RESUMO
BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrinopathy in childbearing-age females which can cause many complications, such as diabetes, obesity, and dyslipidemia. The metabolic disorders in patients with PCOS were linked to gut microbial dysbiosis. However, the correlation between the gut microbial community and dyslipidemia in PCOS remains unillustrated. Our study elucidated the different gut microbiota in patients with PCOS and dyslipidemia (PCOS.D) compared to those with only PCOS and healthy women. RESULTS: In total, 18 patients with PCOS, 16 healthy females, and 18 patients with PCOS.D were enrolled. The 16 S rRNA sequencing in V3-V4 region was utilized for identifying the gut microbiota, which analyzes species annotation, community diversity, and community functions. Our results showed that the ß diversity of gut microbiota did not differ significantly among the three groups. Regarding gut microbiota dysbiosis, patients with PCOS showed a decreased abundance of Proteobacteria, and patients with PCOS.D showed an increased abundance of Bacteroidota compared to other groups. With respect to the gut microbial imbalance at genus level, the PCOS.D group showed a higher abundance of Clostridium_sensu_stricto_1 compared to other two groups. Furthermore, the abundances of Faecalibacterium and Holdemanella were lower in the PCOS.D than those in the PCOS group. Several genera, including Faecalibacterium and Holdemanella, were negatively correlated with the lipid profiles. Pseudomonas was negatively correlated with luteinizing hormone levels. Using PICRUSt analysis, the gut microbiota community functions suggested that certain metabolic pathways (e.g., amino acids, glycolysis, and lipid) were altered in PCOS.D patients as compared to those in PCOS patients. CONCLUSIONS: The gut microbiota characterizations in patients with PCOS.D differ from those in patients with PCOS and controls, and those might also be related to clinical parameters. This may have the potential to become an alternative therapy to regulate the clinical lipid levels of patients with PCOS in the future.
Assuntos
Bactérias , Disbiose , Dislipidemias , Microbioma Gastrointestinal , Síndrome do Ovário Policístico , RNA Ribossômico 16S , Humanos , Síndrome do Ovário Policístico/microbiologia , Feminino , Dislipidemias/microbiologia , Adulto , Disbiose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Adulto Jovem , Fezes/microbiologiaRESUMO
AIMS/INTRODUCTION: Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non-producers and type 2 diabetes. MATERIALS AND METHODS: The participants included 147 patients with type diabetes mellitus aged 70-89 years, and 147 age- and sex-matched controls. To ascertain the equol producers or non-producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut-off value -1.75). RESULTS: The urinary equol concentration was significantly lower in the diabetes group compared with the non-diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non-diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non-diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non-equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r = 0.55, P < 0.01). CONCLUSIONS: Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia.
Assuntos
Diabetes Mellitus Tipo 2 , Equol , Microbioma Gastrointestinal , Glycine max , Isoflavonas , Idoso , Feminino , Humanos , Masculino , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/urina , População do Leste Asiático , Equol/metabolismo , Equol/urina , Isoflavonas/metabolismo , Isoflavonas/urina , Idoso de 80 Anos ou mais , Microbioma Gastrointestinal/fisiologia , Glycine max/metabolismo , Fitoestrógenos/metabolismo , Fatores Sexuais , Pós-Menopausa/metabolismo , Pós-Menopausa/urina , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Dislipidemias/urinaRESUMO
BACKGROUND & AIMS: In our early feeding trial among overweight and obese Chinese women, both low-carbohydrate (LC) and calorie-restricted (CR) diets reduced weight and fat mass, but only the LC diet significantly improved dyslipidemia. We aimed to investigate the impacts of altered gut microbiota, fatty acid (FAs), and acylcarnitines, markers of mitochondrial function on blood lipids. METHODS: Fecal and blood samples from 48 participants at baseline and the end of a 12-week trial were used to perform metagenomics and targeted-metabolomics including erythrocyte FAs and plasma acylcarnitines, respectively. RESULTS: The two diets altered microbial structure and co-abundance gene clusters (CAGs) at different magnitudes. After a 12-week intervention, the Bacteroidetes/Firmicutes ratio increased significantly in the LC diet (P = 0.015) but not in the CR diet, which only showed an increased trend (P = 0.28). At the microbial function level, the LC group showed lower branched-chain amino acid biosynthesis and higher serine biosynthesis than the CR group. Moreover, the LC diet reduced levels of 14:0 and 16:1n-7 FAs in the de novo lipogenesis pathway, but increased 20:5n-3 compared with the CR diet. Both groups had increased plasma acylcarnitines except that the LC group had larger elevated short-chain acylcarnitines. After backward stepwise selection, a cluster of changed CAGs, FAs and acylcarnitines were found to be associated with improved lipid profile. However, changed CAGs showed higher contribution rates in elevating HDL-cholesterol (81.6%) and reducing triglycerides (89.3%) than changed FAs and acylcarnitines. CONCLUSIONS: The two weight-loss diets induced different changes of gut microbiota, plasma acylcarnitines, and erythrocyte FAs. Changes in gut microbiota rather than FA or acylcarnitine profiles showed greater contribution to improved lipid profile in these overweight and obese Chinese women. TRIAL REGISTRATION: The trial was registered at http://clinicaltrials.gov/show/NCT01358890.
