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Depression is a highly prevalent disorder and a leading cause of disability worldwide. It has a major impact on the affected individual and on society as a whole. Regrettably, current available treatments for this condition are insufficient in many patients. In recent years, the gut microbiome has emerged as a promising alternative target for treating and preventing depressive disorders. However, the microbes that form this ecosystem do not act alone but are part of a complicated network connecting the gut and the brain that influences our mood. Host cells that are in intimate contact with gut microbes, such as the epithelial cells forming the gut barrier and the immune cells in their vicinity, play a key role in the process. These cells continuously shape immune responses to maintain healthy communication between gut microbes and the host. In this article, we review how the interplay among epithelial cells, the immune system, and gut microbes mediates gut-brain communication to influence mood. We also discuss how advances in our knowledge of the mechanisms underlying the gut-brain axis could contribute to addressing depression. SIGNIFICANCE STATEMENT: This review does not aim to systematically describe intestinal microbes that might be beneficial or detrimental for depression. We have adopted a novel point of view by focusing on potential mechanisms underlying the crosstalk between gut microbes and their intestinal environment to control mood. These pathways could be targeted by well defined and individually tailored dietary interventions, microbes, or microbial metabolites to ameliorate depression and decrease its important social and economic impact.
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Eixo Encéfalo-Intestino , Depressão , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Animais , Eixo Encéfalo-Intestino/fisiologia , Depressão/imunologia , Depressão/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismoRESUMO
This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.
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Early-life stress (ELS) has been robustly associated with a range of poor mental and physical health outcomes. Recent studies implicate the gut microbiome in stress-related mental, cardio-metabolic and immune health problems, but research on humans is scarce and thus far often based on small, selected samples, often using retrospective reports of ELS. We examined associations between ELS and the human gut microbiome in a large, population-based study of children. ELS was measured prospectively from birth to 10 years of age in 2,004 children from the Generation R Study. We studied overall ELS, as well as unique effects of five different ELS domains, including life events, contextual risk, parental risk, interpersonal risk, and direct victimization. Stool microbiome was assessed using 16S rRNA sequencing at age 10 years and data were analyzed at multiple levels (i.e. α- and ß-diversity indices, individual genera and predicted functional pathways). In addition, we explored potential mediators of ELS-microbiome associations, including diet at age 8 and body mass index at 10 years. While no associations were observed between overall ELS (composite score of five domains) and the microbiome after multiple testing correction, contextual risk - a specific ELS domain related to socio-economic stress, including risk factors such as financial difficulties and low maternal education - was significantly associated with microbiome variability. This ELS domain was associated with lower α-diversity, with ß-diversity, and with predicted functional pathways involved, amongst others, in tryptophan biosynthesis. These associations were in part mediated by overall diet quality, a pro-inflammatory diet, fiber intake, and body mass index (BMI). These results suggest that stress related to socio-economic adversity - but not overall early life stress - is associated with a less diverse microbiome in the general population, and that this association may in part be explained by poorer diet and higher BMI. Future research is needed to test causality and to establish whether modifiable factors such as diet could be used to mitigate the negative effects of socio-economic adversity on the microbiome and related health consequences.
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Experiências Adversas da Infância , Microbioma Gastrointestinal , Criança , Humanos , Microbioma Gastrointestinal/genética , Estudos Retrospectivos , RNA Ribossômico 16S/genética , FezesRESUMO
The role of the gut microbiota and its interplay with host metabolic health, particularly in the context of type 2 diabetes mellitus (T2DM) management, is garnering increasing attention. Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, constitute a class of drugs extensively used in T2DM treatment. However, their potential interactions with gut microbiota remain poorly understood. In this study, we employed computational methodologies to investigate the binding affinities of various gliptins to DPP4-like homologs produced by intestinal bacteria. The 3D structures of DPP4 homologs from gut microbiota species, including Segatella copri, Phocaeicola vulgatus, Bacteroides uniformis, Parabacteroides merdae, and Alistipes sp., were predicted using computational modeling techniques. Subsequently, molecular dynamics simulations were conducted for 200 ns to ensure the stability of the predicted structures. Stable structures were then utilized to predict the binding interactions with known gliptins through molecular docking algorithms. Our results revealed binding similarities of gliptins toward bacterial DPP4 homologs compared to human DPP4. Specifically, certain gliptins exhibited similar binding scores to bacterial DPP4 homologs as they did with human DPP4, suggesting a potential interaction of these drugs with gut microbiota. These findings could help in understanding the interplay between gliptins and gut microbiota DPP4 homologs, considering the intricate relationship between the host metabolism and microbial communities in the gut.
