RESUMEN
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.
Asunto(s)
Calorimetría , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Microbioma Gastrointestinal/fisiología , ARN Ribosómico 16S/genética , Faecalibacterium prausnitzii/genética , Akkermansia/crecimiento & desarrollo , Akkermansia/fisiología , Consorcios Microbianos/fisiología , Consorcios Microbianos/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Butiratos/metabolismo , Probióticos , Verrucomicrobia/genética , Verrucomicrobia/crecimiento & desarrollo , Bacteroides/genética , Bacteroides/crecimiento & desarrollo , ADN Bacteriano/genéticaRESUMEN
The mucin-degrading gut commensal Akkermansia muciniphila (A. muciniphila) negatively correlates with various diseases, including metabolic disorders, neurodegenerative disorders, and cancers, through interacting with host receptors by diverse molecules. Still, their exact metabolic capability within the nutrient-rich environment (such as in the human gut) is not fully characterized. Therefore, in the present study, we investigated the comprehensive metabolome and lipidome of A. muciniphila after supplementation of four major gut microbial nutrients: mucin, inorganic salts, bile salts, and short-chain fatty acids (SCFAs). Our results showed that mucin is the predominant driver of the different lipidomic and metabolomic profiles of A. muciniphila, and it promotes the overall growth of this bacteria. While the addition of inorganic salts, bile salts, and SCFAs was found to inhibit the growth of A. muciniphila. Interestingly, inorganic salts affected the purine metabolism in A. muciniphila cultures, while adding bile salts significantly increased the production of other bile acids and N-acyl amides. Lastly, SCFAs were identified to alter the A. muciniphila energy utilization of triglycerides, fatty acyls, and phosphatidylethanolamines. To our knowledge, this is the first study to examine the comprehensive lipidome and metabolome of A. muciniphila, which highlights the importance of nutritional impacts on the lipidome and metabolome of A. muciniphila and hence providing foundational knowledge to unveil the potential effects of A. muciniphila on host health.
Asunto(s)
Akkermansia , Ácidos y Sales Biliares , Microbioma Gastrointestinal , Lipidómica , Metabolómica , Probióticos , Akkermansia/metabolismo , Akkermansia/crecimiento & desarrollo , Metabolómica/métodos , Ácidos y Sales Biliares/metabolismo , Lipidómica/métodos , Probióticos/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Cromatografía Liquida/métodos , Metaboloma , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/análisis , Mucinas/metabolismo , Espectrometría de Masas/métodosRESUMEN
Eicosapentaenoic acid (EPA) ethyl esters are of interest given their clinical approval for lowering circulating triglycerides and cardiometabolic disease risk. EPA ethyl esters prevent metabolic complications driven by a high fat diet in male mice; however, their impact on female mice is less studied. Herein, we first investigated how EPA influences the metabolic profile of female C57BL/6J mice consuming a high fat diet. EPA lowered murine fat mass accumulation, potentially through increased biosynthesis of 8-hydroxyeicosapentaenoic acid (HEPE), as revealed by mass spectrometry and cell culture studies. EPA also reversed the effects of a high fat diet on circulating levels of insulin, glucose, and select inflammatory/metabolic markers. Next, we studied if the improved metabolic profile of obese mice consuming EPA was associated with a reduction in the abundance of key gut Gram-negative bacteria that contribute toward impaired glucose metabolism. Using fecal 16S-ribosomal RNA gene sequencing, we found EPA restructured the gut microbiota in a time-dependent manner but did not lower the levels of key Gram-negative bacteria. Interestingly, EPA robustly increased the abundance of the Gram-negative Akkermansia muciniphila, which controls glucose homeostasis. Finally, predictive functional profiling of microbial communities revealed EPA-mediated reversal of high fat diet-associated changes in a wide range of genes related to pathways such as Th-17 cell differentiation and PI3K-Akt signaling. Collectively, these results show that EPA ethyl esters prevent some of the deleterious effects of a high fat diet in female mice, which may be mediated mechanistically through 8-HEPE and the upregulation of intestinal Akkermansia muciniphila.
