RESUMO
BACKGROUND: Gut microbiota plays an important role in many metabolic diseases such as diabetes and atherosclerosis. Apolipoprotein E (apoE) knock-out (KO) mice are frequently used for the study of hyperlipidemia and atherosclerosis. However, it is unknown whether apoE KO mice have altered gut microbiota when challenged with a Western diet. METHODS: In the current study, we assessed the gut microbiota profiling of apoE KO mice and compared with wild-type mice fed either a normal chow or Western diet for 12 weeks using 16S pyrosequencing. RESULTS: On a western diet, the gut microbiota diversity was significantly decreased in apoE KO mice compared with wild type (WT) mice. Firmicutes and Erysipelotrichaceae were significantly increased in WT mice but Erysipelotrichaceae was unchanged in apoE KO mice on a Western diet. The weighted UniFrac principal coordinate analysis exhibited clear separation between WT and apoE KO mice on the first vector (58.6%) with significant changes of two dominant phyla (Bacteroidetes and Firmicutes) and seven dominant families (Porphyromonadaceae, Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, Helicobacteraceae, Erysipelotrichaceae and Veillonellaceae). Lachnospiraceae was significantly enriched in apoE KO mice on a Western diet. In addition, Lachnospiraceae and Ruminococcaceae were positively correlated with relative atherosclerosis lesion size in apoE KO. CONCLUSIONS: Collectively, our study showed that there are marked changes in the gut microbiota of apoE KO mice, particularly challenged with a Western diet and these alterations may be possibly associated with atherosclerosis.
Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/microbiologia , Dieta Ocidental/efeitos adversos , Microbioma Gastrointestinal/genética , Hiperlipidemias/microbiologia , Animais , Apolipoproteínas E/genética , Aterosclerose/etiologia , Aterosclerose/genética , Aterosclerose/patologia , Bacteroidetes/classificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , DNA Ribossômico/genética , Desulfovibrionaceae/classificação , Desulfovibrionaceae/genética , Desulfovibrionaceae/isolamento & purificação , Modelos Animais de Doenças , Firmicutes/classificação , Firmicutes/genética , Firmicutes/isolamento & purificação , Helicobacteraceae/classificação , Helicobacteraceae/genética , Helicobacteraceae/isolamento & purificação , Hiperlipidemias/etiologia , Hiperlipidemias/genética , Hiperlipidemias/patologia , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Porphyromonas/classificação , Porphyromonas/genética , Porphyromonas/isolamento & purificação , RNA Ribossômico 16S/genética , Ruminococcus/classificação , Ruminococcus/genética , Ruminococcus/isolamento & purificação , Análise de Sequência de DNA , Índice de Gravidade de Doença , Veillonellaceae/classificação , Veillonellaceae/genética , Veillonellaceae/isolamento & purificaçãoRESUMO
Mercury methylation converts inorganic mercury into the toxic methylmercury, and the consequences of this transformation are worrisome for human health and the environment. This process is performed by anaerobic microorganisms, such as several strains related to Pseudodesulfovibrio and Desulfovibrio genera. In order to provide new insights into the molecular mechanisms of mercury methylation, we performed a comparative genomic analysis on mercury methylators and non-methylators from (Pseudo)Desulfovibrio strains. Our results showed that (Pseudo)Desulfovibrio species are phylogenetically and metabolically distant and consequently, these genera should be divided into various genera. Strains able to perform methylation are affiliated with one branch of the phylogenetic tree, but, except for hgcA and hgcB genes, no other specific genetic markers were found among methylating strains. hgcA and hgcB genes can be found adjacent or separated, but proximity between those genes does not promote higher mercury methylation. In addition, close examination of the non-methylator Pseudodesulfovibrio piezophilus C1TLV30 strain, showed a syntenic structure that suggests a recombination event and may have led to hgcB depletion. The genomic analyses identify also arsR gene coding for a putative regulator upstream hgcA. Both genes are cotranscribed suggesting a role of ArsR in hgcA expression and probably a role in mercury methylation.
Assuntos
Desulfovibrio/metabolismo , Desulfovibrionaceae/metabolismo , Genoma Bacteriano , Mercúrio/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Desulfovibrio/classificação , Desulfovibrio/genética , Desulfovibrionaceae/classificação , Desulfovibrionaceae/genética , Regulação Bacteriana da Expressão Gênica , Metilação , FilogeniaRESUMO
The intestinal microbiota plays a key role in the maintenance of human health. Alterations in this microbiota have been described in several autoimmune diseases, including nervous system diseases. Nevertheless, the information regarding neuromuscular conditions is still limited. In this study, we aimed at characterizing the intestinal microbiota composition in myasthenia gravis patients (MG). To this end fecal samples were taken from ten patients, with antibodies against the acetylcholine receptor, and ten age and sex matched controls from the same population (Asturias region, Spain). Fecal samples were submitted to microbiota analyses by 16S rRNA gene profiling, bifidobacterial ITS-region profiling and qPCR. The fecal levels of short chain fatty acids were determined by gas chromatography. MG patients were found to harbor lower relative proportions of Verrucomicrobiaceae and Bifidobacteriaceae, among others, and increased of the phylum Bacteroidetes and the family Desulfovibrionaceae. The increase of these latter microbial groups was also confirmed at quantitative level by qPCR. In contrast, no statistically significant differences were found between MG patients and the control group in the bifidobacterial population at the species level or in short chain fatty acids profiles. Our data indicates an altered fecal microbiota pattern in MG patients and point out at specific microbiota targets for intervention in this population.