GREAT ARTICLE ON DYSBIOSIS OF THE MICROBIOME AND THE INFLAMMATORY PROCESS DISCOVERY MEDICINE...
Discussion
The discovery of the human microbiome marks one of the most important milestones in the history of science. Vast ecosystems of bacteria, viruses, bacteriophages, and fungi are now understood to persist in nearly every human body site, including tissue and blood. Metabolism of the human superorganism is regulated by a constant interplay between the genomes of these microbes and the host genome.
Seemingly disparate inflammatory conditions (autoimmune, neurological, and malignant) are now repeatedly tied to a common trend: dysbiosis or imbalance of these microbiome populations. While many studies have linked this dysbiosis to shifts in microbial species composition, it is the collective activity of the microbiome that drives inflammatory processes. Much of the microbiome persists in polymicrobial communities where gene expression is coordinated in a manner that promotes virulence. Other microbes persist inside the cells of the immune system where they directly interfere with host transcription, translation, and DNA repair mechanisms. The numerous proteins and metabolites expressed by these pathogens further dysregulate human gene expression in a manner that leads to immunosuppression and metabolic imbalance. Molecular mimicry or homology between host and microbial proteins further complicates the dysregulation. These dysbiotic processes can most readily be observed by studying microbial gene expression.
Many components of the microbiome change their genomic activity in order to persist in both “commensal” and virulent forms. This may explain why both individuals with disease and healthy controls often test positive for the same microbe. Consequently, future diagnostic tools should aim to characterize microbial activity in addition to species composition.
The immune response is now understood to be driven largely by environmental factors and not human genes. This, together with the high volume of host genome and microbiome crosstalk, suggests that attempts to study the human genome in isolation cannot provide a complete picture of inflammatory disease processes. The research community may want to de-prioritize genome-wide association studies, and divert increased resources towards the study of shared mechanisms of microbial persistence, signaling, and survival.
A great deal of time and energy is also spent separating subsets of inflammatory disease into distinct specialties. However, when the microbiome is taken into consideration, these diseases share much of the same underlying pathogenesis. The high incidence of multimorbidity observed in patients with chronic disease further suggests that these comorbid conditions arise in a synergistic fashion. It follows that an increased focus on multidisciplinary research would allow the human superorganism to be explored most comprehensively.