Asunto(s)
Ácido Eicosapentaenoico/farmacología , Microbioma Gastrointestinal/genética , Ácidos Hidroxieicosatetraenoicos/biosíntesis , Akkermansia/genética , Akkermansia/crecimiento & desarrollo , Animales , Factores de Riesgo Cardiometabólico , Diferenciación Celular/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Ácido Eicosapentaenoico/metabolismo , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Glucosa/metabolismo , Humanos , Ácidos Hidroxieicosatetraenoicos/sangre , Masculino , Espectrometría de Masas , Ratones , Ratones Obesos/genética , Ratones Obesos/microbiología , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Ribosómico 16S/genética , Caracteres Sexuales , Células Th17/metabolismo , Triglicéridos/sangreRESUMEN
Akkermansia muciniphila is a Gram-negative bacterium that resides within the gut mucus layer, and plays an important role in promoting gut barrier integrity, modulating the immune response and inhibiting gut inflammation. Growth stimulation of A. muciniphila by polyphenols including epigallocatechin-3-gallate (EGCG) from difference sources is well-documented. However, no published in vitro culture data on utilization of polyphenols by A. muciniphila are available, and the mechanism of growth-stimulating prebiotic effect of polyphenols on it remains unclear. Here in vitro culture studies have been carried out on the metabolism of EGCG by A. muciniphila in the presence of either mucin or glucose. We found that A. muciniphila did not metabolize EGCG alone but could co-metabolize it together with both these substrates in the presence of mineral salts and amino acids for mucin and protein sources for glucose. Our metabolomic data show that A. muciniphila converts EGCG to gallic acid, epigallocatechin, and (-)-epicatechin through ester hydrolysis. The (-)-epicatechin formed is then further converted to hydroxyhydroquinone. Co-metabolism of A. muciniphila of EGCG together with either mucin or glucose promoted substantially its growth, which serves as a further demonstration of the growth-promoting effect of polyphenols on A. muciniphila and provides an important addition to the currently available proposed mechanisms of polyphenolic prebiotic effects on A. muciniphila.
Asunto(s)
Catequina/análogos & derivados , Glucosa/metabolismo , Metaboloma , Mucinas/metabolismo , Akkermansia/crecimiento & desarrollo , Akkermansia/metabolismo , Catequina/metabolismo , Técnicas In VitroRESUMEN
The total flavone of Abelmoschus manihot (TFA), a compound extracted from the flowers of Abelmoschus manihot (L.) Medic, has been widely used for the treatment of Crohn's disease, chronic glomerulonephritis and other diseases. The aim of this study was to investigate the effect of TFA on the gut microbiota and intestinal barrier in dextran sulfate sodium (DSS)-induced experimental colitis. C57BL/6J mice were treated with 2.5% DSS in drinking water to induce colitis. Mice were orally administered TFA (62.5 mg/kg, 125 mg/kg) or prednisone acetate (PAT, 2.5 mg/kg) once daily for 7 days. Biological samples were collected for analysis of inflammatory cytokines, gut microbiota and intestinal barrier integrity. TFA-H (125 mg/kg) markedly attenuated DSS-induced colon shortening and histological injury in experimental colitis. The therapeutic effect was similar to that of PAT administration. TFA-H notably modulated the dysbiosis of gut microbiota induced by DSS and greatly enriched Akkermansia muciniphila (A. muciniphila). Moreover, TFA-H remarkably ameliorated the colonic inflammatory response and intestinal epithelial barrier dysfunction. Interestingly, TFA directly promotes the growth of A. muciniphila in vitro. Taken together, the results revealed for the first time that TFA, as a prebiotic of A. muciniphila, improved DSS-induced experimental colitis, at least partly by modulating the gut microflora profile to maintain colonic integrity and inhibit the inflammatory response.
