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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.
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
3.
Am J Physiol Endocrinol Metab ; 319(2): E305-E314, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32516028

RESUMO

Obesity promotes nonalcoholic fatty liver disease (NAFLD). The intestinal microbiota contributes to NAFLD progression through a gut-to-liver pathway that promotes inflammation and fibrosis. Gut microbiota-derived factors can travel to the liver and activate immune responses in liver resident cells to promote inflammation and NAFLD. Little is known about bacterial sensors or immune responses that can protect against NAFLD. We tested whether the bacterial cell wall sensor nucleotide-binding oligomerization domain-containing (NOD)2 protects against diet-induced NAFLD in mice. Whole body deletion of NOD2 exacerbated liver steatosis and fibrosis in mice fed a NAFLD-promoting diet. Mice with a hepatocyte-specific deletion of NOD2 (Nod2-/-HKO) also had higher liver steatosis and fibrosis compared with littermate wild-type mice (WT) fed a NAFLD-promoting diet. Hepatocyte-specific NOD2 deletion altered the composition of the gut microbiome. Nod2-/-HKO mice had increased relative abundance of Clostridiales and lower Erysipelotrichaceae among other changes in cecal bacteria compared with littermate WT mice. Hepatocyte-specific NOD2 deletion altered a transcriptional program of liver inflammation, metabolism, and fibrosis. Nod2-/-HKO mice had higher levels of transcripts involved in lipid and cholesterol metabolism. Nod2-/-HKO mice had higher transcript levels of transforming growth factor-ß and collagen isoforms, which coincided with higher levels of liver collagen compared with WT mice. These data show that bacterial cell wall sensing within hepatocytes can engage retrograde cross-talk from the liver to the gut, where liver immunity communicates with the gut to influence the intestinal host-microbe relationship during diet-induced NAFLD, and NOD2 within the hepatocyte confers protection from liver steatosis and fibrosis.


Assuntos
Disbiose/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Cirrose Hepática/fisiopatologia , Fígado/fisiopatologia , Proteína Adaptadora de Sinalização NOD2/fisiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Dieta , Disbiose/prevenção & controle , Hepatócitos/química , Hepatócitos/fisiologia , Cirrose Hepática/etiologia , Cirrose Hepática/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Adaptadora de Sinalização NOD2/deficiência , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Receptor Cross-Talk
4.
Nature ; 581(7808): 310-315, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32433607

RESUMO

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.


Assuntos
Disbiose/epidemiologia , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Bacteroides/isolamento & purificação , Estudos de Coortes , Estudos Transversais , Faecalibacterium/isolamento & purificação , Fezes/microbiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Obesidade/microbiologia , Prevalência
5.
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
6.
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
7.
PLoS One ; 15(1): e0226128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940312

RESUMO

Secondary manifestations of spinal cord injury beyond motor and sensory dysfunction can negatively affect a person's quality of life. Spinal cord injury is associated with an increased incidence of depression and anxiety; however, the mechanisms of this relationship are currently not well understood. Human and animal studies suggest that changes in the composition of the intestinal microbiota (dysbiosis) are associated with mood disorders. The objective of the current study is to establish a model of anxiety following a cervical contusion spinal cord injury in rats and to determine whether the microbiota play a role in the observed behavioural changes. We found that spinal cord injury caused dysbiosis and increased symptoms of anxiety-like behaviour. Treatment with a fecal transplant prevented both spinal cord injury-induced dysbiosis as well as the development of anxiety-like behaviour. These results indicate that an incomplete unilateral cervical spinal cord injury can cause affective disorders and intestinal dysbiosis, and that both can be prevented by treatment with fecal transplant therapy.


Assuntos
Ansiedade/complicações , Ansiedade/prevenção & controle , Comportamento Animal , Disbiose/complicações , Disbiose/prevenção & controle , Transplante de Microbiota Fecal , Traumatismos da Medula Espinal/complicações , Animais , Disbiose/microbiologia , Microbioma Gastrointestinal , Aprendizagem em Labirinto , Ratos , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/microbiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/psicologia
8.
BJOG ; 127(2): 287-299, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299136

RESUMO

BACKGROUND: Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. OBJECTIVES: We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. SEARCH STRATEGY: We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. SELECTION CRITERIA: There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. DATA COLLECTION AND ANALYSIS: The authors independently extracted data. MAIN RESULTS: All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. CONCLUSIONS: Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development and to conduct future trials more rigorously. TWEETABLE ABSTRACT: Lactobacilli-containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis.


