Microbiome-targeted Therapies Research Articles

Rola mikrobiomu skóry w trądziku pospolitym

W ostatnich latach nastąpił rozkwit badań nad drobnoustrojami bytującymi w organizmie człowieka, zwanymi kolektywnie mikrobiomem. Prawidłowa fl ora bakteryjna człowieka chroni organizm przed kolonizacją fl orą patogenną, moduluje nabytą i wrodzoną odporność poprzez wpływ na układ immunologiczny, uczestniczy w procesie trawiennym czy w syntezie witamin. Mikroorganizmy bakteryjne i produkty ich przemiany materii pomagają ponadto w utrzymaniu funkcji barierowej skóry. Badanie zarówno całego składu mikrobiomu, jak i genetycznych oraz metabolicznych zależności pomiędzy poszczególnymi mikroorganizmami stało się możliwe dzięki wprowadzeniu nowoczesnych technik biologii molekularnej, takich jak analiza bakteryjnego genu 16S rRNA oraz sekwencjonowanie kompletnych genomów bakteryjnych.Zaburzenia mikrobiomu obserwuje się w wielu chorobach, zatem przywracanie równowagi mikrobiologicznej jako formy terapii jest poddawane obecnie intensywnym badaniom w wielu dziedzinach medycyny. Wśród schorzeń dermatologicznych do tej pory najwięcej uwagi poświęcono atopowemu zapaleniu skóry, co zaowocowało powstaniem nowej grupy emolientów opartych na prebiotykach, których skuteczność znajduje potwierdzenie w badaniach klinicznych.W artykule przedstawiono aktualny stan wiedzy na temat mikrobiomu w kontekście patofizjologii i leczenia chorób skóry ze szczególnym uwzględnieniem trądziku pospolitego. Liczne badania wskazują, że również w przypadku tej choroby terapia ukierunkowana na mikrobiom może dać korzystne efekty przy minimalnych działaniach niepożądanych.

The remedy within: will the microbiome fulfill its therapeutic promise?

The last decade of research has witnessed a tremendous upsurge in our understanding of the intestinal microbiome and its role in a large range of human diseases, which has incited hopes for a rapid clinical utilization of the new insights for the development of microbiome-based therapies. Nonetheless, only a single microbiome-targeted therapy has so far found its way into clinical routine: fecal microbiota transplantation for patients suffering from recurrent Clostridium difficile infections. Herein, we discuss the current hopes, advances, challenges, and obstacles for translating basic microbiome research into therapeutic applications for a larger number of diseases and provide an outline of how such clinical applications might emerge.

The path towards microbiome-based metabolite treatment.

The increasing evidence pointing towards the involvement of the gut microbiome in multiple diseases, as well as its plasticity, renders it a desirable potential therapeutic target. Nevertheless, classical therapies based on the consumption of live probiotic bacteria, or their enrichment by prebiotics, exhibit limited efficacy. Recently, a novel therapeutic approach has been suggested based on metabolites secreted, modulated or degraded by the microbiome. As many of the host-microorganism interactions pertaining to human health are mediated by metabolites, this approach may be able to provide therapeutic efficacy while overcoming caveats of current microbiome-targeting therapies, such as colonization resistance and inter-individual variation in microbial composition. In this Perspective, we will discuss the evidence that supports pursuing the metabolite-based therapeutic approach as well as issues critical for its implementation. In a broader context, we will discuss how recent advances in microbiome research may improve and refine current treatment modalities, and the potential of combining them with metabolite-based interventions as a means of achieving a person-specific, integrated and efficient therapy.

Dysbiosis and the immune system.

Throughout the past century, we have seen the emergence of a large number of multifactorial diseases, including inflammatory, autoimmune, metabolic, neoplastic and neurodegenerative diseases, many of which have been recently associated with intestinal dysbiosis - that is, compositional and functional alterations of the gut microbiome. In linking the pathogenesis of common diseases to dysbiosis, the microbiome field is challenged to decipher the mechanisms involved in the de novo generation and the persistence of dysbiotic microbiome configurations, and to differentiate causal host-microbiome associations from secondary microbial changes that accompany disease course. In this Review, we categorize dysbiosis in conceptual terms and provide an overview of immunological associations; the causes and consequences of bacterial dysbiosis, and their involvement in the molecular aetiology of common diseases; and implications for the rational design of new therapeutic approaches. A molecular- level understanding of the origins of dysbiosis, its endogenous and environmental regulatory processes, and its downstream effects may enable us to develop microbiome-targeting therapies for a multitude of common immune-mediated diseases.

Systems-level metabolism of the altered Schaedler flora, a complete gut microbiota

The altered Schaedler flora (ASF) is a model microbial community with both in vivo and in vitro relevance. Here we provide the first characterization of the ASF community in vitro, independent of a murine host. We compared the functional genetic content of the ASF to wild murine metagenomes and found that the ASF functionally represents wild microbiomes better than random consortia of similar taxonomic composition. We developed a chemically defined medium that supported growth of seven of the eight ASF members. To elucidate the metabolic capabilities of these ASF species—including potential for interactions such as cross-feeding—we performed a spent media screen and analyzed the results through dynamic growth measurements and non-targeted metabolic profiling. We found that cross-feeding is relatively rare (32 of 3570 possible cases), but is enriched between Clostridium ASF356 and Parabacteroides ASF519. We identified many cases of emergent metabolism (856 of 3570 possible cases). These data will inform efforts to understand ASF dynamics and spatial distribution in vivo, to design pre- and probiotics that modulate relative abundances of ASF members, and will be essential for validating computational models of ASF metabolism. Well-characterized, experimentally tractable microbial communities enable research that can translate into more effective microbiome-targeted therapies to improve human health.

Crohn's Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies.

Crohn's disease (CD) is a chronic, systemic, immune-mediated inflammation of the gastrointestinal tract. Originally described in 1932 as non-caseating granulomatous inflammation limited to the terminal ileum, it is now recognized as an expanding group of heterogeneous diseases defined by intestinal location, extent, behavior, and systemic extraintestinal manifestations. Joint diseases, including inflammatory spondyloarthritis and ankylosing spondylitis, are the most common extraintestinal manifestations of CD and share more genetic susceptibility loci than any other inflammatory bowel disease (IBD) trait. The high frequency and overlap with genes associated with infectious diseases, specifically Mendelian susceptibility to mycobacterial diseases (MSMD), suggest that CD may represent an evolutionary adaptation to environmental microbes. Elucidating the diversity of the enteric microbiota and the protean mucosal immune responses in individuals may personalize microbiome-targeted therapies and molecular classifications of CD. This review will focus on CD's natural history and therapies in the context of epigenetics, immunogenetics, and the microbiome.