RESUMO
AIMS: To evaluate a mixture of selected lactic acid bacteria (LAB) (a riboflavin-producer, a folate-producer and an immunomodulatory strain) as co-adjuvant for 5-fluorouracil (5-FU) chemotherapy in cell culture and using a 4T1 cell animal model of breast cancer. METHODS AND RESULTS: The viability of Caco-2 cells exposed to 5-FU and/or LAB was analysed. Mice bearing breast tumour were treated with 5-FU and/or LAB. Tumour growth was measured. Intestinal mucositis (IM) was evaluated in small intestine; haematological parameters and plasma cytokines were determined. The bacterial mixture did not negatively affect the cytotoxic activity of 5-FU on Caco-2 cells. The LAB mixture attenuated the IM and prevented blood cell decreases associated with 5-FU treatment. Mice that received 5-FU and LAB mixture decreased tumour growth and showed modulation of systemic cytokines modified by both tumour growth and 5-FU treatment. The LAB mixture by itself delayed tumour growth. CONCLUSIONS: The mixture of selected LAB was able to reduce the side-effects associated with chemotherapy without affecting its primary anti-tumour activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This bacterial mixture could prevent the interruption of conventional oncologic therapies by reducing undesirable side-effects. In addition, this blend would provide essential nutrients (vitamins) to oncology patients.
Assuntos
Adjuvantes Imunológicos , Neoplasias da Mama/terapia , Fluoruracila/uso terapêutico , Lactobacillales/imunologia , Lactobacillales/metabolismo , Animais , Antineoplásicos/uso terapêutico , Células CACO-2 , Linhagem Celular , Sobrevivência Celular , Citocinas/sangue , Modelos Animais de Doenças , Feminino , Ácido Fólico/metabolismo , Humanos , Imunomodulação , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mucosite/microbiologia , Mucosite/patologia , Riboflavina/metabolismo , VitaminasRESUMO
Lactic acid bacteria (LAB), widely used as starter cultures for the fermentation of a large variety of food, can improve the safety, shelf life, nutritional value and overall quality of the fermented products. In this regard, the selection of strains delivering health-promoting compounds is now the main objective of many researchers. Although most LAB are auxotrophic for several vitamins, it is known that certain strains have the capability to synthesize B-group vitamins. This is an important property since humans cannot synthesize most vitamins, and these could be obtained by consuming LAB fermented foods. This review discusses the use of LAB as an alternative to fortification by the chemical synthesis to increase riboflavin and folate concentrations in food. Moreover, it provides an overview of the recent applications of vitamin-producing LAB with anti-inflammatory/antioxidant activities against gastrointestinal tract inflammation. This review shows the potential uses of riboflavin and folates producing LAB for the biofortification of food, as therapeutics against intestinal pathologies and to complement anti-inflammatory/anti-neoplastic treatments.
Assuntos
Ácido Fólico/biossíntese , Alimentos Fortificados , Doenças Inflamatórias Intestinais/terapia , Lactobacillales/metabolismo , Mucosite/terapia , Riboflavina/biossíntese , Animais , Antioxidantes/análise , Fermentação , Alimentos Fermentados , Ácido Fólico/análise , Humanos , Lactobacillales/isolamento & purificação , Riboflavina/análise , Vitaminas/análise , Vitaminas/biossínteseRESUMO
AIM: To evaluate two folate-producing strains, Streptococcus (Strep.) thermophilus CRL 808 and Strep. thermophilus CRL 415, against chemically induced mucositis in mice. METHODS AND RESULTS: In vitro assays with Caco-2 cells were performed to evaluate the effect of the bacteria in the presence of 5-fluorouracil (5-FU). For in vivo studies, mice were daily injected with 5-FU to induce intestinal mucositis (IM) and orally administered with folate-producing strains during 6 days. Clinical symptoms, histological parameters and cytokine profiles were assessed. The results showed that Strep. thermophilus CRL 808 increased the cytotoxicity of 5-FU against Caco-2 cells. Administration of this strain in mice with chemically induced IM resulted in a reduction in diarrhoea score and restoration of the intestinal architecture. Cytokine analysis showed that the anti-inflammatory effect by the bacterium is not associated with an immune mechanism. Regarding Strep. thermophilus CRL 415, no improvements were observed in any of the parameters evaluated. CONCLUSION: The administration of the folate-producing Strep. thermophilus CRL 808 has the potential to prevent IM induced by 5-FU in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: Folate-producing LAB could be used in chemotherapy patients to reduce the symptoms of IM, improve their nutritional status and increase the effectiveness of 5-FU.
