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1.
Anim Sci J ; 91(1): e13475, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33078490

RESUMO

Growth performance of pigs has been associated with healthy gut microbiota. To improve production, pigs are usually treated with antimicrobials. Nonetheless, while antimicrobials harm the gut-indigenous microbiota, probiotic supplementation seems to help keep it healthy. Here, using antimicrobials, we artificially induced dysbiosis in pigs and evaluated a possible preventive effect of probiotic supplementation. Three 6-week-old piglets were given a basal feed, and 3 more the feed supplemented with 2.0 × 106  CFU of Bacillus subtilis QST713/g of feed. After 14 days, antimicrobial enrofloxacin (5 mg/kg B.W.) was injected intramuscularly to all pigs on days 14-16. Feces were collected on days 14, 17, 19, 21, and 23. Total bacteria count was unaffected by enrofloxacin or QST713. However, Lactobacillus spp. and, in particular, Escherichia coli were affected by enrofloxacin, the latter not being observed in the feces on days 17 and 19. Interestingly, a reciprocal increase in E. coli was observed in control pigs on days 21 and 23, although in QST713-supplemented piglets, this increase was attenuated. While the gut microbiota composition did not return to initial levels in antimicrobial-administered piglets, it did in QST713-supplemented piglets. QST713 supplementation was likely crucial to keep the microbiota of piglets healthy.


Assuntos
Antibacterianos/efeitos adversos , Bacillus subtilis , Suplementos Nutricionais , Disbiose/prevenção & controle , Disbiose/veterinária , Enrofloxacina/efeitos adversos , Probióticos/administração & dosagem , Doenças dos Suínos/prevenção & controle , Animais , Antibacterianos/administração & dosagem , Disbiose/induzido quimicamente , Disbiose/microbiologia , Enrofloxacina/administração & dosagem , Fezes/microbiologia , Microbioma Gastrointestinal , Injeções Intramusculares , Suínos , Doenças dos Suínos/induzido quimicamente , Doenças dos Suínos/microbiologia
2.
Ecotoxicol Environ Saf ; 204: 111072, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758694

RESUMO

Zearalenone (ZEN) is a mycotoxin that causes serious health problems in humans and animals. However, few studies have focused on the destruction of the intestinal barrier caused by ZEN. In this study, rats were exposed to different dosages of ZEN (0, 0.2, 1.0 and 5.0 mg/kg bw) by gavage for 4 weeks. The results showed that 1.0 and 5.0 mg/kg ZEN impaired gut morphology, induced the inflammatory response, reduced mucin expression, increased intestinal permeability, decreased the expression of TJ proteins and activated the RhoA/ROCK pathway. However, 0.2 mg/kg ZEN had no significant effect on intestinal barrier except for reducing the expression of some TJ proteins and mucins. Moreover, exposure to ZEN led to slight imbalance in microbiota. In conclusion, ZEN exposure resulted in intestinal barrier dysfunction by inducing intestinal microbiota dysbiosis, decreasing the expression of TJ proteins, activating the RhoA/ROCK pathway, and inducing the inflammatory response.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Relação Dose-Resposta a Droga , Disbiose/induzido quimicamente , Feminino , Microbioma Gastrointestinal/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Jejuno/microbiologia , Jejuno/patologia , Masculino , Mucinas/metabolismo , Permeabilidade , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
3.
Lancet Gastroenterol Hepatol ; 5(11): 986-995, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818437

RESUMO

BACKGROUND: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study. METHODS: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD. FINDINGS: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1·88 (95% CI 1·79-1·98) for diagnosis of incident IBD, 1·74 (1·64-1·85) for ulcerative colitis, and 2·27 (2·06-2·49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1·11, 1·07-1·15), two antibiotic dispensations (1·38, 1·32-1·44), and three or more antibiotic dispensations (1·55, 1·49-1·61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1·47, 95% CI 1·40-1·54) and Crohn's disease (1·64, 1·53-1·76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1·35 (95% CI 1·28-1·43) for patients who had received three or more dispensations, compared with general population controls. INTERPRETATION: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD. FUNDING: National Institutes of Health. Crohn's and Colitis Foundation.