Asunto(s)
Abelmoschus/química , Colitis/tratamiento farmacológico , Flavonas/uso terapéutico , Prebióticos , Akkermansia/crecimiento & desarrollo , Animales , Colitis/microbiología , Citocinas/biosíntesis , Flavonas/administración & dosificación , Flavonas/aislamiento & purificación , Microbioma Gastrointestinal , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Prednisona/administración & dosificaciónRESUMEN
Two homogeneous polysaccharides, GEP-3 and GEP-4, were purified from Gastrodia elata, a precious traditional Chinese medicine. Their structural characteristics were obtained using HPGPC, PMP-HPLC, LC/MS, FT-IR, NMR, and SEM methods. GEP-3 was 1,4-glucan with molecular weight of 20 kDa. Interestingly, GEP-4 comprised of a backbone of â[4)-α-Glcp-(1]10â[4)-α-Glcp-(1â]5[6)-ß-Glcp-(1]11â6)-α-Glcp-(3â and two branches of ß-Glcp and p-hydroxybenzyl alcohol citrate, with repeating p-hydroxybenzyl alcohol attached to the backbone chain at O-6 position of â4,6)-α-Glcp-(1â and O-1 position of â3,6)-α-Glcp-(1â. GEP-4 is a novel polysaccharide obtained and characterized for the first time. Bioactivity test indicated that both of them significantly promote the growth of Akkermansia muciniphila (Akk. muciniphila). Furthermore, GEP-3 and GEP-4 promoted the growth of Akk. muciniphila from high-fat diet (HFD) fecal microbiota. These results indicated that GEP-3 and GEP-4 were potential Akk. muciniphila growth promoters.
Asunto(s)
Gastrodia , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Akkermansia/efectos de los fármacos , Akkermansia/crecimiento & desarrollo , Akkermansia/aislamiento & purificación , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Heces/microbiología , Gastrodia/química , Microbioma Gastrointestinal , Ratones , Estructura Molecular , Enfermedad del Hígado Graso no Alcohólico/microbiología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polisacáridos/química , Polisacáridos/aislamiento & purificaciónRESUMEN
BACKGROUND: Akkermansia spp. plays important roles in maintenance of host health. Increasing evidence reveals that berberine (BBR) may exert its pharmacological effects via, at least partially, promotion of Akkermansia spp. However, how BBR stimulates Akkermansia remains largely unknown. PURPOSE: In this study, we investigated the mechanism underlying the Akkermansia-promoting effect of BBR. MATERIALS AND METHODS: The effect of BBR on Akkermansia was assessed in BBR-gavaged mice and direct incubation. The influence of BBR on intestinal mucin production was determined by alcian-blue staining and real-time PCR. The feces were analysis by gas chromatography-time-of-flight mass spectrometry (GC-TOF/MS) metabolomics. The role of polyamines in BBR-elicited mucin secretion and Akkermansia growth was evaluated by administration of difluoromethylornithine (DFMO) in mice. RESULTS: Gavage of BBR dose-dependently and time-dependently increased the abundance of Akkermansia in mice. However, it did not stimulate Akkermansia growth in direct incubation, suggesting that BBR may promote Akkermansia in a host-dependent way. Oral administration of BBR significantly increased the transcription of mucin-producing genes and mucin secretion in colon. Untargeted metabolomics analysis showed that BBR increased polyamines production in feces which are known to stimulate goblet cell proliferation and differentiation, but treatment with eukaryotic polyamine synthase inhibitor DFMO did not abolish the stimulating effect of BBR on mucin secretion and Akkermansia growth, indicating that the gut bacteria-derived but not the host-derived polyamines may involve in the BBR-promoted Akkermansia growth. CONCLUSIONS: Our results reveal that BBR is a promising prebiotic for Akkermansia, and it promotes Akkermansia growth via stimulating mucin secretion in colon.
