Milk kefir alters fecal microbiota impacting gut and brain health in mice.

Kefir is a fermented beverage made of a symbiotic microbial community that stands out for health benefits. Although its microbial profile is still little explored, its effects on modulation of gut microbiota and production of short-chain fatty acids (SCFAs) seems to act by improving brain health. This work aimed to analyze the microbiota profile of milk kefir and its effect on metabolism, oxidative stress, and in the microbiota-gut-brain axis in a murine model. The experimental design was carried out using C57BL-6 mice (n = 20) subdivided into groups that received 0.1 mL water or 0.1 mL (10% w/v) kefir. The kefir proceeded to maturation for 48 h, and then it was orally administered, via gavage, to the animals for 4 weeks. Physicochemical, microbiological, antioxidant analyzes, and microbial profiling of milk kefir beverage were performed as well as growth parameters, food intake, serum markers, oxidative stress, antioxidant enzymes, SCFAs, and metabarcoding were analyzed in the mice. Milk kefir had 76.64 ± 0.42% of free radical scavenging and the microbiota composed primarily by the genus Comamonas. Moreover, kefir increased catalase and superoxide dismutase (colon), and SCFAs in feces (butyrate), and in the brain (butyrate and propionate). Kefir reduced triglycerides, uric acid, and affected the microbiome of animals increasing fecal butyrate-producing bacteria (Lachnospiraceae and Lachnoclostridium). Our results on the brain and fecal SCFAs and the antioxidant effect found were associated with the change in the gut microbiota caused by kefir, which indicates that kefir positively influences the gut-microbiota-brain axis and contributes to the preservation of gut and brain health. KEY POINTS: • Milk kefir modulates fecal microbiota and SCFA production in brain and colon. • Kefir treatment increases the abundance of SCFA-producing bacteria. • Milk kefir increases antioxidant enzymes and influences the metabolism of mice.

Diet-induced obesity in animal models: points to consider and influence on metabolic markers.

Overweight and obesity are a worldwide public health problem. Obesity prevalence has increased considerably, which indicates the need for more studies to better understand these diseases and related complications. Diet induced-obesity (DIO) animal models can reproduce human overweight and obesity, and there are many protocols used to lead to excess fat deposition. So, the purpose of this review was to identify the key points for the induction of obesity through diet, as well as identifying which are the necessary endpoints to be achieved when inducing fat gain. For this, we reviewed the literature in the last 6 years, looking for original articles that aimed to induce obesity through the diet. All articles evaluated should have a control group, in order to verify the results found, and had worked with Sprague-Dawley and Wistar rats, or with C57BL-/-6 mice strain. Articles that induced obesity by other methods, such as genetic manipulation, surgery, or drugs were excluded, since our main objective was to identify key points for the induction of obesity through diet. Articles in humans, in cell culture, in non-rodent animals, as well as review articles, articles that did not have obesity induction and book chapters were also excluded. Body weight and fat gain, as well as determinants related to inflammation, hormonal concentration, blood glycemia, lipid profile, and liver health, must be evaluated together to better determination of the development of obesity. In addition, to select the best model in each circumstance, it should be considered that each breed and sex respond differently to diet-induced obesity. The composition of the diet and calorie overconsumption are also relevant to the development of obesity. Finally, it is important that a non-obese control group is included in the experimental design.

Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeostasis after mucositis induced by 5- fluorouracil.

The beneficial effects of prebiotic, such as fructo-oligosaccharides (FOS), in intestinal inflammation have been demonstrated in several studies. Herein, we evaluate whether joint treatment with FOS, both before and during mucositis, had additional beneficial effects and investigated the mechanisms underlying in the action of FOS on the intestinal barrier. BALB/c mice were randomly divided into five groups: CTR (without mucositis + saline solution), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + 6 % FOS supplementation before disease induction), and TT (mucositis + 6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300 mg/kg) of 5-fluorouracil (5-FU). After 72 h, the animals were euthanized and intestinal permeability (IP), tight junction, bacterial translocation (BT), histology and morphometry, and immunoglobulin A secretory (sIgA), inflammatory infiltrate, and production of short-chain fatty acids (acetate, butyrate and propionate) were evaluated. The MUC group showed an increase in the IP, BT, and inflammatory infiltrate but a decrease in the tight junction expression and butyrate and propionate levels (P < 0.05). In the PT and TT groups, FOS supplementation maintained the IP, tight junction expression, and propionate concentration within physiologic levels, increased butyrate levels, and reduced BT and inflammatory infiltrate (P < 0.05). Total treatment with FOS (TT group) was more effective in maintaining histological score, morphometric parameters, and sIgA production. Thus, total treatment (prophylactic and therapeutic supplementation) with FOS was more effective than pretreatment alone, in reducing 5-FU-induced damage to the intestinal barrier.