Assuntos
Antibacterianos , Disbiose , Doenças Inflamatórias Intestinais , Adolescente , Adulto , Idade de Início , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Biópsia/estatística & dados numéricos , Estudos de Casos e Controles , Sistemas de Informação em Farmácia Clínica/estatística & dados numéricos , Disbiose/induzido quimicamente , Disbiose/prevenção & controle , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Irmãos , Suécia/epidemiologia
4.
J Urol ; 204(6): 1320-1325, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32614253

RESUMO

PURPOSE: We evaluated the effect of long-term low dose antibiotic prophylaxis on children's gut microbiota. MATERIALS AND METHODS: We conducted 16S ribosomal RNA gene sequencing using stool samples from 35 patients younger than 3 years old (median age 5.2 months; male-to-female ratio 17:18) who underwent antibiotic treatment during the acute phase of febrile urinary tract infection. Samples were collected at 5 time points, ie before, during and at 1 to 2, 3 to 4, and 5 to 6 months after febrile urinary tract infection onset and antibiotic treatment. Continuous antibiotic prophylaxis using trimethoprim-sulfamethoxazole was initiated in 23 patients with grade III or higher vesicoureteral reflux and was not administered in 12 patients without reflux. RESULTS: Within 2 weeks after initiation of treatment for febrile urinary tract infection almost all enteric bacteria belonged to the order Lactobacillales, and gut microbiota diversity decreased compared to the pretreatment level (average Shannon index 2.9 before treatment, 1.4 during treatment). The diversity recovered within 1 to 2 months after febrile urinary tract infection onset in both groups. Diversity was maintained during the study period in both groups (p=0.43). A smaller proportion of gut microbiota component belonged to the order Enterobacteriales (p=0.002) in the antibiotic prophylaxis group. CONCLUSIONS: Our results revealed that patients receiving continuous antibiotic prophylaxis had normal gut microbiota diversity, indicating that the effect of trimethoprim-sulfamethoxazole on gut microbiota was insignificant. Furthermore, prophylaxis with trimethoprim-sulfamethoxazole might selectively suppress the growth of bacteria belonging to the order Enterobacteriales, such as Escherichia coli and Klebsiella species, which are the main causative bacteria of febrile urinary tract infections.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/efeitos adversos , Disbiose/diagnóstico , Microbioma Gastrointestinal/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Refluxo Vesicoureteral/tratamento farmacológico , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/métodos , Bactérias/genética , Bactérias/isolamento & purificação , Pré-Escolar , DNA Bacteriano/isolamento & purificação , Relação Dose-Resposta a Droga , Esquema de Medicação , Disbiose/induzido quimicamente , Disbiose/epidemiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Lactente , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Masculino , RNA Ribossômico 16S/genética , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/complicações , Refluxo Vesicoureteral/diagnóstico , Refluxo Vesicoureteral/etiologia
5.
Chemosphere ; 258: 127067, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32544817

RESUMO

Dichloroacetonitrile (DCAN) is one of the emerging nitrogenous disinfection by-products (DBPs) in drinking water. However, its potential toxicological effects remain poorly understood, especially at a low concentration found in the environment. In the present study, we investigated whether the consumption of low-concentration DCAN through drinking water would produce significant effects in male SD rats, with particular focus on their physiological traits and changes in their gut microbiome and metabolite profiles. After a 4-weeks DCAN intervention, significant changes were observed in the body weight, blood indices, and histology in DCAN-treated (100 µg/L) group. Proteobacteria was relatively less abundant in 20 and 100 µg/L DCAN-treated groups compared with that in the control group at phylum level. At genus level, Parasutterella and Anaerotruncus were significantly less abundant in both 20 and 100 µg/L DCAN-treated groups than that in the control group. Furthermore, the gut microbiota-related metabolites were dramatically perturbed after DCAN consumption. In the 20 and 100 µg/L DCAN-treated groups, there were 48 and 95 altered metabolites, respectively, and were found to be involved in sphingolipid signaling pathway, fatty acid biosynthesis, and cGMP-PKG signaling pathway. In summary, we demonstrated that consumption of low-concentration DCAN through drinking water could impair host health and induce gut microbiota dysbiosis and gut microflora-related metabolic disorders in male SD rats. Our findings highlight the potential toxicity of low-concentration DBPs and provide new insight into potential causal relationship between low concentration DBPs found in the drinking water and the host health.


