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1.
Probiotics Antimicrob Proteins ; 16(1): 275-292, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36652108

RESUMO

Mucositis is a high-incidence side effect in cancer patients undergoing chemotherapy. Next-generation probiotics are emerging as new therapeutic tools for managing various disorders. Studies have demonstrated the potential of Akkermansia muciniphila to increase the efficiency of anticancer treatment and to mitigate mucositis. Due to the beneficial effect of A. muciniphila on the host, we evaluated the dose-response, the microorganism viability, and the treatment protocol of A. muciniphila BAA-835 in a murine model of chemotherapy-induced mucositis. Female Balb/c mice were divided into groups that received either sterile 0.9% saline or A. muciniphila by gavage. Mucositis was induced using a single intraperitoneal injection of 5-fluorouracil. The animals were euthanized three days after the induction of mucositis, and tissue and blood were collected for analysis. Prevention of weight loss and small intestine shortening and reduction of neutrophil and eosinophil influx were observed when animals were pretreated with viable A. muciniphila at 1010 colony-forming units per mL (CFU/mL). The A. muciniphila improved mucosal damage by preserving tissue architecture and increasing villus height and goblet cell number. It also improved the integrity of the epithelial barrier, decreasing intestinal permeability and bacterial translocation. In addition, the treatment prevented the expansion of Enterobacteriaceae. The immunological parameters were also improved by decreasing the expression of pro-inflammatory cytokines (IL6, IL1ß, and TNF) and increasing IL10. In conclusion, pretreatment with 1010 CFU/mL of viable A. muciniphila effectively controlled inflammation, protected the intestinal mucosa and the epithelial barrier, and prevented Enterobacteriaceae expansion in treated mice.


Assuntos
Antineoplásicos , Mucosite , Humanos , Camundongos , Feminino , Animais , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/metabolismo , Citocinas/metabolismo , Mucosa Intestinal/metabolismo , Antineoplásicos/farmacologia , Akkermansia
2.
Artigo em Inglês | MEDLINE | ID: mdl-37097372

RESUMO

Next-generation microorganisms have recently gained prominence in the scientific community, mainly due to their probiotic and postbiotic potentials. However, there are few studies that investigate these potentials in food allergy models. Therefore, the present study was designed to evaluate the probiotic potential of Akkermansia muciniphila BAA-835 in an ovalbumin food allergy (OVA) model and also analyse possible postbiotic potential. To access the probiotic potential, clinical, immunological, microbiological, and histological parameters were evaluated. In addition, the postbiotic potential was also evaluated by immunological parameters. Treatment with viable A. muciniphila was able to mitigate weight loss and serum levels of IgE and IgG1 anti-OVA in allergic mice. In addition, the ability of the bacteria to reduce the injury of the proximal jejunum, the eosinophil and neutrophil influx, and the levels of eotaxin-1, CXCL1/KC, IL4, IL6, IL9, IL13, IL17, and TNF, was clear. Furthermore, A. muciniphila was able to attenuate dysbiotic signs of food allergy by mitigating Staphylococcus levels and yeast frequency in the gut microbiota. In addition, the administration of the inactivated bacteria attenuated the levels of IgE anti-OVA and eosinophils, indicating its postbiotic effect. Our data demonstrate for the first time that the oral administration of viable and inactivated A. muciniphila BAA-835 promotes a systemic immunomodulatory protective effect in an in vivo model of food allergy to ovalbumin, which suggests its probiotic and postbiotic properties.

