RESUMO
BACKGROUND: Metabolic syndrome (MetS) is highly prevalent in individuals with schizophrenia (SZ), leading to negative consequences like premature mortality. Gut dysbiosis, which refers to an imbalance of the microbiota, and chronic inflammation are associated with both SZ and MetS. However, the relationship between gut dysbiosis, host immunological dysfunction, and SZ comorbid with MetS (SZ-MetS) remains unclear. This study aims to explore alterations in gut microbiota and their correlation with immune dysfunction in SZ-MetS, offering new insights into its pathogenesis. METHODS AND RESULTS: We enrolled 114 Chinese patients with SZ-MetS and 111 age-matched healthy controls from Zhejiang, China, to investigate fecal microbiota using Illumina MiSeq sequencing targeting 16 S rRNA gene V3-V4 hypervariable regions. Host immune responses were assessed using the Bio-Plex Pro Human Cytokine 27-Plex Assay to examine cytokine profiles. In SZ-MetS, we observed decreased bacterial α-diversity and significant differences in ß-diversity. LEfSe analysis identified enriched acetate-producing genera (Megamonas and Lactobacillus), and decreased butyrate-producing bacteria (Subdoligranulum, and Faecalibacterium) in SZ-MetS. These altered genera correlated with body mass index, the severity of symptoms (as measured by the Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms), and triglyceride levels. Altered bacterial metabolic pathways related to lipopolysaccharide biosynthesis, lipid metabolism, and various amino acid metabolism were also found. Additionally, SZ-MetS exhibited immunological dysfunction with increased pro-inflammatory cytokines, which correlated with the differential genera. CONCLUSION: These findings suggested that gut microbiota dysbiosis and immune dysfunction play a vital role in SZ-MetS development, highlighting potential therapeutic approaches targeting the gut microbiota. While these therapies show promise, further mechanistic studies are needed to fully understand their efficacy and safety before clinical implementation.
Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Esquizofrenia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , China , Comorbidade , Citocinas/metabolismo , Disbiose/microbiologia , Disbiose/imunologia , Disbiose/complicações , População do Leste Asiático , Fezes/microbiologia , Imunidade , Síndrome Metabólica/microbiologia , Síndrome Metabólica/imunologia , Síndrome Metabólica/complicações , Esquizofrenia/microbiologia , Esquizofrenia/imunologia , Esquizofrenia/complicaçõesRESUMO
The Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads, with differing fermentation times but similar nutritional profiles, on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. In a double-blind clinical trial, participants were randomized to consume either Elias Boulanger® long-fermentation (48 h) sourdough bread (EBLong) or Elias Boulanger® short-fermentation (2 h) sourdough bread (EBShort) over a two-month period. We assessed clinical parameters, inflammatory biomarkers, satiety-related hormones, and the richness and abundance of gut microbiota at baseline and follow-up. The participants included 31 individuals (mean age, 67, 51.6% female). EBShort was associated with reduced levels of soluble intercellular adhesion molecule (sICAM), and all participants, regardless of the intervention, exhibited a decrease in sICAM and diastolic pressure from baseline (p < 0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. No differences in microbiota richness or abundance were observed. EBShort bread was effective in reducing some inflammation markers. The consumption of sourdough bread may offer potential benefits in reducing inflammation markers in individuals with metabolic syndrome; however, longer fermentation times did not show additional benefits.
Assuntos
Pão , Dieta Mediterrânea , Fermentação , Microbioma Gastrointestinal , Síndrome Metabólica , Humanos , Síndrome Metabólica/dietoterapia , Síndrome Metabólica/microbiologia , Síndrome Metabólica/terapia , Feminino , Masculino , Método Duplo-Cego , Pessoa de Meia-Idade , Idoso , Biomarcadores/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Fatores de Tempo , Molécula 1 de Adesão Intercelular/sangue , InflamaçãoRESUMO
In recent years, the incidence of metabolic syndrome (MS) has increased due to lifestyle-related factors in developed countries. MS represents a group of conditions that increase the risk of diabetes, cardiovascular diseases, and other severe health problems. Low-grade chronic inflammation is now considered one of the key aspects of MS and could be defined as a new cardiovascular risk factor. Indeed, an increase in visceral adipose tissue, typical of obesity, contributes to the development of an inflammatory state, which, in turn, induces the production of several proinflammatory cytokines responsible for insulin resistance. Psoriasis is a chronic relapsing inflammatory skin disease and is characterized by the increased release of pro-inflammatory cytokines, which can contribute to different pathological conditions within the spectrum of MS. A link between metabolic disorders and Psoriasis has emerged from evidence indicating that weight loss obtained through healthy diets and exercise was able to improve the clinical course and therapeutic response of Psoriasis in patients with obesity or overweight patients and even prevent its occurrence. A key factor in this balance is the gut microbiota; it is an extremely dynamic system, and this makes its manipulation through diet possible via probiotic, prebiotic, and symbiotic compounds. Given this, the gut microbiota represents an additional therapeutic target that can improve metabolism in different clinical conditions.