Assuntos
Acetonitrilos/toxicidade , Água Potável , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Purificação da Água/métodos , Animais , Análise Química do Sangue , Desinfecção/métodos , Água Potável/efeitos adversos , Água Potável/química , Disbiose/induzido quimicamente , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/genética , Masculino , Ratos Sprague-Dawley , Esfingolipídeos/metabolismo
6.
Arch Oral Biol ; 114: 104730, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371145

RESUMO

OBJECTIVES: Antibiotics play a great role in the treatment of infectious diseases, but meantime, they cause great disturbances to host microbiota. Studies on different antibiotic-induced changes in host microbiota are relatively scarce. This study aimed to investigate the changes in oral and gut microbiota and possible alterations of gut resistance to Salmonella induced by the administration of antibiotics. METHODS: The experiment was conducted by administering antibiotics to rats and detecting oral and gut microbiota by 16S rRNA gene sequencing. In second part, after treating with antibiotics or Lactobacillus rhamnosus the rats were infected by Salmonella Typhimurium and the pathogen burden in the gut was counted by colony forming unit assay. RESULTS: The gut microbiota underwent dramatic changes after both vancomycin and ampicillin treatment. The alpha diversity sharply decreased, and the microbiota composition showed a significant difference. However, the gut microbiota recovered within four weeks after stopping antibiotics administration, although this recovery was incomplete. Oral microbiota did not show significant alterations in both alpha and beta diversities. The number of pathogens in the gut in the control group was significantly lower than that in the antibiotic-treated group but only lasted for the first 4 days after infection. CONCLUSIONS: Antibiotics cause dramatic alterations in the number and diversity of gut microbiota but not oral microbiota. These changes in the gut microbiota could incompletely recover four weeks later. When infected with pathogens after antibiotic administration, the rats show a decrease in colonization resistance in the gut for the first four days after infection.


Assuntos
Antibacterianos/efeitos adversos , Resistência à Doença , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Salmonelose Animal , Ampicilina/efeitos adversos , Animais , Boca/microbiologia , RNA Ribossômico 16S , Ratos , Salmonella typhimurium , Vancomicina/efeitos adversos
7.
J Food Sci ; 85(6): 1872-1890, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32460371

RESUMO

Cancer represents a major disease burden worldwide. Despite continuous advances obtained in medical therapies recently, resistance to standard drugs and adverse effects still represent important causes of therapeutic failure. There is growing evidence that the gut microbiota can affect the response to chemo- and immunotherapeutic drugs by modulating efficacy and/or toxicity, and diet is the most important factor affecting the gut microbiota. In this study, we assessed the auxiliary antitumor effects of immunomodulatory fungal proteins from Hericium erinaceus (HEP) administered with the chemotherapy drug 5-Fluorouracil (5-Fu), and we attempted to identify new potential prebiotic bacteria for auxiliary antitumor treatment. There were 1,455 proteins identified from H. erinaceus. In a xenografted mouse model of cancer, HEP with 5-Fu significantly suppressed tumor growth, inhibited inflammatory markers such as interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS), and regulated the expression of Akt, CCDN1, CKD4, FOXM1, MMP7, MYC, PPAR-α, and PPAR-γ. 16S rRNA sequencing showed that HEP ameliorated the dysbacteriosis induced by 5-Fu, as it inhibited certain aerobic and microaerobic bacteria including Parabacteroides, Flavobacteriaceae, Christensenellaceae, Anoxybacillus, Aggregatibacter, Comamonadaceae, Planococcaceae, Desulfovibrionaceae, Sporosarcina, Staphylococcus, Aerococcaceae, and Bilophila in the xenografted mice, and increase some probiotic bacteria such as Bifidobacterium, Gemellales, Blautia, Sutterella, Anaerostipes, Roseburia, Lachnobacterium, Lactobacillus, and Desulfovibrio. This demonstrates that HEP could promote the antitumor efficacy of 5-Fu by improving the microbiota composition, the immune inflammatory response, and homeostasis.


Assuntos
Basidiomycota/química , Disbiose/tratamento farmacológico , Disbiose/microbiologia , Proteínas Fúngicas/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Neoplasias/microbiologia , Prebióticos/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Disbiose/induzido quimicamente , Disbiose/imunologia , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Proteínas Fúngicas/química , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
8.
Transl Res ; 220: 167-181, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32275896

RESUMO

Despite advances in antimicrobial treatments, infection remains a common complication of intensive chemotherapy in patients with acute leukemia. It has become progressively apparent that the current antimicrobial focus has shortcomings that result from disruption of the commensal microbial communities of the gut. These effects, collectively known as dysbiosis, have been increasingly associated worldwide with growing complications such as Clostridioides difficile infection, systemic infections, and antibiotic resistance. A revision of the current practice is overdue. Several innovative concepts have been proposed and tested in animal models and humans, with the overarching goal of preventing damage to the microbiota and facilitating its recovery. In this review, we discuss these approaches, examine critical knowledge gaps, and explore how they may be filled in future research.