Assuntos
Candidíase Vulvovaginal , Disbiose/prevenção & controle , Disbiose/terapia , Lactobacillus , Microbiota , Probióticos/administração & dosagem , Vagina/microbiologia , Vaginose Bacteriana , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/prevenção & controle , Candidíase Vulvovaginal/terapia , Disbiose/microbiologia , Feminino , Humanos , Resultado do Tratamento , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/prevenção & controle , Vaginose Bacteriana/terapia
9.
Appl Microbiol Biotechnol ; 104(3): 981-987, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853562

RESUMO

Tea is one of the most popular beverages in the world and possesses a wide range of beneficial effects for human health. The modulation of tea on gut microbiota has gained much interest in recent years. The present study discussed the modulation effect of various types of tea on gut microbiota, which plays crucial roles in human health, as investigated by in vitro animal and human studies. The currently available findings from a total of 23 studies support the modulation effects of tea liquid, tea extract, and its major active components, including polyphenols, polysaccharides, and teasaponin, on gut microbiota. Overall, tea possesses prebiotic-like effect and can alleviate the gut microbiota dysbiosis induced by high-fat diet in gut microbiota, despite the detailed bacterial taxa may alter depending on the types of tea supplemented. Current evidence implies that the modulation effect on gut microbiota may be an important action mechanism underlying the beneficial effect of tea consumption in daily life and also the great potential of strategically chosen tea extract to develop functional foods.


Assuntos
Microbioma Gastrointestinal , Chá , Animais , Bactérias/classificação , Disbiose/prevenção & controle , Humanos , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Polifenóis/administração & dosagem , Polissacarídeos/administração & dosagem , Prebióticos
10.
Crit Rev Food Sci Nutr ; 60(11): 1783-1796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31062600

RESUMO

In recent years, scientific community has been gathering increasingly more insight on the dynamics that are at play in metabolic and inflammatory disorders. These rapidly growing conditions are reaching epidemic proportions, bringing clinicians and researcher's new challenges. The specific roles and modulating properties that beneficial/probiotic bacteria hold in the context of the gut ecosystem seem to be key to avert these inflammatory and diet-related disorders. Faecalibacterium prausnitzii, Akkermansia muciniphila and Eubacterium hallii have been identified as candidates for next generation probiotics (NGPs) with exciting potential for the prevention and treatment of such of dysbiosis-associated diseases. The challenges of these non-conventional native gut bacteria lie mainly on their extreme sensitivity to O2 traces. If these strains are to be used successfully in food, supplements or drugs they need to be stable and active in humans. In the present review, we present an overall perspective of the most updated scientific literature on the newly called NGPs through the 5W1H (What, Why, Who, Where, When, and How) method, an innovative and attractive problem-solving approach that provides the reader an effective understanding of the issue at hand.


Assuntos
Microbioma Gastrointestinal , Probióticos , Clostridiales , Disbiose/prevenção & controle , Faecalibacterium prausnitzii , Humanos , Verrucomicrobia
11.
BMJ Open ; 9(11): e032617, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31753895

