Abstract
Recent studies have shown perturbed gut microbiota associated with gouty arthritis, a metabolic disease characterized by an imbalance between uric acid production and excretion. To mechanistically investigate altered microbiota metabolism associated with gout disease, 16S rRNA gene amplicon sequence data from stool samples of gout patients and healthy controls were computationally analyzed through bacterial community metabolic models. Patient‐specific community models constructed with the metagenomics modeling pipeline, mgPipe, were used to perform k‐means clustering of samples according to their metabolic capabilities. The clustering analysis generated statistically significant partitioning of samples into a Bacteroides‐dominated, high gout cluster and a Faecalibacterium‐elevated, low gout cluster. The high gout cluster was predicted to allow elevated synthesis of the amino acids D‐alanine and L‐alanine and byproducts of branched‐chain amino acid catabolism, while the low gout cluster allowed higher production of butyrate, the sulfur‐containing amino acids L‐cysteine and L‐methionine, and the L‐cysteine catabolic product H2S. By expanding the capabilities of mgPipe to provide taxa‐level resolution of metabolite exchange rates, acetate, D‐lactate and succinate exchanged from Bacteroides to Faecalibacterium were predicted to enhance butyrate production in the low gout cluster. Model predictions suggested that sulfur‐containing amino acid metabolism generally and H2S more specifically could be novel gout disease markers.
Highlights
IntroductionThe human gut microbiota play essential roles in digestion of plant polysaccharides [1, 2], synthesis of essential and health-promoting metabolites [3, 4], development of host immune response [5], and maintenance ofEng Life Sci. 2021;21:489–501.www.els-journal.com 489HENSON colonization resistance to pathogens [6]
Gout patients have been reported to have elevated abundances of Prevotella intermedia in the oral microbiota [38]. These results suggested that elevated Bacteroides abundance may result from the gout disease process
Recent findings that the gut microbiota are perturbed by gout disease [30, 32,33,34,35,36] motivated this in silico modeling study aimed at identifying putative metabolic features associated with gout development
Summary
The human gut microbiota play essential roles in digestion of plant polysaccharides [1, 2], synthesis of essential and health-promoting metabolites [3, 4], development of host immune response [5], and maintenance ofEng Life Sci. 2021;21:489–501.www.els-journal.com 489HENSON colonization resistance to pathogens [6]. Several recent studies in humans [29,30,31] and murine models [32,33,34,35, 52] have correlated changes in gut microbiota composition to the presence of gout disease, suggesting that microbiota properties could be used to monitor disease development, progression and recovery Several of these 16S-based studies have been combined with gene catalog [36] and metabolomic [29] analyses to better understand metabolic changes that accompanied compositional dysbiosis. While they provided new insights into the association between gout disease and altered gut microbiota, these studies were inherently limited in their ability to quantify the functional metabolic differences between the gut communities of gout patients versus healthy controls
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