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1.
Gut Microbes ; 16(1): 2410476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39360551

RESUMO

The gut microbiome is indispensable for the host physiological functioning. Yet, the impact of non-nutritious dietary compounds on the human gut microbiota and the role of the gut microbes in their metabolism and potential adverse biological effects have been overlooked. Identifying potential hazards and benefits would contribute to protecting and harnessing the gut microbiome's role in supporting human health. We discuss the evidence on the potential detrimental impact of certain food additives and microplastics on the gut microbiome and human health, with a focus on underlying mechanisms and causality. We provide recommendations for the incorporation of gut microbiome science in food risk assessment and identify the knowledge and tools needed to fill these gaps. The incorporation of gut microbiome endpoints to safety assessments, together with well-established toxicity and mutagenicity studies, might better inform the risk assessment of certain contaminants in food, and/or food additives.


Assuntos
Aditivos Alimentares , Inocuidade dos Alimentos , Microbioma Gastrointestinal , Humanos , Aditivos Alimentares/efeitos adversos , Aditivos Alimentares/metabolismo , Medição de Risco , Animais , Contaminação de Alimentos/análise , Microplásticos/toxicidade , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação
2.
JBI Evid Implement ; 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39445577

RESUMO

INTRODUCTION: The occiput-posterior (OP) fetal position is the most frequent form of labor dystocia. This position has been associated with delaying the second stage of labor and adverse outcomes. OBJECTIVES: This project aimed to improve the quality of intrapartum care provided by midwives for OP fetal positions during the second stage of labor. METHODS: This best practice implementation project was conducted at the Río Hortega University Hospital in Valladolid, Spain. The project followed the JBI Evidence Implementation Framework, which is based on an audit, feedback, and re-audit process. Current practices were compared against best practices in a baseline audit using 13 audit criteria. Barriers to compliance with best practices were identified and improvement strategies were implemented. An initial follow-up audit was carried out after 4 months to avoid secondary bias. After another 4 months, a second follow-up audit was conducted. Data were collected and compared using the JBI Practical Application of Clinical Evidence System (JBI PACES). RESULTS: The results revealed an improvement in all structure criteria (1-3), five of the process criteria (4-6, 8, 10), and all results criteria (11-13). One process criterion (8) reached maximum compliance in all audits. A key finding was the inadequate recording of upright positions (criterion 7) and the interpretation of cardiotocography (criterion 9). CONCLUSIONS: Evidence-based interventions for managing OP labor improved the quality of care and underlined the importance of ongoing training for midwives. Additional studies are required on positions and fetal monitoring during labor. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A279.

3.
Foods ; 13(19)2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39410056

RESUMO

Novel probiotic yoghurt was produced using the combination of bacterial cultures Lactobacillus plantarum HA119 and Bifidobacterium animalis subsp. lactis B94 and yoghurt bacteria Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus. Its basic nutritional composition, colour, texture, rheological properties, and sensory profile were compared with yoghurt produced using the same technological process and standard yoghurt cultures (control sample), as well as other commercially available yoghurts with different milk fat contents. Despite the fat content of the yoghurt made with the new probiotic cultures being 1.44%, its apparent viscosity was similar to that of high-fat yoghurt (2.99%). Other results from rheological measurements indicate that the new yoghurt had a stronger protein network, presumably due to the higher number of exopolysaccharides compared to both control and commercial yoghurts. Sensory analysis revealed that there were no statistically significant differences between the novel probiotic yoghurt and high-fat yoghurt as perceived by panellists. In conclusion, this combination of probiotic cultures can be used to produce yoghurt with rheological and sensory properties similar to high-fat yoghurts, without the need for hydrocolloids or changes in the production process.

4.
Microb Biotechnol ; 17(9): e14550, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39236296

RESUMO

In recent years, microbiomes and their potential applications for human, animal or plant health, food production and environmental management came into the spotlight of major national and international policies and strategies. This has been accompanied by substantial R&D investments in both public and private sectors, with an increasing number of products entering the market. Despite widespread agreement on the potential of microbiomes and their uses across disciplines, stakeholders and countries, there is no consensus on what defines a microbiome application. This often results in non-comprehensive communication or insufficient documentation making commercialisation and acceptance of the novel products challenging. To showcase the complexity of this issue we discuss two selected, well-established applications and propose criteria defining a microbiome application and their conditions of use for clear communication, facilitating suitable regulatory frameworks and building trust among stakeholders.