RESUMO

INTRODUCTION: The healthy 'eubiosis' microbiome in infancy is regarded as the microbiome derived from term, vaginally delivered, antibiotic free, breastfed infants at 4-6 months. Dysbiosis is regarded as a deviation from a healthy state with reduced microbial diversity and deficient capacity to control drug-resistant organisms. Preterm infants are highly sensitive to early gut dysbiosis. Latter has been associated with sepsis and necrotising enterocolitis, but may also contribute to long-term health problems. Probiotics hold promise to reduce the risk for adverse short-term outcomes but the evidence from clinical trials remains inconclusive and none has directly assessed the effects of probiotics on the microbiome at high resolution. METHODS AND ANALYSIS: A randomised, double blind, placebo-controlled study has been designed to assess the safety and efficacy of the probiotic mix of Bifidobacterium longum and infantis and Lactobacillus acidophilus in the prevention of gut dysbiosis in preterm infants between 28+0 and 32+6 weeks of gestation. The study is conducted in 18 German neonatal intensive care units. Between April 2018 and March 2020, 654 preterm infants of 28+0-32+6 weeks of gestation will be randomised in the first 48 hours of life to 28 days of once daily treatment with either probiotics or placebo. The efficacy endpoint is the prevention of gut dysbiosis at day 30 of life. A compound definition of gut dysbosis is used: (1) colonisation with multidrug-resistant organisms or gram-negative bacteria with high epidemic potential or (2) a significant deviation of the gut microbiota composition as compared with healthy term infants. Dysbiosis is determined by (1) conventional microbiological culture and (2) phylogenetic microbiome analysis by high-throughput 16S rRNA and metagenome sequencing. Persistence of dysbiosis will be assessed at 12-month follow-up visits. Side effects and adverse events related to the intervention will be recorded. Key secondary endpoint(s) are putative consequences of dysbiosis. A subgroup of infants will be thoroughly phenotyped for immune parameters using chipcytometry. ETHICS AND DISSEMINATION: Ethics approval was obtained in all participating sites. Results of the trial will be published in peer-review journals, at scientific meetings, on the website (www.primal-study.de) and via social media of parent organisations. TRIAL REGISTRATION NUMBER: DRKS00013197; Pre-results.


Assuntos
Bifidobacterium longum subspecies infantis , Bifidobacterium longum , Disbiose/prevenção & controle , Recém-Nascido Prematuro , Lactobacillus acidophilus , Probióticos/administração & dosagem , Método Duplo-Cego , Enterocolite Necrosante/prevenção & controle , Fezes/microbiologia , Microbioma Gastrointestinal , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Estudos Multicêntricos como Assunto , RNA Ribossômico 16S/análise , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/prevenção & controle
12.
Nat Med ; 25(11): 1772-1782, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700190

RESUMO

Late-onset sepsis (LOS) is thought to result from systemic spread of commensal microbes from the intestines of premature infants. Clinical use of probiotics for LOS prophylaxis has varied owing to limited efficacy, reflecting an incomplete understanding of relationships between development of the intestinal microbiome, neonatal dysbiosis and LOS. Using a model of LOS, we found that components of the developing microbiome were both necessary and sufficient to prevent LOS. Maternal antibiotic exposure that eradicated or enriched transmission of Lactobacillus murinus exacerbated and prevented disease, respectively. Prophylactic administration of some, but not all Lactobacillus spp. was protective, as was administration of Escherichia coli. Intestinal oxygen level was a major driver of colonization dynamics, albeit via mechanisms distinct from those in adults. These results establish a link between neonatal dysbiosis and LOS, and provide a basis for rational selection of probiotics that modulate primary succession of the microbiome to prevent disease.


Assuntos
Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Sepse/tratamento farmacológico , Idade de Início , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Disbiose/microbiologia , Disbiose/prevenção & controle , Humanos , Recém-Nascido Prematuro , Camundongos , Probióticos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Sepse/microbiologia , Sepse/prevenção & controle
13.
Artigo em Inglês | MEDLINE | ID: mdl-31636067

RESUMO

Fluoroquinolone treatments induce dysbiosis of the intestinal microbiota, resulting in loss of resistance to colonization by exogenous bacteria such as Clostridioides difficile that may cause severe diarrhea in humans and lethal infection in hamsters. We show here that DAV131A, a charcoal-based adsorbent, decreases the intestinal levels of the fluoroquinolone antibiotics levofloxacin and ciprofloxacin in hamsters, protects their intestinal microbiota, and prevents lethal infection by C. difficile.