Asunto(s)
Akkermansia/efectos de los fármacos , Berberina/farmacología , Colon/efectos de los fármacos , Mucinas/metabolismo , Prebióticos , Akkermansia/crecimiento & desarrollo , Animales , Colon/metabolismo , Dieta Alta en Grasa , Heces/química , Heces/microbiología , Microbioma Gastrointestinal/genética , Proteína Jagged-1/genética , Masculino , Metabolómica , Ratones Endogámicos ICR , Poliaminas/metabolismo , ARN Ribosómico 16S , Receptor Notch1/genética , Factor de Transcripción HES-1/genéticaRESUMEN
Obesity, a major healthcare problem worldwide, induces metabolic endotoxemia through the gut translocation of lipopolysaccharides (LPS), a major cell wall component of Gram-negative bacteria, causing a chronic inflammatory state. A combination of several probiotics including Lactobacillus acidophilus 5 (LA5), a potent lactic acid-producing bacterium, has previously been shown to attenuate obesity. However, data on the correlation between a single administration of LA5 versus microbiota alteration might be helpful for the probiotic adjustment. LA5 was administered daily together with a high-fat diet (HFD) for 8 weeks in mice. Furthermore, the condition media of LA5 was also tested in a hepatocyte cell-line (HepG2 cells). Accordingly, LA5 attenuated obesity in mice as demonstrated by weight reduction, regional fat accumulation, lipidemia, liver injury (liver weight, lipid compositions, and liver enzyme), gut permeability defect, endotoxemia, and serum cytokines. Unsurprisingly, LA5 improved these parameters and acidified fecal pH leads to the attenuation of fecal dysbiosis. The fecal microbiome analysis in obese mice with or without LA5 indicated; (i) decreased Bacteroidetes (Gram-negative anaerobes that predominate in non-healthy conditions), (ii) reduced total fecal Gram-negative bacterial burdens (the sources of gut LPS), (iii) enhanced Firmicutes (Gram-positive bacteria with potential benefits) and (iv) increased Verrucomycobia, especially Akkermansia muciniphila, a bacterium with the anti-obesity property. With LA5 administration, A. muciniphila in the colon were more than 2,000 folds higher than the regular diet mice as determined by 16S rRNA. Besides, LA5 produced anti-inflammatory molecules with a similar molecular weight to LPS that reduced cytokine production in LPS-activated HepG2 cells. In conclusion, LA5 attenuated obesity through (i) gut dysbiosis attenuation, partly through the promotion of A. muciniphila (probiotics with the difficulty in preparation processes), (ii) reduced endotoxemia, and (iii) possibly decreased liver injury by producing the anti-inflammatory molecules.
Asunto(s)
Disbiosis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Obesidad/tratamiento farmacológico , Probióticos/farmacología , Akkermansia/efectos de los fármacos , Akkermansia/crecimiento & desarrollo , Animales , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Disbiosis/dietoterapia , Disbiosis/microbiología , Disbiosis/patología , Humanos , Lactobacillus acidophilus/química , Lactobacillus acidophilus/metabolismo , Ratones , Ratones Obesos , Obesidad/etiología , Obesidad/microbiología , Obesidad/patología , Probióticos/química , ARN Ribosómico 16S/genéticaRESUMEN
BACKGROUND: As a kind of potential probiotic, Akkermansia muciniphila abundance in human body is directly causally related to obesity, diabetes, inflammation and abnormal metabolism. In this study, A. muciniphila dynamic cultures using five different media were implemented in an in vitro bionic intestinal reactor for the first time instead of the traditional static culture using brain heart infusion broth (BHI) or BHI + porcine mucin (BPM). RESULTS: The biomass under dynamic culture using BPM reached 1.92 g/L, which improved 44.36% compared with the value under static culture using BPM. The biomass under dynamic culture using human mucin (HM) further increased to the highest level of 2.89 g/L. Under dynamic culture using porcine mucin (PM) and HM, the main metabolites were short-chain fatty acids (acetic acid and butyric acid), while using other media, a considerable amount of branched-chain fatty acids (isobutyric and isovaleric acids) were produced. Under dynamic culture Using HM, the cell diameters reached 999 nm, and the outer membrane protein concentration reached the highest level of 26.26 µg/mg. CONCLUSIONS: This study provided a preliminary theoretical basis for the development of A. muciniphila as the next generation probiotic.
