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CONTEXT: Kefir consumption has been associated with immune response modulation, antioxidant, and anti-inflammatory effects. OBJECTIVE: The objective of this systematic review was to investigate the role of kefir against inflammation and the main response mechanisms involved in this process in a murine model. DATA SOURCES: The searches were searched in the PubMed, Science Direct, and LILACS databases. Only murine model studies, according to PRISMA guidelines, published in the past 10 years were included. STUDY SELECTION: Only articles about original and placebo-controlled experiments in murine models used to investigate the anti-inflammatory mechanisms of kefir were considered. Of the articles found, 349 were excluded according to the following criteria: duplicate articles (n = 99), off-topic title and abstract (n = 157), reviews (n = 47), studies in vitro (n = 29), and studies with humans (n = 17). In total, 23 studies were included in this review. DATA EXTRACTION: Two independently working authors assessed the risk of bias and extracted data from the included studies. RESULTS: Kefir consumption had positive effects on inflammation modulation. The main mechanisms involved were the reduction of pro-inflammatory and molecular markers; reduction in inflammatory infiltrate in tissues, serum biomarkers, risk factors for chronic diseases, and parasitic infection; composition and metabolic activity change of intestinal microbiota and mycobiota; activation of humoral and cellular immunity; and modulation of oxidative stress. CONCLUSIONS: Kefir modulates the immune system in different experimental models, among other secondary outcomes, to improve overall health. The beverage reduces inflammation through the alternation between innate, Th1, and Th2 responses, reducing levels of pro-inflammatory cytokines while increasing those of anti-inflammatory ones. In addition, it also mediates immunomodulatory and protective effects through the numerous molecular biomarkers and organic acids produced and secreted by kefir in the intestinal microbiota. The health-promoting effects attributed to kefir may help in the different treatments of inflammatory, chronic, and infectious diseases in the population.
Assuntos
Kefir , Animais , Camundongos , Anti-Inflamatórios , Biomarcadores , Modelos Animais de Doenças , Inflamação/metabolismoRESUMO
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.
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Kefir , Microbiota , Camundongos , Animais , Kefir/microbiologia , Leite/metabolismo , Antioxidantes , Camundongos Endogâmicos C57BL , Fezes/microbiologia , Ácidos Graxos Voláteis/metabolismo , Butiratos , Encéfalo/metabolismoRESUMO
Kefir has been suggested as a possible bacterial prophylaxis against Salmonella and IL-10 production seems to be crucial in the pathogenesis of salmonellosis in mice. This study evaluated the role of IL-10 in the inflammation and gut microbiome in mice consuming milk kefir and orally challenged with Salmonella enterica serovar Typhimurium. C57BL wild type (WT) (n = 40) and C57BL IL-10-/- (KO) (n = 40) mice were subdivided into eight experimental groups either treated or not with kefir. In the first 15 days, the water groups received filtered water (0.1 mL) while the kefir groups received milk kefir (10% w/v) orally by gavage. Then, two groups of each strain received a single dose (0.1 mL) of the inoculum of S. Typhimurium (ATCC 14028, dose: 106 CFU mL-1). After four weeks, the animals were euthanized to remove the colon for further analysis. Kefir prevented systemic infections only in IL-10-/- mice, which were able to survive, regulate cytokines, and control colon inflammation. The abundance in Lachnospiraceae and Roseburia, and also the higher SCFA production in the pre-infection, showed that kefir has a role in intestinal health and protection, colonizing and offering competition for nutrients with the pathogen as well as acting in the regulation of salmonella infectivity only in the absence of IL-10. These results demonstrate the role of IL-10 in the prognosis of salmonellosis and how milk kefir can be used in acute infections.
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Microbioma Gastrointestinal , Kefir , Infecções por Salmonella , Camundongos , Animais , Leite , Interleucina-10/genética , Camundongos Endogâmicos C57BL , Infecções por Salmonella/prevenção & controle , Inflamação , Salmonella typhimurium/genéticaRESUMO
The polymorphisms of fatty acid desaturase genes FADS1 and FADS2 have been associated with an increase in weight gain. We investigated FADS1 and FADS2 gene polymorphisms and the relation between ω-3 and ω-6 fatty acid plasma concentrations and gestational weight gain. A prospective cohort study of 199 pregnant women was followed in Santo Antônio de Jesus, Brazil. Plasma levels of polyunsaturated fatty acids (PUFAs) were measured at baseline and gestational weight gain during the first, second, and third trimesters. Fatty acid recognition was carried out with the aid of gas chromatography. Single nucleotide polymorphisms (SNPs) were genotyped using real-time PCR. Statistical analyses included Structural Equation Modelling. A direct effect of FADS1 and FADS2 gene polymorphisms on gestational weight was observed; however, only the SNP rs174575 (FADS2) showed a significant positive direct effect on weight over the course of the pregnancy (0.106; p = 0.016). In terms of the influence of SNPs on plasma levels of PUFAs, it was found that SNP rs174561 (FADS1) and SNP rs174575 (FADS2) showed direct adverse effects on plasma concentrations of ω-3 (eicosapentaenoic acid and alpha-linoleic acid), and only SNP rs174575 had positive direct effects on plasma levels of ARA and the ARA/LA (arachidonic acid/linoleic acid) ratio, ω-6 products, while the SNP rs3834458 (FADS2) had an adverse effect on plasma concentrations of EPA, leading to its increase. Pregnant women who were heterozygous and homozygous for the minor allele of the SNP rs3834458 (FADS2), on the other hand, showed larger concentrations of series ω-3 substrates, which indicates a protective factor for women's health.