Chemoprevention of DMH-Induced Early Colon Carcinogenesis in Male BALB/c Mice by Administration of Lactobacillus Paracasei DTA81.

We evaluated the effects of the probiotic candidate Lactobacillus paracasei DTA81 (DTA81) on liver oxidative stress, colonic cytokine profile, and gut microbiota in mice with induced early colon carcinogenesis (CRC) by 1,2-dimethylhydrazine (DMH). Animals were divided into four different groups (n = 6) and received the following treatments via orogastric gavage for 8 weeks: Group skim milk (GSM): 300 mg/freeze-dried skim milk/day; Group L. paracasei DTA81 (DTA81): 3 × 109 colony-forming units (CFU)/day; Group Lactobacillus rhamnosus GG (LGG): 3 × 109 CFU/day; Group non-intervention (GNI): 0.1 mL/water/day. A single DMH dose (20 mg/kg body weight) was injected intraperitoneally (i.p), weekly, in all animals (seven applications in total). At the end of the experimental period, DTA81 intake reduced hepatic levels of carbonyl protein and malondialdehyde (MDA). Moreover, low levels of the pro-inflammatory cytokines Interleukin-6 (IL-6) and IL-17, as well as a reduced expression level of the proliferating cell nuclear antigen (PCNA) were observed in colonic homogenates. Lastly, animals who received DTA81 showed an intestinal enrichment of the genus Ruminiclostridium and increased concentrations of caecal acetic acid and total short-chain fatty acids. In conclusion, this study indicates that the administration of the probiotic candidate DTA81 can have beneficial effects on the initial stages of CRC development.

Synbiotic VSL#3 and yacon-based product modulate the intestinal microbiota and prevent the development of pre-neoplastic lesions in a colorectal carcinogenesis model.

Colorectal cancer is a public health problem, with dysbiosis being one of the risk factors due to its role in intestinal inflammation. Probiotics and synbiotics have been used in order to restore the microbiota balance and to prevent colorectal carcinogenesis. We aimed to investigate the effects of the probiotic VSL#3® alone or in combination with a yacon-based prebiotic concentrate on the microbiota modulation and its influence on colorectal carcinogenesis in an animal model. C57BL/6J mice were divided into three groups: control (control diet), probiotic (control diet + VSL#3®), and synbiotic (yacon diet + VSL#3®). The diets were provided for 13 weeks and, from the third one, all animals were subjected to induction of colorectal cancer precursor lesions. Stool samples were collected to evaluate organic acids, feces pH, ß-glucuronidase activity, and microbiota composition. The colon was used to count pre-neoplastic lesions and to determine the cytokines. The microbiota composition was influenced by the use of probiotic and synbiotic. Modifications were also observed in the abundance of bacterial genera with respect to the control group, which confirms the interference of carcinogenesis in the microbiota. Pre-neoplastic lesions were reduced by the use of the synbiotic, but not with the probiotic. The protection provided by the synbiotic can be attributed to the modulation of the intestinal inflammatory response, to the inhibition of a pro-carcinogenic enzyme, and to the production of organic acids. The modulation of the composition and activity of the microbiota contributed to beneficial changes in the intestinal microenvironment, which led to a reduction in carcinogenesis. KEY POINTS: • Synbiotic reduces the incidence of colorectal cancer precursor lesions. • Synbiotic modulates the composition and activity of intestinal microbiota. • Synbiotic increases the abundance of butyrate-producing bacteria.

Does aerobic exercise associated with tryptophan supplementation attenuates hyperalgesia and inflammation in female rats with experimental fibromyalgia?