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Diabetes Mellitus Tipo 2 , Dipeptidil Peptidase 4 , Inibidores da Dipeptidil Peptidase IV , Microbioma Gastrointestinal , Humanos , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Sítios de Ligação , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação ProteicaRESUMO
Plant cell walls are complex structures mainly made up of carbohydrate and phenolic polymers. In addition to their structural roles, cell walls function as external barriers against pathogens and are also reservoirs of glycan structures that can be perceived by plant receptors, activating Pattern-Triggered Immunity (PTI). Since these PTI-active glycans are usually released upon plant cell wall degradation, they are classified as Damage Associated Molecular Patterns (DAMPs). Identification of DAMPs imply their extraction from plant cell walls by using multistep methodologies and hazardous chemicals. Subcritical water extraction (SWE) has been shown to be an environmentally sustainable alternative and a simplified methodology for the generation of glycan-enriched fractions from different cell wall sources, since it only involves the use of water. Starting from Equisetum arvense cell walls, we have explored two different SWE sequential extractions (isothermal at 160 ºC and using a ramp of temperature from 100 to 160 ºC) to obtain glycans-enriched fractions, and we have compared them with those generated with a standard chemical-based wall extraction. We obtained SWE fractions enriched in pectins that triggered PTI hallmarks in Arabidopsis thaliana such as calcium influxes, reactive oxygen species production, phosphorylation of mitogen activated protein kinases and overexpression of immune-related genes. Notably, application of selected SWE fractions to pepper plants enhanced their disease resistance against the fungal pathogen Sclerotinia sclerotiorum. These data support the potential of SWE technology in extracting PTI-active fractions from plant cell wall biomass containing DAMPs and the use of SWE fractions in sustainable crop production.
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Proteínas de Arabidopsis , Arabidopsis , Equisetum , Resistência à Doença , Proteínas de Arabidopsis/genética , Equisetum/metabolismo , Imunidade Vegetal , Biomassa , Arabidopsis/genética , Plantas/metabolismo , Parede Celular/metabolismo , Polissacarídeos/metabolismo , Doenças das Plantas/microbiologiaRESUMO
Bile acids (BAs) are a complex class of metabolites that have been described as specific biomarkers of gut microbiota activity. The development of analytical methods allowing the quantification of an ample spectrum of BAs in different biological matrices is needed to enable a wider implementation of BAs as complementary measures in studies investigating the functional role of the gut microbiota. This work presents results from the validation of a targeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 28 BAs and six sulfated BAs, covering primary, secondary, and conjugated BAs. The analysis of 73 urine and 20 feces samples was used to test the applicability of the method. Concentrations of BAs in human urine and murine feces were reported, ranging from 0.5 to 50 nmol/g creatinine and from 0.012 to 332 nmol/g, respectively. Seventy-nine percent of BAs present in human urine samples corresponded to secondary conjugated BAs, while 69% of BAs present in murine feces corresponded to primary conjugated BAs. Glycocholic acid sulfate (GCA-S) was the most abundant BA in human urine samples, while taurolithocholic acid was the lowest concentrated compound detected. In murine feces, the most abundant BAs were α-murocholic, deoxycholic, dehydrocholic, and ß-murocholic acids, while GCA-S was the lowest concentrated BA. The presented method is a non-invasive approach for the simultaneous assessment of BAs and sulfated BAs in urine and feces samples, and the results will serve as a knowledge base for future translational studies focusing on the role of the microbiota in health.