Assuntos
Antineoplásicos/efeitos adversos , Infecções Bacterianas/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Leucemia/tratamento farmacológico , Doença Aguda , Animais , Antibacterianos/uso terapêutico , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/fisiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia/complicações , Leucemia/microbiologia
9.
Int J Mol Med ; 45(4): 1130-1140, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32124946

RESUMO

The gut microbiota is important for maintaining the integrity of the intestinal barrier, promoting immunological tolerance and carrying out metabolic activities that have not evolved in hosts. Intestinal dysbiosis is associated with chronic kidney disease and probiotic supplementation has been shown to be beneficial. However, it is not known whether gut microorganisms­specifically, lactic acid bacteria (LAB) can protect against acute kidney injury (AKI). To address this issue, the present study investigated the effects of Lactobacillus salivarius BP121, an intestinal LAB isolated from the feces of newborns, in a rat model of cisplatin­induced AKI and also in Caco­2 human intestinal epithelial cells. BP121 prevented cisplatin­induced AKI in rats, as demonstrated by decreases in inflammation and oxidative stress in kidney tissue and in serum levels of uremic toxins such as indoxyl sulfate (IS) and p­cresol sulfate (PCS). BP121 also reduced intestinal permeability, as determined using fluorescein isothiocyanate­dextran by immunohistochemical detection of tight junction (TJ) proteins such as zona occludens­1 and occludin. The abundance of Lactobacillus spp., which are beneficial intestinal flora, was increased by BP121; this was accompanied by an increase in the concentrations of short­chain fatty acids in feces. Additionally, H2O2­induced TJ protein damage was reduced in Caco­2 cells treated with BP121 culture supernatant, an effect that was reversed by the 5' AMP­activated protein kinase (AMPK) inhibitor Compound C and Toll­like receptor (TLR)4 inhibitor TLR4­IN­C34. In conclusion, this study demonstrated that L. salivarius BP121 protects against cisplatin­induced AKI by decreasing inflammation and oxidative stress and this renoprotective effect is partially mediated by modulating the gut environment and thereby suppressing IS and PCS production as well as by regulating AMPK and TLR4 dependent TJ assembly.


Assuntos
Lesão Renal Aguda , Cisplatino/efeitos adversos , Cresóis/metabolismo , Disbiose , Indicã/metabolismo , Lactobacillus salivarius/metabolismo , Ésteres do Ácido Sulfúrico/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/microbiologia , Lesão Renal Aguda/prevenção & controle , Animais , Células CACO-2 , Cisplatino/farmacologia , Disbiose/induzido quimicamente , Disbiose/metabolismo , Disbiose/mortalidade , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
10.
Toxicology ; 433-434: 152395, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32027963

RESUMO

Copper, an essential microelement, can still be harmful to health and has a significant impact on the gut microbiota, which is closely related to health when copper is ingested excessively. However, the effects of low dose exposure to copper early in life on health and the gut microbiota are not well understood. Here, the effects of early-life exposure of copper on the toxicity, gut microbiota and the metabolome were investigated in Sprague-Dawley (SD) rats. The results showed that 0.20 and 1.00 mg/kg BW copper early-life exposure in SD rats significantly increased ALT, AST, and ALP levels in the blood and caused liver damage. Copper exposure had a dose-dependent effect on the alpha and beta diversity and reduced the abundance of probiotics, the ratio of Firmicutes to Bacteroidetes (F/B), and changed the abundance of fat metabolism and intestinal inflammation-related bacteria. The results of the fecal metabolome also demonstrated the effects of early-life copper exposure on liver damage and intestinal inflammation-related metabolic pathways. Together, our findings demonstrated that copper exposure during early life induced liver damage and gut microbiota dysbiosis and affected the relevant metabolic pathways.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cobre/toxicidade , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Fatores Etários , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cobre/administração & dosagem , Relação Dose-Resposta a Droga , Fezes/química , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley
11.
mSphere ; 5(1)2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075882