3.
Probiotics Antimicrob Proteins ; 15(1): 63-73, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-34558015

RESUMO

Food allergy is a pathological condition that can lead to hives, swelling, gastrointestinal distress, cardiovascular and respiratory compromise, and even anaphylaxis. The lack of treatment resources emphasizes the necessity for new therapeutic strategies, and in this way, probiotics has been pointed out as an alternative, especially because of its immunomodulatory properties. The goal of this study was to evaluate the probiotic effect of Bifidobacterium longum subsp. longum 51A (BL51A) in a murine model of ovalbumin (OVA) food allergy, as well as to investigate the effect of the dose and viability of the bacteria on the proposed model. For this purpose, the probiotic effect was assessed by clinical, immunological, and histological parameters in mice treated or not with the BL51A and sensitized or not with OVA. Oral administration of BL51A prevented weight loss and reduced serum levels of IgE anti-OVA and of sIgA in the intestinal fluid. Also, it reduced the intestinal permeability, proximal jejunum damage, recruitment of eosinophils and neutrophils, and levels of eotaxin-1, CXCL1/KC, IL4, IL5, IL6, IL13, and TNF. Furthermore, the treatment was able to increase the levels of IL10. Investigating different doses administered, the level of 108 CFU showed the best results in terms of protective effect. In addition, the administration of the inactivated bacteria did not present any beneficial effect. Results demonstrate that BL51A promotes a systemic immunomodulatory protective effect in a murine model of food allergy that depends on the dose and viability of the bacteria, suggesting its use as probiotic in such disease.


Assuntos
Hipersensibilidade Alimentar , Probióticos , Animais , Camundongos , Modelos Animais de Doenças , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/prevenção & controle , Bifidobacterium , Inflamação/tratamento farmacológico
4.
Probiotics Antimicrob Proteins ; 15(3): 491-501, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-34671923

RESUMO

Breast milk was long considered a sterile environment, but now it is known to harbor many bacteria that will shape the newborn microbiota. The benefits of breastfeeding to newborn health are, on some level, related to the presence of beneficial bacteria in human milk. Therefore, this study aims to investigate and isolate potential probiotics present in human milk that might be associated with improved health in infants, being potential candidates to be used in simulated human milk formula. Milk samples of 24 healthy mothers were collected at three time points: 30 min (colostrum), 5-9 days (transitional milk), and 25-30 days (mature milk) postpartum. Samples were evaluated by culturing, and the isolated bacteria were identified by MALDI-TOF MS and 16S DNA sequencing. In vitro screening for probiotics properties was performed, and the potential probiotics were mono-associated with germ-free mice to evaluate their ability to colonize the gastrointestinal tract. The microorganisms were submitted to the spray-drying process to check their viability for a potential simulated milk formula production. Seventy-seven bacteria were isolated from breast milk pertaining to four bacterial genera (Staphylococcus, Streptococcus, Leuconostoc, and Lacticaseibacillus). Four potential probiotics were selected: Lacticaseibacillus rhamnosus (n = 2) and Leuconostoc mesenteroides (n = 2). Isolates were able to colonize the gastrointestinal tract of germ-free mice and remained viable after the spray-drying process. In conclusion, breast milk harbors a unique microbiota with beneficial microorganisms that will impact the newborn gut colonization, being an essential source of probiotic candidates to be used in a formula of simulated maternal milk.


Assuntos
Leite Humano , Probióticos , Lactente , Feminino , Gravidez , Humanos , Animais , Camundongos , Leite Humano/microbiologia , Bifidobacterium/genética , Bactérias/genética , Colostro/microbiologia
5.
Probiotics Antimicrob Proteins ; 15(5): 1180-1192, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35907169

RESUMO

Functional foods containing probiotics are generally administered as dairy products. Non-dairy beverages are another possibility, but probiotic functionality must be confirmed in such vehicles. In the present study, a craft wheat beer brewed with the probiotic yeast Saccharomyces cerevisiae UFMG A-905 (905) was evaluated in a murine model of Salmonella Typhimurium infection. Unfiltered or filtered beer brewed with 905, a commercial wheat beer used as a negative control, or saline were administered orally to mice before and during oral S. Typhimurium challenge. High fecal levels of yeast were only counted in mice treated with the unfiltered 905 beer, which also had reduced mortality and body weight loss due to S. Typhimurium infection. Increased levels of intestinal IgA, translocation to liver and spleen, liver and intestinal lesions, pro-inflammatory cytokines in liver and ileum, and hepatic and intestinal myeloperoxidase and eosinophilic peroxidase activities were observed in animals infected with S. Typhimurium. All these parameters were reduced by the treatment with unfiltered 905 beer. In conclusion, the results show that a craft wheat beer brewed with S. cerevisiae UFMG A-905 maintained the probiotic properties of this yeast when administered orally to mice challenged with S. Typhimurium.