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Ácidos e Sais Biliares , Espectrometria de Massas em Tandem , Humanos , Camundongos , Animais , Ácidos e Sais Biliares/análise , Espectrometria de Massas em Tandem/métodos , Sulfatos/análise , Cromatografia Líquida de Alta Pressão/métodos , Fezes/químicaRESUMO
BACKGROUND: Obesity and related co-morbidities represent a major health challenge nowadays, with a rapidly increasing incidence worldwide. The gut microbiome has recently emerged as a key modifier of human health that can affect the development and progression of obesity, largely due to its involvement in the regulation of food intake and metabolism. However, there are still few studies that have in-depth explored the functionality of the human gut microbiome in obesity and even fewer that have examined its relationship to eating behaviors. METHODS: In an attempt to advance our knowledge of the gut-microbiome-brain axis in the obese phenotype, we thoroughly characterized the gut microbiome signatures of obesity in a well-phenotyped Italian female cohort from the NeuroFAST and MyNewGut EU FP7 projects. Fecal samples were collected from 63 overweight/obese and 37 normal-weight women and analyzed via a multi-omics approach combining 16S rRNA amplicon sequencing, metagenomics, metatranscriptomics, and lipidomics. Associations with anthropometric, clinical, biochemical, and nutritional data were then sought, with particular attention to cognitive and behavioral domains of eating. RESULTS: We identified four compositional clusters of the gut microbiome in our cohort that, although not distinctly associated with weight status, correlated differently with eating habits and behaviors. These clusters also differed in functional features, i.e., transcriptional activity and fecal metabolites. In particular, obese women with uncontrolled eating behavior were mostly characterized by low-diversity microbial steady states, with few and poorly interconnected species (e.g., Ruminococcus torques and Bifidobacterium spp.), which exhibited low transcriptional activity, especially of genes involved in secondary bile acid biosynthesis and neuroendocrine signaling (i.e., production of neurotransmitters, indoles and ligands for cannabinoid receptors). Consistently, high amounts of primary bile acids as well as sterols were found in their feces. CONCLUSIONS: By finding peculiar gut microbiome profiles associated with eating patterns, we laid the foundation for elucidating gut-brain axis communication in the obese phenotype. Subject to confirmation of the hypotheses herein generated, our work could help guide the design of microbiome-based precision interventions, aimed at rewiring microbial networks to support a healthy diet-microbiome-gut-brain axis, thus counteracting obesity and related complications.
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Microbioma Gastrointestinal , Humanos , Feminino , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Multiômica , Obesidade/genética , Dieta , Comportamento Alimentar/fisiologia , Fezes/microbiologiaRESUMO
Impaired glucose homeostasis in obesity is mitigated by enhancing the glucoregulatory actions of glucagon-like peptide 1 (GLP-1), and thus, strategies that improve GLP-1 sensitivity and secretion have therapeutic potential for the treatment of type 2 diabetes. This study shows that Holdemanella biformis, isolated from the feces of a metabolically healthy volunteer, ameliorates hyperglycemia, improves oral glucose tolerance and restores gluconeogenesis and insulin signaling in the liver of obese mice. These effects were associated with the ability of H. biformis to restore GLP-1 levels, enhancing GLP-1 neural signaling in the proximal and distal small intestine and GLP-1 sensitivity of vagal sensory neurons, and to modify the cecal abundance of unsaturated fatty acids and the bacterial species associated with metabolic health. Our findings overall suggest the potential use of H biformis in the management of type 2 diabetes in obesity to optimize the sensitivity and function of the GLP-1 system, through direct and indirect mechanisms.
