RESUMO
Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson's disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by Lactiplantibacillus plantarum CRL2130 (riboflavin overproducing strain), Streptococcus thermophilus CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies.
Assuntos
Benserazida , Levodopa , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Transtornos Parkinsonianos , Animais , Levodopa/farmacologia , Benserazida/farmacologia , Benserazida/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/metabolismo , Masculino , Camundongos , Combinação de Medicamentos , Microbioma Gastrointestinal/efeitos dos fármacos , Modelos Animais de Doenças , Lactobacillales , Probióticos/uso terapêutico , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Streptococcus thermophilus/efeitos dos fármacosRESUMO
Inorganic phosphate (Pi) concentration modulates polyphosphate (polyP) levels in diverse bacteria, affecting their physiology and survival. Lactiplantibacillus paraplantarum CRL 1905 is a lactic acid bacterium isolated from quinoa sourdough with biotechnological potential as starter, for initiating fermentation processes in food, and as antimicrobial-producing organism. The aim of this work was to evaluate the influence of the environmental Pi concentration on different physiological and molecular aspects of the CRL 1905 strain. Cells grown in a chemically defined medium containing high Pi (CDM + P) maintained elevated polyP levels up to late stationary phase and showed an enhanced bacterial survival and tolerance to oxidative stress. In Pi sufficiency condition (CDM-P), cells were ~ 25% longer than those grown in CDM + P, presented membrane vesicles and a ~ 3-fold higher capacity to form biofilm. Proteomic analysis indicated that proteins involved in the "carbohydrate transport and metabolism" and "energy production and conversion" categories were up-regulated in high Pi stationary phase cells, implying an active metabolism in this condition. On the other hand, stress-related chaperones and enzymes involved in cell surface modification were up-regulated in the CDM-P medium. Our results provide new insights to understand the CRL 1905 adaptations in response to differential Pi conditions. The adjustment of environmental Pi concentration constitutes a simple strategy to improve the cellular fitness of L. paraplantarum CRL 1905, which would benefit its potential as a microbial cell factory.
RESUMO
Early weaning is an important stressor that impairs the piglet´s health, and essential oils appear as promising candidates to improve it instead of antibiotics. The aim of this study was to evaluate the effect of oral supplementation of free and nanoencapsulated Minthostachys verticillata essential oil (EO and NEO, respectively) on immunological, biochemical and antioxidants parameters as well as on gut microbiota in weaned piglets. EO was extracted by hydrodistillation and nanoencapsulation was performed by high-energy method using Tween 80 and Span 60 as surfactants. EO and NEO were chemically analyzed by gas chromatography-mass spectrometry (GC-MS). The cytotoxic effects of both EO and NEO was evaluated on Caco-2 cell line. For in vivo assay, male weaned piglets (age: 28 days, mean initial body weight: 11.63 ± 0.37 kg) were randomly distributed in six groups of six animals each (n = 6) and received orally EO (10.0 mg/kg/day) or NEO (2.5, 5.0 and 10.0 mg/kg/day), named hereinafter as EO-10, NEO-2.5, NEO-5 and NEO-10, for 30 consecutive days. Animals not treated or treated with surfactants mixture were evaluated as control and vehicle control. Subsequently, histological, hematological and biochemical parameters, cytokines production, oxidative markers, CD4+/CD8+ T cells and gut microbiota were evaluated. GC-MS analysis was similar in both EO and NEO. The NEO was more toxic on Caco-2 cells than EO. Oral supplementation of EO-10 or NEO-10 improved growth performance compared to control group NEO-2.5 or NEO-5 (p < 0.05) groups. NEO-2.5, NEO-5 and NEO-10 did not alter the morpho-physiology of digestive organs and decreased malondialdehyde (MDA) levels in liver compared to control (p < 0.05) or EO-10 groups (p < 0.05, p < 0.01). In addition, NEO-10 showed an increase in CD4+/CD8+ T cells ratio (p < 0.001), and induced the highest serum levels of IL-10 (p < 0.01). Serum triglycerides levels were significantly lower in animals treated with EO-10 or NEO-2.5, NEO-5 and NEO-10 compared to control group (p < 0.001). Gut microbiota analysis showed that NEO-10 favor the development of beneficial intestinal microorganisms to improve parameters related to early weaning of piglets. In conclusion, EO and NEO improved parameters altered by early weaning in piglets however, NEO was safer and powerful. Therefore, NEO should be further studied to be applied in swine health.