Asunto(s)
Medios de Cultivo/química , Técnicas In Vitro/instrumentación , Mucinas/farmacología , Akkermansia/citología , Akkermansia/crecimiento & desarrollo , Akkermansia/aislamiento & purificación , Akkermansia/metabolismo , Animales , Biomasa , Medios de Cultivo/clasificación , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Técnicas In Vitro/métodos , Probióticos , PorcinosRESUMEN
In recent years, the relationship between type 2 diabetes (T2D) and gut microbiota has attracted much interest. Dendrobium officinale is a valuable traditional Chinese medicine (TCM) with anti-T2D potential, while its action mechanism remains to be further studied. This study was designed to investigate the modulation effects of D. officinale on gut microbiota of T2D model mice to provide clues to its pharmacology by high-throughput sequencing techniques. It was found that D. officinale supplement could significantly reduce the fasting blood glucose levels of T2D mice. Dendrobium officinale supplement could modulate the composition of gut microbiota and increase the relative abundances of key bacterial taxa associated with T2D development, including Akkermansia and Parabacteroides. Compared with placebo group mice, several Kyoto Encyclopedia of Gene and Genomes pathways associated with T2D altered in the D. officinale treated group. These findings indicated the modulation of D. officinale on gut microbiota of T2D mice, which provide potential pharmacological implications.
Asunto(s)
Akkermansia/crecimiento & desarrollo , Bacteroidetes/crecimiento & desarrollo , Dendrobium/química , Diabetes Mellitus Tipo 2/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Preparaciones de Plantas/farmacología , Akkermansia/clasificación , Animales , Bacteroidetes/clasificación , Diabetes Mellitus Tipo 2/patología , Microbioma Gastrointestinal/fisiología , Masculino , Medicina Tradicional China , Ratones , Ratones TransgénicosRESUMEN
The commensal gut bacterium Akkermansia muciniphila is well known as a promising probiotic candidate that improves host health and prevents diseases. However, the biological interaction of A. muciniphila with human gut epithelial cells has rarely been explored for use in biotherapeutics. Here, we developed an in vitro device that simulates the gut epithelium to elucidate the biological effects of living A. muciniphila via multiomics analysis: the Mimetic Intestinal Host-Microbe Interaction Coculture System (MIMICS). We demonstrated that both human intestinal epithelial cells (Caco-2) and the anaerobic bacterium A. muciniphila can remain viable for 12 h after coculture in the MIMICS. The transcriptomic and proteomic changes (cell-cell junctions, immune responses, and mucin secretion) in gut epithelial cells treated with A. muciniphila closely correspond with those reported in previous in vivo studies. In addition, our proteomic and metabolomic results revealed that A. muciniphila activates glucose and lipid metabolism in gut epithelial cells, leading to an increase in ATP production. This study suggests that A. muciniphila improves metabolism for ATP production in gut epithelial cells and that the MIMICS may be an effective general tool for evaluating the effects of anaerobic bacteria on gut epithelial cells.
Asunto(s)
Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Akkermansia/crecimiento & desarrollo , Células CACO-2 , Técnicas de Cocultivo , HumanosRESUMEN
Gut microorganisms are vital for many aspects of human health, and the commensal bacterium Akkermansia muciniphila has repeatedly been identified as a key component of intestinal microbiota. Reductions in A. muciniphila abundance are associated with increased prevalence of metabolic disorders such as obesity and type 2 diabetes. It was recently discovered that administration of A. muciniphila has beneficial effects and that these are not diminished, but rather enhanced after pasteurization. Pasteurized A. muciniphila is proposed for use as a food ingredient, and was therefore subjected to a nonclinical safety assessment, comprising genotoxicity assays (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day toxicity study. For the latter, Han Wistar rats were administered with the vehicle or pasteurized A. muciniphila at doses of 75, 375 or 1500 mg/kg body weight/day (equivalent to 4.8 × 109 , 2.4 × 1010 , or 9.6 × 1010 A. muciniphila cells/kg body weight/day) by oral gavage for 90 consecutive days. The study assessed potential effects on clinical observations (including detailed arena observations and a modified Irwin test), body weight, food and water consumption, clinical pathology, organ weights, and macroscopic and microscopic pathology. The results of both in vitro genotoxicity studies were negative. No test item-related adverse effects were observed in the 90-day study; therefore, 1500 mg/kg body weight/day (the highest dose tested, equivalent to 9.6 × 1010 A. muciniphila cells/kg body weight/day) was established as the no-observed-adverse-effect-level. These results support that pasteurized A. muciniphila is safe for use as a food ingredient.