Assuntos
Probióticos , Infecções por Salmonella , Animais , Camundongos , Saccharomyces cerevisiae , Salmonella typhimurium , Triticum , Cerveja
6.
Int. microbiol ; 25(4): 803-815, Nov. 2022. graf
Artigo em Inglês | IBECS | ID: ibc-216248

RESUMO

Raw milk samples were collected from 200 dairy cows belonging to Girolando 1/2, Gyr, Guzera, and Holstein breeds, and the bacterial diversity was explored using 16S rRNA amplicon sequencing. SCC analysis showed that 69 animals were classified as affected with subclinical mastitis. The milk bacterial microbiome was dominated by Firmicutes, Proteobacteria, and Actinobacteria, with an increase of Firmicutes in animals with subclinical mastitis and Proteobacteria in healthy animals. At the family and genus level, the milk bacterial microbiome was dominated by Staphylococcus, Acinetobacter, Pseudomonas, members of the family Enterobacteriaceae, Lactococcus, Aerococcus, members of the family Rhizobiaceae, Anaerobacillus, Streptococcus, members of the family Intrasporangiaceae, members of the family Planococcaceae, Corynebacterium, Nocardioides, and Chryseobacterium. Significant differences in alpha and beta diversity analysis suggest an effect of udder health status and breed on the composition of raw bovine milk microbiota. LEfSe analysis showed 45 and 51 discriminative taxonomic biomarkers associated with udder health status and with one of the four breeds respectively, suggesting an effect of subclinical mastitis and breed on the microbiota of milk in cattle.(AU)


Assuntos
Animais , Bovinos , Substitutos do Leite Humano , Infecções Estafilocócicas , Microbiota , Mastite Bovina , Microbiologia
7.
Int Microbiol ; 25(4): 803-815, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35838927

RESUMO

Raw milk samples were collected from 200 dairy cows belonging to Girolando 1/2, Gyr, Guzera, and Holstein breeds, and the bacterial diversity was explored using 16S rRNA amplicon sequencing. SCC analysis showed that 69 animals were classified as affected with subclinical mastitis. The milk bacterial microbiome was dominated by Firmicutes, Proteobacteria, and Actinobacteria, with an increase of Firmicutes in animals with subclinical mastitis and Proteobacteria in healthy animals. At the family and genus level, the milk bacterial microbiome was dominated by Staphylococcus, Acinetobacter, Pseudomonas, members of the family Enterobacteriaceae, Lactococcus, Aerococcus, members of the family Rhizobiaceae, Anaerobacillus, Streptococcus, members of the family Intrasporangiaceae, members of the family Planococcaceae, Corynebacterium, Nocardioides, and Chryseobacterium. Significant differences in alpha and beta diversity analysis suggest an effect of udder health status and breed on the composition of raw bovine milk microbiota. LEfSe analysis showed 45 and 51 discriminative taxonomic biomarkers associated with udder health status and with one of the four breeds respectively, suggesting an effect of subclinical mastitis and breed on the microbiota of milk in cattle.


Assuntos
Mastite Bovina , Microbiota , Animais , Bactérias/genética , Bovinos , Feminino , Nível de Saúde , Humanos , Mastite Bovina/microbiologia , Leite/microbiologia , RNA Ribossômico 16S/genética
9.
Int. microbiol ; 25(1): 189-206, Ene. 2022. graf
Artigo em Inglês | IBECS | ID: ibc-216022