Assuntos
Microbioma Gastrointestinal , Inflamação , Síndrome Metabólica , Psoríase , Psoríase/microbiologia , Psoríase/metabolismo , Psoríase/complicações , Humanos , Síndrome Metabólica/microbiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/complicações , Inflamação/metabolismo , Animais , Obesidade/complicações , Obesidade/microbiologia , Obesidade/metabolismoRESUMO
Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.
Assuntos
Tecido Adiposo Marrom , Ácidos e Sais Biliares , Metabolismo Energético , Microbioma Gastrointestinal , Síndrome Metabólica , Camundongos Endogâmicos C57BL , Quercetina , Termogênese , Quercetina/farmacologia , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Metabolismo Energético/efeitos dos fármacos , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Síndrome Metabólica/tratamento farmacológico , Masculino , Ácidos e Sais Biliares/metabolismo , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Modelos Animais de Doenças , Transplante de Microbiota FecalRESUMO
Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.
Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Síndrome Metabólica , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Metabólica/terapia , Síndrome Metabólica/microbiologia , Feminino , Fezes/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/genética , Adulto , Pressão Sanguínea , Resultado do TratamentoRESUMO
Obesity is a global health concern implicated in numerous chronic degenerative diseases, including type 2 diabetes, dyslipidemia, and neurodegenerative disorders. It is characterized by chronic low-grade inflammation, gut microbiota dysbiosis, insulin resistance, glucose intolerance, and lipid metabolism disturbances. Here, we investigated the therapeutic potential of environmental enrichment (EE) to prevent the progression of gut dysbiosis in mice with high-fat diet (HFD)-induced metabolic syndrome. C57BL/6 male mice with obesity and metabolic syndrome, continuously fed with an HFD, were exposed to EE. We analyzed the gut microbiota of the mice by sequencing the 16s rRNA gene at different intervals, including on day 0 and 12 and 24 weeks after EE exposure. Fasting glucose levels, glucose tolerance, insulin resistance, food intake, weight gain, lipid profile, hepatic steatosis, and inflammatory mediators were evaluated in serum, adipose tissue, and the colon. We demonstrate that EE intervention prevents the progression of HFD-induced dysbiosis, reducing taxa associated with metabolic syndrome (Tepidimicrobium, Acidaminobacteraceae, and Fusibacter) while promoting those linked to healthy physiology (Syntrophococcus sucrumutans, Dehalobacterium, Prevotella, and Butyricimonas). Furthermore, EE enhances intestinal barrier integrity, increases mucin-producing goblet cell population, and upregulates Muc2 expression in the colon. These alterations correlate with reduced systemic lipopolysaccharide levels and attenuated colon inflammation, resulting in normalized glucose metabolism, diminished adipose tissue inflammation, reduced liver steatosis, improved lipid profiles, and a significant reduction in body weight gain despite mice's continued HFD consumption. Our findings highlight EE as a promising anti-inflammatory strategy for managing obesity-related metabolic dysregulation and suggest its potential in developing probiotics targeting EE-modulated microbial taxa.