Assuntos
Dislipidemias/sangue , Dislipidemias/microbiologia , Ácidos Graxos/sangue , Microbioma Gastrointestinal , Sobrepeso/dietoterapia , Adulto , Restrição Calórica , Carnitina/análogos & derivados , Carnitina/sangue , Dieta com Restrição de Carboidratos , Dieta Redutora , Dislipidemias/etiologia , Eritrócitos/metabolismo , Fezes/microbiologia , Feminino , Humanos , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Resultado do Tratamento , Redução de PesoRESUMO
SCOPE: Obesity is a common disease worldwide and there is an urgent need for strategies to preventing obesity. METHODS AND RESULTS: The anti-obesity effect and mechanism of Ligilactobacillus salivarius LCK11 (LCK11) is studied using a C57BL/6J male mouse model in which obesity is induced by a high-fat diet (HFD). Results show that LCK11 can prevent HFD-induced obesity, reflected as inhibited body weight gain, abdominal and liver fat accumulation and dyslipidemia. Analysis of its mechanism shows that on the one hand, LCK11 can inhibit food intake through significantly improving the transcriptional and translational levels of peptide YY (PYY) in the rectum, in addition to the eventual serum PYY level; this is attributed to the activation of the toll-like receptor 2/nuclear factor-κB signaling pathway in enteroendocrine L cells by the peptidoglycan of LCK11. On the other hand, LCK11 supplementation effectively reduces the Firmicutes/Bacteroidetes ratio and shifts the overall structure of the HFD-disrupted gut microbiota toward that of mice fed on a low-fat diet; this also contributes to preventing obesity. CONCLUSION: LCK11 shows the potential to be used as a novel probiotic for preventing obesity by both promoting PYY secretion to inhibit food intake and regulating gut microbiota.
Assuntos
Microbioma Gastrointestinal/fisiologia , Lactobacillaceae , Obesidade/prevenção & controle , Peptídeo YY/metabolismo , Tecido Adiposo/fisiologia , Animais , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/microbiologia , Dislipidemias/terapia , Ingestão de Alimentos , Células Enteroendócrinas/metabolismo , Intestinos/microbiologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/microbiologia , Probióticos/farmacologia , Aumento de PesoRESUMO
Bile salt hydrolase (BSH)-producing bacteria are negatively related to the body weight gain and energy storage of the host. We aimed to obtain a novel BSH-producing strain with excellent anti-obesity effect and explained its mechanism. Here, we selected a strain named Lactiplantibacillus plantarum H-87 (H-87) with excellent ability to hydrolyze glycochenodeoxycholic acid (GCDCA) and tauroursodeoxycholic acid (TUDCA) in vitro from 12 lactobacilli, and evaluated its anti-obesity effect in high-fat diet (HFD)-fed C57BL/6J mice. The results suggested that H-87 could inhibit HFD-induced body weight gain, fat accumulation, liver lipogenesis and injury, insulin resistance and dyslipidemia. In addition, H-87 could colonize in the ileum and hydrolyze GCDCA and TUDCA, reflected as changes in the concentrations of GCDCA, TUDCA, CDCA and UDCA in the ileum or liver. Furthermore, the study identified that H-87 reduced TUDCA and GCDCA levels in the ileum, which decreased the GLP-1 secretion by L cells to alleviate insulin resistance in HFD-fed mice. Furthermore, H-87 increased the CDCA level in the ileum and liver to activate FXR signaling pathways to inhibit liver lipogenesis in HFD-fed mice. In addition, the decrease of intestinal conjugated bile acids (TUDCA and GCDCA) also increased fecal lipid content and decreased intestinal lipid digestibility. In conclusion, H-87 could inhibit liver fat deposition, insulin resistance and lipid digestion by changing bile acid enterohepatic circulation, and eventually alleviate HFD-induced obesity.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Lactobacillus plantarum/metabolismo , Obesidade/microbiologia , Obesidade/prevenção & controle , Animais , Ácidos e Sais Biliares/metabolismo , Dislipidemias/microbiologia , Dislipidemias/prevenção & controle , Ácido Glicoquenodesoxicólico/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Fígado/metabolismo , Hepatopatias/microbiologia , Hepatopatias/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Ácido Tauroquenodesoxicólico/metabolismoRESUMO