Assuntos
Microbiota , Humanos , Animais
5.
FEBS J ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39159270

RESUMO

Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.

6.
Genome Biol ; 25(1): 174, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961511

RESUMO

BACKGROUND: The gut microbiota controls broad aspects of human metabolism and feeding behavior, but the basis for this control remains largely unclear. Given the key role of human dipeptidyl peptidase 4 (DPP4) in host metabolism, we investigate whether microbiota DPP4-like counterparts perform the same function. RESULTS: We identify novel functional homologs of human DPP4 in several bacterial species inhabiting the human gut, and specific associations between Parabacteroides and Porphyromonas DPP4-like genes and type 2 diabetes (T2D). We also find that the DPP4-like enzyme from the gut symbiont Parabacteroides merdae mimics the proteolytic activity of the human enzyme on peptide YY, neuropeptide Y, gastric inhibitory polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) hormones in vitro. Importantly, administration of E. coli overexpressing the P. merdae DPP4-like enzyme to lipopolysaccharide-treated mice with impaired gut barrier function reduces active GIP and GLP-1 levels, which is attributed to increased DPP4 activity in the portal circulation and the cecal content. Finally, we observe that linagliptin, saxagliptin, sitagliptin, and vildagliptin, antidiabetic drugs with DPP4 inhibitory activity, differentially inhibit the activity of the DPP4-like enzyme from P. merdae. CONCLUSIONS: Our findings confirm that proteolytic enzymes produced by the gut microbiota are likely to contribute to the glucose metabolic dysfunction that underlies T2D by inactivating incretins, which might inspire the development of improved antidiabetic therapies.


Assuntos
Diabetes Mellitus Tipo 2 , Dipeptidil Peptidase 4 , Microbioma Gastrointestinal , Incretinas , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidil Peptidase 4/metabolismo , Animais , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Incretinas/metabolismo , Polipeptídeo Inibidor Gástrico/metabolismo , Masculino
7.
Pharmacol Rev ; 76(5): 956-969, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39084934

RESUMO

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.


Assuntos
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/metabolismo
8.
Diabetes Care ; 47(9): 1491-1508, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38996003

RESUMO

This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized 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 randomization in humans; 2) the highly individualized 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.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus/microbiologia
9.
Diabetologia ; 67(9): 1760-1782, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38910152

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Pesquisa Translacional Biomédica
10.
Microbiome ; 12(1): 103, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845049

RESUMO

BACKGROUND: The metabolic disturbances of obesity can be mitigated by strategies modulating the gut microbiota. In this study, we sought to identify whether innate or adaptive immunity mediates the beneficial metabolic effects of the human intestinal bacterium Bacteroides uniformis CECT 7771 in obesity. METHODS: We evaluated the effects of orally administered B. uniformis on energy homeostasis, intestinal immunity, hormone levels, and gut microbiota in wild-type and Rag1-deficient mice with diet-induced obesity. We also assessed whether B. uniformis needed to be viable to exert its beneficial effects in obesity and to directly induce immunoregulatory effects. RESULTS: The administration of B. uniformis to obese mice improved glucose tolerance and insulin secretion, restored the caloric intake suppression after an oral glucose challenge, and reduced hyperglycemia. The pre- and post-prandial glucose-related benefits were associated with restoration of the anti-inflammatory tone mediated by type 2 macrophages and regulatory T cells (Tregs) in the lamina propria of the small intestine. Contrastingly, B. uniformis administration failed to improve glucose tolerance in obese Rag1-/- mice, but prevented the increased body weight gain and adiposity. Overall, the beneficial effects seemed to be independent of enteroendocrine effects and of major changes in gut microbiota composition. B. uniformis directly induced Tregs generation from naïve CD4+ T cells in vitro and was not required to be viable to improve glucose homeostasis but its viability was necessary to prevent body weight gain in diet-induced obese wild-type mice. CONCLUSIONS: Here we demonstrate that B. uniformis modulates the energy homeostasis in diet-induced obese mice through different mechanisms. The bacterium improves oral glucose tolerance by adaptive immunity-dependent mechanisms that do not require cell viability and prevents body weight gain by adaptive immunity-independent mechanisms which require cell viability. Video Abstract.