Assuntos
Dieta Hiperlipídica , Disbiose , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Obesidade , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Camundongos , Obesidade/metabolismo , Obesidade/microbiologia , Masculino , Glucose/metabolismo , Camundongos Obesos , Resistência à Insulina , Síndrome Metabólica/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/microbiologiaRESUMO
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, ß-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
Assuntos
Microbioma Gastrointestinal , Receptor do Peptídeo Semelhante ao Glucagon 1 , Fígado , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Animais , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Incretinas/uso terapêutico , Incretinas/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
BACKGROUND: Schizophrenia (SCZ) patients undergoing antipsychotic treatment demonstrated a high prevalence and harmful effects of metabolic syndrome (MetS), which acted as the major cause of cardiovascular disease. The major clinical challenge is the lack of biomarkers to identify MetS episodes and prevent further damage, while the mechanisms underlying these drug-induced MetS remain unknown. METHODS: This study divided 173 participants with SCZ into 3 groups (None, High risk, and MetS, consisting of 22, 88, and 63 participants, respectively). The potential biomarkers were searched based on 16S rRNA gene sequence together with metabolism analysis. Logistic regression was used to test the effects of the genus-metabolites panel on early MetS diagnoses. RESULTS: A genus-metabolites panel, consisting of Senegalimassilia, sphinganine, dihomo-gamma-linolenoylcholine, isodeoxycholic acid, and MG (0:0/22:5/0:0), which involved in sphigolipid metabolism, fatty acid metabolism, secondary bile acid biosynthesis and glycerolipid metabolism, has a great discrimination efficiency to MetS with an area under the curve (AUC) value of 0.911 compared to the None MetS group (P = 1.08E-8). Besides, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) distinguished between subgroups robustly and exhibited a potential correlation with the severity of MetS in patients with SCZ, and may act as the biomarkers for early MetS diagnosis. CONCLUSIONS: Our multi-omics study showed that one bacterial genus-five lipid metabolites panel is the potential risk factor for MetS in SCZ. Furthermore, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) could serve as novel diagnostic markers in the early stage. So, it is obvious that the combination of bacterial genus and metabolites yields excellent discriminatory power, and the lipid metabolism provide new understanding to the pathogenesis, prevention, and therapy for MetS in SCZ.
Assuntos
Biomarcadores , Microbioma Gastrointestinal , Síndrome Metabólica , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Esquizofrenia/microbiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Adulto , Biomarcadores/metabolismo , Pessoa de Meia-Idade , Antipsicóticos/uso terapêutico , RNA Ribossômico 16S/genéticaRESUMO
Pulses, as an important part of the human diet, can act as a source of high-quality plant proteins. Pulse proteins and their hydrolysates have shown promising results in alleviating metabolic syndrome and modulating the gut microbiome. Their bioactivities have become a focus of research, with many new findings added in recent studies. This paper comprehensively reviews the anti-hypertension, anti-hyperglycemia, anti-dyslipidemia and anti-obesity bioactivities of pulse proteins and their hydrolysates in recent in vitro and in vivo studies, which show great potential for the prevention and treatment of metabolic syndrome. In addition, pulse proteins and their hydrolysates can regulate the gut microbiome, which in turn can have a positive impact on the treatment of metabolic syndrome. Furthermore, the beneficial effects of some pulse proteins and their hydrolysates on metabolic syndrome have been supported by clinical studies. This review might provide a reference for the application of pulse proteins and their hydrolysates in functional foods or nutritional supplements for people with metabolic syndrome.
Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Hidrolisados de Proteína , Síndrome Metabólica/microbiologia , Síndrome Metabólica/dietoterapia , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/administração & dosagem , Animais , Proteínas de PlantasRESUMO
Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.
Assuntos
Autofagia , Microbioma Gastrointestinal , Resistência à Insulina , Síndrome Metabólica , Autofagia/fisiologia , Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/microbiologia , Síndrome Metabólica/metabolismo , Humanos , Resistência à Insulina/fisiologia , Animais , Transdução de SinaisRESUMO
The prevalence of childhood and adolescent obesity has globally reached alarming dimensions and many adolescents affected by obesity already present one or more obesity-related comorbidities. In recent years, emerging evidence supporting the role of gut microbiota in the pathophysiology of metabolic diseases has been reported and the use of prebiotics, probiotics, synbiotics and postbiotics as a strategy to manipulate gut microbiota has become popular. The aim of this review is to explore the relationship between gut microbiota and metabolic syndrome in adolescents and to discuss the potential use of prebiotics, probiotics, synbiotics and postbiotics for the prevention and treatment of this clinical picture in adolescence. According to the most recent literature, prebiotics, probiotics and synbiotics have no clear effect on MetS, but a possible modulation of anthropometric parameters has been observed after synbiotic supplementation. Only one study has examined the role of postbiotics in alleviating metabolic complications in children with obesity but not in adolescents. More extensive research is needed to support the conclusions drawn so far and to develop effective microbiome-based interventions that may help improving the quality of life of children and adolescents exposed to the increasing prevalence of MetS.
Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Obesidade Infantil , Prebióticos , Probióticos , Simbióticos , Humanos , Síndrome Metabólica/terapia , Síndrome Metabólica/microbiologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Simbióticos/administração & dosagem , Adolescente , Obesidade Infantil/terapia , Obesidade Infantil/microbiologia , CriançaRESUMO
In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in highIPA group while in lowIPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant. Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis.
Assuntos
Microbioma Gastrointestinal , Humanos , Masculino , Animais , Feminino , Pessoa de Meia-Idade , Resistência à Insulina , Indóis , Camundongos Endogâmicos C57BL , Metabolômica , Camundongos , Adulto , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Comorbidade , Músculo Esquelético/metabolismo , Músculo Esquelético/microbiologia , MultiômicaRESUMO
Microbial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders (n = 21) and HOMA-IR non-responders (n = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders (p = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) (p < .05). Microbiota engraftment was strongly associated with recipients' factors at baseline including initial gut microbial diversity, fiber and nutrient intakes, inflammatory markers, and bile acid derivative levels. This study identified that responders to FMT therapy had a higher engraftment rate in the transplantation of specific donor-specific microbes, which were strongly correlated with insulin sensitivity improvements. Further, the recipient baseline gut microbiota and related factors were identified as the determinants for responsiveness to FMT and fiber supplementation. The findings provide a basis for the development of precision microbial therapeutics for the treatment of metabolic syndrome.
Assuntos
Bactérias , Ácidos e Sais Biliares , Transplante de Microbiota Fecal , Fezes , Microbioma Gastrointestinal , Síndrome Metabólica , Humanos , Síndrome Metabólica/terapia , Síndrome Metabólica/microbiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fezes/microbiologia , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/sangue , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , Obesidade/terapia , Obesidade/microbiologia , Fibras na Dieta/administração & dosagem , Fibras na Dieta/metabolismo , Resistência à Insulina , Resultado do TratamentoRESUMO
BACKGROUND: Over recent decades, a growing body of evidence has emerged linking the composition of the gut microbiota to sleep regulation. Interestingly, the prevalence of sleep disorders is commonly related to cardiometabolic comorbidities such as diabetes, impaired lipid metabolism, and metabolic syndrome (MetS). In this complex scenario, the role of the gut-brain axis as the main communicating pathway between gut microbiota and sleep regulation pathways in the brain reveals some common host-microbial biomarkers in both sleep disturbances and MetS. As the biological mechanisms behind this complex interacting network of neuroendocrine, immune, and metabolic pathways are not fully understood yet, the present systematic review aims to describe common microbial features between these two unrelated chronic conditions. RESULTS: This systematic review highlights a total of 36 articles associating the gut microbial signature with MetS or sleep disorders. Specific emphasis is given to studies evaluating the effect of dietary patterns, dietary supplementation, and probiotics on MetS or sleep disturbances. CONCLUSIONS: Dietary choices promote microbial composition and metabolites, causing both the amelioration and impairment of MetS and sleep homeostasis.
Assuntos
Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Síndrome Metabólica , Transtornos do Sono-Vigília , Humanos , Síndrome Metabólica/microbiologia , Microbioma Gastrointestinal/fisiologia , Transtornos do Sono-Vigília/microbiologia , Transtornos do Sono-Vigília/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Probióticos , Suplementos Nutricionais , Dieta , Encéfalo/metabolismoRESUMO
The metabolic syndrome (MetSyn) is currently one of the biggest global health challenges because of its impact on public health. MetSyn includes the cluster of metabolic disorders including obesity, high blood pressure, hyperglycemia, high triglyceride levels, and hepatic steatosis. Together, these abnormalities increase the cardiovascular risk of individuals and pose a threat to healthcare systems worldwide. To better understand and address this complex issue, recent research has been increasingly focusing on unraveling the delicate interplay between metabolic disorders and the intestines and more specifically our gut microbiome. The gut microbiome entails all microorganisms inhabiting the gastrointestinal tract and plays a pivotal role in metabolic processes and overall health of its host. Emerging evidence proves an association between the gut microbiome composition and aspects of MetSyn, such as obesity. Understanding these relationships is crucial because they offer valuable insights into the mechanisms underlying development and progression of metabolic disorders and possible treatment options. Yet, how should we interpret this relationship? This review focuses on the interplay between the gut and MetSyn. In addition, we have reviewed the existing evidence of the gut microbiome and its association with and impact on metabolic disorders, in an attempt to understand the complex interactions and nature of this association. We also explored potential therapeutic options targeting the gut to modify metabolic disorders and obesity.