BACKGROUND & AIMS: Although high-fat diet (HFD) could impact the composition of fecal microbiome and their metabolites, it is still largely unknown which fecal bacteria and metabolites are relatively important in responding to the HFD. This study aimed to identify the crucial fecal bacteria and metabolites in the HFD mice using a microbial-metabolite network, and to investigate the synergistic mediation effect of the crucial fecal bacteria and metabolites on serum dyslipidemia induced by the HFD. METHODS: The 16srDNA sequencing and the ultra-performance liquid chromatography (UPLC/TOF MSMS) platform were performed to characterize the composition and function of fecal microbiome, and metabolites in the HFD. The microbial-metabolite network, correlation and mediation analyses were performed to examine the relationships among fecal microbiome, metabolites, and serum dyslipidemia indicators. Mice models were conducted to evaluate the effect of fecal metabolite on dyslipidemia. RESULTS: Compared to the control, 32 genera were altered in the HFD, including 26 up-regulated and 6 down-regulated. A total of 42 altered pathways were observed between the control and HFD, and the "Glycosphingolipid biosynthesis" was identified as the most significant pathway (fold change = 0.64; p < 0.001). Meanwhile, 49 fecal metabolites were altered in the HFD, and the fecal microbiome was associated with the fecal metabolism (M2 = 0.776, p = 0.008). Based on the microbial-metabolite network, two major hub genera were screened (HUB1: g. Streptococcus, HUB2: g. Eubacterium_coprostanoligenes_group), and one bacterial metabolite, sphingosine, was found in this study. Further, the HUB2 was positively associated with fecal sphingosine (r = 0.646, p = 0.001), and its downstream metabolic pathway, "Glycosphingolipid biosynthesis" pathway (r = 0.544, p = 0.009). The regulatory relationship between the HUB2 and sphingosine synergistically mediated the effect of HFD on TCHO (33.7%), HDL-C (37.3%), and bodyweight (36.7%). Besides, compared to the HFD, the HFD with sphingosine supplementation had lower bodyweight (35.12 ± 1.23 vs. 39.42 ± 1.25, p < 0.001), TG (0.44 ± 0.08 vs. 0.52 ± 0.05, p = 0.002), TCHO (3.81 ± 0.34 vs. 4.51 ± 0.38, p = 0.002), and LDL-c (0.82 ± 0.09 vs. 0.97 ± 0.15, p = 0.016). CONCLUSIONS: The g. Streptococcus and g. Eubacterium_coprostanoligenes are two hub genera in the fecal micro-ecosystem of the HFD, and the g. Eubacterium_coprostanoligenes mediates the effect of HFD on dyslipidemia through sphingosine. Sphingosine supplementation can improve dyslipidemia induced by HFD.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Dislipidemias/microbiologia , Eubacterium/metabolismo , Esfingosina/biossíntese , Streptococcus/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/etiologia , Ecossistema , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Camundongos , RNA Ribossômico 16S/análiseRESUMO
AIM: Fermented milk products are suggested as a supplementary therapy to help reduce blood lipid levels. However, the results of clinical studies are conflicting. DATA SYNTHESIS: This study systematically reviewed 39 randomized controlled trials (n = 2237 participants) to investigate the effect of probiotic fermented milk products on blood lipids. A meta-analysis was performed using random effects models, with weighted mean differences (WMDs) and 95% confidence interval (CI). Statistically significant reductions in blood low-density lipoprotein cholesterol (LDL-C) (WMD: -7.34 mg/dL, 95% CI: from -10.04 to -4.65, and P < 0.001) and total cholesterol (TC) concentrations (WMD: -8.30 mg/dL, 95% CI: from -11.42 to -5.18, and P < 0.001) were observed. No statistically significant effect of probiotic fermented milk was observed on blood high-density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG) levels. The effect on TC and LDL-C level was more pronounced in men, and a greater reduction in TAG was observed in trials with longer interventions (≥8 weeks) as compared to their counterparts. CONCLUSIONS: Available evidence suggests that probiotic fermented milk products may help to reduce serum TC and LDL-C cholesterol levels, particularly in men and when they are consumed for ≥8 weeks.
