akkermansia/química , Akkermansia/fisiologia , Animais , Tetracloreto de Carbono/efeitos adversos , Dieta Hiperlipídica , Vesículas Extracelulares/química , Fezes/microbiologia , Células Estreladas do Fígado , Humanos , Fígado/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Probióticos/química , Substâncias Protetoras/químicaRESUMO
Akkermansia muciniphila is a symbiotic intestinal bacterium with a high medicinal value. Amuc_1100 is the outer membrane protein of A. muciniphila and plays an important role in the interaction between A. muciniphila and its host. The objective of this study was to evaluate the antidepressant activity of Amuc_1100 in a chronic unpredictable mild stress (CUMS) model. Amuc_1100 intervention ameliorated CUMS-induced depression-like behavior and CUMS-induced down-regulation of serotonin (5-hydroxytryptamine, or simply, 5-HT) in the serum and colon of mice. Microbial analysis of mouse feces showed that Amuc_1100 could improve the gut microbiota dysregulation induced by CUMS. In addition, Amuc_1100 intervention could also improve the down-regulation of brain-derived neurotrophic factor (BDNF) and inflammation in the hippocampus induced by CUMS. These results suggest that Amuc_1100 has a good antidepressant effect, and the mechanism may be related to the improvement of gut microbiota, the up-regulation of the BDNF level, and the inhibition of the neuroinflammatory response.
Assuntos
Proteínas de Bactérias/metabolismo , Depressão/microbiologia , Microbioma Gastrointestinal , Camundongos/microbiologia , Akkermansia/fisiologia , Animais , Antidepressivos/metabolismo , Antidepressivos/uso terapêutico , Proteínas de Bactérias/uso terapêutico , Depressão/etiologia , Depressão/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos/metabolismo , Camundongos Endogâmicos C57BL , Estresse Psicológico/complicaçõesRESUMO
In gut, Akkermansia muciniphila (A. muciniphila) probably exerts its probiotic activities by the positive modulation of mucus thickness and gut barrier integrity. However, the potential mechanisms between A. muciniphila and mucin balance have not been fully elucidated. In this study, we cultured the bacterium in a BHI medium containing 0% to 0.5% mucin, and transcriptome and gas chromatography mass spectrometry (GC-MS) analyses were performed. We found that 0.5% (m/v) mucin in a BHI medium induced 1191 microbial genes to be differentially expressed, and 49 metabolites to be changed. The metabolites of sorbose, mannose, 2,7-anhydro-ß-sedoheptulose, fructose, phenylalanine, threonine, lysine, ornithine, asparagine, alanine and glutamic acid were decreased by 0.5% mucin, while the metabolites of leucine, valine and N-acetylneuraminic acid were increased. The association analysis between transcriptome and metabolome revealed that A. muciniphila gave strong responses to energy metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways to adapt to high mucin in the medium. This finding showed that only when mucin reached a certain concentration in a BHI medium, A. muciniphila could respond to the culture environment significantly at the level of genes and metabolites, and changed its metabolic characteristics by altering the effect on carbohydrates and amino acids.
Assuntos
Proteínas de Bactérias/genética , Metabolismo Energético , Homeostase , Metaboloma , Mucinas/metabolismo , Transcriptoma , Akkermansia/genética , Akkermansia/metabolismo , Akkermansia/fisiologia , Regulação Bacteriana da Expressão Gênica , ProbióticosRESUMO
Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host. 5-HT is a neurotransmitter and a key signal molecule regulating the gastrointestinal tract functions and other organs, which is involved in diverse physiological and pathological processes. This study demonstrated that Amuc_1100 could promote the expression of the 5-HT synthesis rate-limiting enzyme Tph1 in RIN-14B cells and reduce the expression of the serotonin reuptake transporter (SERT) in Caco-2 cells through direct interaction with TLR2, thereby improving 5-HT biosynthesis and extracellular availability. Using antibiotic-treated mice as animal models, we found that after gavage with A. muciniphila or Amuc_1100, Tph1 expression increased and SERT expression decreased in colon tissues. The 5-HT concentrations in colon tissues and blood were markedly elevated simultaneously. We also found that A. muciniphila or Amuc_1100 improved the gastrointestinal motility function and restored gut microbiota abundance and species diversity in antibiotic-treated mice. These results suggest that A. muciniphila can regulate the host intestinal 5-HT system via its outer membrane protein Amuc_1100 and TLR2. This mechanism represented an important approach through which A. muciniphila interacts with the host and further influences 5-HT-related physiological functions. These results advance the understanding of interplay mechanisms between the gut microbiota and the host, which could be the basis for new intervention strategies for related diseases.
Assuntos
Akkermansia/fisiologia , Proteínas da Membrana Bacteriana Externa/fisiologia , Microbioma Gastrointestinal/fisiologia , Intestinos/efeitos dos fármacos , Serotonina/biossíntese , Receptor 2 Toll-Like/metabolismo , Animais , Proteínas da Membrana Bacteriana Externa/farmacologia , Células CACO-2 , Linhagem Celular , Células Enterocromafins/efeitos dos fármacos , Células Enterocromafins/metabolismo , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Infants suffer from a severe epileptic encephalopathy known as West syndrome (WS). Treatment with adrenocorticotropic hormone (ACTH) indicates the involvement of the gut-brain axis in WS. Several pieces of evidence show the communication of the gut microbiota (GM) with the brain via the hypothalamic-pituitary-adrenal axis (HPA axis) and blood cytokines. This study aimed at (1) determining the GM diversity in infants having WS and (2) comparing the results of infants having WS with those of the healthy infants and also in the patients with WS before and after the ACTH therapy. RESULTS: In this study, 29 infants with WS and 29 healthy infants aged 3-13 months were recruited. Fecal samples were collected, and DNA was extracted and sequenced on the Illumina MiSeq platform. Kruskal-Wallis rank-sum test was used to analyze the between-group differences in the Chao1 index, Shannon index, and the abundances of GM at different taxonomy levels. R software was used to plot the graphs. The top five dominant GM genera between patients with WS and healthy infants showed no significant differences. However, the relative abundance of genus Akkermansia was observed to be significantly (P = 0.011) higher in the BT group than in the HC group and AT group. After 2 weeks of ACTH therapy, the relative abundance of Akkermansia significantly (P = 0.003) decreased. CONCLUSION: The relative abundance of Akkermansia was observed to be significantly higher in patients with WS than that in healthy infants. However, the relationship between Akkermansia and WS pathogenesis needs to be clarified in further studies.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Hormônio Adrenocorticotrópico/uso terapêutico , Akkermansia/fisiologia , Biodiversidade , Microbioma Gastrointestinal/efeitos dos fármacos , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/microbiologia , Akkermansia/efeitos dos fármacos , Fezes/microbiologia , Humanos , Lactente , Densidade DemográficaRESUMO
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.