Abstract
Biosynthesis of butyrate by commensal bacteria plays a crucial role in maintenance of human gut health while dysbiosis in gut microbiome has been linked to several enteric disorders. Contrastingly, butyrate shows cytotoxic effects in patients with oral diseases like periodontal infections and oral cancer. In addition to these host associations, few syntrophic bacteria couple butyrate degradation with sulfate reduction and methane production. Thus, it becomes imperative to understand the distribution of butyrate metabolism pathways and delineate differences in substrate utilization between pathogens and commensals. The bacteria utilize four pathways for butyrate production with different initial substrates (Pyruvate, 4-aminobutyrate, Glutarate and Lysine) which follow a polyphyletic distribution. A comprehensive mining of complete/draft bacterial genomes indicated conserved juxtaposed genomic arrangement in all these pathways. This gene context information was utilized for an accurate annotation of butyrate production pathways in bacterial genomes. Interestingly, our analysis showed that inspite of a beneficial impact of butyrate in gut, not only commensals, but a few gut pathogens also possess butyrogenic pathways. The results further illustrated that all the gut commensal bacteria (Faecalibacterium, Roseburia, Butyrivibrio, and commensal species of Clostridia etc) ferment pyruvate for butyrate production. On the contrary, the butyrogenic gut pathogen Fusobacterium utilizes different amino acid metabolism pathways like those for Glutamate (4-aminobutyrate and Glutarate) and Lysine for butyrogenesis which leads to a concomitant release of harmful by-products like ammonia in the process. The findings in this study indicate that commensals and pathogens in gut have divergently evolved to produce butyrate using distinct pathways. No such evolutionary selection was observed in oral pathogens (Porphyromonas and Filifactor) which showed presence of pyruvate as well as amino acid fermenting pathways which might be because the final product butyrate is itself known to be cytotoxic in oral diseases. This differential utilization of butyrogenic pathways in gut pathogens and commensals has an enormous ecological impact taking into consideration the immense influence of butyrate on different disorders in humans. The results of this study can potentially guide bioengineering experiments to design therapeutics/probiotics by manipulation of butyrate biosynthesis gene clusters in bacteria.
Highlights
Humans harbor a plethora of micro-organisms comprising of around 1000 species inhabiting different body sites
After establishing the conserved genomic arrangement of butyrate production pathways, this Hidden Markov Model (HMM) based analysis was extended to 8027 sequenced genomes in NCBI to understand butyrate pathway composition across all bacteria
Results of the analyses indicated presence of one or more of these pathways in butyrate producing organisms. 2180 out of 8027 bacteria were found to have all genes that are involved in butyrate production from pyruvate
Summary
Humans harbor a plethora of micro-organisms comprising of around 1000 species inhabiting different body sites. Some of them are beneficial bacteria which help in metabolism and absorption of nutrients by the human host and in regulation of our immune system (Bhattacharya et al, 2015). These bacteria can influence epithelial cell growth and differentiation (Schwabe and Jobin, 2013; Sears and Garrett, 2014). The human body sites with the most diverse microbiome are gut followed by oral cavity (Corpet et al, 1995). Recent studies have indicated that the onset of disease cannot be accredited to a single pathogen, but to the entire microbiome (Schwabe and Jobin, 2013)
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