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Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Firmicutes/fisiologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Camundongos Obesos/metabolismo , Camundongos Obesos/microbiologia , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Gluconeogênese/fisiologia , Glucose/metabolismo , Teste de Tolerância a Glucose/métodos , Hiperglicemia/metabolismo , Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologiaRESUMO
PURPOSE OF REVIEW: Gluten is a complex mixture of highly immunogenic glutamine- and proline-rich proteins found in some cereals. In celiac disease (CeD), gluten triggers an autoimmune response due to its interaction with the human leukocyte antigen heterodimers that confer the genetic risk. The involvement of gluten in other disorders has also been investigated, but its role beyond CeD is still unclear. Here, we review the most recent evidence of the involvement of gluten in diseases and the opportunities of manipulating the gut microbiota to treat or prevent gluten-related conditions. RECENT FINDINGS: Most of the new studies have been conducted in the context of CeD, where important evidence has been gained on associations between the gut microbiota, genotype, and environmental factors such as breastfeeding and antibiotics. The role of the microbiota has been investigated in several prospective, observational and interventional studies with probiotics, which together showed that the gut microbiota could be targeted to ameliorate and aid in the prevention of CeD development. SUMMARY: Several studies have evidenced how genetic and environmental factors influence the gut microbiome with consequences in CeD. These findings could inspire the development of microbiota modulation strategies to support the prevention or treatment of CeD.
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Doença Celíaca , Microbioma Gastrointestinal , Dieta Livre de Glúten , Glutens/efeitos adversos , Humanos , Estudos ProspectivosRESUMO
Scientific and consumer interest in healthy foods (also known as functional foods), nutraceuticals and cosmeceuticals has increased in the recent years, leading to an increased presence of these products in the market. However, the regulations across different countries that define the type of claims that may be made, and the degree of evidence required to support these claims, are rather inconsistent. Moreover, there is also controversy on the effectiveness and biological mode of action of many of these products, which should undergo an exhaustive approval process to guarantee the consumer rights. Computational approaches constitute invaluable tools to facilitate the discovery of bioactive molecules and provide biological plausibility on the mode of action of these products. Indeed, methodologies like QSAR, docking or molecular dynamics have been used in drug discovery protocols for decades and can now aid in the discovery of bioactive food components. Thanks to these approaches, it is possible to search for new functions in food constituents, which may be part of our daily diet, and help to prevent disorders like diabetes, hypercholesterolemia or obesity. In the present manuscript, computational studies applied to this field are reviewed to illustrate the potential of these approaches to guide the first screening steps and the mechanistic studies of nutraceutical, cosmeceutical and functional foods.
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Quimioinformática/métodos , Cosmecêuticos/química , Suplementos Nutricionais/análise , Alimento Funcional/análise , Modelos Moleculares , Relação Quantitativa Estrutura-Atividade , Algoritmos , Cosmecêuticos/farmacologia , Bases de Dados de Compostos Químicos , Humanos , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Simulação de Dinâmica MolecularRESUMO
Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Gut microbiota-diet interactions might interfere in nutrient sensing and signalling from the gut to the brain, where the information is processed to control energy homeostasis. This gut microbiota-brain crosstalk is mediated by metabolites, mainly short chain fatty acids, secondary bile acids or amino acids-derived metabolites and subcellular bacterial components. These activate gut-endocrine and/or neural-mediated pathways or pass to systemic circulation and then reach the brain. Feeding time and dietary composition are the main drivers of the gut microbiota structure and function. Therefore, aberrant feeding patterns or unhealthy diets might alter gut microbiota-diet interactions and modify nutrient availability and/or microbial ligands transmitting information from the gut to the brain in response to food intake, thus impairing energy homeostasis. Herein, we update the scientific evidence supporting that gut microbiota is a source of novel dietary and non-dietary biological products that may beneficially regulate gut-to-brain communication and, thus, improve metabolic health. Additionally, we evaluate how the feeding time and dietary composition modulate the gut microbiota and, thereby, the intraluminal availability of these biological products with potential effects on energy homeostasis. The review also identifies knowledge gaps and the advances required to clinically apply microbiome-based strategies to improve the gut-brain axis function and, thus, combat obesity.