RESUMO

Mastitis is one of the most important causes of loss of cattle production, burdening producers due to the increased cost of milk production and decreased herd productivity. The development of alternative methods for the treatment and prevention of mastitis other than traditional chemical antibiotic therapy needs to be implemented to meet international pressures to reduce the use of these drugs and promote the elimination of multiresistant microbial strains from the environment. Treatment with probiotic bacteria or yeast strains offers a possible strategy for the control of mastitis. The objective of this work was to isolate, identify, and characterize lactic bacteria from milk and the intramammary duct of Gyr, Guzerat, Girolando 1/2, and Holstein cattle breeds from Brazil. Samples of 115 cows were taken, a total of 192 bacteria isolates belonging to 30 species were obtained, and 81 were selected to evaluate their probiotic potential in in vitro characterization tests. In general, bacteria isolated from the mammary gland have low autoaggregation, cell surface hydrophobicity, and co-aggregation with mastitis etiological bacteria Staphylococcus aureus and Escherichia coli. Also, they have biofilm assembly capacity, inability to produce exopolysaccharides, high production of H2O2, and strong antagonism against mastitis pathogens. Ten lactic bacteria isolates were used in co-culture with human MDA-MB-231 breast epithelial cells to assess their adhesion capacity and impairment of the S. aureus invasion. Our results, therefore, contribute to the future production of new prevention and treatment tools for bovine mastitis.(AU)


Assuntos
Humanos , Animais , Ácido Láctico , Bactérias , Weissella , Lactobacillus plantarum , Bem-Estar do Animal , Glândulas Mamárias Animais , Microbiologia , Mastite Bovina
10.
Life Sci ; 289: 120243, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34922941

RESUMO

Intestinal mucositis (IM) is a critical side-effect associated with antineoplastic therapy. Treatment available is only palliative and often not effective. However, alternative therapeutic strategies, such as probiotics, have attracted significant attention due to their immune-modulatory action in several diseases. Thus, the present study aims to elucidate the therapeutic potential of the probiotic strain Bifidobacterium longum 51A in a murine model of mucositis induced by irinotecan. Due to the scarcity of studies on dose-response and viability (probiotic vs paraprobiotic), we first evaluated which dose and cell viability would be most effective in treating mucositis. In this study, the oral pretreatment with viable B. longum 51A at a concentration of 1 × 109 CFU/mL reduced the daily disease activity index (p < 0.01), protected the intestinal architecture, preserved the length of the intestine (p < 0.05), and reduced intestinal permeability (p < 0.01), inflammation, and oxidative damage (p < 0.01) induced by irinotecan. Also, treatment with B. longum 51A increased the production of secretory immunoglobulin A (p < 0.05) in the intestinal fluid of mice with mucositis. Furthermore, B. longum 51A reversed the mucositis-induced increase in Enterobacteriaceae bacterial group in the gut (p < 0.01). In conclusion, these results showed that oral administration of B. longum 51A protects mice against intestinal damage caused by irinotecan, suggesting its use as a potential probiotic in therapy during mucositis.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal/efeitos dos fármacos , Enteropatias , Irinotecano/efeitos adversos , Mucosite , Probióticos/farmacologia , Animais , Feminino , Enteropatias/induzido quimicamente , Enteropatias/microbiologia , Enteropatias/terapia , Irinotecano/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Mucosite/induzido quimicamente , Mucosite/microbiologia , Mucosite/terapia
11.
Probiotics Antimicrob Proteins ; 14(3): 486-500, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34255281

RESUMO

Mucositis is one of the most strenuous side effects caused by chemotherapy drugs, such as 5-fluorouracil (5-FU), during the treatment of several types of cancers. The disease is so prevalent and aggressive that many patients cannot resist such symptoms. However, despite its frequency and clinical significance, there is no effective treatment to prevent or treat mucositis. Thus, the use of probiotics as an adjuvant for the treatment has gained prominence. In the present study, we evaluated the effectiveness of oral administration of the Antarctic strain of Rhodotorula mucilaginosa UFMGCB 18,377 as an alternative to minimize side effects of 5-FU-induced mucositis in mice. Body weight, food consumption, stool consistency, and presence of blood in the feces were assessed daily in mice orally treated or not with the yeast and submitted or not to experimental mucositis. Blood, bones, and intestinal tissues and fluid were used to determine intestinal permeability and immunological, microbiological, and histopathological parameters. Treatment with R. mucilaginosa UFMGCB 18,377 was able to decrease clinical signs of the disease, such as reduction of food intake and body weight loss, and also decreased the number of intestinal enterobacteria and intestinal length shortening. Additionally, treatment was able to decrease the levels of MPO and EPO activities and inflammatory infiltrates, as well as the histopathological lesions characteristic of mucositis in the jejunum and ileum. Results of the present study showed that the oral administration of R. mucilaginosa UFMGCB 18,377 protected mice against mucositis induced by 5-FU.