Assuntos
Imunidade Adaptativa , Bacteroides , Microbioma Gastrointestinal , Obesidade , Aumento de Peso , Animais , Camundongos , Obesidade/imunologia , Obesidade/microbiologia , Dieta Hiperlipídica/efeitos adversos , Camundongos Obesos , Linfócitos T Reguladores/imunologia , Camundongos Endogâmicos C57BL , Masculino , Humanos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Probióticos/administração & dosagem , Camundongos Knockout , Glucose/metabolismo
11.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891933

RESUMO

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.


Assuntos
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 Proteica
12.
Diabetes ; 73(9): 1391-1410, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38912690

RESUMO

This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized 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 randomization in humans; 2) the highly individualized 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.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiologia , Humanos , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Pesquisa Translacional Biomédica
13.
EFSA J ; 22(5): e8784, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38803682

RESUMO

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) DSM 18112 as a technological additive (functional group: silage additive) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the Panel concluded that owing to the nature of the additive, Lactiplantibacillus plantarum DSM 18112 should be considered a potential skin and respiratory sensitiser, and that any exposure through the skin and respiratory tract is considered a risk. The Panel could not conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

14.
EFSA J ; 22(5): e8799, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38756350

RESUMO

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil obtained from the wood of Juniperus deppeana Steud. (cedarwood Texas oil), when used as a sensory additive for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the essential oil under assessment is safe up to the maximum proposed use levels in complete feed of 15 mg/kg for veal calves (milk replacer), cattle for fattening, sheep, goats, horses, dogs, salmonids and ornamental fish. For the other species, the calculated safe concentrations in complete feed were 5 mg/kg for chickens for fattening, 8 mg/kg for laying hens, 7 mg/kg for turkeys for fattening, 10 mg/kg for piglets, 12 mg/kg for pigs for fattening, 14 mg/kg for sows and dairy cows, 8.5 mg/kg for rabbits and 4 mg/kg for cats. These conclusions were extrapolated to other physiologically related species. For any other species, the additive was considered safe at 4 mg/kg complete feed. The use of cedarwood Texas oil in water for drinking was considered safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. No concerns for consumers and the environment were identified following the use of the additive up to the maximum proposed use level in feed. The additive under assessment should be considered as irritant to skin and eyes, and as a skin and respiratory sensitiser. Since the individual components of cedarwood Texas oil are recognised to flavour food and their function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.

15.
Commun Biol ; 7(1): 219, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388698

RESUMO

Recent evidence suggests a role of sensory neurons expressing the sodium channel Nav1.8 on the energy homeostasis control. Using a murine diphtheria toxin ablation strategy and ad libitum and time-restricted feeding regimens of control or high-fat high-sugar diets, here we further explore the function of these neurons on food intake and on the regulation of gastrointestinal elements transmitting immune and nutrient sensing.The Nav1.8+ neuron ablation increases food intake in ad libitum and time-restricted feeding, and exacerbates daily body weight variations. Mice lacking Nav1.8+ neurons show impaired prandial regulation of gut hormone secretion and gut microbiota composition, and altered intestinal immunity.Our study demonstrates that Nav1.8+ neurons are required to control food intake and daily body weight changes, as well as to maintain physiological enteroendocrine and immune responses and the rhythmicity of the gut microbiota, which highlights the potential of Nav1.8+ neurons to restore energy balance in metabolic disorders.


Assuntos
Microbioma Gastrointestinal , Animais , Camundongos , Peso Corporal , Dieta Hiperlipídica , Ingestão de Alimentos/fisiologia , Microbioma Gastrointestinal/fisiologia , Células Receptoras Sensoriais/metabolismo
16.
Brain Behav Immun ; 118: 117-127, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38402916

RESUMO

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.


Assuntos
Experiências Adversas da Infância , Microbioma Gastrointestinal , Criança , Humanos , Microbioma Gastrointestinal/genética , Estudos Retrospectivos , RNA Ribossômico 16S/genética , Fezes
17.
Mol Nutr Food Res ; 68(3): e2300474, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38038153