Assuntos
Ácido Fólico/biossíntese , Lactobacillales/metabolismo , Mucosite/terapia , Probióticos/uso terapêutico , Animais , Células CACO-2 , Citocinas/metabolismo , Diarreia/prevenção & controle , Fluoruracila , Humanos , Inflamação/patologia , Mucosa Intestinal/patologia , Intestinos/patologia , Lactobacillales/genética , Camundongos , Mucosite/induzido quimicamente , Streptococcus thermophilus/genética , Streptococcus thermophilus/metabolismoRESUMO
It is known that certain lactic acid bacterial (LAB) strains can produce folates, a B-group vitamin that cannot be synthesized by humans and must be exogenously obtained. The aim of this study was to select folate-producing LAB and evaluate their probiotic characteristics in order to obtain a tuber-based food with elevated folate content. Several LAB strains were isolated from a traditional Andean fermented potato product tocosh and cultured in folate-free culture medium. Five folate-producing strains (29-138â¯ng/mL) were selected to ferment three Andean tubers (potato S. tuberosum spp. andigena, oca Oxalis tuberosa and papalisa Ullucus tuberosus). Sterile purees were inoculated and samples were collected at 0, 6 and 24â¯h of fermentation and after 28â¯days of cold storage. Cell growth, pH and total folate were determined. All selected strains were able to grow and produce folates in the substrates and two Lactobacillus sakei strains, CRL 2209 and CRL 2210, produced the highest folate concentrations (730-1484â¯ng/g after 24â¯h fermentation). These strains were selected to ferment potato substrates supplemented with amaranth (Amaranthus caudathus) and chia (Salvia hispanica) flour to increase the nutritional value. This addition increased folate synthesis in 89-95%. Furthermore, the ability to survive under simulated gastrointestinal conditions was evaluated and cell counts of the 5 strains remained above the recommended for a probiotic candidate (8.0 logâ¯CFU/mL). In conclusion, the selected LAB could be considered potentially probiotic strains and could be used to produce novel tuber based products with elevated folate concentrations. These products could also be used as novel food matrixes for the delivery of probiotic microorganisms.
Assuntos
Ácido Fólico/análise , Lactobacillales/metabolismo , Probióticos/metabolismo , Solanum tuberosum/metabolismo , Solanum tuberosum/microbiologia , Fermentação , Ácido Fólico/metabolismo , Tecnologia de Alimentos , Modelos Biológicos , TubérculosRESUMO
AIM: To assess the anti-inflammatory effect associated with individual probiotic suspensions of riboflavin-producing lactic acid bacteria (LAB) in a colitis murine model. METHODS AND RESULTS: Mice intrarectally inoculated with trinitrobenzene sulfonic acid (TNBS) were orally administered with individual suspensions of riboflavin-producing strains: Lactobacillus (Lact.) plantarum CRL2130, Lact. paracasei CRL76, Lact. bulgaricus CRL871 and Streptococcus thermophilus CRL803; and a nonriboflavin-producing strain or commercial riboflavin. The extent of colonic damage and inflammation and microbial translocation to liver were evaluated. iNOs enzyme was analysed in the intestinal tissues and cytokine concentrations in the intestinal fluids. Animals given either one of the four riboflavin-producing strains showed lower macroscopic and histologic damage scores, lower microbial translocation to liver, significant decreases of iNOs+ cells in their large intestines and decreased proinflammatory cytokines, compared with mice without treatment. The administration of pure riboflavin showed similar benefits. Lact. paracasei CRL76 accompanied its anti-inflammatory effect with increased IL-10 levels demonstrating other beneficial properties in addition to the vitamin production. CONCLUSION: Administration of riboflavin-producing strains prevented the intestinal damage induced by TNBS in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: Riboflavin-producing phenotype in LAB represents a potent tool to select them for preventing/treating IBD.
Assuntos
Colite/tratamento farmacológico , Lactobacillus/metabolismo , Probióticos/administração & dosagem , Riboflavina/metabolismo , Streptococcus thermophilus/metabolismo , Animais , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Fezes/microbiologia , Feminino , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Ácido Trinitrobenzenossulfônico/efeitos adversosRESUMO
Inflammatory bowel diseases (IBD) are idiopathic diseases of the gastrointestinal tract characterised by recurrent inflammation that require lifelong treatments. It has been shown that certain strains of lactic acid bacteria (LAB) can produce specific health-promoting compounds in foods or in the gastrointestinal tract that can in turn prevent and/or treat IBD. This study was designed to evaluate the possible therapeutic potential of soymilk fermented by the riboflavin-producing strain Lactobacillus plantarum CRL 2130 in a trinitrobenzene sulfonic induced colitis mouse model. Mice that received soymilk fermented by L. plantarum CRL 2130 showed a decrease in weight loss, lower damage scores in their large intestines, lower microbial translocation to liver and decreased cytokines levels in their intestinal fluids compared to animals that received unfermented soymilk or soymilk fermented by a non-riboflavin-producing L. plantarum strain. This is the first report that demonstrates that a riboflavin-producing LAB was able to prevent experimental colitis in a murine model.
