RESUMO
In a previous study, we reported the in vitro potential probiotic and gamma-aminobutyric acid (GABA) production, of several strains from a collection of Lactiplantibacillus (Lpb) strains within the community of natural whey starters from the artisanal cheese industry. GABA is a non-protein amino acid widely distributed in nature and produced in animals, plants, and microorganisms. However, the best known role of GABA is its function as the major inhibitory neurotransmitter of the central nervous system. Preclinical and clinical evidence suggests that the GABAergic system has a relevant role in mental health disorders, such as anxiety and major depression. The modulation of the GABAergic system has been suggested as a potential strategy for treatment, one such mechanism of modulation is the influence of the microbiota-gut-brain axis through probiotic treatments. The present study was designed to investigate the in vivo probiotic potential of LPB145, a Lactiplantibacillus strain previously characterised as a GABA-producing potentially probiotic strain. Therefore, we evaluated the behavioural effects of chronic oral administration of LPB145 on rats' anxiety- and depression-like behaviours, using the elevated plus maze, open field, and the forced swimming test. The impact of LPB145 strain treatment on the gut microbiota structure and diversity was assessed to discern a possible mechanism of action of the LPB145 treatment through the microbiota-gut-brain axis. Our results showed that LPB145 administration induced an antidepressive-like behaviour without changes in locomotor activity. In contrast, the treatment did not modify the experimental anxiety. The structure and diversity of the intestinal microbiota remained unaffected by the treatment when compared to the control. However, specific clades that could be implicated in the behavioural changes did show differences in their relative abundance. These findings provide evidence regarding the potential of probiotic strains isolated from alimentary sources, to modulate the microbiota-gut-brain axis and positively impact mental health.
Assuntos
Ansiedade , Queijo , Depressão , Microbioma Gastrointestinal , Probióticos , Ácido gama-Aminobutírico , Animais , Probióticos/administração & dosagem , Probióticos/farmacologia , Ansiedade/microbiologia , Ratos , Ácido gama-Aminobutírico/metabolismo , Queijo/microbiologia , Depressão/microbiologia , Depressão/terapia , Masculino , Ratos Wistar , Comportamento Animal/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.
Assuntos
Ansiedade , Eixo Encéfalo-Intestino , Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Ansiedade/microbiologia , Eixo Encéfalo-Intestino/fisiologia , Ratos , Ratos Sprague-Dawley , Obesidade/microbiologia , Obesidade/psicologia , Obesidade/metabolismo , Transdução de Sinais/fisiologia , Comportamento Animal/fisiologiaRESUMO
Tuberculosis (TB) is a chronic infectious disease in which prolonged, non-resolutive inflammation of the lung may lead to metabolic and neuroendocrine dysfunction. Previous studies have reported that individuals coursing pulmonary TB experience cognitive or behavioural changes; however, the pathogenic substrate of such manifestations have remained unknown. Here, using a mouse model of progressive pulmonary TB, we report that, even in the absence of brain infection, TB is associated with marked increased synthesis of both inflammatory and anti-inflammatory cytokines in discrete brain areas such as the hypothalamus, the hippocampal formation and cerebellum accompanied by substantial changes in the synthesis of neurotransmitters. Moreover, histopathological findings of neurodegeneration and neuronal death were found as infection progressed with activation of p38, JNK and reduction in the BDNF levels. Finally, we perform behavioural analysis in infected mice throughout the infection, and our data show that the cytokine and neurochemical changes were associated with a marked onset of cognitive impairment as well as depressive- and anxiety-like behaviour. Altogether, our results suggest that besides pulmonary damage, TB is accompanied by an extensive neuroinflammatory and neurodegenerative state which explains some of the behavioural abnormalities found in TB patients.
