Southern Medical University has made progress in the research on the mechanism of enterogenic lung injury

Fig.
The intestinal flora metabolite succinic acid acts on its receptor SUCNR1 to promote the M1 polarization of alveolar macrophages and aggravates acute lung injury after intestinal ischemia and reperfusion

With the support of the National Natural Science Foundation of China (grant numbers: 81730058, 82172141, 82002088), Professor Liu Kexuan's team at Southern Medical University has made progress in the study of the mechanism of intestinal lung injury, and the research results are "Gut microbiota-derived succinate aggravatesacute lung.
" injury after intestinalischemia/reperfusion in mice", published online in the European Respiratory Journal on October 13, 2022
.
Links to papers: https://doi.
org/10.
1183/13993003.
00840-2022
.

Intestinal ischemia/reperfusion injury (Ischemia/reperfusion, I/R) is a common clinical acute and critical condition, often occurring in clinical scenarios such as trauma, infection, shock, intestinal obstruction and extracorporeal bypass surgery, which not only causes intestinal injury, but also leads to sepsis and extraintestinal multi-organ dysfunction
due to intestinal barrier disruption and endotoxin displacement 。 Acute lung injury (ALI), as the most common distant organ complication of intestinal I/R, is the leading cause of death in such patients, and is also one of the scientific problems that need to be solved urgently in the field of
respiratory and critical illness.
The intestinal flora and its metabolites can be involved in many lung diseases by affecting immune system function, but the mechanism of action of intestinal I/R induced ALI is unknown
.

The team replicated the mouse intestinal I/R-induced ALI model, and at the same time used 16S rRNA microbiota sequencing analysis to find that intestinal I/R caused an increase in the abundance of intestinal succinic acid-producing bacteria and a decrease
in the abundance of succinic acid-degrading bacteria.
In addition, enteral I/R can also lead to aggregation of succinic acid in the lungs, and the amount of succinic acid in the lungs is positively correlated
with the intestinal succinic acid-producing bacteria/succinic acid-degrading bacterial ratio.
Further experiments have shown that the accumulation of succinic acid in the lungs during intestinal I/R comes from the intestinal flora, and the intestinal flora metabolite succinic acid is an important vector
leading to ALI after intestinal I/R.
The team also collected data from patients undergoing cardiopulmonary bypass cardiac surgery clinically, and found that plasma succinic acid content was elevated in the early postoperative period, and plasma succinic acid content was significantly positively correlated with the relevant indicators reflecting lung injury after surgery, further confirming that succinic acid was related
to ALI caused by intestinal I/R.
Molecular mechanisms were discussed, and succinic acid mediated apoptosis and ALI by promoting M1 polarization of alveolar macrophages.
It was also confirmed that succinic acid mediates alveolar macrophage polarization and downstream reactions through its receptor SUCNR1 and downstream PI3K/AKT/HIF-1α pathway (Fig).

This study revealed the pathogenesis of enterogenic ALI from the perspective of "intestinal microbiota-gut-lung axis", and proposed that succinic acid is a potential target for the prevention and treatment of enterogenic ALI in critically ill patients
.