Assuntos
Ração Animal , Antioxidantes , Suplementos Nutricionais , Microbioma Gastrointestinal , Óleos Voláteis , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/administração & dosagem , Óleos Voláteis/química , Antioxidantes/farmacologia , Masculino , Suplementos Nutricionais/análise , Suínos , Ração Animal/análise , Células CACO-2 , Desmame , Dieta/veterinária , Humanos , Administração OralRESUMO
There is now strong evidence to support the interest in using lactic acid bacteria (LAB)in particular, strains of lactococci and lactobacilli, as well as bifidobacteria, for the development of new live vectors for human and animal health purposes. LAB are Gram-positive bacteria that have been used for millennia in the production of fermented foods. In addition, numerous studies have shown that genetically modified LAB and bifodobacteria can induce a systemic and mucosal immune response against certain antigens when administered mucosally. They are therefore good candidates for the development of new mucosal delivery strategies and are attractive alternatives to vaccines based on attenuated pathogenic bacteria whose use presents health risks. This article reviews the most recent research and advances in the use of LAB and bifidobacteria as live delivery vectors for human and animal health.
Assuntos
Microbioma Gastrointestinal , Lactobacillales , Vacinas , Animais , Bifidobacterium/genética , Vetores Genéticos/genética , Humanos , Lactobacillales/genéticaRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by deterioration and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in motor deficits. Many studies have revealed an inverse relationship between thiamine consumption and susceptibility to PD. Previously, Lactiplantibacillus (L.) plantarum CRL 1905 was selected as thiamine-producing lactic acid bacteria (LAB), and its amprolium-resistant clone, L. plantarum CRL 1905*, was able to produce higher levels of this vitamin and inhibited neuronal death in an in vitro model. The present work aimed to evaluate the neuroprotective effect of these thiamine-producing LAB in an in vivo parkinsonian mouse model. Male C57BL/6 mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were orally administered with one of the LAB strains or commercial thiamine for 1 month. The administration of either thiamine-producing LAB prevented the motor deficits of mice similar to the effects of the commercial vitamin. These benefits were associated with increased number of tyrosine hydroxylase positive (TH+) neurons in the SNpc. The evaluation of the inflammatory response caused by the neurotoxin showed that both LAB decreased pro-inflammatory cytokines in serum; moreover, the strain selected as the higher thiamine producer showed the best anti-inflammatory effect locally in the brain and significantly decreased the levels of IL-6, TNF-α, IFN-γ and MCP-1, which remained similar to the levels of healthy control animals. These results demonstrated that thiamine-producing L. plantatum CRL 1905* has the potential to be used as part of a strategy to prevent or to complement the treatments of neurodegenerative diseases such as PD. A limitation of this study is that we cannot guarantee whether LAB are capable of producing thiamine in the intestinal tract or release the vitamin after lysis; however, the results show that thiamine production by L. plantarum CRL 1905 is implicated in the observed effect, in addition to other benefits associated with the LAB strain that are also involved and are currently under study.