Assuntos
Mucosite , Animais , Regiões Antárticas , Fluoruracila/efeitos adversos , Humanos , Mucosa Intestinal , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Rhodotorula
12.
Int Microbiol ; 25(1): 189-206, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34498226

RESUMO

Mastitis is one of the most important causes of loss of cattle production, burdening producers due to the increased cost of milk production and decreased herd productivity. The development of alternative methods for the treatment and prevention of mastitis other than traditional chemical antibiotic therapy needs to be implemented to meet international pressures to reduce the use of these drugs and promote the elimination of multiresistant microbial strains from the environment. Treatment with probiotic bacteria or yeast strains offers a possible strategy for the control of mastitis. The objective of this work was to isolate, identify, and characterize lactic bacteria from milk and the intramammary duct of Gyr, Guzerat, Girolando 1/2, and Holstein cattle breeds from Brazil. Samples of 115 cows were taken, a total of 192 bacteria isolates belonging to 30 species were obtained, and 81 were selected to evaluate their probiotic potential in in vitro characterization tests. In general, bacteria isolated from the mammary gland have low autoaggregation, cell surface hydrophobicity, and co-aggregation with mastitis etiological bacteria Staphylococcus aureus and Escherichia coli. Also, they have biofilm assembly capacity, inability to produce exopolysaccharides, high production of H2O2, and strong antagonism against mastitis pathogens. Ten lactic bacteria isolates were used in co-culture with human MDA-MB-231 breast epithelial cells to assess their adhesion capacity and impairment of the S. aureus invasion. Our results, therefore, contribute to the future production of new prevention and treatment tools for bovine mastitis.


Assuntos
Lactobacillales , Mastite Bovina , Probióticos , Infecções Estafilocócicas , Animais , Bovinos , Ecossistema , Feminino , Peróxido de Hidrogênio , Mastite Bovina/prevenção & controle , Staphylococcus aureus
13.
Drug Alcohol Depend ; 229(Pt A): 109105, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34628094

RESUMO

BACKGROUND: The present study aimed to identify for the first time sex differences in the development of CPP induced by intragastric alcohol administration in mice. METHODS: Male and female adult Swiss mice were submitted to 16 days of conditioning with alcohol (0.5-3.0 g/kg, N = 8/dose/sex), with 2 post-conditioning tests (after 8 and 16 sessions) during the protocol. RESULTS: 8 days of conditioning (4 alcohol sessions, 4 saline sessions) with intragastric alcohol administration were sufficient to induce CPP in male mice at the doses of 1.0, 1.5 and 2.0 g/kg. However, only higher doses (2.0, 2.5 and 3.0 g/kg) induced CPP in female mice using an 8-day conditioning protocol, while a 16-day conditioning protocol was necessary for the development of intragastric alcohol-induced CPP at the doses of 1.0 and 1.5 g/kg. Regardless of the conditioning protocol, higher doses or alcohol that had rewarding effects in females (2.5 and 3.0 g/kg) did not induce CPP in males, with a significant difference between males and females at those doses. Analysis of the potency (EC50) and efficacy (Emax) of alcohol in inducing CPP when administered intragastrically in male and female mice showed significant sex differences with 8 conditioning sessions. CONCLUSIONS: Our data show a clear protocol (8 vs 16 days) and dose difference between male and female Swiss mice regarding the development of CPP induced by intragastric alcohol administration. Intragastric alcohol administration is closer to human drinking, and our protocol provides a more translational approach to studying the rewarding effects of alcohol in mice.