Assuntos
Colesterol/sangue , Produtos Fermentados do Leite/microbiologia , Dislipidemias/dietoterapia , Probióticos/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , LDL-Colesterol/sangue , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Long-time use of pharmacological immunosuppressive agents frequently leads to metabolic disorders. Most studies have focused on islet toxicity leading to posttransplantation diabetes mellitus. In contrast, the link between intestinal dysbiosis and immunosuppressive drug-induced metabolic disorders remains unclear. METHODS: We established a mouse model of metabolic abnormality via sirolimus treatment. Fecal microbiota was examined using 16S rRNA gene MiSeq sequencing. Intestinal barrier function was assessed using fluorescein isothiocyanate-dextran assay and mucus immunostaining. Systemic inflammation was determined using a multiplexed fluorescent bead-based immunoassay. RESULTS: Sirolimus induced dyslipidemia and glucose intolerance in mice in a dose-dependent manner. Interestingly, the clinical-mimicking dose of sirolimus altered the intestinal microbiota community, which was characterized by the enrichment of Proteobacteria, depletion of Akkermansia, and potential function shifts to those involved in lipid metabolism and the immune system. In addition, the clinical-mimicking dose of sirolimus reduced the thickness of the intestinal mucosal layer, increased the intestinal permeability, and enriched the circulating pro-inflammatory factors, including interleukin (IL)-12, IL-6, monocyte chemotactic protein 1, granulocyte-macrophage colony stimulating factor, and IL-1ß. Our results showed a close association between intestinal dysbiosis, intestinal barrier failure, systemic inflammation, and metabolic disorders. Furthermore, we demonstrated that oral intervention in the gut microbiota by Lactobacillus rhamnosus HN001 protected against intestinal dysbiosis, especially by depleting the lipopolysaccharide-producing Proteobacteria, and attenuated the sirolimus-induced systemic inflammation, dyslipidemia, and insulin resistance. CONCLUSIONS: Our study demonstrated a potentially causative role of intestinal dysbiosis in sirolimus-induced metabolic disorders, which will provide a novel therapeutic target for transplant recipients.
Assuntos
Bactérias/metabolismo , Dislipidemias/microbiologia , Microbioma Gastrointestinal , Resistência à Insulina , Mucosa Intestinal/microbiologia , Síndrome Metabólica/microbiologia , Sirolimo , Animais , Bactérias/crescimento & desenvolvimento , Citocinas/metabolismo , Modelos Animais de Doenças , Disbiose , Dislipidemias/induzido quimicamente , Dislipidemias/metabolismo , Dislipidemias/prevenção & controle , Fezes/microbiologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Lacticaseibacillus rhamnosus/crescimento & desenvolvimento , Lacticaseibacillus rhamnosus/metabolismo , Masculino , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Camundongos Endogâmicos C57BL , ProbióticosRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome closely linked to dyslipidemia and gut microbiome dysbiosis. Bilberry anthocyanins (BA) have been reported to have preventive effects against metabolic syndrome. This study aimed to investigate the protective effects and mechanisms of BA in a Western diet (WD)-induced mouse model. The results revealed that supplementation with BA attenuated the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-c), fat content in liver, 2-thiobarbituric acid reactive substances (TBARS) and α-smooth muscle actin (α-SMA) caused by WD. Furthermore, gut microbiota characterized by 16S rRNA sequencing revealed that BA reduced remarkably the ratio of Firmicutes/Bacteroidetes (F/B) and modified gut microbiome. In particular, BA increased the relative abundance of g_Akkermansia and g_Parabacteroides. Taken together, our data demonstrated that BA might ameliorate WD-induced NAFLD by attenuating dyslipidemia and gut microbiome dysbiosis.