Assuntos
Microbioma Gastrointestinal , Síndrome Metabólica , Obesidade , Humanos , Síndrome Metabólica/microbiologia , Microbioma Gastrointestinal/fisiologia , Obesidade/microbiologia , Intestinos/microbiologiaRESUMO
The epidemy of metabolic syndrome (MetS) is typically preceded by adoption of a "risky" lifestyle (e.g., dietary habit) among populations. Evidence shows that those with low socioeconomic status (SES) are at an increased risk for MetS. To investigate this, we recruited 123 obese subjects (body mass index [BMI] ≥ 30) from Chicago. Multi-omic data were collected to interrogate fecal microbiota, systemic markers of inflammation and immune activation, plasma metabolites, and plasma glycans. Intestinal permeability was measured using the sugar permeability testing. Our results suggest a heterogenous metabolic dysregulation among obese populations who are at risk of MetS. Systemic inflammation, linked to poor diet, intestinal microbiome dysbiosis, and gut barrier dysfunction may explain the development of MetS in these individuals. Our analysis revealed 37 key features associated with increased numbers of MetS features. These features were used to construct a composite metabolic-inflammatory (MI) score that was able to predict progression of MetS among at-risk individuals. The MI score was correlated with several markers of poor diet quality as well as lower levels of gut microbial diversity and abnormalities in several species of bacteria. This study reveals novel targets to reduce the burden of MetS and suggests access to healthy food options as a practical intervention.
Assuntos
Síndrome Metabólica , Microbiota , Humanos , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Multiômica , Disparidades Socioeconômicas em Saúde , Dieta , Obesidade/metabolismo , Inflamação , Disbiose/complicações , Disbiose/microbiologiaRESUMO
BACKGROUND: Evidence on the effect of gut microbiota on the number of metabolic syndrome (MetS) risk factors among children is scarce. We aimed to examine the alterations of gut microbiota with different numbers of MetS risk factors among children. METHODS: Data were collected from a nested case-control study at the baseline of the Huantai Childhood Cardiovascular Health Cohort Study in Zibo, China. We compared the differences in gut microbiota based on 16S rRNA gene sequencing among 72 children with different numbers of MetS risk factors matched by age and sex (i.e., none, one, and two-or-more MetS risk factors; 24 children for each group). RESULTS: The community richness (i.e., the total number of species in the community) and diversity (i.e., the richness and evenness of species in the community) of gut microbiota decreased with an increased number of MetS risk factors in children (P for trend < 0.05). Among genera with a relative abundance greater than 0.01%, the relative abundance of Lachnoclostridium (PFDR = 0.009) increased in the MetS risk groups, whereas Alistipes (PFDR < 0.001) and Lachnospiraceae_NK4A136_group (PFDR = 0.043) decreased in the MetS risk groups compared to the non-risk group. The genus Christensenellaceae_R-7_group excelled at distinguishing one and two-or-more risk groups from the non-risk group (area under the ROC curve [AUC]: 0.84 - 0.92), while the genera Family_XIII_AD3011_group (AUC: 0.73 - 0.91) and Lachnoclostridium (AUC: 0.77 - 0.80) performed moderate abilities in identifying none, one, and two-or-more MetS risk factors in children. CONCLUSIONS: Based on the nested case-control study and the 16S rRNA gene sequencing technology, we found that dysbiosis of gut microbiota, particularly for the genera Christensenellaceae_R-7_group, Family_XIII_AD3011_group, and Lachnoclostridium may contribute to the early detection and the accumulation of MetS risk factors in childhood.