The objective of this study was to verify the effects of aerobic exercise associated with tryptophan (TRP) supplementation on hyperalgesia, as well as on cortisol, IL-6 and TNF concentrations in female rats with experimental fibromyalgia (FM). Female Wistar rats (initial body weight: ~ 350 g; age: 12 months) were randomly divided into 5 groups: CON (Control); F (Fibromyalgia induced); FE (Fibromyalgia induced plus exercise); FES (Fibromyalgia induced plus exercise and TRP supplementation) and FS (Fibromyalgia induced plus TRP supplementation). Fibromyalgia was induced with two injections (20 µL) of acidic saline (pH 4.0) into the right gastrocnemius muscle with a 3-day interval. Control animals received the same doses of neutral saline (pH 7.4). The exercised animals underwent progressive low-intensity aerobic exercise (LIAE) on a treadmill (10-12 m/min, 30-45 min/day, 5 days/week) for three weeks. During this period, the supplemented animals received a TRP supplemented diet (210 g/week), while the others received a control diet. Mechanical hyperalgesia was evaluated weekly and serum cortisol and muscle IL-6 and TNF concentrations were assessed after three weeks of interventions. Experimental FM caused bilateral hind paw hyperalgesia and augmented serum cortisol and muscle IL-6 concentrations. After 3 weeks of interventions, LIAE alone reduced hyperalgesia (151%) and reduced serum cortisol concentrations (72%). Tryptophan supplementation itself diminished hyperalgesia (57%) and reduced serum cortisol concentrations (67%). Adding TRP supplementation to LIAE did not further reduce hyperalgesia significantly (11%), which was followed by an important decrease in muscle IL-6 concentrations (68%), though reduction in serum cortisol pulled back to 45%. Muscle TNF concentrations were not affected. In conclusion, the association of TRP supplementation to LIAE does not potentiate significantly the reduction of bilateral mechanical hyperalgesia promoted by LIAE in female rats with experimental FM, however an important decrease in IL-6 is evident.

Consumption of extra virgin olive oil improves body composition and blood pressure in women with excess body fat: a randomized, double-blinded, placebo-controlled clinical trial.

PURPOSE: Despite the fact that extra virgin olive oil (EVOO) is widely used in obese individuals to treat cardiovascular diseases, the role of EVOO on weight/fat reduction remains unclear. We investigated the effects of energy-restricted diet containing EVOO on body composition and metabolic disruptions related to obesity. METHODS: This is a randomized, double-blinded, placebo-controlled clinical trial in which 41 adult women with excess body fat (mean ± SD 27.0 ± 0.9 year old, 46.8 ± 0.6% of total body fat) received daily high-fat breakfasts containing 25 mL of soybean oil (control group, n = 20) or EVOO (EVOO group, n = 21) during nine consecutive weeks. Breakfasts were part of an energy-restricted normal-fat diets (-2090 kJ, ~32%E from fat). Anthropometric and dual-energy X-ray absorptiometry were assessed, and fasting blood was collected on the first and last day of the experiment. RESULTS: Fat loss was ~80% higher on EVOO compared to the control group (mean ± SE: -2.4 ± 0.3 kg vs. -1.3 ± 0.4 kg, P = 0.037). EVOO also reduced diastolic blood pressure when compared to control (-5.1 ± 1.6 mmHg vs. +0.3 ± 1.2 mmHg, P = 0.011). Within-group differences (P < 0.050) were observed for HDL-c (-2.9 ± 1.2 mmol/L) and IL-10 (+0.9 ± 0.1 pg/mL) in control group, and for serum creatinine (+0.04 ± 0.01 µmol/L) and alkaline phosphatase (-3.3 ± 1.8 IU/L) in the EVOO group. There was also a trend for IL-1ß EVOO reduction (-0.3 ± 0.1 pg/mL, P = 0.060). CONCLUSION: EVOO consumption reduced body fat and improved blood pressure. Our results indicate that EVOO should be included into energy-restricted programs for obesity treatment.

CHEMICAL COMPOSITION, CHARACTERIZATION OF ANTHOCYANINS AND ANTIOXIDANT POTENTIAL OF EUTERPE EDULIS FRUITS: APPLICABILITY ON GENETIC DYSLIPIDEMIA AND HEPATIC STEATOSIS IN MICE.