Assuntos
Lactobacillales , Fármacos Neuroprotetores , Doença de Parkinson , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Substância Negra , Tiamina , Vitaminas/farmacologiaRESUMO
Oxidative stress and inflammatory processes might contribute to the cascade of events leading Parkinson disease (PD); and vitamins such as riboflavin can exert protection on vulnerable neurons in neurodegenerative conditions. Previously, it was demonstrated that a mixture of lactic acid bacteria (including a riboflavin-producing strain) improved motor skills in a parkinsonian model. The aim of the present work was to investigate the neuroprotective potential of Lactiplantibacillus (L.) plantarum CRL2130, a riboflavin-producing strain in PD models. In vitro, N2a differentiated neurons were exposed the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or commercial riboflavin. In vivo, adult male C57BL/6 mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid, and received orally L. plantarum CRL2130, L. plantarum CRL725 (parent strain that produces low levels of riboflavin) or commercial vitamin. Results showed that when N2a cells were incubated with intracellular extract from L. plantarum CRL2130 maintained the viability, and significantly decreased the release of IL-6 and the formation of reactive oxygen species (ROS), all affected by MPP+. In vivo, the administration of L. plantarum CRL2130 attenuated motor deficits and prevented dopaminergic neuronal death. Decrease of pro-inflammatory cytokines and increase of IL-10 in both serum and brain were observed in samples from mice that received L. plantarum CRL2130 compared to MPTP control group (without treatment). In addition, these beneficial effects were similar or improved when compared with animals that received commercial riboflavin. In conclusion, L. plantarum CRL2130 showed a neuroprotective effect in both PD models through anti-oxidant/anti-inflammatory mechanisms.
Assuntos
Lactobacillales , Fármacos Neuroprotetores , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Riboflavina/farmacologia , Riboflavina/uso terapêuticoRESUMO
Thiamine or vitamin B1, an essential micronutrient mainly involved in energy production, has a beneficial impact on the nervous system, and its deficiency can be associated with the development and progression of neurodegenerative diseases. The aim of this work was to select thiamine-producing lactic acid bacteria (LAB) and study their physiological effects using neuron cell cultures. In this study, 23 LAB able to produce thiamine were identified by growth in thiamine-free synthetic medium. Intra- and extracellular thiamine concentrations were determined using a microbiological method and results confirmed by HPLC techniques. A wide variation in vitamin production was found showing that this property was not only species specific but also a strain-dependent trait. Five of these strains were pre-selected for their capacity to produce higher concentrations of thiamine. Only the pre-treatment with the intracellular extract of Lactiplantibacillus (L.) plantarum CRL 1905 increased significantly neuronal survival in N2a cells' model of neurotoxicity (MPP+) with thiamine deficiency conditions (amprolium). Furthermore, amprolium-resistant variants of CRL 1905 were isolated by exposition of the strain to increasing concentrations of this toxic thiamine analogue. The variant A9 was able to increase more than 2 times the intracellular thiamine production of the original strain. A9 bacterial extract significantly prevented neuronal cell death and the increase of IL-6. The amprolium-resistant strain A9 showed a modulating and neuroprotective effect in an in vitro model of neurotoxicity constituting a potential bio-strategy to counteract thiamine deficiencies and thus prevent or treat neurodegenerative diseases. KEY POINTS: ⢠LAB can produce thiamine in a species- and strain-dependant manner. ⢠L. plantarum CRL 1905 significantly reduce MPP+-induced neurotoxicity in N2a cells. ⢠Amprolium-resistant strain A9 has neuroprotective effect and prevents IL-6 increase.
Assuntos
Lactobacillales , Doenças Neurodegenerativas , Amprólio , Morte Celular , Humanos , Doenças Neurodegenerativas/prevenção & controle , TiaminaRESUMO
OBJECTIVES: Parkinson's disease (PD) is a neurodegenerative process that affects the motor function and involves an inflammatory response and B vitamin deficiencies. The aim of this study was to evaluate the effect of B-group vitamin-producing and immunomodulatory lactic acid bacteria (LAB) in a murine model of PD. METHODS: The effect of Lactobacillus plantarum CRL 2130 (a riboflavin producer), Streptococcus thermophilus CRL 807 (an immunomodulatory strain), and Streptococcus thermophilus CRL 808 (a folate producer) were evaluated individually and as a mixture in mice injected with 1-methyl-4-fenil-1,2,3,6-tetrahidropiridina. Motor capacity, tyrosine hydrolase in the brain, and cytokine concentrations in serum and brain tissues were evaluated in 1-methyl-4-fenil-1,2,3,6-tetrahidropiridina-treated mice after bacterial supplementation. RESULTS: The mice receiving the selected LAB showed significantly improved motor skills compared with those that did not receive bacterial supplementation. When given the mixture of all 3 strains together, the animals had higher brain tyrosine hydrolase-positive cell counts, decreased inflammatory cytokines interleukin 6 and tumor necrosis factor alpha in serum, and increased antiinflammatory cytokine interleukin 10 in serum and brain tissues compared with animals that did not receive LAB supplementation. CONCLUSIONS: The results showed the potential of a selected LAB mixture to improve motor behavior and neuroinflammation in PD. This probiotic mixture could be used as an adjunct treatment in the control of PD.