Assuntos
Carvão Vegetal/administração & dosagem , Infecções por Clostridium/prevenção & controle , Administração Oral , Adsorção , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Ciprofloxacino/efeitos adversos , Ciprofloxacino/farmacocinética , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Disbiose/metabolismo , Disbiose/prevenção & controle , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/farmacocinética , Microbioma Gastrointestinal/efeitos dos fármacos , Levofloxacino/efeitos adversos , Levofloxacino/farmacocinética , Masculino , Mesocricetus
14.
Nutrients ; 11(10)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623411

RESUMO

In recent years, the gut microbiome has become a focal point of interest with growing recognition that a well-balanced gut microbiota composition is highly relevant to an individual's health status and well-being. Its profile can be modulated by a number of dietary factors, although few publications have focused on the effects of what we drink. The present review performed a systematic review of trials and mechanistic studies examining the effects of tea consumption, its associated compounds and their effects on the gut microbiome. Registered articles were searched up to 10th September 2019, in the PubMed and Cochrane library databases along with references of original articles. Human trials were graded using the Jadad scale to assess quality. Altogether 24 publications were included in the main review-six were human trials and 18 mechanistic studies. Of these, the largest body of evidence related to green tea with up to 1000 mL daily (4-5 cups) reported to increase proportions of Bifidobacterium. Mechanistic studies also show promise suggesting that black, oolong, Pu-erh and Fuzhuan teas (microbially fermented 'dark tea') can modulate microbial diversity and the ratio of Firmicutes to Bacteroidetes. These findings appear to support the hypothesis that tea ingestion could favourably regulate the profile of the gut microbiome and help to offset dysbiosis triggered by obesity or high-fat diets. Further well-designed human trials are now required to build on provisional findings.


Assuntos
Microbioma Gastrointestinal/fisiologia , Chá , Bifidobacterium/crescimento & desenvolvimento , Ensaios Clínicos como Assunto , Disbiose/prevenção & controle , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Nível de Saúde , Humanos , National Library of Medicine (U.S.) , Extratos Vegetais/farmacologia , Polifenóis/administração & dosagem , Polifenóis/fisiologia , PubMed , Chá/química , Estados Unidos
15.
Nat Commun ; 10(1): 4715, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31624266

RESUMO

Infections by multidrug-resistant bacteria (MDRB) remain a leading cause of morbidity and mortality after liver transplantation (LT). Gut dysbiosis characteristic of end-stage liver disease may predispose patients to intestinal MDRB colonization and infection, in turn exacerbating dysbiosis. However, relationships between MDRB colonization and dysbiosis after LT remain unclear. We prospectively recruited 177 adult patients undergoing LT at a single tertiary care center. 16 S V3-V4 rRNA sequencing was performed on 723 fecal samples collected pre-LT and periodically until one-year post-LT to test whether MDRB colonization was associated with decreased microbiome diversity. In multivariate linear mixed-effect models, MDRB colonization predicts reduced Shannon α-diversity, after controlling for underlying liver disease, antibiotic exposures, and clinical complications. Importantly, pre-LT microbial markers predict subsequent colonization by MDRB. Our results suggest MDRB colonization as a major, previously unrecognized, marker of persistent dysbiosis. Therapeutic approaches accounting for microbial and clinical factors are needed to address post-transplant microbiome health.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Doença Hepática Terminal/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Transplante de Fígado/métodos , Adulto , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Disbiose/genética , Disbiose/microbiologia , Disbiose/prevenção & controle , Doença Hepática Terminal/microbiologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Ribossômico 16S/genética
16.
J Nutr Biochem ; 73: 108224, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31654895

RESUMO

The identification of natural bioactive compounds aimed at promoting optimal gut health and improving lipid metabolism is paramount in the prevention of chronic disease. In this review, we summarize basic science and clinical research examining the protective properties of milk sphingomyelin (SM) against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. Dietary SM dose-dependently reduces the intestinal absorption of cholesterol, triglycerides, and fatty acids in cell culture and rodent studies. Overall, rodent feeding studies show dietary milk SM, milk polar lipid mixtures, and milk fat globule membrane reduce serum and hepatic lipid concentrations. Furthermore, these hypolipidemic effects are observed in some supplementation studies in humans, although the extent of reductions in serum cholesterol is typically smaller and only one trial was conducted with purified SM. Dietary milk SM has been reported to affect the gut microbiota in rodent studies and its hydrolytic product, sphingosine, displays bactericidal activity in vitro. Milk SM may also improve gut barrier function to prevent the translocation of inflammatory gut bacteria-derived molecules. Current evidence from pre-clinical studies indicates that dietary milk SM has protective properties against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. The hypolipidemic effects of milk SM observed in animal studies have been reported in some human studies, although the magnitude of such effects is typically smaller. More research is warranted to clearly define how dietary milk SM influences lipid metabolism, gut microbiota, and inflammation in humans.