Assuntos
Disbiose , População do Leste Asiático , Microbioma Gastrointestinal , Síndrome Metabólica , Criança , Humanos , Estudos de Casos e Controles , Estudos de Coortes , Microbioma Gastrointestinal/genética , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Fatores de Risco , RNA Ribossômico 16S , Disbiose/complicações , Disbiose/metabolismo , Disbiose/microbiologiaRESUMO
Several studies have suggested a role for gut mucosa-associated microbiota in the development of obesity, but the mechanisms involved are poorly defined. Here, the impact of the gut mucosa-associated microbiota on obesity and related metabolic disorders was evaluated in a metabolic syndrome (MetS) porcine model. Body composition was determined among male Wuzhishan minipigs consuming a high-energy diet (HED) and compared to that of those consuming a normal diet (ND), and gut segments (duodenum, jejunum, ileum, cecum, colon, and rectum) were sampled for paired analysis of mucosa-associated microbiota and transcriptome signatures with 16S rRNA gene and RNA sequencing, respectively. Our data indicated that long-term HED feeding significantly increased body weight and visceral fat deposition and aggravated metabolic disorders. Specially, HED feeding induced mucosa-associated microbiota dysbiosis and selectively increased the abundance of the families Enterobacteriaceae, Moraxellaceae, and Lachnospiraceae in the upper intestine. The association analysis indicated that specific bacteria play key roles in adiposity, e.g., Lactobacillus johnsonii in the duodenum, Actinobacillus indolicus in the jejunum, Acinetobacter johnsonii in the ileum, Clostridium butyricum in the cecum, Haemophilus parasuis in the colon, and bacterium NLAEzlP808, Halomonas taeheungii, and Shewanella sp. JNUH029 in the rectum. Transcriptome data further revealed intestinal lipid metabolism and immune dysfunction in the MetS individuals, which may be associated with obesity and related metabolic disorders. Our results indicated that gut mucosa-associated microbiota dysbiosis has the potential to exacerbate obesity, partially through modulating systemic inflammatory responses. IMPORTANCE Obesity is a major risk factor for metabolic syndrome, which is the most common cause of death worldwide, especially in developed countries. The link between obesity and gut mucosa-associated microbiota is unclear due to challenges associated with the collection of intestinal samples from humans. The current report provides the first insight into obesity-microbiome-gut immunity connections in a metabolic syndrome (MetS) porcine model. The present results show that dysbiosis of mucosal microbiota along the entire digestive tract play a critical role in the proinflammatory response in the host-microbial metabolism axis, resulting in obesity and related metabolic disorders in the MetS model.
Assuntos
Síndrome Metabólica , Microbiota , Animais , Bactérias/genética , Bactérias/metabolismo , Disbiose/microbiologia , Humanos , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Mucosa , Obesidade/microbiologia , RNA Ribossômico 16S/genética , Suínos , Porco Miniatura/genética , TranscriptomaRESUMO
Fecal microbiota transplantation (FMT) is currently used for treating Clostridium difficile infection and explored for other clinical applications in experimental trials. However, the effectiveness of this therapy could vary, and partly depend on the donor's bacterial species engraftment, whose evaluation is challenging because there are no cost-effective strategies for accurately tracking the microbe transference. In this regard, the precise identification of bacterial species inhabiting the human gut is essential to define their role in human health unambiguously. We used Nanopore-based device to sequence bacterial rrn operons (16S-ITS-23S) and to reveal species-level abundance changes in the human gut microbiota of a FMT trial. By assessing the donor and recipient microbiota before and after FMT, we further evaluated whether this molecular approach reveals strain-level genetic variation to demonstrate microbe transfer and engraftment. Strict control over sequencing data quality and major microbiota covariates was critical for accurately estimating the changes in gut microbial species abundance in the recipients after FMT. We detected strain-level variation via single-nucleotide variants (SNVs) at rrn regions in a species-specific manner. We showed that it was possible to explore successfully the donor-bacterial strain (e.g., Parabacteroides merdae) engraftment in recipients of the FMT by assessing the nucleotide frequencies at rrn-associated SNVs. Our findings indicate that the engraftment of donors' microbiota is to some extent correlated with the improvement of metabolic health in recipients and that parameters such as the baseline gut microbiota configuration, sex, and age of donors should be considered to ensure the success of FMT in humans. The study was prospectively registered at the Dutch Trial registry - NTR4488 (https://www.trialregister.nl/trial/4488).