Project description:In the last two decades it has become clear that Parkinson's disease (PD) is associated with a plethora of gastrointestinal symptoms originating from functional and structural changes in the gut and its associated neural structures. This is of particular interest not only because such symptoms have a major impact on the quality of life of PD patients, but also since accumulating evidence suggests that in at least a subgroup of patients, these disturbances precede the motor symptoms and diagnosis of PD by years and may thus give important insights into the origin and pathogenesis of the disease. In this mini-review we attempt to concisely summarize the current knowledge after two decades of research on the gut-brain axis in PD. We focus on alpha-synuclein pathology, biomarkers, and the gut microbiota and envision the development and impact of these research areas for the two decades to come.
Project description:The past 15 years have seen a boom in the use and integration of 'omic' approaches (limited here to genomic, transcriptomic, and epigenomic techniques) to study neurodegenerative disease in an unprecedented way. We first highlight advances in and the limitations of using such approaches in the neurodegenerative disease literature, with a focus on Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). We next discuss how these studies can advance human health in the form of generating leads for downstream mechanistic investigation or yielding polygenic risk scores (PRSs) for prognostication. However, we argue that these approaches constitute a new form of molecular description, analogous to clinical or pathological description, that alone does not hold the key to solving these complex diseases.
Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global health. SARS-CoV-2 infects host cells primarily by binding to angiotensin-converting enzyme 2, which is coexpressed in alveolar type 2 cells and gut epithelial cells. It is known that COVID-19 often presents with gastrointestinal symptoms and gut dysbiosis, mainly characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. In recent years, multiple studies have comprehensively explored gut microbiota alterations in COVID-19 and highlighted the clinical correlation between dysbiosis and COVID-19. SARS-CoV-2 causes gastrointestinal infections and dysbiosis mainly through fecal-oral transmission and the circulatory and immune pathways. Studies have shown that the gut microbiota and its metabolites can regulate the immune response and modulate antiviral effects. In addition, the gut microbiota is closely related to gastrointestinal symptoms, such as diarrhea, a common gastrointestinal symptom among COVID-19. Therefore, the contribution of the gut microbiota in COVID-19 should not be overlooked. Strategies targeting the gut microbiota via probiotics, prebiotics and fecal microbiota transplantation should be considered to treat this patient population in the future. However, the specific alterations and mechanisms as well as the contributions of gut microbiota in COVID-19 should be urgently further explored.
Project description:Probiotic bacteria have been associated with various health benefits and included in overwhelming number of foods. Today, probiotic supplements are consumed with increasing regularity and record a rapidly growing economic value. With billions of heterogeneous populations of probiotics per serving, probiotic supplements contain the largest quantity of probiotics across all functional foods. They often carry antibiotic-resistant determinants that can be transferred to and accumulate in resident bacteria of the gastrointestinal tract and risk their acquisitions by opportunistic pathogens. While the health benefits of probiotics have been widely publicized, this health risk, however, is underrepresented in both scientific studies and public awareness. On the other hand, the human gut presents conditions that are unfavorable for bacteria, including probiotics. It remains uncertain if probiotics from supplements can tolerate acids and bile salts that may undermine their effectiveness in conferring health benefits. Here, we put into perspective the perceived health benefits and the long-term safety of consuming probiotic supplements, specifically bringing intolerance to acids and bile salts, and the long-standing issue of antibiotic-resistant gene transfer into sharp focus. We report that probiotics from supplements examined in this study have poor tolerance to acids and bile salts while also displaying resistance to multiple antibiotics. They could also adapt and gain resistance to streptomycin in vitro. In an environment where consuming supplements is considered a norm, our results and that of others will put in perspective the persisting concerns surrounding probiotic supplements so that the current hype does not overpower the hope.
Project description:The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variable fragments (scFv) and "third generation" (3G), each representing a successive wave of antibody fragment technology. In parallel, drug developers have explored multi-specificity and conjugation with exogenous functional moieties in all three fragment types. Despite high hopes and an active pipeline, enthusiasm for differentiating performance of fragments should, perhaps, be tempered as there are yet few data that suggest these molecules have distinct clinical properties due only to their size.
Project description:The investigational scale of the gut microbiome is expanding rapidly. In 2018, the intersection of gut microbiota and immuno-oncology received much attention. While the impact of gut microbiota on the immune system was already established, the year received an exponential expansion of microbiome's role in the immunotherapy setting. The microbiome research pipeline is ripe for large-scale, prospective trials. Working knowledge of immune-based cancer treatments, heterogeneity in their responses and resistance mechanisms, relevant immunological and microbiological pathways and potential for gut microbiome in enhancing the responses, is critical.
Project description:Several lines of evidence support a link between the essential element zinc and the coronavirus disease 2019 (COVID-19). An important fact is that zinc is present in proteins of humans and of viruses. Some zinc sites in viral enzymes may serve as drug targets and may liberate zinc ions, thus leading to changes in intracellular concentration of zinc ions, while increased intracellular zinc may induce biological effects in both the host and the virus. Drugs such as chloroquine may contribute to increased intracellular zinc. Moreover, clinical trials on the use of zinc alone or in addition to other drugs in the prophylaxis/treatment of COVID-19 are ongoing. Thereby, we aim to discuss the rationale for targeting zinc metalloenzymes as a new strategy for the treatment of COVID-19. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.
Project description:Gastrointestinal and respiratory tract diseases often occur together. There are many overlapping pathologies, leading to the concept of the 'gut-lung axis' in which stimulation on one side triggers a response on the other side. This axis appears to be implicated in infections involving severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has triggered the global coronavirus disease 2019 (COVID-19) pandemic, in which respiratory symptoms of fever, cough and dyspnoea often occur together with gastrointestinal symptoms such as nausea, vomiting, abdominal pain and diarrhoea. Besides the gut-lung axis, it should be noted that the gut participates in numerous axes which may affect lung function, and consequently the severity of COVID-19, through several pathways. This article focuses on the latest evidence and the mechanisms that drive the operation of the gut-lung axis, and discusses the interaction between the gut-lung axis and its possible involvement in COVID-19 from the perspective of microbiota, microbiota metabolites, microbial dysbiosis, common mucosal immunity and angiotensin-converting enzyme II, raising hypotheses and providing methods to guide future research on this new disease and its treatments.