Assuntos
Disbiose/prevenção & controle , Inflamação/prevenção & controle , Metabolismo dos Lipídeos/efeitos dos fármacos , Leite/química , Esfingomielinas/administração & dosagem , Animais , Colesterol na Dieta/farmacocinética , Dieta , Dieta Ocidental , Gorduras na Dieta/farmacocinética , Digestão/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Absorção Intestinal/efeitos dos fármacos , Lipídeos/análise , Lipídeos/sangue , Fígado/química , Fígado/efeitos dos fármacos , Esfingomielinas/farmacocinética
17.
J Cell Mol Med ; 23(12): 8161-8172, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31565850

RESUMO

Numerous data show that taraxacum officinale extract (TOE) exerts protective effects on inflammatory diseases. However, the underlying mechanisms by which TOE affects dextran sulphate sodium (DSS)-induced colitis remain unclear. After DSS-induced colitis were treated with different concentrations of TOE for 8 days, the bodyweight, disease activity index (DAI), colon lengths and pathological scoring were assessed, and histopathological examination was confirmed by HE staining. Furthermore, a transcriptome sequencing was performed by using the colon tissues between TOE and DSS groups, and the differentially expressed genes were conducted for the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) and were validated by qRT-PCR and immunohistochemistry analysis. In addition, a 16S rDNA sequencing was carried out to distinguish the differential gut microbiota by using the mouse faecal samples between TOE and DSS groups. We found that TOE attenuated the clinical symptoms, lowered the inflammatory scoring and inhibited the secretion of proinflammatory factors TNF-α, IL-1ß and IL-6 in DSS-induced colitis. KEGG and GSEA analysis demonstrated that fatty acid degradation and cytokine-receptor signalling were predominantly enriched in TOE-treated colitis as compared with the DSS group. Further investigations revealed that TOE increased the expression levels of Adh5, Aldh3a2 and Acox3, but decreased those of CCL20, CCR6 and CXCL1/5 in DSS-induced colitis, where TOE also induced the enrichment of S24-7 and adlercreutzia, but decreased the amount of anaerostipes, enterococcus, enterobacteriaceae and peptostreptococcaceae. In conclusion, TOE ameliorated DSS-induced colitis by regulating fatty acid degradation and microbial dysbiosis.


Assuntos
Colite/prevenção & controle , Disbiose/prevenção & controle , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Taraxacum/química , Animais , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Disbiose/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Perfilação da Expressão Gênica/métodos , Masculino , Camundongos Endogâmicos C57BL , Fitoterapia/métodos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
18.
PLoS One ; 14(9): e0223231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31568499

RESUMO

BACKGROUND: Cinobufacini, the sterilized hot water extraction of dried toad skin, has been widely used in the treatment of inflammation and cancers. Recently we found cinobufacini could ameliorate dextran sulfate sodium (DSS)-induced colitis in mice, but the underlying mechanism was not fully understood. In current study, we explored the effect of cinobufacini on gut microbiota in DSS-induced acute colitic mouse model by pyrosequencing of colonic contents. METHODS: C57BL/6 mice were supplied with normal or 3.0% DSS containing drinking water. DSS-treat mice were gavaged daily either with vehicle (water) or cinobufacini (10.0 or 30.0 mg/kg) for 7 days. The composition of the gut microbiota was assessed by analyzing 16S rRNA gene sequences. RESULTS: Our data indicated that cinobufacini reversed DSS-induced gut dysbiosis and enhanced intestinal barrier integrity. Moreover, changing of some specific microbial groups such as Proteobacteria and Bacteroides was closely correlated with the re-establishment of intestinal equilibrium and the recovery of intestinal function. CONCLUSION: Cinobufacini prevents colitis in mice by modifying the composition and function of gut microbiota. The current study provides additional mechanistic insight in the therapeutic effect of cinobufacini treatment and may pave the way for clinical application of cinobufacini in colitis therapy.