RESUMO

Intrapartum antibiotic prophylaxis reduces the risk of infection to a mother and neonate, but antibiotic-mediated maternal and neonatal microbiota dysbiosis increases other health risks to newborn infants. We studied the impact of perinatal antibiotic prophylaxis on the microbiota in mothers and newborns with full-term or preterm delivery. Ninety-eight pregnant women and their neonates were divided into the following four groups: full term without antibiotic exposure (FT), full term with antibiotic exposure (FTA), preterm without antibiotic exposure (PT), and preterm with antibiotic exposure (PTA). Bacterial composition was analyzed by sequencing the 16S rRNA gene from maternal vaginal swabs (V) and neonatal meconium (F). The results showed that in maternal vaginal and neonatal meconium microbiota, FT and PT groups had a higher load of Lactobacillus spp. than did the FTA and PTA groups. In addition, whether in the mother or newborn, the dissimilarity in microbiota between FT and PT was the lowest compared to that between other groups. Compared to the FT and PT groups, the dissimilarity in microbial structures between the vagina and meconium decreased in the FTA and PTA groups. The health outcome of infants reveals an association between early-onset sepsis and antibiotic-mediated microbiota dysbiosis. In conclusion, perinatal antibiotic exposure is related to the establishment of gut microbiota and health risks in newborns. Promoting the rational usage of antibiotics with pregnant women will improve neonatal health.IMPORTANCE Perinatal antibiotic prophylaxis is an effective method for preventing group B Streptococcus (GBS) infection in newborns. Antibiotic exposure unbalances women's vaginal microbiota, which is associated with the establishment of the newborn gut microbiota. However, the influence of perinatal antibiotic exposure on neonatal gut microbiota colonization and health outcomes remains unclear. In this study, we found that perinatal antibiotic exposure induced microbiota dysbiosis in a woman's vagina and the neonatal gut, and we highlight a significant decrease in the abundance of Lactobacillus spp. The influence of antibiotic use on the microbiota was greater than that from gestational age. Additionally, full-term newborns without antibiotic exposure had no evidence of early-onset sepsis, whereas in full-term or preterm newborns with antibiotic exposure before birth, at least one infant was diagnosed with early-onset sepsis. These results suggest an association between perinatal antibiotic exposure and microbial dysbiosis in maternal vaginal and neonatal gut environments, which may be related to the occurrence of early-onset sepsis.


Assuntos
Antibacterianos/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Exposição Materna/efeitos adversos , Sepse/etiologia , Adulto , Antibacterianos/administração & dosagem , Feminino , Idade Gestacional , Humanos , Saúde do Lactente , Recém-Nascido , Troca Materno-Fetal , Mecônio/microbiologia , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , RNA Ribossômico 16S/genética , Fatores de Risco , Sepse/microbiologia , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/etiologia , Vagina/microbiologia , Adulto Jovem
12.
Sci Rep ; 10(1): 2961, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076013

RESUMO

Sucrose has long been regarded as the most cariogenic carbohydrate. However, why sucrose causes severer dental caries than other sugars is largely unknown. Considering that caries is a polymicrobial infection resulting from dysbiosis of oral biofilms, we hypothesized that sucrose can introduce a microbiota imbalance favoring caries to a greater degree than other sugars. To test this hypothesis, an in vitro saliva-derived multispecies biofilm model was established, and by comparing caries lesions on enamel blocks cocultured with biofilms treated with sucrose, glucose and lactose, we confirmed that this model can reproduce the in vivo finding that sucrose has the strongest cariogenic potential. In parallel, compared to a control treatment, sucrose treatment led to significant changes within the microbial structure and assembly of oral microflora, while no significant difference was detected between the lactose/glucose treatment group and the control. Specifically, sucrose supplementation disrupted the homeostasis between acid-producing and alkali-producing bacteria. Consistent with microbial dysbiosis, we observed the most significant disequilibrium between acid and alkali metabolism in sucrose-treated biofilms. Taken together, our data indicate that the cariogenicity of sugars is closely related to their ability to regulate the oral microecology. These findings advance our understanding of caries etiology from an ecological perspective.


Assuntos
Biofilmes/efeitos dos fármacos , Cárie Dentária/microbiologia , Disbiose/induzido quimicamente , Microbiota/efeitos dos fármacos , Sacarose/efeitos adversos , Adulto , Contagem de Colônia Microbiana , Esmalte Dentário/microbiologia , Glucose/efeitos adversos , Humanos , Concentração de Íons de Hidrogênio , Lactose/efeitos adversos , Saliva/microbiologia
13.
Bull Cancer ; 107(4): 458-464, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32057465