Assuntos
Lactobacillales , Fármacos Neuroprotetores , Doença de Parkinson , Probióticos , Animais , Camundongos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Streptococcus thermophilusRESUMO
Recent studies have shown that inflammatory diseases are becoming more frequent throughout the world. The causes of these disorders are multifactorial and include genetic, immunological, and environmental factors, and intestinal microbiota dysbiosis. The use of beneficial microorganisms has shown to be useful in the prevention and treatment of disorders such as colitis, mucositis, and even colon cancer by their immune-stimulating properties. It has also been shown that certain vitamins, especially riboflavin and folate derivatives, have proven to be helpful in the treatment of these diseases. The application of vitamin-producing lactic acid bacteria, especially strains that produce folate and riboflavin together with immune-stimulating strains, could be used as adjunct treatments in patients suffering from a wide range of inflammatory diseases since they could improve treatment efficiency and prevent undesirable side effects in addition to their nutrition values. In this review, the most up to date information on the current knowledge and uses of vitamin-producing lactic acid bacteria is discussed in order to stimulate further studies in this field.
Assuntos
Inflamação/terapia , Doenças Inflamatórias Intestinais/terapia , Lactobacillales/metabolismo , Probióticos/uso terapêutico , Vitaminas/biossíntese , Animais , Anti-Inflamatórios/uso terapêutico , Ensaios Clínicos como Assunto , Colite/tratamento farmacológico , Ácido Fólico/biossíntese , Humanos , Inflamação/complicações , Doenças Inflamatórias Intestinais/classificação , Riboflavina/biossíntese , Vitamina KRESUMO
In recent years, quinoa (Chenopodium quinoa Willd), an ancestral crop of the Andean region of South America, has gained worldwide attention due to its high nutritional value. This grain is a good source of several vitamins and minerals; however, their bioavailability is decreased by the presence of antinutritional factors such as phytic acid. These compounds can be reduced using lactic acid bacteria (LAB), that have a GRAS (Generally Recognized as Safe) status and have traditionally been associated with food fermentation due to their biosynthetic capacity and metabolic versatility. The objective of this study was to evaluate the effectiveness of a pasta made with quinoa sourdough fermented by L. plantarum strains producing vitamins B2 and B9 and phytase to prevent vitamins and minerals deficiency using an in vivo mouse model. The results showed that the pasta fermented with the mixed culture containing L. plantarum CRL 2107â¯+â¯L. plantarum CRL 1964 present increased B2 and B9 levels in mice blood. Likewise, higher concentrations of P, Ca+2, Fe+2, Mg+2 (18.75, 10.70, 0.37, 4.85â¯mg/dL, respectively) were determined with respect to the deficient group (DG) (9.85, 9.90, 0.26, 3.34â¯mg/dL, respectively). Hematological studies showed an increase in hemoglobin (14.4⯱â¯0.6â¯g/dL), and hematocrit (Htc, 47.0⯱â¯0.6%) values, compared to the DG (Hb: 12.6⯱â¯0.5â¯g/dL, Hto: 39.9⯱â¯1.1%). Furthermore, histological evaluations of the intestines showed an increase of the small intestine villi length in this latter group. The results allow us to conclude that bio-enrichment of quinoa pasta using LAB could be a novel strategy to increase vitamin and minerals bioavailability in cereal/pseudocereal - derived foods.