Assuntos
Venenos de Anfíbios/farmacologia , Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Administração Oral , Animais , Anuros , Bacteroides/classificação , Bacteroides/genética , Bacteroides/isolamento & purificação , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Sulfato de Dextrana/administração & dosagem , Modelos Animais de Doenças , Esquema de Medicação , Disbiose/induzido quimicamente , Disbiose/microbiologia , Disbiose/patologia , Microbioma Gastrointestinal/genética , Inflamação , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteobactérias/classificação , Proteobactérias/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/genética
19.
Pharmacol Res ; 149: 104459, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31541689

RESUMO

Gut microbiota and their metabolites (short-chain fatty acids, SCFAs) are associated with the pathogenesis of rheumatoid arthritis (RA). Total Clematis triterpenoid saponins (CTSs) prepared from Clematis mandshurica Rupr. possess therapeutic benefits for arthritic diseases. However, the poor pharmacokinetic properties of CTSs have obstructed the translation of these natural agents to drugs. Here, we examined the effects of CTSs on arthritis symptoms, gut microbiota and SCFAs in rats with collagen-induced arthritis (CIA). Our results showed that the arthritis index scores of CIA rats treated with CTSs were significantly lower than those of the model group. Most importantly, CTSs moderated gut microbial dysbiosis and significantly downregulated the total SCFA concentration in CIA rats. Compared to the control group, CTSs treatment have no significant side effects on the gut microbiota and SCFA metabolism in normal rats. Two differential analyses (LEfSe and DESeq2) were combined to study the details of the changes in gut microbiome, and twenty-four marker taxa at the genus level were identified via a comparison among control, model and CIA rats treated with high doses of CTSs. In particular, the mostly significantly increased gram-negative (G-) and decreased gram-positive (G+) genera in CIA rats were well restored by CTSs. The observed SCFA concentrations demonstrated that CTSs tend to maintain the balance of the gut microbiota. The data presented herein suggest that CTSs could ameliorate arthritis-associated gut microbial dysbiosis and may be potential adjuvant drugs that could provide relief from the gastrointestinal damage caused as a side effect of commonly used drugs.


Assuntos
Artrite Experimental/tratamento farmacológico , Clematis/química , Disbiose/prevenção & controle , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Animais , Artrite Experimental/microbiologia , Disbiose/microbiologia , Feminino , Ratos , Ratos Wistar , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação
20.
Sci Rep ; 9(1): 13263, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520001

RESUMO

Previous studies have demonstrated that patients with Crohn's disease (CD) in remission do not exhibit an improvement in gut microbiota composition, which might trigger relapses. The present study investigated the dysbiosis and mucins production in CD patients during remission. We performed an analytical cross-sectional single center study, which recruited 18 CD patients and 18 healthy controls (CG) residing in the same home, meaning that all of the participants experienced the same environmental factors, with similar hygiene status, diet, pollution and other common lifestyle characteristics that may influence the composition of the gut microbiota. When compared to healthy controls, the CD patients exhibited lower microbial α-diversity (p = 0.047), a greater abundance of the Proteobacteria phylum (p = 0.037) and a reduction in the Deltaproteobacteria class (p = 0.0006). There was also a reduction in the Akkermansia (p = 0.002) and Oscillospira (p = 0.024) genera and in the proportion of the yeast Saccharomyces cerevisiae (p = 0.01). Additionally, CD patients in remission presented increased neutral (p = 0.001) and acid mucin (p = 0.002) concentrations. The reductions in the proportions of Oscollospira and Akkermansia genera, sulfate-reducing bacteria and Saccharomyces cerevisiae, observed in the CD group, may account for the increased mucins production observed in these patients.


Assuntos
Bactérias/isolamento & purificação , Doença de Crohn/microbiologia , Disbiose/prevenção & controle , Microbioma Gastrointestinal , Mucinas/metabolismo , Adulto , Bactérias/classificação , Bactérias/genética , Estudos de Casos e Controles , Doença de Crohn/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Adulto Jovem
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