RESUMO

Proton pump inhibitors, a major progress in gastro-enterology, are globally among the most widely prescribed drugs. But, due to their strong gastric acid inhibition, they can be responsible for side effects, particularly in cancer patients. They are involved in renal function impairment, bone fractures, digestive bacterial overgrowth, particularlyclostridium difficile infections, anemia and hypomagnesemia. Long term use can increase the risks of gastric, pancreatic and liver cancers. They decrease absorption of weak bases drugs, particularly tyrosine kinase inhibitors and capecitabine and are responsible for a poorer prognosis if taken concomitantly with erlotinib, gefitinib and pazopanib. Modification of cyclin dependent kinases is also possible as well as decrease of efficacy of immune check point inhibitors (microbiome modifications). Absoption and efficacy of capecitabine seem also poorer with negative prognosis effect on treatment of gastric and colon cancer. Their long term use, particularly in cancer patients, should probably be avoided.


Assuntos
Neoplasias/complicações , Inibidores da Bomba de Prótons/efeitos adversos , Antineoplásicos/farmacocinética , Infecções Bacterianas/induzido quimicamente , Capecitabina/farmacocinética , Contraindicações de Medicamentos , Interações Medicamentosas , Disbiose/induzido quimicamente , Cloridrato de Erlotinib/administração & dosagem , Fraturas Ósseas/induzido quimicamente , Absorção Gastrointestinal/efeitos dos fármacos , Neoplasias Gastrointestinais/induzido quimicamente , Gefitinibe/administração & dosagem , Humanos , Rim/efeitos dos fármacos , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidores , Inibidores da Bomba de Prótons/farmacologia , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem
14.
Sci Rep ; 10(1): 2723, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066847

RESUMO

Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (-18.8 ng/mg; 95%CI: -50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (-46.3 ng/mg; 95%CI: -71.4; -21.2; p < 0.001). The abundance of Stomatobaculum in the microbiome was reduced and Bacillus increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.


Assuntos
Antiulcerosos/efeitos adversos , Disbiose/prevenção & controle , Refluxo Gastroesofágico/terapia , Úlcera Péptica/terapia , Prebióticos/administração & dosagem , Probióticos/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Idoso , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Antiulcerosos/administração & dosagem , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Bacillus/classificação , Bacillus/isolamento & purificação , Clostridiales/classificação , Clostridiales/isolamento & purificação , Disbiose/induzido quimicamente , Disbiose/fisiopatologia , Esomeprazol/administração & dosagem , Esomeprazol/efeitos adversos , Feminino , Refluxo Gastroesofágico/microbiologia , Refluxo Gastroesofágico/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Regulação da Expressão Gênica , Haptoglobinas/genética , Haptoglobinas/metabolismo , Humanos , Lactobacillus/classificação , Lactobacillus/isolamento & purificação , Lactococcus/classificação , Lactococcus/isolamento & purificação , Complexo Antígeno L1 Leucocitário/genética , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Pantoprazol/administração & dosagem , Pantoprazol/efeitos adversos , Úlcera Péptica/microbiologia , Úlcera Péptica/fisiopatologia , Projetos Piloto , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Inibidores da Bomba de Prótons/administração & dosagem , Qualidade de Vida
15.
Nat Microbiol ; 5(4): 630-641, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31959968

RESUMO

Intestinal microbiotas contain beneficial microorganisms that protect against pathogen colonization; treatment with antibiotics disrupts the microbiota and compromises colonization resistance. Here, we determine the impact of exchanging microorganisms between hosts on resilience to the colonization of invaders after antibiotic-induced dysbiosis. We assess the functional consequences of dysbiosis using a mouse model of colonization resistance against Escherichia coli. Antibiotics caused stochastic loss of members of the microbiota, but the microbiotas of co-housed mice remained more similar to each other compared with the microbiotas among singly housed animals. Strikingly, co-housed mice maintained colonization resistance after treatment with antibiotics, whereas most singly housed mice were susceptible to E. coli. The ability to retain or share the commensal Klebsiella michiganensis, a member of the Enterobacteriaceae family, was sufficient for colonization resistance after treatment with antibiotics. K. michiganensis generally outcompeted E. coli in vitro, but in vivo administration of galactitol-a nutrient that supports the growth of only E. coli-to bi-colonized gnotobiotic mice abolished the colonization-resistance capacity of K. michiganensis against E. coli, supporting the idea that nutrient competition is the primary interaction mechanism. K. michiganensis also hampered colonization of the pathogen Salmonella, prolonging host survival. Our results address functional consequences of the stochastic effects of microbiota perturbations, whereby microbial transmission through host interactions can facilitate reacquisition of beneficial commensals, minimizing the negative impact of antibiotics.