Asunto(s)
Akkermansia/crecimiento & desarrollo , Akkermansia/efectos de la radiación , Suplementos Dietéticos/toxicidad , Inocuidad de los Alimentos , Microbioma Gastrointestinal/efectos de la radiación , Pasteurización , Animales , Humanos , Masculino , Modelos Animales , Ratas , Ratas WistarRESUMEN
Akkermansia muciniphila, a common colonizer in the intestinal mucus layer of humans, has gradually been considered as promising candidate for the next-generation probiotic, given its physiological benefits from animal and human studies. This article comprehensively reviewed A. muciniphila from the published peer-reviewed articles in the aspects of its role in the host physiology and commonly consumed food that can boost its abundance, which should provide useful and fundamental information for scientists and engineers and even ordinary consumers. Akkermansia muciniphila is not only a crucial biomarker that indicates the physiology of human beings but also has huge potential to become a probiotic given its physiological benefits in various clinical scenarios. Current barriers in terms of regulations, necessity for large-scale clinical experiments and production feasibility need to be resolved before A. muciniphila can be widely applied as the next-generation probiotic.
Asunto(s)
Probióticos/administración & dosificación , Envejecimiento/efectos de los fármacos , Akkermansia/crecimiento & desarrollo , Akkermansia/metabolismo , Animales , Microbioma Gastrointestinal , Humanos , Probióticos/efectos adversosRESUMEN
BACKGROUND: Intestinal microbiota is a novel drug target of metabolic diseases, especially for those with poor oral bioavailability. Nuciferine, with poor bioavailability, has an anti-hyperlipidemic effect at low dosages. PURPOSE: In the present study, we aimed to explore the role of intestinal microbiota in the anti-hyperlipidemic function of nuciferine and identify the key bacterial targets that might confer the therapeutic actions. METHODS: The contribution of gut microbes in the anti-hyperlipidemic effect of nuciferine was evaluated by conventional and antibiotic-established pseudo-sterile mice. Whole-metagenome shotgun sequencing was used to characterize the changes in microbial communities by various agents. RESULTS: Nuciferine exhibited potent anti-hyperlipidemic and liver steatosis-alleviating effects at the doses of 7.5-30 mg/kg. The beneficial effects of nuciferine were substantially abolished when combined with antibiotics. Metagenomic analysis showed that nuciferine significantly shifted the microbial structure, and the enrichment of Akkermansia muciniphila was closely related to the therapeutic effect of nuciferine. CONCLUSIONS: Our results revealed that gut microbiota played an essential role in the anti-hyperlipidemic effect of nuciferine, and enrichment of Akkermansia muciniphila represented a key mechanism through which nuciferine exerted its therapeutic effects.
Asunto(s)
Aporfinas/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/farmacología , Intestinos/microbiología , Lípidos/sangre , Akkermansia/efectos de los fármacos , Akkermansia/genética , Akkermansia/crecimiento & desarrollo , Animales , Antibacterianos/farmacología , Bacteroides/efectos de los fármacos , Bacteroides/genética , Bacteroides/crecimiento & desarrollo , Biomarcadores/sangre , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Hiperlipidemias/sangre , Hiperlipidemias/microbiología , Masculino , Metagenoma , Metagenómica , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/sangre , Obesidad/microbiología , Obesidad/prevención & control , RNA-SeqRESUMEN
The microbiota profile of children changes with age. To investigate the differences in the gut microbiota profile of 1- and 4-year-old children, we collected fecal samples and sequenced the V3-V4 hypervariable region of the 16S rRNA gene via high-throughput DNA sequencing. From phylum to species level, the microbiota underwent significant changes with age. The abundance of phyla Proteobacteria and Actinobacteria declined with age, whereas phyla Firmicutes and Bacteroidetes increased with age and dominated the gut microbiota of 4-year-olds. The intestinal environment of children at age four is closer to maturity. Hence, the abundance of Bifidobacterium significantly decreased in the gut of 4-year-olds, whereas Akkermansia muciniphila increased from 0.14% in 1-year-olds to 4.25% in 4-year-olds. The functional change in gut microbiota is consistent with changes in infant food, as microbiota participating in amino acid and vitamin metabolism were enriched in 1-year-olds, whereas microbiota involved in lipid metabolism increased with age.