Assuntos
Antocianinas/farmacologia , Disbiose/terapia , Dislipidemias/terapia , Microbioma Gastrointestinal/genética , Hepatopatia Gordurosa não Alcoólica/terapia , Vaccinium myrtillus/química , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , LDL-Colesterol/sangue , Dieta Ocidental/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Disbiose/sangue , Disbiose/complicações , Dislipidemias/sangue , Dislipidemias/microbiologia , Fígado/metabolismo , Síndrome Metabólica/microbiologia , Síndrome Metabólica/prevenção & controle , Camundongos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/microbiologia , RNA Ribossômico 16S/metabolismoRESUMO
BACKGROUND AND AIM: Maternal dyslipidemia is recognized as a risk factor for the development of arterial hypertension (AH) and cardiovascular dysfunction in offspring. Here we evaluated the effects of probiotic administration of a specific strain of Lactiplantibacillus plantarum (WJL) during pregnancy and lactation on gut microbiota and metabolic profile in dams fed with a high-fat and high-cholesterol (HFHC) diet and its long-term effects on the cardiovascular function in male rat offspring. METHODS AND RESULTS: Pregnant Wistar rats were allocated into three groups: dams fed a control diet (CTL = 5), dams fed a HFHC diet (DLP = 5) and dams fed a HFHC diet and receiving L. plantarum WJL during pregnancy and lactation (DLP-LpWJL). L. plantarum WJL (1 × 109 CFU) or vehicle (NaCl, 0.9%) was administered daily by oral gavage for 6 weeks, covering the pregnancy and lactation periods. After weaning, male offspring received a standard diet up to 90 days of life. Biochemical measurements and gut microbiota were evaluated in dams. In male offspring, blood pressure (BP), heart rate (HR) and vascular reactivity were evaluated at 90 days of age. Dams fed with a HFHC diet during pregnancy and lactation had increased lipid profile and insulin resistance and showed dysbiotic gut microbiota. Administration of L. plantarum WJL to dams having maternal dyslipidemia improved gut microbiota composition, lipid profile and insulin resistance in them. Blood pressure was augmented and vascular reactivity was impaired with a higher contractile response and a lower response to endothelium-dependent vasorelaxation in DLP male offspring. In contrast, male offspring of DLP-LpWJL dams had reduced blood pressure and recovered vascular function in later life. CONCLUSION: Administration of L. plantarum WJL during pregnancy and lactation in dams improved gut microbiota diversity, reduced maternal dyslipidemia and prevented cardiovascular dysfunction in male rat offspring.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/microbiologia , Complicações na Gravidez/microbiologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Probióticos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Animais , Colesterol na Dieta/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/fisiologia , Resistência à Insulina , Lactação/fisiologia , Lipídeos/sangue , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Ratos , Ratos WistarRESUMO
Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.
Assuntos
Dislipidemias/induzido quimicamente , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/induzido quimicamente , Bifenilos Policlorados/toxicidade , Animais , Biomarcadores/análise , Colo/microbiologia , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Feminino , Conteúdo Gastrointestinal/microbiologia , Microbioma Gastrointestinal/genética , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , RNA Ribossômico 16SRESUMO
Lipocalin 2 (Lcn2) is a multifunctional innate immune protein that limits microbial overgrowth. Our previous study demonstrated that the gut microbiota directly induces intestinal Lcn2 production, and Lcn2-deficient (Lcn2-/-) mice exhibit gut dysbiosis. Coincidentally, gut dysbiosis is associated with metabolic syndrome pathogenesis, and elevated Lcn2 levels has been considered a potential clinical biomarker of metabolic syndrome. Yet whether Lcn2 mitigates or exacerbates metabolic syndrome remains inconclusive. Our objective was to determine whether Lcn2 deficiency-induced compositional changes in gut microbiota contribute to gain in adiposity in aged mice. Utilizing Lcn2-/- mice and their wild-type (WT) littermates, we measured metabolic markers, including fasting blood glucose, serum lipids, fat pad weight, and insulin resistance at ages 3, 6, and 9 mo old. Relative to WT mice, aged Lcn2-/- mice exhibited a gain in adiposity associated with numerous features of metabolic syndrome, including insulin resistance and dyslipidemia. Surprisingly, supplementation with a high-fat diet did not further aggravate metabolic syndrome that spontaneously occurs in Lcn2-/- mice by 6 mo of age. Interestingly, chow-fed Lcn2-/- mice displayed marked differences in the bacterial abundance and metabolomic profile of the gut microbiota compared with WT mice. Overall, our results demonstrate that Lcn2 is essential to maintain metabolic and gut microbiotal homeostasis, where deficiency induces spontaneous delayed onset of metabolic syndrome.