Assuntos
Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Klebsiella/fisiologia , Interações Microbianas , Simbiose/fisiologia , Animais , Antibacterianos/farmacologia , Bacteroidetes/classificação , Bacteroidetes/isolamento & purificação , Ciprofloxacino/farmacologia , Contagem de Colônia Microbiana , Disbiose/induzido quimicamente , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/patogenicidade , Firmicutes/classificação , Firmicutes/isolamento & purificação , Vida Livre de Germes , Klebsiella/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/crescimento & desenvolvimento , Salmonella typhimurium/patogenicidade , Estreptomicina/farmacologia , Verrucomicrobia/classificação , Verrucomicrobia/isolamento & purificação
16.
Mar Drugs ; 18(1)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968646

RESUMO

Chitooligosaccharides (COS) have a variety of biological activities due to their positively charged amino groups. Studies have shown that COS have antidiabetic effects, but their molecular mechanism has not been fully elucidated. The present study confirmed that COS can reduce hyperglycemia and hyperlipidemia, prevent obesity, and enhance histological changes in the livers of mice with type 2 diabetes mellitus (T2DM). Additionally, treatment with COS can modulate the composition of the gut microbiota in the colon by altering the abundance of Firmicutes, Bacteroidetes, and Proteobacteria. Furthermore, in T2DM mice, treatment with COS can upregulate the cholesterol-degrading enzymes cholesterol 7-alpha-hydroxylase (CYP7A1) and incretin glucagon-like peptide 1 (GLP-1) while specifically inhibiting the transcription and expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the key enzyme in cholesterol synthesis. Furthermore, using an oleic acid-induced hepatocyte steatosis model, we found that HMGCR can be directly transactivated by SET and MYND domain containing 3 (SMYD3), a transcriptional regulator, via 5'-CCCTCC-3' element in the promoter. Overexpression of SMYD3 can suppress the inhibitory effect of COS on HMGCR, and COS might regulate HMGCR by inhibiting SMYD3, thereby exerting hypolipidemic functions. To the best of our knowledge, this study is the first to illustrate that COS mediate glucose and lipid metabolism disorders by regulating gut microbiota and SMYD3-mediated signaling pathways.


Assuntos
Quitosana/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glucose/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Oligossacarídeos/farmacologia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Disbiose/induzido quimicamente , Dislipidemias/tratamento farmacológico , Células Hep G2 , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos
17.
Aliment Pharmacol Ther ; 51(5): 505-526, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31990420

RESUMO

BACKGROUND: Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health. AIM: To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease. METHODS: A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria. RESULTS: Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users). CONCLUSION: PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.


Assuntos
DNA Bacteriano/análise , Disbiose/induzido quimicamente , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Inibidores da Bomba de Prótons/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Estudos de Coortes , DNA Bacteriano/efeitos dos fármacos , DNA Bacteriano/genética , Disbiose/epidemiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Humanos , Estudos Observacionais como Assunto/estatística & dados numéricos , Inibidores da Bomba de Prótons/administração & dosagem , Análise de Sequência de DNA/métodos
18.
Chemosphere ; 246: 125791, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31927375

RESUMO

The gut microbial compositions are easily affected by the environmental chemicals like arsenic (As) leading to dysbiosis. The dysbiosis of gut microbiome has associated with numerous diseases; among which cancer is one of the major diseases. The meticulous mechanism underlying As- altered gut microbiome, Nucleotide domine containing protein 2 (NOD2) and how altered gut microbiome disturbs the intestinal homeostasis to regulate colon cancer markers remains unclear. For this, one hundred twenty 8-week old age male mice were divided into two exposure periods (3 and 6 months), and each exposure group animals were further divided into four groups as control (received only distilled H2O), low (0.15 mg As2O3/L), medium (1.5 mg As2O3/L) and high (15 mg As2O3/L) dose (each group containing 15 mice) administrated for 3 and 6 months. The results showed that As exposure highly altered gut microbiome with a significant depletion in NOD2 in contrast to control groups. Moreover, the dendritic cells (CD11a, CD103, CX3CR1) and macrophages (F4/80) were significantly increased by As exposure. Interestingly, increased trend of inflammatory cytokines (TNF-α, IFN-γ, IL-17) and depleted anti-inflammatory cytokines (IL-10) was observed in As exposed mice. Furthermore, the colon cancer markers ß-catenin has increased while APC was arrested by As both in 3 and 6 months treated animals. Many studies reported that As altered gut microbial compositions, in this study, our results suggested that altered gut microbiome indirectly regulates colon cancer marker through immune system destruction mediated by inflammatory cytokines.


