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

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.

Alterations in the gut bacterial microbiome in fungal Keratitis patients.

Dysbiosis in the gut microbiome has been implicated in several diseases including auto-immune diseases, inflammatory diseases, cancers and mental disorders. Keratitis is an inflammatory disease of the eye significantly contributing to corneal blindness in the developing world. It would be worthwhile to investigate the possibility of dysbiosis in the gut microbiome being associated with Keratitis. Here, we have analyzed fungal and bacterial populations in stool samples through high-throughput sequencing of the ITS2 region for fungi and V3-V4 region of 16S rRNA gene for bacteria in healthy controls (HC, n = 31) and patients with fungal keratitis (FK, n = 32). Candida albicans (2 OTUs), Aspergillus (1 OTU) and 3 other denovo-OTUs were enriched in FK samples and an unclassified denovo-OTU was enriched in HC samples. However, the overall abundances of these 'discriminatory' OTUs were very low (< 0.001%) and not indicative of significant dysbiosis in the fungal community inhabiting the gut of FK patients. In contrast, the gut bacterial richness and diversity in FK patients was significantly decreased when compared to HC. 52 OTUs were significantly enriched in HC samples whereas only 5 OTUs in FK. The OTUs prominently enriched in HC were identified as Faecalibacterium prausnitzii, Bifidobacterium adolescentis, Lachnospira, Mitsuokella multacida, Bacteroides plebeius, Megasphaera and Lachnospiraceae. In FK samples, 5 OTUs affiliated to Bacteroides fragilis, Dorea, Treponema, Fusobacteriaceae, and Acidimicrobiales were significantly higher in abundance. The functional implications are that Faecalibacterium prausnitzii, an anti-inflammatory bacterium and Megasphaera, Mitsuokella multacida and Lachnospira are butyrate producers, which were enriched in HC patients, whereas Treponema and Bacteroides fragilis, which are pathogenic were abundant in FK patients, playing a potential pro-inflammatory role. Heatmap, PCoA plots and functional profiles further confirm the distinct patterns of gut bacterial composition in FK and HC samples. Our study demonstrates dysbiosis in the gut bacterial microbiomes of FK patients compared to HC. Further, based on inferred functions, it appears that dysbiosis in the gut of FK subjects is strongly associated with the disease phenotype with decrease in abundance of beneficial bacteria and increase in abundance of pro-inflammatory and pathogenic bacteria.