Assuntos
Envelhecimento/metabolismo , Disbiose/complicações , Disbiose/metabolismo , Dislipidemias/complicações , Microbioma Gastrointestinal/genética , Lipocalina-2/deficiência , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Tecido Adiposo , Adiposidade/genética , Animais , Glicemia/análise , Dieta Hiperlipídica , Modelos Animais de Doenças , Disbiose/sangue , Disbiose/microbiologia , Dislipidemias/sangue , Dislipidemias/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Homeostase/genética , Lipocalina-2/genética , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismoRESUMO
The long-chain omega-3 polyunsaturated fatty acids (LC-omega-3 PUFAs) eicosapentaenoic acid and docosahexaenoic acid are the most popular dietary supplements recommended for the prevention/management of lipid dysmetabolisms and related diseases. However, remarkable inconsistencies exist among the outcomes of the human intervention studies in this field, which contrast with the impressive homogeneity of positive results of most of the preclinical studies. In the present review, we will firstly examine a series of factors-such as background diet composition, gut microbiota and genetic/epigenetic variants, which may lie beneath these inconsistencies. Moreover, we will discuss the recent advance in the knowledge of possible specific biomarkers (genetic-, epigenetic- and microbiota-related) that are being investigated with the goal to apply them in a personalized supplementation with omega-3 PUFAs. We will also consider the possibility of using already available parameters (Omega-3 index, Omega-6 PUFA/Omega-3 PUFA ratio) able to predict the individual responsiveness to these fatty acids and will discuss the optimal timing for their use. Finally, we will critically examine the results of those human studies that have already adopted the distinction of the subjects into omega-3 PUFA responders and non-responders and will discuss the advantage of using such an approach.
Assuntos
Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Dislipidemias/prevenção & controle , Ingestão de Alimentos/fisiologia , Ácido Eicosapentaenoico/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Fenômenos Fisiológicos da Nutrição/fisiologia , Dislipidemias/genética , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Epigênese Genética , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Microbioma Gastrointestinal , Humanos , Resultado do TratamentoRESUMO
Endocannabinoids modulate insulin and adipokine expression in adipocytes through cannabinoid receptors and their levels are elevated during hyperglycemia and obesity, but little is known about how diets affect them. We assessed the effects of dietary casein, chicken, beef, and pork proteins in a high-fat diet mode, on endocannabinoids, adipogenesis, and biomarkers associated with dyslipemdia. A high-fat beef or chicken diet upregulated cannabinoid 1 receptor, N-acyl phosphatidylethanolamine-selective phospholipase-D and diacylglycerol lipase α in adipose tissue and reduced the immunoreactivity of mitochondrial uncoupling protein 1 in brown adipose tissue. In addition, the high-fat diets with beef and chicken protein had a significant impact on adipocyte differentiation and mitochondrial biogenesis in obese mice. A 16S rRNA gene sequencing indicated that high-fat diets, regardless of the protein source, significantly enhanced the ratio of Firmicutes to Bacteroidetes in colon. Meat proteins in a high-fat diet significantly decreased the relative abundances of Akkermansia and Bifidobacteria but enhanced the lipopolysaccharides level in the serum, which promoted the adipogenesis process by causing dysregulation in the endocannabinoid receptors. Consumption of meat protein with high-fat-induced adiposity, visceral obesity, and dyslipidemia reduced the thermogenesis and had a distinctive effect on the mitochondrial biogenesis compared with casein protein.