Assuntos
Chenopodium quinoa , Culinária , Alimentos Fermentados , Deficiência de Ácido Fólico/prevenção & controle , Lactobacillus plantarum/metabolismo , Deficiência de Riboflavina/prevenção & controle , 6-Fitase , Animais , Ácido Fólico/administração & dosagem , Camundongos , Minerais , Estado Nutricional , Riboflavina/administração & dosagemRESUMO
Inflammatory bowel diseases are chronic and relapsing-remitting disorders that affect the gastrointestinal tract. Previously, the administration of folate and riboflavin-producing lactic acid bacteria (LAB) or an immune-modulating strain showed beneficial effects as they were able to reduce the acute inflammation in mouse models. The aim of this work was to evaluate a mixture of vitamin-producing and immune-modulating LAB administering together with an anti-inflammatory drug during the remission period of a mouse model of recurrent colitis. BALB/c mice were intrarectally instilled with trinitrobenzene sulfonic acid (TNBS) and those who recovered from this acute challenge were given the LAB mixture, mesalazine, or the combination of both (mesalazine + LAB) during 21 days, followed by a second challenge with TNBS. Control mice instilled with ethanol (vehicle of TNBS) and receiving the different treatments were also evaluated in order to study the effect of chronic anti-inflammatory therapy. The combination of mesalazine and LAB mixture was the most effective to decrease the intestinal damage at macroscopic and histological levels and to reduce pro-inflammatory cytokines (IL-6 and TNF-α) in intestinal fluids. In animals instilled with ethanol, mesalazine produced a loss of body weight and intestinal damages with increased IL-6. These side effects were prevented by the co-administration of mesalazine and the LAB mixture. The LAB blend did not affect the primary anti-inflammatory treatment, was able to improve it, and also prevented the side effects of this therapy.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Colite/tratamento farmacológico , Lactobacillales/metabolismo , Probióticos/administração & dosagem , Vitaminas/metabolismo , Animais , Colite/genética , Colite/imunologia , Modelos Animais de Doenças , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Mandatory fortification of foods with folic acid is being questioned by many scientists principally because of the potential adverse secondary effects associated with their excessive consumption. It has been shown that selected strains of lactic acid bacteria (LAB) are able to produce natural forms of folate and these could be included in foods to prevent deficiencies without causing adverse effects. The aim of this study was to evaluate folate production and fol gene expression by Streptococcus gallolyticus subsp. macedonicus (S. macedonicus) CRL415 under different growth conditions in vitro and to assess its potential probiotic application. Results showed that glucose as the principal carbon source, and incubation at 42⯰C under controlled pH conditions (6.0) increased folate production, fol gene expression, and growth of S. macedonicus CRL415. This strain was able to produce elevated folate concentrations during milk fermentation without the need of prolonged incubation times and was able to resist conditions simulating the gastrointestinal tract. In addition, S. macedonicus was susceptible to all required antibiotics, and had a good adhesion level to intestinal cells in vitro, making it a promising candidate for biotechnological application as functional starter cultures in the dairy industry.