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Encéfalo/fisiologia , Metabolismo Energético , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/fisiologia , Homeostase , Microbiota/fisiologia , Ritmo Circadiano , Dieta , Suscetibilidade a Doenças , Ingestão de Alimentos , Comportamento Alimentar , Humanos , Micronutrientes , Nutrientes , Obesidade/etiologia , Obesidade/metabolismoRESUMO
The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.
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Microbioma Gastrointestinal/fisiologia , Humanos , Sistema Imunitário/fisiologia , Sistemas Neurossecretores/fisiologiaRESUMO
PURPOSE: The objective of this study was to investigate the additive effects of combining energy restriction with dietary fibres on change in body weight and gut microbiota composition. METHODS: The study was a 12-week randomised, placebo-controlled, double-blinded, parallel intervention trial. A total of 116 overweight or obese participants were assigned randomly either to 10 g inulin plus 10 g resistant maltodextrin or to 20 g of placebo supplementation through 400 mL of milk a day, while on a - 500 kcal/day energy restricted diet. RESULTS: Altogether, 86 participants completed the intervention. There were no significant differences in weight loss or body composition between the groups. The fibre supplement reduced systolic (5.35 ± 2.4 mmHg, p = 0.043) and diastolic (2.82 ± 1.3 mmHg, p = 0.047) blood pressure to a larger extent than placebo. Furthermore, a larger decrease in serum insulin was observed in the placebo group compared to the fibre group (- 26.0 ± 9.2 pmol/L, p = 0.006). The intake of fibre induced changes in the composition of gut microbiota resulting in higher abundances of Parabacteroides and Bifidobacteria, compared to placebo. The effects on blood pressure and glucose metabolism were mainly observed in women, and could be attributed to a higher gut microbiota diversity after intervention. Finally, the fibre group experienced a higher degree of gastrointestinal symptoms, which attenuated over time. CONCLUSIONS: Supplementation of inulin and resistant maltodextrin did not provide an additional weight loss during an energy-restricted diet, but reduced both systolic and diastolic blood pressure. Furthermore, the fibre supplement did stimulate the growth of potentially beneficial bacteria genera. CLINICAL TRIAL REGISTRY: The study was registered at http://www.clinicaltrials.gov , NCT03135041.
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Restrição Calórica , Inulina/farmacologia , Polissacarídeos/farmacologia , Redução de Peso/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Ingestão de Energia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: The relationships between gut microbiota and obesity-related co-morbidities have been increasingly recognized. Low-grade inflammation may be the main factor in the pathogenesis of such disorders. We investigated the effect of the potential probiotic Bifidobacterium pseudocatenulatum CECT 7765 on cardiometabolic risk factors, inflammatory cytokines and gut microbiota composition in obese children with insulin resistance. METHODS: The study included 48 obese children (10-15 years old) with insulin resistance. They received dietary advice and were assigned to take the capsules with or without probiotic (109-10 CFU) daily for 13 weeks. Clinical, biochemical and gut microbiome measurements were made at baseline and at the end of the intervention. RESULTS: There was a significant improvement in body mass index in all children after the intervention, suggesting that weight changes are related to the dietary advice. A significant decrease in circulating high-sensitive C-reactive protein (P = 0.026) and monocyte chemoattractant protein-1 (P = 0.032) and an increase in high-density lipoprotein cholesterol (P = 0.035) and omentin-1 (P = 0.023) in children receiving probiotic supplementation were observed compared to the control group. Regarding gut microbiota, probiotic administration significantly increased the proportion of the Rikenellaceae family members, particularly of the Alistipes genus. CONCLUSIONS: The beneficial effects of the intervention on inflammatory markers and lipid profile suggest that B. pseudocatenulatum CECT 7765 intake together with dietary recommendations can improve inflammatory status in children with obesity and insulin resistance. These effects are parallel to increases in bacterial groups associated with a lean phenotype. The modulation of gut microbiota with probiotic supplementation can be considered an effective tool to ameliorate some obesity-related disorders in children.