Assuntos
Adipogenia , Tecido Adiposo Marrom/metabolismo , Dislipidemias/metabolismo , Endocanabinoides/metabolismo , Microbioma Gastrointestinal , Proteínas de Carne/análise , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bovinos , Galinhas , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/genética , Dislipidemias/microbiologia , Dislipidemias/fisiopatologia , Humanos , Insulina/metabolismo , Intestinos/microbiologia , Masculino , Proteínas de Carne/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Suínos , Termogênese , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Obesity and diabetes have been increasing at an alarming rate worldwide. Studies have shown the futility of chemical drugs in the treatment of obesity and diabetes. Bifidobacterium longum (BL), a common member of the gut microbiota throughout the human lifespan, has been widely reported to play a role in host health and disease. Here, we evaluated the effects of inactivated cells of BL (IBL) on obesity and blood glucose levels in TSOD mice by administering IBL orally for 5 weeks. The treated mice showed a significant decrease of body weight gain, adipose tissue mass and blood glucose levels, as well as a significant reduction in blood glucose during an oral glucose tolerance test. The treatment also resulted in reduced levels of cholesterol, triglycerides, and NEFA. Moreover, serum and urine analysis showed low creatinine levels in IBL-treated mice. These data demonstrate that IBL may have the potential to prevent obesity and diabetes.
Assuntos
Bifidobacterium longum/metabolismo , Diabetes Mellitus Experimental , Camundongos Obesos , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Colesterol/sangue , Creatinina/sangue , Creatinina/urina , Diabetes Mellitus/prevenção & controle , Dislipidemias/sangue , Dislipidemias/microbiologia , Ácidos Graxos não Esterificados/sangue , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Masculino , Camundongos , Obesidade/prevenção & controle , Triglicerídeos/sangue , Aumento de PesoRESUMO
This study aimed to investigate the beneficial effects of seabuckthorn freeze-dried powder on high-fat diet-induced obesity and related lipid metabolism disorders, and further explored if this improvement is associated with gut microbiota. Results showed that seabuckthorn freeze-dried powder administration decreased body weight, Lee's index, adipose tissue weight, liver weight, and serum lipid levels. Moreover, treatment with seabuckthorn freeze-dried powder effectively reduced fat accumulation by modulating the relative expression of genes involved in lipid metabolism through down-regulation of encoding lipogenic and store genes, including SREBP-1c, PPAR-γ, ACC, and SCD1, and up-regulation of regulating genes of fatty acid oxidation, including HSL, CPT-1, and ACOX. Especially, seabuckthorn freeze-dried powder regulated the composition of gut microbiota, such as increasing the ratio of Firmicutes/Bacteroidetes, decreasing relative abundance of harmful bacteria (Desulfovibrio), and increasing relative abundance of beneficial bacteria (Akkermansia and Bacteroides). The changes of beneficial bacteria had a positive correlation with genes encoding lipolysis and a negative correlation with genes encoding lipid lipogenesis and store. The harmful bacteria were just the opposite. Besides, changes in gut microbiota had an obvious effect in the secretion of main metabolites-short-chain fatty acids (SCFAs), especially propionic acid. Thus, our results indicated that the seabuckthorn freeze-dried powder could ameliorate high-fat diet-induced obesity and obesity-associated lipid metabolism disorders by changing the composition and structure of gut microbiota.
Assuntos
Fármacos Antiobesidade/farmacologia , Dislipidemias/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Hippophae , Hipolipemiantes/farmacologia , Lipídeos/sangue , Obesidade/prevenção & controle , Extratos Vegetais/farmacologia , Aumento de Peso/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Animais , Fármacos Antiobesidade/isolamento & purificação , Biomarcadores/sangue , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/genética , Dislipidemias/microbiologia , Liofilização , Regulação da Expressão Gênica , Hippophae/química , Hipolipemiantes/isolamento & purificação , Masculino , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/genética , Obesidade/microbiologia , Extratos Vegetais/isolamento & purificação , PósRESUMO
BACKGROUND: To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes. OBJECTIVE: The objective of the study was to compare plasma levels of campesterol and ß-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes. METHODS: Serum samples were obtained from adolescent subjects with type 1 diabetes (n = 175, mean age 15.2 years, mean duration of diabetes 8.2 years) and without diabetes (n = 74, mean age 15.4 years). Campesterol, ß-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, compared between groups, and correlated with the available cardiometabolic variables. RESULTS: Campesterol and ß-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure. CONCLUSION: Plasma markers suggest that cholesterol absorption is increased, whereas cholesterol synthesis is decreased in adolescent subjects with type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed.
