Metabolomics analysis of gut barrier dysfunction in a trauma-hemorrhagic shock rat model

Abstract

Intestinal barrier dysfunction has been implicated in the development of multiorgan dysfunction syndrome caused by the trauma-hemorrhagic shock (THS). However, the mechanisms underlying THS-induced gut barrier injury are still poorly understood. In the present study, we used the metabolomics analysis to test the hypothesis that altered metabolites might be related to the development of THS-induced barrier dysfunction in the large intestine. Under the induction of THS, gut barrier failure was characterized by injury of permeability and mucus layer, which were companied by the decreased expression of zonula occludens-1 in the colon and increased levels of inflammatory factors including tumor necrosis factor-α, interferon-γ, interleukin (IL)-6, and IL-1β in the serum. A total of 16 differential metabolites were identified in colonic tissues from THS-treated rats compared with control rats. These altered metabolites included dihydroxy acetone phosphate, ribose-5-phosphate, fructose, glyceric acid, succinic acid, and adenosine, which are critical intermediates or end products that are involved in pentose phosphate pathway, glycolysis, and tricarboxylic acid cycle as well as mitochondrial adenosine triphosphate biosynthesis. These findings may offer important insight into the metabolic alterations in THS-treated gut injury, which will be helpful for developing effective metabolites-based strategies to prevent THS-induced gut barrier dysfunction.

Diallyl Disulfide (DADS) Ameliorates Intestinal Candida albicans Infection by Modulating the Gut microbiota and Metabolites and Providing Intestinal Protection in Mice

“…Gut metabolites are closely related to some intestinal and extraintestinal diseases, such as inflammatory bowel disease, irritable bowel syndrome, depression, and autism (Duboc et al, 2012;Bjerrum et al, 2015;Sharon et al, 2019;Keshteli et al, 2019). Moreover, some gut metabolites could protect or destroy the gut barrier (Li et al, 2019;Parada Venegas et al, 2019). In this study, the intestinal metabolite profiles were significantly different between the CA + DSS and CA + DSS + DADS groups.…”

Long-Term Cardiac Damage Associated With Abdominal Irradiation in Mice

“…Glyceric acid is a product of the pentose phosphate pathway, and its abnormally high levels in tissues can cause metabolic acidosis. And the pentose phosphate pathway can promote the production of reducing equivalents, such as NADPH, which will be used for reducing biosynthesis reactions in cells ( Sun et al, 2017 ; Li Z. et al, 2019 ). Based on the previous results, our current results suggests that mice from the abdominal irradiation group may have a certain degree of hyperoxidation, which is consistent with the previously reported bystander effect of radiotherapy.…”

Global metabolic profiling of hemorrhagic shock and resuscitation

“…Succinic acid, citrate and malic acid are three important metabolic intermediates in the TCA. Succinic acid is involved in various biological processes such as ATP biosynthesis and signal transduction (Li et al, 2019). These three TCA intermediates increased during HS and recovery to different degrees after blood transfusion, which is consistent with previous reports in the literature, suggesting that they can be used as biomarkers for reperfusion injury (D'Alessandro, Slaughter, et al, 2015).…”

“…If the treatment is not rapid enough, it will result in death owing to multiple organ function injury. It is reported that it is one of the main causes of death among trauma victims, accounting for about 40% of deaths (Li et al, 2019). Plasma contains a large number of proteins and can compensate for the fluid loss caused by HS and increase the supply of oxygen and nutrients in tissues; therefore, timely blood transfusion is one of the common methods to treat hemorrhagic shock (Traverso, Medina, & Bolin, 1985).…”