RESUMO

SCOPE: Sensory neurons expressing the sodium channel Nav1.8 contain a repertoire of receptors for nutrient, hormonal, and inflammatory ligands. However, their function in key regulators of energy homeostasis control is not well understood and is completely unexplored in females. METHODS AND RESULTS: Mice lacking neurons expressing the sodium channel Nav1.8 were generated using an ablation strategy based on cre recombinase-mediated expression of diphtheria toxin fragment A (DTA) (Nav1.8-cre/DTA mice) to investigate whether these neurons modulate body weight, food intake, gut hormone secretion, gastrointestinal transit, and glucose tolerance in response to nutrient challenges in a sex-dependent manner. Male Nav1.8-cre/DTA mice show resistance to gain weight in response to high-fat high-sugar diet (HFHSD), whereas females lacking Nav1.8+ neurons have improved oral glucose tolerance accompanied by higher insulin levels and attenuated glucagon secretion after an oral glucose load. Female Nav1.8-cre/DTA mice also show higher fasting and postprandial glucagon like peptide-1 (GLP-1) levels with an increased number of GLP-1-positive cells. Finally, ablation of Nav1.8-expressing neurons accelerates the gastrointestinal transit in female mice under HFHSD. CONCLUSION: This data demonstrates sex-dependent differences in the Nav1.8-mediated regulation of energy metabolism, and provides new insights that may help in the design of sex-specific neuromodulation therapies for metabolic disorders induced by diets rich in fats and simple sugars.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Glucose , Camundongos , Masculino , Feminino , Animais , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Camundongos Obesos , Glucose/metabolismo , Células Receptoras Sensoriais/metabolismo , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Homeostase , Canais de Sódio , Insulina/metabolismo , Glicemia/metabolismo
18.
EFSA J ; 21(12): e8466, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046201

RESUMO

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of the authorisation of Enterococcus lactis NCIMB 11181 (Lactiferm®) as a zootechnical additive for weaned piglets, calves for fattening and calves for rearing. The product under assessment is based on a strain originally identified as Enterococcus faecium. During the current assessment, the active agent has been reclassified as Enterococcus lactis. The additive currently authorised is marketed in two formulations: Lactiferm Basic 50 (a solid formulation to be used in feed), and Lactiferm WS200 (a solid 'water-soluble' formulation to be used in water for drinking). The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The Panel concludes that the use of Lactiferm® under the authorised conditions of use remains safe for the target species (calves up to 6 months and weaned piglets up to 35 kg), consumers and the environment. The Lactiferm WS200 formulation of the additive is not irritant to skin or eyes. Owing to the proteinaceous nature of the active agent, both formulations of the additive are considered respiratory sensitisers. It is not possible to conclude on the irritating potential for skin and eyes of the Lactiferm Basic 50 formulation or on the potential of both forms of the additive to cause skin sensitisation. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

19.
EFSA J ; 21(10): e08105, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37860125

RESUMO

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of K-9 Heritage Probiotic Blend® when used as a zootechnical additive (functional group: gut flora stabilisers) for dogs. The product under assessment is based on viable cells of Lacticaseibacillus casei IDAC 210415-01, Limosilactobacillus fermentum IDAC 210415-02, Levilactobacillus brevis IDAC 051120-02 and Enterococcus faecium IDAC 181218-03. The FEEDAP Panel was not in the position to conclude on the identification of the strains and, therefore, the safety of the product cannot be based on the presumption of safety of the active agents. The Panel notes that the use of E. faecium IDAC 181218-03 represents a safety concern because it harbours an acquired antimicrobial resistance gene. Moreover, the hazard related to the presence of additional antimicrobial resistance genes in the active agents cannot be excluded. No tolerance trials on the target animals have been provided. Therefore, the Panel is not in the position to conclude on the safety of the additive for dogs. Regarding the user safety, the Panel cannot conclude on the irritant potential of the additive for skin or eyes due to the absence of data. Given the proteinaceous nature of the active agents, the additive should be considered a respiratory sensitiser. No conclusions could be drawn on its potential to be a skin sensitiser. The use of K-9 Heritage Probiotic Blend® in animal nutrition represents a safety concern for the environment due to the potential carryover of at least an antimicrobial resistance gene. The FEEDAP Panel is not in the position to conclude on the efficacy of K-9 Heritage Probiotic Blend® for the target species.

20.
EFSA J ; 21(9): e08249, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37781415

RESUMO

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of sodium hydroxide as a technological additive (acidity regulator) for dogs, cats and ornamental fish. The applicants have provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concluded that the additive remains safe for all animal species and the environment under the authorised conditions of use. Regarding user safety, the additive is corrosive and therefore the provision of the authorisation that 'breathing protection, eye protection, gloves and protective clothing shall be used during handling' should be confirmed. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

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