Assuntos
Condicionamento Clássico , Caracteres Sexuais , Animais , Relação Dose-Resposta a Droga , Etanol , Feminino , Masculino , Camundongos , Recompensa
14.
Front Pharmacol ; 12: 713595, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630089

RESUMO

Periodontitis is an inflammatory disease induced by a dysbiotic oral microbiome. Probiotics of the genus Bifidobacterium may restore the symbiotic microbiome and modulate the immune response, leading to periodontitis control. We evaluated the effect of two strains of Bifidobacterium able to inhibit Porphyromonas gingivalis interaction with host cells and biofilm formation, but with distinct immunomodulatory properties, in a mice periodontitis model. Experimental periodontitis (P+) was induced in C57Bl/6 mice by a microbial consortium of human oral organisms. B. bifidum 1622A [B+ (1622)] and B. breve 1101A [B+ (1101)] were orally inoculated for 45 days. Alveolar bone loss and inflammatory response in gingival tissues were determined. The microbial consortium induced alveolar bone loss in positive control (P + B-), as demonstrated by microtomography analysis, although P. gingivalis was undetected in oral biofilms at the end of the experimental period. TNF-α and IL-10 serum levels, and Treg and Th17 populations in gingiva of SHAM and P + B- groups did not differ. B. bifidum 1622A, but not B. breve 1101A, controlled bone destruction in P+ mice. B. breve 1101A upregulated transcription of Il-1ß, Tnf-α, Tlr2, Tlr4, and Nlrp3 in P-B+(1101), which was attenuated by the microbial consortium [P + B+(1101)]. All treatments downregulated transcription of Il-17, although treatment with B. breve 1101A did not yield such low levels of transcripts as seen for the other groups. B. breve 1101A increased Th17 population in gingival tissues [P-B+ (1101) and P + B+ (1101)] compared to SHAM and P + B-. Administration of both bifidobacteria resulted in serum IL-10 decreased levels. Our data indicated that the beneficial effect of Bifidobacterium is not a common trait of this genus, since B. breve 1101A induced an inflammatory profile in gingival tissues and did not prevent alveolar bone loss. However, the properties of B. bifidum 1622A suggest its potential to control periodontitis.

15.
Probiotics Antimicrob Proteins ; 13(5): 1338-1354, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33759043

RESUMO

Antarctica is one of the most pristine and inhospitable regions of the planet, mostly inhabited by microorganisms that survive due to unusual metabolic pathways to adapt to its extreme conditions, which could be interesting for the selection of new probiotics. The aim of the present study was to screen in vitro and in vivo putative probiotics among 254 yeasts isolated from different habitats of Antarctica. In vitro selection evaluated functional (growth at 37 °C, resistance to simulated gastric environment, and to bile salts), safety (degradation of mucin, production of ß-haemolysis and resistance to antifungal drugs), and beneficial (production of antagonistic substances and adhesion to pathogens) properties. Twelve yeasts were able to grow at 37 °C, one of which was eliminated to present ß-haemolytic ability. The remained yeasts resisted to gastric simulation and bile salts, but none presented antagonism against the pathogens tested. Because of the high co-aggregation with Salmonella enterica Typhimurium and growth yield, Rhodotorula mucilaginosa UFMGCB 18377 and Saccharomyces cerevisiae UFMGCB 11120 were selected for in vivo steps using mice challenged with S. Typhimurium. Both yeasts reached high faecal population levels when daily administered, but only R. mucilaginosa UFMGCB 18377 protected mice against Salmonella infection presenting a higher survival and reduced weight loss, bacterial translocation to the liver, sIgA intestinal levels, and intestinal and hepatic MPO and EPO activities. Our in vitro and in vivo results suggest that R. mucilaginosa UFMGCB 18377 presents probiotic potential and deserve further studies as candidate of probiotic by-products. In addition, this is the first screening study of yeasts isolated from Antarctic environments and of Rhodotorula genus for probiotic use.


