Unravelling the metabolic impact of SBS-associated microbial dysbiosis: Insights from the piglet short bowel syndrome model

Abstract

Liver disease is a major source of morbidity and mortality in children with short bowel syndrome (SBS). SBS-associated microbial dysbiosis has recently been implicated in the development of SBS-associated liver disease (SBS-ALD), however the pathological implications of this association have not been explored. In this study high-throughput sequencing of colonic content from the well-validated piglet SBS-ALD model was examined to determine alterations in microbial communities, and concurrent metabolic alterations identified in urine samples via targeted mass spectrometry approaches (GC-MS, LC-MS, FIA-MS) further uncovered impacts of microbial disturbance on metabolic outcomes in SBS-ALD. Multi-variate analyses were performed to elucidate contributing SBS-ALD microbe and metabolite panels and to identify microbe-metabolite interactions. A unique SBS-ALD microbe panel was clearest at the genus level, with discriminating bacteria predominantly from the Firmicutes and Bacteroidetes phyla. The SBS-ALD metabolome included important alterations in the microbial metabolism of amino acids and the mitochondrial metabolism of branched chain amino acids. Correlation analysis defined microbe-metabolite clustering patterns unique to SBS-ALD and identified a metabolite panel that correlates with dysbiosis of the gut microbiome in SBS.

Gut microbiota derived metabolites in cardiovascular health and disease

“…These uremic toxins are gut microbiota derived metabolites of amino acids (Devlin et al, 2016 ). The aromatic amino acids in proteins, phenylalanine, tyrosine and tryptophan, can be metabolized by gut microbiota (Nallu et al, 2017 ; Pereira-Fantini et al, 2017 ). Both microbiota and host liver are involved in biosynthesis of these uremic toxins (Fig.…”

Circulating Metabolites Originating from Gut Microbiota Control Endothelial Cell Function

“…Uremic toxins are metabolites derived by gut microbiota metabolism of amino acids. The aromatic amino acids in proteins (tyrosine, phenylalanine, and tryptophan) can be metabolized by the GM [64,65] and liver of the host [66] to toxins such as indoxyl sulfate, indoxyl glucuronide, indoleacetic acid, p-cresyl sulfate, p-cresyl glucuronide, phenyl sulfate, phenyl glucuronide, phenylacetic acid, and hippuric acid. Circulating nitrogen metabolites as urea and asymmetric dimethylarginine characterize both chronic kidney disease [67] and CVD [68].…”

Host-Gut Microbiota Crosstalk in Intestinal Adaptation

“… 84 , 85 A recent report using a systems biology approach also showed that dysbiosis was correlated with an altered metabolome in a pig model of SBS-associated liver disease. 86 Alteration of the intestinal microbiota also can lead to insufficient breakdown of dietary components such as lipids and complex polysaccharides. This can result in a decrease in the production of short-chain fatty acids (SCFAs), malabsorption, reduced energy availability, and dysmotility.…”