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Bifidobacterium pseudocatenulatum , Microbioma Gastrointestinal/fisiologia , Inflamação/tratamento farmacológico , Resistência à Insulina , Obesidade/fisiopatologia , Probióticos/farmacologia , Adolescente , Criança , Suplementos Nutricionais , Feminino , Humanos , Inflamação/fisiopatologia , Masculino , Probióticos/administração & dosagem , Estudos ProspectivosRESUMO
PURPOSE: Evaluating whether changes in gut microbiota induced by a bifidobacterial strain may have an effect on the hepatic vascular function in portal hypertensive cirrhotic rats. METHODS: Bile duct ligation (BDL) was performed in rats. A subgroup of animals received B. pseudocatenulatum CECT7765 (109 cfu/daily ig.) for 1 week prior to laparotomy. Hemodynamic, biochemical and inflammatory markers were evaluated. Ileal microbiota composition was identified. Statistical analysis was performed. RESULTS: Sham-operated (n = 6), BDL (n = 6) and BDL treated with bifidobacteria (n = 8) rats were included. B. pseudocatenulatum CECT7765 significantly decreased proteobacteria (p = 0.001) and increased Bacteroidetes (p = 0.001) relative abundance. The bifidobacteria decreased the Firmicutes/Bacteroidetes ratio in the BDL model (p = 0.03). BDL with bifidobacteria vs BDL rats showed: significantly reduced portal vein area, portal flow, congestion index, alkaline phosphatase and total bilirubin, significantly increased serum cytokines and nitric oxide levels, gene expression levels of bile acids receptor FXR and endothelial nitric oxide synthase. Quantitative changes in the Clostridiales and Bacteroidales orders were independently associated with variations in portal vein area and portal flow, while changes in the Proteobacteria phylum were independently associated with congestion. Variations in all liver function markers significantly correlated with total OTUs mainly in the Firmicutes, but only changes in the Clostridiales were independently associated with alkaline phosphatase in the ANCOVA analysis. CONCLUSION: Hemodynamic alterations and liver dysfunction induced by BDL in rats are partially restored after oral administration of B. pseudocatenulatum CECT7765. Results provide a proof-of-concept for the beneficial effect of this bifidobacterial strain in reducing complications derived from portal hypertension in cirrhosis.
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Bifidobacterium pseudocatenulatum , Hemodinâmica/efeitos dos fármacos , Hipertensão Portal/fisiopatologia , Cirrose Hepática/fisiopatologia , Fígado/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Hemodinâmica/fisiologia , Hipertensão Portal/complicações , Hipertensão Portal/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Fígado/fisiologia , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
AIMS: To determine the incidence of drug-related deaths (DRD) in a university hospital in 2015, to describe their characteristics, and to discover risk factors of DRD. METHODS: An analytic and retrospective cohort study. Patients with a death diagnosed predefined from a list of medical conditions potentially caused by drugs were the selected cases for further review. Causality assessment was evaluated by a local drug safety committee. RESULTS: Out of 1135 inpatient deaths, 73 DRD were included (six were hospital-acquired). The incidence of DRD of all hospital admissions was 0.34%, and the incidence of all deaths cases was 7%. Drugs were the cause of death in 38 patients (52%) and a contributive role in 35 (48%). The median age of DRD patients was 72 years (range 19-94) and 72.6% were men. The median hospital stay, Charlson score and number of drugs were 5 days, 2 points and seven drugs respectively. The most frequent DRD were cerebral haemorrhages and infections in drug-immunosuppressed patients (32, 43.8%, each group). The most frequently involved drugs were antineoplastics and glucocorticosteroids (40% and 18%), and antithrombotics (33%); drug-drug interactions were present in 44% DRD. Sex, age and number of drugs were risk factors of DRD. CONCLUSIONS: Adverse drug reactions were a significant cause of death in hospitalized patients, mainly haemorrhages and infections precipitated by drug-drug interactions. Risk factors for DRD were sex, age and number of drugs. Preventable DRD and measures to avoid them should be accurately assessed in further studies.