Assuntos
Doenças Cardiovasculares/metabolismo , Colesterol/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Dislipidemias/microbiologia , Adolescente , Adulto , Antropometria , Biomarcadores/metabolismo , Criança , Feminino , Hemoglobinas Glicadas/genética , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Espectrometria de Massas , Fatores de Risco , Adulto JovemRESUMO
The metabolic syndrome (MetS) is a constellation of risk factors that, if left untreated, will often progress to greater metabolic defects such as type 2 diabetes and nonalcoholic fatty liver disease. While these risk factors have been established for over 40 years, the definition of MetS warrants reconsideration in light of the substantial data that have emerged from studies of the gut microbiome. In this Review we present the existing recent literature that supports the gut microbiome's potential influence on the various risk factors of MetS. The interplay of the intestinal microbiota with host metabolism has been shown to be mediated by a myriad of factors, including a defective gut barrier, bile acid metabolism, antibiotic use, and the pleiotropic effects of microbially produced metabolites. These data show that events that start in the gut, often in response to external cues such as diet and circadian disruption, have far-reaching effects beyond the gut.
Assuntos
Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/etiologia , Animais , Dieta , Dislipidemias/etiologia , Dislipidemias/microbiologia , Transplante de Microbiota Fecal , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Inflamação/etiologia , Inflamação/microbiologia , Resistência à Insulina , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Modelos Biológicos , Obesidade/etiologia , Obesidade/microbiologiaRESUMO
OBJECTIVE: Gut microbiota has a key role in host metabolic regulation and immune response, and its dysbiosis represents one of the main causes of gastrointestinal diseases. In this scenario, Akkermansia muciniphila is a crucial player in keeping the integrity of the gastrointestinal tract. MATERIALS AND METHODS: This review focuses on the correlation between gut microbiota and intestinal homeostasis, primarily exploring A. muciniphila and its involvement in the development of metabolic disorders and gastrointestinal diseases. RESULTS: Akkermansia muciniphila belongs to the Verrucomicrobia phylum, and it colonizes the mucus layer in the gastrointestinal tract, representing 1 to 4% of the fecal microbiota. It stimulates mucosal microbial networks, and it improves intestinal barrier function, providing crucial host immunological responses. Several studies have demonstrated the possible involvement of A. muciniphila in the development of intestinal and metabolic disorders. Indeed, adipose and glucose metabolisms are influenced by A. muciniphila, and its levels inversely correlate to inflammatory conditions, such as inflammatory bowel disease, obesity, and diabetes. Conversely, its therapeutic administration decreases their development. CONCLUSIONS: A. muciniphila exerts a key role in the maintenance of intestinal health and in host metabolic modulation. Future studies could open new horizons towards its potential therapeutic applications in gastrointestinal and extra-intestinal diseases.
Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Disbiose/fisiopatologia , Dislipidemias/microbiologia , Microbioma Gastrointestinal/fisiologia , Doenças Inflamatórias Intestinais/microbiologia , Obesidade/microbiologia , Verrucomicrobia , Akkermansia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Disbiose/metabolismo , Dislipidemias/metabolismo , Gastroenteropatias/metabolismo , Gastroenteropatias/microbiologia , Glucose/metabolismo , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos , Obesidade/metabolismo , PermeabilidadeRESUMO
BACKGROUND AND AIM: High-fat (HF) diet consumption has been associated with gut dysbiosis and increased risk of dyslipidemia, type 2 diabetes mellitus and hypertension. Probiotic administration has been suggested as a safe therapeutic strategy for the treatment of cardiometabolic disorders. This study was designed to assess the effects of probiotic Lactobacillus (L.) fermentum 296, a fruit-derived bacteria strain, against cardiometabolic disorders induced by HF diet. METHODS AND RESULTS: Male Wistar rats were divided into control diet (CTL); HF diet; and HF diet treated with Lactobacillus fermentum 296 (HF + Lf 296). The L. fermentum 296 strain at 1 × 109 colony forming units (CFU)/ml were daily administered by oral gavage for 4 weeks. The results showed that rats fed with HF diet displayed insulin resistance, reduced Lactobacillus spp. counts in feces, serum lipids, and oxidative profile. Rats fed on HF diet also demonstrated augmented blood pressure associated with sympathetic hyperactivity and impaired baroreflex control. The administration of L. fermentum 296 for 4 weeks recovered fecal Lactobacillus sp. counts and alleviated hyperlipidemia, sympathetic hyperactivity, and reduced systolic blood pressure in HF rats without affecting baroreflex sensibility. CONCLUSION: Our results suggest the ability of L. fermentum 296 improve biochemical and cardiovascular parameters altered in cardiometabolic disorders.