Assuntos
Ácido Fólico/biossíntese , Probióticos/metabolismo , Streptococcus/metabolismo , Ácido 4-Aminobenzoico/metabolismo , Animais , Antibacterianos/farmacologia , Aderência Bacteriana , Bile , Células CACO-2 , Produtos Fermentados do Leite/análise , Produtos Fermentados do Leite/microbiologia , Ácido Fólico/genética , Suco Gástrico , Regulação Bacteriana da Expressão Gênica , Glucose/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Streptococcus/genética , Streptococcus/crescimento & desenvolvimento , TemperaturaRESUMO
OBJECTIVES: Intestinal mucositis (IM) is a local inflammatory response that causes alterations of the intestinal structure that in turn affect nutrient absorption and a side effect that is commonly associated with cancer treatments. Lactobacillus plantarum CRL2130 is a riboflavin-overproducing strain that has previously been shown to provide antiinflammatory properties. The objective of this study was to evaluate the effects of this riboflavin-producing strain in a chemically induced murine mucositis model. METHODS: Mucositis was induced by daily injections of 5-fluororacil (5-FU) after which mice were either given L. plantarum CRL2130, CRL725 (strain from which CRL2130 was derived that does not overproduce riboflavin), or commercial riboflavin twice daily during 6 d of chemotherapy agent injections. The effect of the strains and riboflavin was also evaluated in vitro using Caco-2 intestinal cancer cell cultures to determine if they interfere with 5-FU's anticancer activity. RESULTS: The administration of L. plantarum CRL2130 significantly attenuated the pathologic changes induced by 5-FU in mice such as body weight loss, diarrhea, shortening of villus height, increases in proinflammatory cytokine concentrations, and elevated production of interleukin 10. In vitro assays using Caco-2 cells showed that the effectiveness of 5-FU was not affected by L. plantarum CRL2130 and that this strain exerted an inhibitory mechanism against oxidative stress. CONCLUSIONS: These results indicate that the riboflavin-overproducing strain L. plantarum CRL2130 could be useful to prevent mucositis during cancer treatments and would not affect the primary treatment.
Assuntos
Lactobacillus plantarum/fisiologia , Mucosite/prevenção & controle , Probióticos/farmacologia , Substâncias Protetoras/farmacologia , Riboflavina/biossíntese , Animais , Antineoplásicos/efeitos adversos , Células CACO-2/microbiologia , Técnicas de Cultura de Células , Modelos Animais de Doenças , Feminino , Fluoruracila/efeitos adversos , Humanos , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Mucosite/induzido quimicamente , Riboflavina/administração & dosagemRESUMO
BACKGROUND: Current therapies for against inflammatory bowel disease (IBD) are sometimes limited by high costs, high toxicities and/or undesirable side effects, reasons for which new treatments are constantly being developed and studied. In this regards, an increasing mass of data has demonstrated that fecal transplantations and probiotic supplementations have shown promising effects and could be considered as adjunct IBD treatments to decrease some of the unwanted side effects caused by primary treatments. Furthermore, there is also mounting evidence that suggests that certain vitamins could provide antiinflammatory effects and it has been shown that certain strains of lactic acid bacteria (LAB), the most commonly used probiotic microorganisms, can produce biologically active forms of certain vitamins. OBJECTIVE: To discuss the potential role of the vitamin-producing LAB on intestinal inflammatory diseases. METHOD: A thorough search of bibliographic databases for peer-reviewed research on the effect of vitamins produced by LAB on inflammatory processes was performed. RESULTS: There is mounting research that vitamin producing LAB could provide antiinflammatory effects. CONCLUSION: The potential role of vitamin producing LAB was discussed not only because they could be used to decrease inflammation but also because they could provide the host with essential nutrients that are normally deficient in IBD patients due to altered intestinal morphologies.
Assuntos
Doenças Inflamatórias Intestinais/terapia , Lactobacillales/metabolismo , Probióticos/uso terapêutico , Vitaminas/metabolismo , Animais , Terapias Complementares , Humanos , Inflamação/terapiaRESUMO
The association between inflammatory bowel diseases and colorectal cancer is well documented. The genetic modification of lactic acid bacteria as a tool to increase the anti-inflammatory potential of these microorganisms has also been demonstrated. Thus the aim of the present work was to evaluate the anti-cancer potential of different genetically modified lactic acid bacteria (GM-LAB) producing antioxidant enzymes (catalase or superoxide dismutase) or the anti-inflammatory cytokine IL-10 (protein or DNA delivery) using a chemical induced colon cancer murine model. Dimethilhydrazine was used to induce colorectal cancer in mice. The animals received GM-LAB producing anti-oxidant enzymes, IL-10 or a mixture of different GM-LAB. Intestinal damage, enzyme activities and cytokines were evaluated and compared to the results obtained from mice that received the wild type strains from which derived the GM-LAB. All the GM-LAB assayed showed beneficial effects against colon cancer even though they exerted different mechanisms of action. The importance to select LAB with innate beneficial properties as the progenitor strain was demonstrated with the GM-LAB producing anti-oxidant enzymes. In addition, the best effects for the mixtures GM-LAB that combine different anti-inflammatory mechanism. Results indicate that mixtures of selected LAB and GM-LAB could be used as an adjunct treatment to decrease the inflammatory harmful environment associated to colorectal cancer, especially for patients with chronic intestinal inflammation who have an increased risk to develop colorectal cancer.