UNLABELLED: The significance of polyphenol intake for the prevention of chronic diseases is controversial. OBJECTIVE: this study investigated the chemical composition and antioxidant potential of an anthocyanin-rich extract from Euterpe edulis fruits (LPEF) and its effects on liver steatosis in dyslipidemic apoE-/- knockout mice. MATERIALS AND METHODS: mice were divided into G1 (C57BL/6) standard diet; G2 (apoE-/-) standard diet, G3 (apoE-/-) 2% LPEF, G4 (apoE-/-) 6% LPEF, G5 (apoE-/-) 10% LPEF, G6 (apoE-/-) 2% α-tocopherol acetate. After 75 days of treatment, the animals were euthanized. The LPEF contained a high level of monomeric anthocyanins (301.4 mg/100g) and marked antioxidant activity. RESULTS: Catalase activity was reduced in G3, G4, G5 and G6 compared to G2. Superoxide dismutase was reduced only in G4. The animals in G4, G5, and G6 showed low HDL and triglycerides levels compared to G2. The proportion of lipid droplets in liver tissue was reduced in G4 and G5 compared to G2, G3, and G6. CONCLUSION: The results indicated that E. edulis pulp is rich in anthocyanins and the LPEF dietary consumption can reduce the severity of liver steatosis in apoE-/- mice, an effect that is potentially mediated by the antioxidant activity of this extract and modulation of triglyceride serum levels.

El papel de los polifenoles en la prevención de enfermedades crónicas es controvertido. Objetivo: este estudio investigó la composición química y el potencial antioxidante de un extracto del fruto de Euterpe edulis rico en antocianinas (LPEF) y sus efectos en la esteatosis hepática en ratones apoE-/- knockout con dislipidemia. Material y métodos: los ratones fueron divididos en los siguientes grupos; G1 (C57BL/6) con una dieta estándar; G2 (apoE-/-) con dieta estándar; G3 G3 (apoE-/-) con 2% de LPEF; G4 (apoE-/-) con 6% de LPEF; G5 (apoE-/-) con 10% de LPEF y G6 (apoE-/-) con 2% acetato α-tocoferol (α-tocopherol acetate). Después de 75 días de tratamiento, los animales fueron eutanizados. El LPEF contenía un alto nivel de antocianinas monoméricas (301,4 mg/100 g) con notable actividad antioxidante. Resultados: la actividad catalasa fue reducida en los grupos G3, G4, G5 y G6 comparada con G2. La superoxidasa dismutasa solo se redujo en el grupo G4. Los animales de G4, G5 y G6 mostraron bajos niveles de HDL triglicéridos, comparados con G2. La proporción de lípidos en el tejido hepático fue reducida en G4 y G5, comparado con G2, G3 y G6. Conclusión: los resultados indicaron que la pulpa de E. edulis es rica en antocianinas, y que el consumo de LPEF en la dieta puede reducir la severidad de la esteatosis hepática en ratones apoE-/-, un efecto que es potencialmente mediado por la actividad antioxidante de este extracto y la modulación en los niveles séricos de triglicéridos.

Inflammatory markers in relation to body composition, physical activity and assessment of nutritional status of the adolescents.

INTRODUCTION: The evaluation of inflammatory markers during adolescence can monitor different stages and manifestation of chronic diseases in adulthood. The control of the subclinical inflammation process through changes in lifestyle, especially in the practice of physical activity and dietary education can mitigate the effects of risk factors that trigger the process of atherosclerosis. OBJECTIVE: To do a critical review regarding inflammatory markers as a risk factor of cardiovascular disease in relation to body composition, physical activity and assessment of nutritional status of adolescents. METHODS: A literature review was performed in the following electronic databases: PUBMED, SCIELO and CONCHRANE COLLECTION. The following associated terms were used "inflammation AND cardiovascular diseases AND nutritional status OR body composition OR physical activity". There were topics created for the discussion of subjects: obesity and risk factors for cardiovascular disease during adolescence; expression of inflammatory markers in adolescence; development of cardiovascular disease with inflammatory markers, and finally, inflammatory markers, physical activity and nutritional evaluation. RESULTS: It was observed that the inflammatory markers may manifest in adolescence and be related to risk factors for cardiovascular diseases. Physical activity and nutritional evaluation featured as non-pharmacological measures to control the incidence of inflammatory markers and cardiovascular risk factor. CONCLUSIONS: Intervention studies may clarify how the adoption of a more proper lifestyle can influence the inflammatory process.