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Dessaturase de Ácido Graxo Delta-5 , Ácidos Graxos Dessaturases , Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-6 , Ganho de Peso na Gestação , Estudos de Coortes , Dessaturase de Ácido Graxo Delta-5/sangue , Dessaturase de Ácido Graxo Delta-5/genética , Ácidos Graxos Dessaturases/sangue , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Obesity is still a worldwide public health problem, requiring the development of adjuvant therapies to combat it. In this context, modulation of the intestinal microbiota seems prominent, given that the composition of the intestinal microbiota contributes to the outcome of this disease. The aim of this work is to investigate the treatment with an antimicrobial and/or a potential probiotic against overweight. METHODS: Male C57BL/6J mice were subjected to a 12-week overweight induction protocol. After that, 4-week treatment was started, with mice divided into four groups: control, treated with distilled water; potential probiotic, with Lactobacillus gasseri LG-G12; antimicrobial, with ceftriaxone; and antimicrobial + potential probiotic with ceftriaxone in the first 2 weeks and L. gasseri LG-G12 in the subsequent weeks. RESULTS: The treatment with ceftriaxone in isolated form or in combination with the potential probiotic provided a reduction in body fat. However, such effect is supposed to be a consequence of the negative action of ceftriaxone on the intestinal microbiota composition, and this intestinal dysbiosis may have contributed to the destruction of the intestinal villi structure, which led to a reduction in the absorptive surface. Also, the effects of L. gasseri LG-G12 apparently have been masked by the consumption of the high-fat diet. CONCLUSIONS: The results indicate that the use of a ceftriaxone in the adjuvant treatment of overweight is not recommended due to the potential risk of developing inflammatory bowel disease.
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Ceftriaxona/farmacologia , Disbiose , Microbioma Gastrointestinal , Absorção Intestinal , Obesidade , Adjuvantes Farmacêuticos/farmacologia , Animais , Antibacterianos/farmacologia , Disbiose/induzido quimicamente , Disbiose/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Doenças Inflamatórias Intestinais/imunologia , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/imunologia , Lactobacillus gasseri/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Probióticos/farmacologia , Medição de RiscoRESUMO
The development of adjuvant therapies for obesity treatment is justified by the high prevalence of this disease worldwide, and the relationship between obesity and intestinal microbiota is a promising target for obesity treatment. Therefore, this study aimed at investigating the adjuvant treatment of obesity through the use of potential probiotics and antibiotics, either separately or sequentially. In the first phase of the experiment, animals had diet-induced obesity with consumption of a high saturated fat diet and a fructose solution. After this period, there was a reduction in caloric supply, that is the conventional treatment of obesity, and the animals were divided into 5 experimental groups: control group (G1), obese group (G2), potential probiotic group (G3), antibiotic group (G4), and antibiotic followed by potential probiotic group (G5). The adjuvant treatments lasted 4 weeks and were administered daily, via gavage: Animals in G1 and G2 received distilled water, the G3 obtained Lactobacillus gasseri LG-G12, and the G4 received ceftriaxone. The G5 received ceftriaxone for 2 weeks, followed by the offer of Lactobacillus gasseri LG-G12 for another 2 weeks. Parameters related to obesity, such as biometric measurements, food consumption, biochemical tests, histological assessments, short-chain fatty acids concentration, and composition of the intestinal microbiota, were analyzed. The treatment with caloric restriction and sequential supply of antibiotics and potential probiotics was able to reduce biometric measures, increase brown adipose tissue, and alter the intestinal microbiota phyla, standing out as a promising treatment for obesity.
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Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Microbioma Gastrointestinal , Obesidade , Probióticos , Tecido Adiposo Marrom , Biometria , Humanos , Obesidade/tratamento farmacológicoRESUMO
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.
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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 mucositisâ¯+â¯saline solution), FOS (without mucositisâ¯+â¯6 % FOS), MUC (mucositisâ¯+â¯saline solution), PT (mucositisâ¯+â¯6 % FOS supplementation before disease induction), and TT (mucositisâ¯+â¯6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300â¯mg/kg) of 5-fluorouracil (5-FU). After 72â¯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 (Pâ¯<â¯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 (Pâ¯<â¯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.
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Bactérias/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Íleo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosite/induzido quimicamente , Oligossacarídeos/farmacologia , Prebióticos , Junções Íntimas/efeitos dos fármacos , Acetatos/metabolismo , Animais , Bactérias/metabolismo , Translocação Bacteriana/efeitos dos fármacos , Butiratos/metabolismo , Modelos Animais de Doenças , Fluoruracila , Íleo/metabolismo , Íleo/microbiologia , Íleo/patologia , Imunoglobulina A Secretora/metabolismo , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos Endogâmicos BALB C , Mucosite/metabolismo , Mucosite/microbiologia , Mucosite/patologia , Permeabilidade , Propionatos/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/microbiologia , Junções Íntimas/patologiaRESUMO
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.
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Neoplasias Colorretais , Microbioma Gastrointestinal , Probióticos , Simbióticos , Animais , Carcinogênese , Neoplasias Colorretais/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Microambiente TumoralRESUMO
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.