Assuntos
Antineoplásicos/uso terapêutico , Catalase/genética , Neoplasias Colorretais/terapia , Doenças Inflamatórias Intestinais/terapia , Interleucina-10/genética , Lactococcus lactis/fisiologia , Superóxido Dismutase/genética , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Neoplasias Colorretais/induzido quimicamente , Modelos Animais de Doenças , Feminino , Humanos , Imunidade nas Mucosas/genética , Interleucina-10/uso terapêutico , Ácido Láctico/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Organismos Geneticamente Modificados , Superóxido Dismutase/metabolismoRESUMO
Inflammatory bowel diseases (IBDs) affect the gastrointestinal tract and are characterized by recurrent inflammation that requires lifelong therapies. Probiotics such as lactic acid bacteria (LAB) have been proposed to complement current treatment protocols for these patients; however, their characteristics are strain dependent. In this regard, certain novel characteristics are only possible through the genetic modification of these beneficial micro-organisms. Different delivery systems, such as protein delivery of anti-oxidant enzymes and anti-inflammatory cytokines, have been shown to be effective in preventing and treating IBD in animal models. In this study, the safety of the recombinant LAB (recLAB) Streptococcus thermophilus CRL807 : CAT, S. thermophilus CRL807 : SOD, Lactococcus lactis NCDO2118 pXILCYT : IL-10, L. lactis MG1363 pValac : IL-10 and L. lactis MG1363 pGroESL : IL-10 with proven beneficial effects was compared to their progenitor strains S. thermophilus CRL807, L. lactis NCDO2118 or L. lactis MG1363. The prolonged administration of these genetically modified strains showed that they were just as safe as the native strains from which they derive, as demonstrated by normal animal growth and relative organ weights, absence of microbial translocation from the gastrointestinal tract, normal blood parameters and intestinal histology. The results show the potential use of these recLAB in future therapeutic formulations; however, the use of modern bio-containment systems is required for the future acceptance of these recLAB by the medical community and patients with IBD.
Assuntos
Terapia Biológica/métodos , Colite/prevenção & controle , Colite/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Lactococcus lactis/patogenicidade , Probióticos/efeitos adversos , Streptococcus thermophilus/patogenicidade , Experimentação Animal , Animais , Feminino , Lactococcus lactis/genética , Camundongos Endogâmicos BALB C , Streptococcus thermophilus/genéticaRESUMO
Mediante modelos con animales se demostró que el consumo de leches fermentadas con microorganismos potencialmente probióticos puede modular la respuesta inmunitaria del hospedador, manteniéndolo en estado de vigilancia, lo que le ayudaría a enfrentar enfermedades como la inflamación intestinal y algunos tipos de cáncer, mejorando su calidad de vida...
Assuntos
Humanos , Bactérias , Leite , Lactobacillus delbrueckii , Probióticos , Sistema Imunitário , Streptococcus thermophilusRESUMO
Inflammatory Bowel Diseases (IBD) are disorders of the gastrointestinal tract characterized by recurrent inflammation that requires lifelong treatments. Probiotic microorganisms appear as an alternative for these patients; however, probiotic characteristics are strain dependent and each probiotic needs to be tested to understand the underlining mechanisms involved in their beneficial properties. Genetic modification of lactic acid bacteria (LAB) was also described as a tool for new IBD treatments. The first part of this review shows different genetically modified LAB (GM-LAB) described for IBD treatment since 2000. Then, the two principally studied strategies are discussed (i) GM-LAB producing antioxidant enzymes and (ii) GM-LAB producing the anti-inflammatory cytokine IL-10. Different delivery systems, including protein delivery and DNA delivery, will also be discussed. Studies show the efficacy of GM-LAB (using different expression systems) for the prevention and treatment of IBD, highlighting the importance of the bacterial strain selection (with anti-inflammatory innate properties) as a promising alternative. These microorganisms could be used in the near future for the development of therapeutic products with anti-inflammatory properties that can improve the quality of life of IBD patients.
