RESUMO
Dialysis and kidney transplantation (Ktx) mitigate some of the physiological deficits in chronic kidney disease (CKD), but it remains to be determined if these mitigate microbial dysbiosis and the production of inflammatory microbial metabolites, which contribute significantly to the uraemic phenotype. We have investigated bacterial DNA signatures present in the circulation of CKD patients and those receiving a KTx. Our data are consistent with increasing dysbiosis as CKD progresses, with an accompanying increase in trimethylamine (TMA) producing pathobionts Pseudomonas and Bacillus. Notably, KTx patients displayed a significantly different microbiota compared with CKD5 patients, which surprisingly included further increase in TMA producing Bacillus and loss of salutogenic Lactobacilli. Only two genera (Viellonella and Saccharimonidales) showed significant differences in abundance following KTx that may reflect a reciprocal relationship between TMA producers and utilisers, which supersedes restoration of a normative microbiome. Our metadata analysis confirmed that TMA N-oxide (TMAO) along with one carbon metabolism had significant impact upon both inflammatory burden and the composition of the microbiome. This indicates that these metabolites are key to shaping the uraemic microbiome and might be exploited in the development of dietary intervention strategies to both mitigate the physiological deficits in CKD and enable the restoration of a more salutogenic microbiome.
Assuntos
Microbioma Gastrointestinal , Transplante de Rim , Microbiota , Insuficiência Renal Crônica , Humanos , Microbioma Gastrointestinal/fisiologia , Transplante de Rim/efeitos adversos , Disbiose/microbiologia , Insuficiência Renal Crônica/cirurgia , Insuficiência Renal Crônica/metabolismoRESUMO
This study investigated the effects of dietary supplements, citrus (CTS) and cucumber (CMB), on the jejunum and cecum microbiota of 14- and 28-days old broiler chickens to evaluate their impact on the gut health and assess their role as alternatives to antibiotic growth promoters (ABGPs). 16SrRNA gene sequencing revealed the overall bacterial microbiota composition was significantly affected by the gut site (p?0.001) but not by either of the dietary supplements, CTS and CMB, at both 14 and 28 days of age. However, as a result of Linear discriminant analysis (LDA) effect size (LEfSE), CTS dietary supplements significantly increased the counts of Lactobacillus (p?0.01) and decreased the counts of Enterococcus (p?0.01) and Clostridium (p?0.05) in the jejunum, whereas the counts of Blautia were increased (p?0.01) and Enterococcus were decreased (p?0.05) in the cecum at both ages. Only minor CMB effects were identified in the cecum and non in the jejunum. The use of CTS dietary supplements has been shown to be associated to the reduction of potentially pathogenic bacteria (Enterococcus and Clostridium) and to the growth of beneficial bacteria (Lactobacillus and Blautia) which are known to have positive effects on chicken health in terms of nutrients absorption, stimulation and production of short chain fatty acids (SCFAs). Therefore, this study suggests that the use of a CTS supplemented diet could promote gut health while no clear advantages have been identified with the use of CMB as a dietary supplement.
Assuntos
Ração Animal , Galinhas , Citrus , Cucumis sativus , Dieta , Suplementos Nutricionais , Microbioma Gastrointestinal , Extratos Vegetais , RNA Ribossômico 16S , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Suplementos Nutricionais/análise , Galinhas/microbiologia , RNA Ribossômico 16S/genética , Citrus/química , Ração Animal/análise , Dieta/veterinária , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Cucumis sativus/microbiologia , Ceco/microbiologia , Jejuno/microbiologiaRESUMO
The role of the equine gastrointestinal microbiota in the pathogenesis of equine glandular gastric disease (EGGD) is poorly understood. To investigate whether the glandular gastric microbiota is altered in horses with EGGD. Prospective longitudinal study. Five Thoroughbred racehorses from one training center underwent gastroscopy as part of poor performance investigation. Samples were taken from EGGD lesions and adjacent normal mucosa using sheathed transendoscopic cytology brushes and frozen at -80°C. DNA was extracted for 16S rRNA sequencing, and sequences compared against a database to generate taxonomic classification of the microbiota. The same horses were sampled 6 months later. Normal glandular mucosal samples were characterized by a higher proportion of Proteobacteria (46.3%) than EGGD lesions (18.9%). Relative abundance of Firmicutes was lower in samples from normal mucosa (20.0%) than EGGD lesions (41.2%). Linear discriminant analysis effect size (LEfSe) confirmed a greater proportion of Firmicutes species was characteristic of samples collected from EGGD lesions due to a very high relative abundance of Sarcina (up to 92.4%) in two horses with EGGD. We were unable to comment on the stability of the glandular gastric microbiota over time. Small sample population. None of the horses examined had grossly normal gastric mucosa. The gastric microbiota appears altered in EGGD, although we are unable to demonstrate a causative effect. Sarcina was particularly increased in abundance in EGGD and may be a useful biomarker of disease. Sheathed cytology brushes were an effective method for sampling the gastric mucosa.
Assuntos
Doenças dos Cavalos , Microbiota , Gastropatias , Animais , Doenças dos Cavalos/epidemiologia , Cavalos , Estudos Longitudinais , Microbiota/genética , Estudos Prospectivos , RNA Ribossômico 16S/genética , Gastropatias/etiologia , Gastropatias/veterináriaRESUMO
Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.
Assuntos
Envelhecimento/sangue , Bactérias/classificação , Betaína/sangue , Análise de Sequência de DNA/métodos , Adulto , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , Feminino , Humanos , Estilo de Vida , Masculino , Metilaminas , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , RNA Ribossômico 16S/genética , Fatores SocioeconômicosRESUMO
Recent pioneering advances in understanding how plants, insects and worms eliminate pathogens has led to the realization that innate immunity plays a vital role in protecting humans from infection. This comprehensive review examines the molecules involved in innate immune responses, how they act to control parasites and if their engagement can explain many immune features characteristic of parasitic infections.
Assuntos
Imunidade Inata , Parasitos/imunologia , Doenças Parasitárias/imunologia , Animais , Interações Hospedeiro-Parasita , Humanos , Glicoproteínas de Membrana/fisiologia , Doenças Parasitárias/parasitologia , Fagócitos/fisiologia , Receptores de Superfície Celular/fisiologia , Receptores Toll-LikeRESUMO
Parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. The success of passive immunization suggests that immunoglobulin (Ig)-based therapies are effective. To further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric IgG1 and IgA1 and a single-chain diabody specific for the C-terminal 19-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP119), a major target of protective immune responses. These novel human reagents triggered in vitro phagocytosis of merozoites but, unlike their parental mouse IgG2b, failed to protect against parasite challenge in vivo. Therefore, the Fc region appears critical for mediating protection in vivo, at least for this MSP119 epitope. Such antibodies may serve as prototype therapeutic agents, and as useful tools in the development of in vitro neutralization assays with Plasmodium parasites.