Introducción: La evaluación de los marcadores inflamatorios en la adolescencia puede monitorear diferentes etapas y manifestación de las enfermedades crónicas en la edad adulta. El control del proceso de inflamación subclínica mediante cambios en el estilo de vida, especialmente en la práctica de la actividad física y la educación dietética puede mitigar los efectos de los factores de riesgo que desencadenan el proceso de la aterosclerosis. Objetivo: Hacer una revisión crítica sobre los marcadores inflamatorios como un factor de riesgo de enfermedad cardiovascular (ECV) en relación con la composición corporal, la actividad física y la evaluación del estado nutricional de los adolescentes. Métodos: Una revisión de la literatura se realizó en las siguientes bases de datos electrónicas: PUBMED, SCIELO y COLECCIÓN CONCHRANE. Los siguientes términos asociados se utilizaron "composición de la inflamación y las enfermedades cardiovasculares y el estado nutricional, organismo o la actividad física". Había temas creados para la discusión de la materia: factores de obesidad y riesgo de enfermedad cardiovascular en la adolescencia; expresión de marcadores inflamatorios en la adolescencia; desarrollo de la enfermedad cardiovascular con marcadores inflamatorios y, por último, los marcadores de inflamación, la actividad física y la evaluación nutricional. Resultados: Se observó que los marcadores inflamatorios pueden manifestarse en la adolescencia y se relaciona con factores de riesgo de enfermedades cardiovasculares. La actividad física y la evaluación nutricional ofrecida como medidas no farmacológicas para el control de la incidencia de los marcadores inflamatorios y factores de riesgo cardiovascular. Conclusiones: Los estudios de intervención pueden aclarar cómo la adopción de un estilo de vida más adecuada puede influir en el proceso inflamatorio.

Intestinal microbiota and probiotics in celiac disease.

Celiac disease (CD) is a common chronic autoimmune enteropathy caused by gluten intake. To date, the only therapy for CD is the complete exclusion of dietary sources of grains and any food containing gluten. It has been hypothesized that the intestinal microbiota is somehow involved in CD. For this reason, probiotics are appearing as an interesting adjuvant in the dietetic management of CD. This review aims to discuss the characteristics of the microbiota in CD subjects and the use of probiotics as a novel therapy for CD. Comparisons between children with CD and controls show that their microbiota profiles differ; the former have fewer lactobacilli and bifidobacteria. Specific probiotics have been found to digest or alter gluten polypeptides. It has also been demonstrated that some bacterial species belonging to the genera Lactobacillus and Bifidobacterium exert protective properties on epithelial cells from damage caused by gliadin.

Efeitos biológicos das antocianinas no processo aterosclerótico / Biological effects of anthocyanins on the atherosclerotic process

As antocianinas são metabólitos secundários biossintetizados por plantas e pertencentes ao grupo dos flavonóides. Pesquisas indicam que as antocianinas podem aumentar a resistência da LDL à oxidação, comparado a outros compostos com alto poder antioxidante, como o ácido L-ascórbico, e reduzir fatores pró-inflamatórios, como citocinas, quimiocinas, moléculas de adesão e metaloproteinases. Como a inflamação e a oxidação são processos característicos da aterosclerose, tem se investigado o efeito das antocianinas no processo aterosclerótico e há evidências que estes compostos podem diminuir o desenvolvimento e a progressão das lesões ateroscleróticas.

Anthocyanins are secondary metabolites biosynthesized by plants and belonging to the group of flavonoids. Research indicates that anthocyanins can increase resistance of LDL to oxidation, compared to other compounds with high antioxidant properties, such as L-ascorbic acid, and reduce pro-inflammatory factors such as cytokines, chemokines, adhesion molecules and metalloproteinases. As inflammation and oxidation processes are characteristic of atherosclerosis, has investigated the effect of anthocyanins in the atherosclerotic process and there is evidence that these compounds can reduce the development and progression of atherosclerotic lesions.