RESUMO
OBJECTIVES: Obesity is a chronic disease associated with an inflammatory process in which cytokines play an important role. Probiotic microorganisms have been associated with modulation of the host immune system. The aim of this study was to evaluate the influence of the probiotic bacterium Lactobacillus casei CRL 431 on the cytokine response in a model of mice under high-fat diet (HFD) conditions. METHODS: BALB/c mice received a conventional balanced diet or an HFD. The test groups received milk, milk fermented by L. casei (FM), or L. casei as suspension in the drinking water. Proinflammatory and regulatory cytokine producer cells were evaluated in the small intestine and liver; the cytokine levels in the intestinal fluids were also evaluated. The percentages of immune cells as macrophages (F4/80), NKT, CD4+, CD8+ populations were determined in the liver. Adipocytes were also isolated and cultured to evaluate cytokines and the chemokine monocyte chemoattractant protein (MCP)-1 produced by them. RESULTS: The administration of probiotic L. casei CRL 431 exerted an anti-inflammatory response in mice fed an HFD, evidenced mainly by decreasing proinflammatory cytokines, such as interleukin (IL)-6, IL-17, and tumor necrosis factor-α. Probiotic administration also was associated with fewer immune-infiltrating cells in the liver of mice that received the HFD and decreased secretion of MCP-1 by the adipocytes. This last observation could be associated with less macrophage accumulation in the adipose tissues, which is characteristic in the obese host and contributes to maintaining the inflammatory response in this organ. The results obtained show an anti-inflammatory effect of L. casei CRL 431 when it is administered as a supplement of the HFD in a mouse model.
Assuntos
Citocinas/análise , Inflamação/dietoterapia , Lacticaseibacillus casei/metabolismo , Macrófagos/imunologia , Probióticos/administração & dosagem , Adipócitos/efeitos dos fármacos , Adipócitos/imunologia , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fermentação , Inflamação/imunologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/imunologia , Lacticaseibacillus casei/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Obesos , Leite/microbiologia , Probióticos/uso terapêutico , Resultado do TratamentoRESUMO
Breast cancer is the second cause of death in women, who are especially related to uncontrolled metastasis. It was previously demonstrated that the administration of milk fermented by Lactobacillus casei CRL 431 [fermented milk (FM)] delayed the tumor growth in a murine breast cancer model. In this work we evaluated if the administration of FM to mice, starting when the tumor was measurable, can affect not only the tumor growth, but also the extravasation of tumor cells and the lung metastasis. The evaluation of immune cells-infiltrating tumors and lungs was also performed. Tumor volume was calculated. Whole blood, lungs, and liver were processed to count the number of colonies formed by tumor cells. Blood serum was obtained for monocyte chemoattractant protein-1, interleukin (IL)-10, and IL-6 determination, lung tissues for histologic observations, and tumor tissues for angiogenesis determination. Mice that received FM were compared with animals given milk or to the controls without any especial supplementation. The results showed that FM administration to mice decreased or suppressed tumor growth, with less tumor vascularity, extravasation of tumor cells, and lung metastasis. These benefits were associated to modulation of the immune response by decreasing the infiltration of macrophages in both the tumor and the lungs. FM administration maintained an increased antitumor response associated to CD8 lymphocytes, and also increased CD4 lymphocytes that can be involved in the modulation of the immune response. The future evaluation of cytokine profiles will allow knowing more about subpopulation of macrophages and lymphocytes associated to the beneficial effect of this probiotic in the breast cancer model.