Assuntos
Colite/terapia , Doenças Inflamatórias Intestinais/terapia , Lactobacillus plantarum/fisiologia , Probióticos/uso terapêutico , Leite de Soja/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Fezes , Feminino , Fermentação , Inflamação/terapia , Camundongos , Camundongos Endogâmicos BALB C , Riboflavina/metabolismoRESUMO
It has been previously shown that Lactobacillus plantarum CRL 2130 is able to produce riboflavin in soyamilk. The aim of the present study was to evaluate the efficiency of this riboflavin-bio-enriched soyamilk to revert and/or prevent the nutritional deficiency of riboflavin using different animal models. When used to supplement the diets of previously depleted animals, it was shown that the growth, riboflavin status and morphology of the small intestines reverted to normal parameters and were similar to animals supplemented with commercial riboflavin. In the prevention model, the same tendency was observed, where animals that received soyamilk fermented with L. plantarum CRL 2130 did not show signs of riboflavin deficiency. This new bio-fortified soya-based product could be used as part of normal diets to provide a more natural alternative to mandatory fortification with riboflavin for the prevention of its deficiency.
Assuntos
Fermentação , Lactobacillus plantarum/metabolismo , Deficiência de Riboflavina/prevenção & controle , Riboflavina/biossíntese , Leite de Soja/química , Animais , Dieta , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Riboflavina/administração & dosagem , Deficiência de Riboflavina/etiologia , Leite de Soja/metabolismoRESUMO
AIMS: To evaluate the beneficial properties of a potentially probiotic yoghurt obtained by the fermentation of two selected anti-inflammatory bacterial strains using in vivo mouse models of intestinal inflammation and colon carcinogenesis. METHODS AND RESULTS: Yoghurt was administered to mice suffering chemically induced intestinal inflammation or colon carcinogenesis. It was shown that this novel yoghurt was able to prevent local inflammation in the intestines of mice through a regulation of the immune response, prevent macroscopic and histological damages, and prevent colon carcinogenesis through an anti-inflammatory response. CONCLUSIONS: The developed yoghurt showed in vivo anti-inflammatory properties by modulation of the host immune response for the prevention of colon inflammation and carcinogenesis. SIGNIFICANCE AND IMPACT OF THE STUDY: This new yoghurt could thus be considered a probiotic food and be useful as a complement to current treatment protocols for inflammatory bowel diseases and colon cancer, a first since there are no current functional foods specifically oriented for these patients.
Assuntos
Colite/prevenção & controle , Neoplasias do Colo/prevenção & controle , Probióticos/administração & dosagem , Iogurte/microbiologia , Animais , Carcinogênese , Colite/imunologia , Colite/microbiologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/microbiologia , Feminino , Fermentação , Humanos , Intestinos/imunologia , Intestinos/microbiologia , Ácido Láctico/metabolismo , Lactobacillaceae/imunologia , Lactobacillaceae/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Probióticos/classificação , Probióticos/isolamento & purificaçãoRESUMO
In this study, Lactococcus lactis was engineered to express mutated internalin A on its surface and to secrete large amounts of listeriolysin O (LLO) in order to improve its potential as a vehicle for DNA vaccination. Western blotting experiments demonstrated that the bacterium expressed LLO in both the cytoplasmic and extracellular compartments, with higher quantities found in the culture supernatants. A hemolytic assay showed that the recombinant strain secreted 250 ng active LLO/mg total protein. This mInlA/LLO-producing strain of L. lactis may be used as an alternative tool in DNA vaccination against a number of infectious diseases or in cancer therapy.
Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Toxinas Bacterianas/genética , Toxinas Bacterianas/imunologia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/imunologia , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/imunologia , Lactococcus lactis/genética , Listeria monocytogenes/imunologia , Mutação , Proteínas Recombinantes , Vacinas Bacterianas , Membrana Celular/metabolismo , Expressão Gênica , Hemólise , Lactococcus lactis/metabolismo , VacinaçãoRESUMO
Although most vitamins are present in a variety of foods, human vitamin deficiencies still occur in many countries, mainly because of malnutrition not only as a result of insufficient food intake but also because of unbalanced diets. Even though most lactic acid bacteria (LAB) are auxotrophic for several vitamins, it is now known that certain strains have the capability to synthesize water-soluble vitamins such as those included in the B-group (folates, riboflavin and vitamin B(12) amongst others). This review article will show the current knowledge of vitamin biosynthesis by LAB and show how the proper selection of starter cultures and probiotic strains could be useful in preventing clinical and subclinical vitamin deficiencies. Here, several examples will be presented where vitamin-producing LAB led to the elaboration of novel fermented foods with increased and bioavailable vitamins. In addition, the use of genetic engineering strategies to increase vitamin production or to create novel vitamin-producing strains will also be discussed. This review will show that the use of vitamin-producing LAB could be a cost-effective alternative to current vitamin fortification programmes and be useful in the elaboration of novel vitamin-enriched products.