RESUMO
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide but still lacks specific treatment modalities. The gut microbiota and its metabolites have been shown to be intimately involved in NAFLD development, participating in and regulating disease progression. Trimethylamine N-oxide (TMAO), a metabolite highly dependent on the gut microbiota, has been shown to play deleterious regulatory roles in cardiovascular disease, but the relationship between it and NAFLD lacks validation from basic experiments. This research applied TMAO intervention by constructing fatty liver cell models in vitro to observe its effect on fatty liver cells and potential key genes and performed siRNA interference on the gene to verify the action. The results showed that TMAO intervention promoted the appearance of more red-stained lipid droplets in Oil-red O staining results, increased triglyceride (TG) levels and increased mRNA levels of liver fibrosis-related genes, and also identified one of the key genes, keratin17 (KRT17) via transcriptomics. Following the reduction in its expression level, under the same treatment, there were decreased red-stained lipid droplets, decreased TG levels, decreased indicators of impaired liver function as well as decreased mRNA levels of liver fibrosis-related genes. In conclusion, the gut microbiota metabolite TMAO could promote lipid deposition and fibrosis process via the KRT17 gene in fatty liver cells in vitro.
Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Fibrose , Metilaminas/farmacologia , Metilaminas/metabolismo , Cirrose Hepática , LipídeosRESUMO
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship between specific strains and NAFLD has not been fully elucidated. We aimed to investigate whether Akkermansia muciniphila and Bifidobacterium bifidum could prevent NAFLD, the effects of their action alone or in combination, possible mechanisms, and modulation of the gut microbiota. Methods: Mice were fed with high-fat diets (HFD) for 20 weeks, in which experimental groups were pretreated with quadruple antibiotics and then given the corresponding bacterial solution or PBS. The expression of the glycolipid metabolism indicators, liver, and intestinal farnesol X receptors (FXR), and intestinal mucosal tight junction proteins were detected. We also analyzed the alterations of inflammatory and immune status and the gut microbiota of mice. Results: Both strains were able to attenuate mass gain (p<0.001), insulin resistance (p<0.001), and liver lipid deposition (p<0.001). They also reduced the levels of the pro-inflammatory factors (p<0.05) and the proportion of Th17 (p<0.001), while elevating the proportion of Treg (p<0.01). Both strains activated hepatic FXR while suppressing intestinal FXR (p<0.05), and elevating tight junction protein expression (p<0.05). We also perceived changes in the gut microbiota and found both strains were able to synergize beneficial microbiota to function. Conclusions: Administration of A. muciniphila or B. bifidum alone or in combination was protective against HFD-induced NAFLD formation and could be used as alternative treatment strategy for NAFLD after further exploration.
RESUMO
The global pandemic caused by COVID-19 has resulted in major costs around the world, costs with dimensions in every aspect, from peoples' daily living to the global economy. As the pandemic progresses, the virus evolves, and more vaccines become available, and the 'battle against the virus' continues. As part of the battle, Wastewater-Based Epidemiology (WBE) technologies are being widely deployed in essential roles for SARS-CoV-2 detection and monitoring. While focusing on demonstrating the advantages of passive samplers as a tool in WBE, this review provides a holistic view of the current WBE applications in monitoring SARS-CoV-2 with the integration of the most up-to-date data. A novel scenario example based on a recent Nanjing (China) outbreak in July 2021 is used to illustrate the potential benefits of using passive samplers to monitor COVID-19 and to facilitate effective control of future major outbreaks. The presented contents and how the application of passive samplers indicates that this technology can be beneficial at different levels, varying from building to community to regional. Countries and regions that have the pandemic well under control or have low positive case occurrences have the potential to significantly benefit from deploying passive samplers as a measure to identify and suppress outbreaks.