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Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Causas de Morte , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/mortalidade , Feminino , Mortalidade Hospitalar , Hospitalização , Hospitais Universitários , Humanos , Incidência , Pacientes Internados/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Lactobacilli and bifidobacteria play a primary role in modulation of gut immunity. By considering that microbiota composition depends on various factors, including diet, we asked whether functional differences could characterize faecal populations of lactobacilli and bifidobacteria isolated from individuals with different dietary habits. 155 healthy volunteers who followed omnivorous, ovo-lacto-vegetarian or vegan diets were recruited at four Italian centres (Turin, Parma, Bologna and Bari). Faecal samples were collected; lactobacilli and bifidobacteria were isolated on selective media and their immunomodulatory activity was tested in mouse dendritic cells (DCs). Pre-incubation with lactobacilli increased LPS-induced expression of the maturation markers CD80 and CD86, whereas pre-incubation with bifidobacteria decreased such expression. Analysis of the cytokine profile indicated that strains of both genera induced down-regulation of IL-12 and up-regulation of IL-10, whereas expression of TNF-α was not modulated. Notably, analysis of anti-inflammatory potential (IL-10/IL-12 ratio) showed that lactobacilli evoked a greater anti-inflammatory effect than did bifidobacteria in the omnivorous group (P<0.05). We also found significantly reduced anti-inflammatory potential in the bacterial strains isolated from Bari's volunteers in comparison with those from the cognate groups from the other centres. In conclusion, lactobacilli and bifidobacteria showed a genus-specific ability of modulating in vitro innate immunity associated with a specific dietary habit. Furthermore, the geographical area had a significant impact on the anti-inflammatory potential of some components of faecal microbiota.
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Bifidobacterium/imunologia , Células Dendríticas/imunologia , Dieta Vegana , Dieta , Microbioma Gastrointestinal/imunologia , Imunomodulação , Lactobacillus/imunologia , Animais , Antígeno B7-1/genética , Antígeno B7-2/genética , Bifidobacterium/isolamento & purificação , Citocinas/genética , Células Dendríticas/microbiologia , Regulação para Baixo , Fezes/microbiologia , Humanos , Interleucina-10/genética , Interleucina-12/genética , Lactobacillus/isolamento & purificação , Camundongos , Fator de Necrose Tumoral alfa/genética , Regulação para Cima , VegetarianosRESUMO
PURPOSE OF REVIEW: Update on the development of microbiome-based interventions and dietary supplements to combat obesity and related comorbidities, which are leading causes of global mortality. RECENT FINDINGS: The role of intestinal dysbiosis, partly resulting from unhealthy diets, in the development of obesity and metabolic disorders, is well documented by recent translational research. Human experimental trials with whole-faecal transplants are ongoing, and their results will be crucial as proof of concept that interventions intended to modulate the microbiome composition and function could be alternatives for the management of obesity and related comorbidities. Potential next-generation probiotic bacteria (Akkermansia, Bacteroides spp., Eubacterium halli) and microbiota-derived molecules (e.g. membrane proteins, short-chain fatty acids) are being evaluated in preclinical and clinical trials to promote the development of innovative dietary supplements. The fact that live or inactivated bacteria and their products can regulate pathways that increase energy expenditure, and reduce energy intake, and absorption and systemic inflammation make them attractive research targets from a nutritional and clinical perspective. SUMMARY: Understanding which are the beneficial bacteria and their bioactive products is helping us to envisage innovative microbiome-based dietary interventions to tackle obesity. Advances will likely result from future refinements of these strategies according to the individual's microbiome configuration and its particular response to interventions, thereby progressing towards personalized nutrition.