Assuntos
Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Mycobacterium tuberculosis/metabolismo , Neurônios/patologia , Tuberculose Pulmonar/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/microbiologia , Sintomas Comportamentais/microbiologia , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Encéfalo/citologia , Encéfalo/enzimologia , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Disfunção Cognitiva/microbiologia , Depressão/metabolismo , Depressão/microbiologia , Modelos Animais de Doenças , Regulação para Baixo , Hipocampo/citologia , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/patologia , Janus Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/patogenicidade , Neurônios/citologia , Neurotransmissores/metabolismo , Tuberculose Pulmonar/enzimologia , Tuberculose Pulmonar/patologia , Tuberculose Pulmonar/psicologia , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Psychobiotics correspond to a class of probiotics, mainly of the genus Lactobacillus and Bifidobacterium, capable of producing neuroactive substances, such as γ-aminobutyric acid (GABA) and serotonin, which exert effects on the brain-gut axis. Evidence suggests that psychobiotics can have a beneficial effect on mood, anxiety and cognition. The present study evaluated the effects of chronic administration of two new strains of Lactobacillus plantarum, L. plantarum 286 (Lp 286) and L. plantarum 81 (Lp 81) isolated from the fermentation of cocoa (Theobroma cacao L.) and cupuaçu (Theobroma grandiflorum), respectively, on cognitive, anxiety- and depressive-like behaviors in male Swiss mice. Different groups of animals were administered (oral gavage) solutions of vehicle (0.85% saline plus 15% skim milk), Lp 286 (109/0.1 ml CFU) or Lp 81 (109/0.1 ml CFU) for 30 days, and animals were tested for general locomotor activity, depressive-like behavior in the forced swim test, and learning/memory and anxiety-like behavior in the plus-maze discriminative avoidance task. Treatment with the strains Lp 286 and Lp 81 did not interfere with locomotor activity or learning and memory. The Lp 286 strain exerted anti-depressant- and anxiolytic-like effects under our experimental conditions. Our findings add to the current body of evidence suggesting that probiotics from the genus Lactobacillus may exert psychobiotic potential and introduce a new strain, Lp 286, as a potential candidate in the prevention or as therapeutic adjuvant in the treatment of mental disorders.
Assuntos
Ansiedade/microbiologia , Comportamento Animal , Cognição , Depressão/microbiologia , Lactobacillus plantarum/fisiologia , Animais , Locomoção , Masculino , Aprendizagem em Labirinto , CamundongosRESUMO
OBJECTIVES: To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. SUBJECTS AND METHODS: A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. RESULTS: Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. CONCLUSIONS: Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Dispepsia/complicações , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Transtornos do Humor/complicações , Adulto , Ansiedade/metabolismo , Ansiedade/microbiologia , Biópsia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/microbiologia , Duodeno/metabolismo , Duodeno/microbiologia , Duodeno/patologia , Dispepsia/microbiologia , Feminino , Mucosa Gástrica/metabolismo , Gastroscopia , Infecções por Helicobacter/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/microbiologia , Estado Nutricional , Estômago/microbiologia , Estômago/patologiaRESUMO
Objectives To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. Subjects and methods A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. Results Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. Conclusions Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients. .
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 1/complicações , Dispepsia/complicações , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Transtornos do Humor/complicações , Ansiedade/metabolismo , Ansiedade/microbiologia , Biópsia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/microbiologia , Duodeno/metabolismo , Duodeno/microbiologia , Duodeno/patologia , Dispepsia/microbiologia , Gastroscopia , Infecções por Helicobacter/metabolismo , Transtornos do Humor/microbiologia , Estado Nutricional , Estômago/metabolismo , Estômago/microbiologia , Estômago/patologiaRESUMO
In the past few years, intestinal microbiota has emerged as a novel target for the treatment of gut-brain axis alterations. These include functional gastrointestinal disorders, such as irritable bowel syndrome (IBS), which can be comorbid with stress-related psychiatric conditions. Thus, modulation of the microbiota (e.g. with the use of probiotics) could be proposed as a novel strategy not only for the treatment of IBS but also as an adjuvant for psychiatric treatment of anxiety and depression.
Assuntos
Gastroenteropatias/microbiologia , Trato Gastrointestinal/microbiologia , Síndrome do Intestino Irritável/microbiologia , Animais , Ansiedade/tratamento farmacológico , Ansiedade/microbiologia , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/fisiopatologia , Depressão/tratamento farmacológico , Depressão/microbiologia , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/fisiopatologia , Trato Gastrointestinal/fisiopatologia , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/fisiopatologia , Probióticos/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/microbiologiaRESUMO
It has been suggested that the parasite Toxoplasma gondii reduces the fear of rodents toward their feline predators, which may lead to an augmented rate of predation and multiplication of the parasite through an increased number of life cycles. To investigate whether T. gondii infection induces selective effects on behavior associated with anxiety, Wistar rats were inoculated i.p. with several doses of T. gondii tachyzoites and tested in two animal tests of anxiety. In the third week following inoculation, rats infected with 100 and 1000 tachyzoites increased plus-maze open arm exploration in a dose-related manner. However, no effect was detected in either social interaction levels or motor activity measures. In the seventh week after inoculation, rats infected with 100 and 1000 tachyzoites showed increased open arm exploration and social investigation without change on any motor activity measures. However, rats infected with a higher dose (1500 tachyzoites) showed a drop in locomotion. These data support the hypothesis that T. gondii impairs mechanism of warning as a function of reduced anxiety. The pattern of brain colonization by the parasite and the host immune response suggests that the predominant invasion to limbic areas works as a natural anxiolytic mechanism.