Assuntos
Probióticos , Leveduras , Animais , Regiões Antárticas , Camundongos , Rhodotorula
16.
Gut Microbes ; 11(6): 1531-1546, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32573321

RESUMO

Although dysbiosis in the gut microbiota is known to be involved in several inflammatory diseases, whether any specific bacterial taxa control host response to inflammatory stimuli is still elusive. Here, we hypothesized that dysbiotic indigenous taxa could be involved in modulating host response to inflammatory triggers. To test this hypothesis, we conducted experiments in germ-free (GF) mice and in mice colonized with dysbiotic taxa identified in conventional (CV) mice subjected to chemotherapy-induced mucositis. First, we report that the absence of microbiota decreased inflammation and damage in the small intestine after administration of the chemotherapeutic agent 5-fluorouracil (5-FU). Also, 5-FU induced a shift in CV microbiota resulting in higher amounts of Enterobacteriaceae, including E. coli, in feces and small intestine and tissue damage. Prevention of Enterobacteriaceae outgrowth by treating mice with ciprofloxacin resulted in diminished 5-FU-induced tissue damage, indicating that this bacterial group is necessary for 5-FU-induced inflammatory response. In addition, monocolonization of germ-free (GF) mice with E. coli led to reversal of the protective phenotype during 5-FU chemotherapy. E. coli monocolonization decreased the basal plasma corticosterone levels and blockade of glucocorticoid receptor in GF mice restored inflammation upon 5-FU treatment. In contrast, treatment of CV mice with ciprofloxacin, that presented reduction of Enterobacteriaceae and E. coli content, induced an increase in corticosterone levels. Altogether, these findings demonstrate that Enterobacteriaceae outgrowth during dysbiosis impacts inflammation and tissue injury in the small intestine. Importantly, indigenous Enterobacteriaceae modulates host production of the anti-inflammatory steroid corticosterone and, consequently, controls inflammatory responsiveness in mice.


Assuntos
Corticosterona/metabolismo , Disbiose/microbiologia , Enterobacteriaceae/crescimento & desenvolvimento , Animais , Antineoplásicos/efeitos adversos , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Corticosterona/imunologia , Disbiose/etiologia , Disbiose/imunologia , Disbiose/metabolismo , Enterobacteriaceae/genética , Fluoruracila/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Intestino Delgado/microbiologia , Masculino , Camundongos
17.
J Neuroimmunol ; 346: 577292, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32580070

RESUMO

Growing evidence suggests a role for brain-gut-microbiota axis in affective disorders including major depression and bipolar disorder (BD). Herein, we aim to explore, by employing germ-free (GF) mice, the effect of the indigenous microbiota in the development of mania-like behavior. Conventional and GF mice were evaluated for the hyperlocomotion induced by the dopamine transporter inhibitor GBR12909 (15 mg/Kg), a validated model for mania-like behavior. Inflammatory mediators and neurotrophic factors were quantified in the prefrontal cortex, hippocampus and striatum. Mice lacking indigenous microbiota were less susceptible to the mania-like behavior induced by GBR12909. This effect was associated with decreased levels of inflammatory cytokines such as IL-6 and TNF-α, along with increased concentrations of anti- inflammatory cytokines (IL-10) and of neurotrophins (BDNF and NGF). We provided the first evidence that gut-microbiota-brain axis participates in the development of mania-like behavior in rodents, possibly through neuroimmunepathways.

18.
Cancer Chemother Pharmacol ; 84(1): 117-126, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31079219

RESUMO

PURPOSE: Gastrointestinal mucositis is a major problem associated with cancer therapy. To minimize these deleterious effects, simultaneous administration of antioxidant components, such as selenium, can be considered. There is a growing interest in the use of yeasts because they are able to convert inorganic selenium into selenomethionine. In the present study, oral administration of Saccharomyces cerevisiae UFMG A-905 enriched with selenium was evaluated as an alternative in minimizing the side effects of 5FU-induced mucositis in mice. METHODS: Mice body weight, food consumption, faeces consistency and the presence of blood in faeces were assessed daily during experimental mucositis induced by 5-fluorouracil (5FU). Blood was used for intestinal permeability determination, and small intestine for oxidative stress, immunological and histopathological examination. RESULTS: The increased intestinal permeability observed with mucositis induction was partially reverted by S. cerevisiae and selenium-enriched yeast. Both treatments were able to reduce myeloperoxidase activity, but only selenium-enriched yeast reduced eosinophil peroxidase activity. CXCL1/KC levels, histopathological tissue damage and oxidative stress (lipid peroxidation and nitrite production) in the small intestine were reduced by both treatments; however, this reduction was always higher when treatment with selenium-enriched yeast was evaluated. CONCLUSIONS: Results of the present study showed that the oral administration of S. cerevisiae UFMG A-905 protected mice against mucositis induced by 5-FU, and that this effect was potentiated when the yeast was enriched with selenium.