Asunto(s)
Bacterias/genética , Heces/microbiología , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Actinobacteria/genética , Actinobacteria/crecimiento & desarrollo , Akkermansia/crecimiento & desarrollo , Pueblo Asiatico , Bacterias/clasificación , Bacterias/crecimiento & desarrollo , Bacteroidetes/genética , Bacteroidetes/crecimiento & desarrollo , Bifidobacterium/genética , Bifidobacterium/crecimiento & desarrollo , Preescolar , China , Firmicutes/genética , Firmicutes/crecimiento & desarrollo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Lactante , Dinámica Poblacional , Proteobacteria/genética , Proteobacteria/crecimiento & desarrollo , ARN Ribosómico 16S/químicaRESUMEN
Akkermansia muciniphila is a well-studied anaerobic bacterium specialized in mucus degradation and associated with human health. Because of the structural resemblance of mucus glycans and free human milk oligosaccharides (HMOs), we studied the ability of A. muciniphila to utilize human milk oligosaccharides. We found that A. muciniphila was able to grow on human milk and degrade HMOs. Analyses of the proteome of A. muciniphila indicated that key-glycan degrading enzymes were expressed when the bacterium was grown on human milk. Our results display the functionality of the key-glycan degrading enzymes (α-L-fucosidases, ß-galactosidases, exo-α-sialidases and ß-acetylhexosaminidases) to degrade the HMO-structures 2'-FL, LNT, lactose, and LNT2. The hydrolysation of the host-derived glycan structures allows A. muciniphila to promote syntrophy with other beneficial bacteria, contributing in that way to a microbial ecological network in the gut. Thus, the capacity of A. muciniphila to utilize human milk will enable its survival in the early life intestine and colonization of the mucosal layer in early life, warranting later life mucosal and metabolic health.
Asunto(s)
Leche Humana/microbiología , Oligosacáridos/metabolismo , Akkermansia/enzimología , Akkermansia/crecimiento & desarrollo , Glicósido Hidrolasas/metabolismo , Humanos , Moco/metabolismoRESUMEN
Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. Huoxue Yiqi Recipe-2 (HYR-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "Synopsis of Prescriptions of the Golden Chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways, which were closely associated with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1). Then, data about NSCLC was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 related signaling pathway). In vivo and in vitro experiments showed that HYR and HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia muciniphila was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia muciniphila.
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Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Medicina Tradicional China , Células A549 , Akkermansia/efectos de los fármacos , Akkermansia/crecimiento & desarrollo , Animales , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular/efectos de los fármacos , Redes Reguladoras de Genes , Células Hep G2 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Células MCF-7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Fenotipo , Mapas de Interacción de Proteínas , Transducción de Señal , Carga Tumoral/efectos de los fármacosRESUMEN
Trillions of microorganisms reside in the hosts' gut. Since diverse activities of gut microbiota affect the hosts' health status, maintenance of gut microbiota is important for maintaining human health. Green tea (GT) has multiple beneficial effects on energy metabolism with antiobesity, antidiabetic, and hypolipidemic properties. As GT contains a large amount of bioactive ingredients (e.g., catechins), which can be metabolized by microorganisms, it would be feasible that consumption of GT may cause compositional changes in gut microbiota, and that the changes in gut microbiota would be associated with the beneficial effects of GT. In this study, we demonstrated that consumption of GT extract relieves high-fat diet-induced metabolic abnormalities. Interestingly, GT administration significantly encouraged the growth of Akkermansia muciniphila (Akkermansia), a beneficial microorganism to relieve obesity and related metabolic disorders. Finally, we found that epigallocatechin gallate is the component of GT that stimulates the growth of Akkermansia. According to these data, we propose that GT could be a prebiotic agent for Akkermansia to treat metabolic syndromes.
