Sensing Host Health: Insights from Sensory Protein Signature of the Metagenome.

ABSTRACT

The human microbiota, which comprises an ensemble of taxonomically and functionally diverse but often mutually cooperating microorganisms, benefits its host by shaping the host immunity, energy harvesting, and digestion of complex carbohydrates as well as production of essential nutrients. Dysbiosis in the human microbiota, especially the gut microbiota, has been reported to be linked to several diseases and metabolic disorders. Recent studies have further indicated that tracking these dysbiotic variations could potentially be exploited as biomarkers of disease states. However, the human microbiota is not geography agnostic, and hence a taxonomy-based (microbiome) biomarker for disease diagnostics has certain limitations. In comparison, (microbiome) function-based biomarkers are expected to have a wider applicability. Given that (i) the host physiology undergoes certain changes in the course of a disease and (ii) host-associated microbial communities need to adapt to this changing microenvironment of their host, we hypothesized that signatures emanating from the abundance of bacterial proteins associated with the signal transduction system (herein referred to as sensory proteins [SPs]) might be able to distinguish between healthy and diseased states. To test this hypothesis, publicly available metagenomic data sets corresponding to three diverse health conditions, namely, colorectal cancer, type 2 diabetes mellitus, and schizophrenia, were analyzed. Results demonstrated that SP signatures (derived from host-associated metagenomic samples) indeed differentiated among healthy individual and patients suffering from diseases of various severities. Our finding was suggestive of the prospect of using SP signatures as early biomarkers for diagnosing the onset and progression of multiple diseases and metabolic disorders. IMPORTANCE The composition of the human microbiota, a collection of host-associated microbes, has been shown to differ among healthy and diseased individuals. Recent studies have investigated whether tracking these variations could be exploited for disease diagnostics. It has been noted that compared to microbial taxonomies, the ensemble of functional proteins encoded by microbial genes are less likely to be affected by changes in ethnicity and dietary preferences. These functions are expected to help the microbe adapt to changing environmental conditions. Thus, healthy individuals might harbor a different set of genes than diseased individuals. To test this hypothesis, we analyzed metagenomes from healthy and diseased individuals for signatures of a particular group of proteins called sensory proteins (SP), which enable the bacteria to sense and react to changes in their microenvironment. Results demonstrated that SP signatures indeed differentiate among healthy individuals and those suffering from diseases of various severities.