Assuntos
Arsênico/toxicidade , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/imunologia , Animais , Arsênico/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo , Citocinas/metabolismo , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Intestinos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Testes de Toxicidade Crônica
19.
J Invest Dermatol ; 140(3): 676-687.e6, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31472106

RESUMO

Vitiligo is impacted by environmental triggers. We studied the contribution of the microbiome in FH mice, in which depigmentation is mediated by tyrosinase-reactive T cells. The mice received oral antibiotics and were monitored for depigmentation. The microbiome was studied in fecal and skin samples using 16S rRNA analysis. The resulting T-cell distributions were evaluated. In untreated mice, pigment loss did not expand to the pelage, whereas mice in the ampicillin group were approximately 1/3 depigmented at 30 weeks. In contrast to models of autoimmunity that are less dependent on IFN-γ, ampicillin but not neomycin treatment correlated with accelerated disease and reduced bacteria in the fecal pellets. Modified cytokine patterns in the tissue and serum suggest a response that transcends the gut. Ampicillin-induced depigmentation was accompanied by gut but not skin dysbiosis, and reduced T cell numbers in both sites. Neomycin induced a redistribution of gut T cells and an accumulation of skin regulatory T cells. This treatment spurred a Bacteroides-dominated population of fecal bacteria. Reduced diversity is prominent particularly after ampicillin treatment, when the gut is dominated by Pseudomonas species. In line with current concepts relating the microbiome and the immune system, we predict that dietary measures might promote skin health and delay vitiligo onset.


Assuntos
Antibacterianos/efeitos adversos , Disbiose/induzido quimicamente , Microbiota/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Vitiligo/imunologia , Administração Oral , Ampicilina/administração & dosagem , Ampicilina/efeitos adversos , Animais , Antibacterianos/administração & dosagem , Bacteroides/genética , Bacteroides/isolamento & purificação , Citocinas/análise , Citocinas/imunologia , Citocinas/metabolismo , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Modelos Animais de Doenças , Disbiose/imunologia , Disbiose/microbiologia , Fezes/microbiologia , Feminino , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Microbiota/imunologia , Neomicina/administração & dosagem , Neomicina/efeitos adversos , Pseudomonas/genética , Pseudomonas/isolamento & purificação , RNA Ribossômico 16S/genética , Pele/citologia , Pele/imunologia , Pele/microbiologia , Pele/patologia , Vitiligo/sangue , Vitiligo/microbiologia , Vitiligo/patologia
20.
Med Hypotheses ; 134: 109421, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31634771

RESUMO

Added sugars are ubiquitous in contemporary Western diets. Although excessive sugar consumption is now robustly associated with an array of adverse health consequences, comparatively little research has thus far addressed its impact on the risk of mental illness. But ample evidence suggests that high-dose sugar intake can perturb numerous metabolic, inflammatory, and neurobiological processes. Many such effects are of particular relevance to the onset and maintenance of depressive illness, among them: systemic inflammation, gut microbiota disruption, perturbed dopaminergic reward signaling, insulin resistance, oxidative stress, and the generation of toxic advanced glycation end-products (AGEs). Accordingly, we hypothesize that added dietary sugars carry the potential to increase vulnerability to major depressive disorder, particularly at high levels of consumption. The present paper: (a) summarizes the existing experimental and epidemiological research regarding sugar consumption and depression vulnerability; (b) examines the impact of sugar ingestion on known depressogenic physiological processes; and (c) outlines the clinical and theoretical implications of the apparent sugar-depression link. We conclude that the extant literature supports the hypothesized depressogenic impact of added dietary sugars, and propose that an improved understanding of the effects of sugar on body and mind may aid in the development of novel therapeutic and preventative measures for depression.


Assuntos
Transtorno Depressivo Maior/induzido quimicamente , Açúcares da Dieta/efeitos adversos , Anedonia , Animais , Transtorno Depressivo Maior/epidemiologia , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Dopamina/metabolismo , Disbiose/induzido quimicamente , Feminino , Seguimentos , Saúde Global , Produtos Finais de Glicação Avançada/efeitos adversos , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Inflamação/induzido quimicamente , Resistência à Insulina , Microbiota/efeitos dos fármacos , Obesidade/epidemiologia , Obesidade/etiologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Bebidas Adoçadas com Açúcar/efeitos adversos
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