Assuntos
Fluoruracila/toxicidade , Mucosite/prevenção & controle , Probióticos/administração & dosagem , Saccharomyces cerevisiae , Selênio/administração & dosagem , Animais , Antimetabólitos Antineoplásicos/toxicidade , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Modelos Animais de Doenças , Feminino , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Mucosite/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Probióticos/farmacologia , Selênio/farmacologia
19.
Microbiology (Reading) ; 164(3): 349-358, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29458690

RESUMO

Lactobacilli are the dominant bacteria of the vaginal tract of healthy women and they play a major role in the maintenance of mucosal homeostasis, preventing genital infections, such as bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It is now known that one mechanism of this protection is the influence that lactobacilli can exert on host immune responses. In this context, we evaluated two Lactobacillus strains (L. plantarum 59 and L. fermentum 137) for their immunomodulatory properties in response to Gardnerella vaginalis (BV) or Candida albicans (VVC) infections in a HeLa cell infection model. G. vaginalis and C. albicans triggered the secretion of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-8) and the activation of NF-κB in HeLa cells, in contrast to L. plantarum 59 and L. fermentum 137. Treatments with the Lactobacillus strains or their cell-free supernatants before (pre-treatment) or after (post-treatment) the challenge with the pathogens resulted in decreased secretion of pro-inflammatory cytokines and decreased activation of NF-κB. The treatments with Lactobacillus strains not only decreased the secretion of IL-8, but also its expression, as confirmed by gene reporter luciferase assay, suggesting transcription-level control by lactobacilli. In conclusion, L. plantarum 59 and L. fermentum 137 were confirmed to have an anti-inflammatory effect against G. vaginalis and C. albicans and they were able to influence signalling in NF-κB pathway, making them interesting candidates as probiotics for the prevention or treatment of BV and VVC.


Assuntos
Anti-Inflamatórios/farmacologia , Candida albicans/efeitos dos fármacos , Gardnerella vaginalis/efeitos dos fármacos , Lactobacillus plantarum/fisiologia , Limosilactobacillus fermentum/fisiologia , Probióticos/farmacologia , Candida albicans/crescimento & desenvolvimento , Técnicas de Cocultura , Meios de Cultivo Condicionados , Citocinas/genética , Citocinas/metabolismo , Feminino , Gardnerella vaginalis/crescimento & desenvolvimento , Células HeLa , Humanos , Fator de Transcrição RelA/metabolismo , Transcrição Gênica/efeitos dos fármacos
20.
Water Res ; 132: 79-89, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29306702

RESUMO

Gut microbiota exerts a fundamental role on host physiology, and how extrinsic perturbations influence its composition has been increasingly examined. However, the effect of drinking water on gut microbiota is still poorly understood. In this study, we explored the response of mouse gut bacterial community (fecal and mucosa-adhered) to the ingestion of different types of drinking water. The experimental cohort was divided according to different water sources into four groups of mice that consumed autoclaved tap water (control group), water collected directly from a drinking water treatment plant, tap water, and commercial bottled mineral water. Differences among groups were observed, especially related to control group, which exhibited the smallest intra-group variation, and the largest distance from test groups on the last experimental day. Clinically important taxa, such as Acinetobacter and Staphylococcus, increased in feces of mice that drank tap water and in mucosa-adhered samples of animals from disinfected and tap water groups. Furthermore, statistical analyses showed that both time elapsed between samplings and water type significantly influenced the variation observed in the samples. Our results reveal that drinking water potentially affects gut microbiota composition. Additionally, the increase of typical drinking water clinically relevant and antibiotic resistance-associated bacteria in gut microbiota is a cause of concern.


Assuntos
Bactérias/classificação , Água Potável , Microbioma Gastrointestinal , Águas Minerais , Animais , Desinfecção , Fezes/microbiologia , Feminino , Camundongos Endogâmicos BALB C , Purificação da Água , Abastecimento de Água
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