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Akkermansia/crecimiento & desarrollo , Catequina/análogos & derivados , Microbioma Gastrointestinal , Té/química , Akkermansia/efectos de los fármacos , Animales , Catequina/farmacología , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
This study aimed to investigate the protective effects of walnut green husk polysaccharide (WGHP) on liver injury, vascular endothelial dysfunction and disorder of gut microbiota in mice induced by high fructose (HF) diet. The chemical analysis results show that the walnut green husk polysaccharide is a low molecular weight acidic heteropolysaccharide, composed mainly of glucuronic acid, arabinose and galactose. Biochemical analysis showed that WGHP significantly improved glucose metabolism and lipid metabolism and decreased oxidative stress in HF-diet induced obesity mice. Histopathological observation of liver and cardiovascular aorta confirmed the protective effects of WGHP on hepatic steatosis and vascular endothelial dysfunction. Furthermore, 16S rRNA sequencing results demonstrated that WGHP reversed the disorders of gut microbiota caused by HF, decreased the relative abundance of Verrucomicrobia and increased the relative abundance of Deferribacteres at the phylum level, decreased the relative abundance of Akkermansia, Lachnoclostridium and norank_f__Muribaculaceae and increased the relative abundance of Prevotellaceae_UCG-001, Helicobacter, Alloprevotella and Allobaculum at the genus levels. Our results indicate that WGHP may act as a functional polysaccharide for protecting liver and cardiovascular in HF-fed mice.
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Endotelio Vascular/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Juglans/química , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Extractos Vegetales/administración & dosificación , Polisacáridos/administración & dosificación , Akkermansia/crecimiento & desarrollo , Akkermansia/aislamiento & purificación , Animales , Arabinosa/análisis , Clostridiales/crecimiento & desarrollo , Clostridiales/aislamiento & purificación , Dieta de Carga de Carbohidratos/efectos adversos , Dieta Alta en Grasa , Carbohidratos de la Dieta/efectos adversos , Endotelio Vascular/patología , Galactosa/análisis , Microbioma Gastrointestinal/genética , Glucosa/metabolismo , Ácido Glucurónico/análisis , Helicobacter/crecimiento & desarrollo , Helicobacter/aislamiento & purificación , Resistencia a la Insulina , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/inducido químicamente , Obesidad/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Polisacáridos/análisis , Polisacáridos/farmacología , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Suero/efectos de los fármacos , Suero/enzimologíaRESUMEN
BACKGROUND: Proton pump inhibitors (PPIs) can alleviate upper gastrointestinal injury but paradoxically exacerbate aspirin (ASA)-induced small intestine injury. In this study, our goal was to simulate this exacerbation by developing an appropriate animal model, which may help in establishing treatments. Methods: Male mice were fed a 60% fructose diet for 9 weeks, then administered 200 mg/kg ASA 3 h before sacrifice. The PPI omeprazole was administered intraperitoneally once daily for 9 weeks. Bifidobacterium bifidum G9-1 was administered orally for the last week. In addition, Akkermansia muciniphila was administered orally for 9 weeks instead of omeprazole. Results: ASA-induced small-intestine injury was observed in high-fructose fed mice. Omeprazole exacerbated ASA-induced intestinal damage, significantly decreased Bifidobacteria levels, and significantly increased A. muciniphila counts in the jejunum. The direct administration of A. muciniphila caused thinning of the jejunum mucus layer, which was also observed in mice that received ASA and omeprazole. On the other hand, the administration of Bifidobacterium bifidum G9-1 inhibited A. muciniphila growth and reduced thinning of the mucus layer. The number of goblet cells in the jejunum was reduced by the administration of ASA and omeprazole, while Bifidobacterium bifidum G9-1 prevented the reduction. Conclusions: These results suggest that omeprazole-induced gut dysbiosis promotes Akkermansia growth and inhibits Bifidobacterium growth, leading to a thinning of the mucus layer through a reduction in goblet cells in the small intestine. Probiotics are, therefore, a promising approach for the treatment of small intestine injury.