The Role of the Gut Microbiome in the Development of Acute Pancreatitis

Abstract

With the explosion research on the gut microbiome in the recent years, much insight has been accumulated in comprehending the crosstalk between the gut microbiota community and host health. Acute pancreatitis (AP) is one of the gastrointestinal diseases associated with significant morbidity and subsequent mortality. Studies have elucidated that gut microbiota are engaged in the pathological process of AP. Herein, we summarize the major roles of the gut microbiome in the development of AP. We then portray the association between dysbiosis of the gut microbiota and the severity of AP. Finally, we illustrate the promises and challenges that arise when seeking to incorporate the microbiome in acute pancreatitis treatment.

Keywords: acute pancreatitis; dysbiosis of intestinal flora; gut microbiota; intestinal barrier dysfunction.

Figure 1

The close relationship between gut microbiota and the activation of AP. In AP, significant disorganization of the intestinal flora occurs. The first manifestation is the abnormal ratio of intestinal flora species, which is mainly characterized by an increase in harmful bacteria and a decrease in probiotics, resulting in a serious imbalance in the ratio of harmful bacteria to probiotics. Secondly, the alteration in gut flora leads to the explosion of harmful microbiome-released substances. The metabolites of harmful bacteria increase, while the beneficial metabolites of probiotics (e.g., SCFAs) decrease. Altered intestinal permeability also accelerates the progression of AP. The intestinal mucosal barrier, which can be directly and indirectly disrupted, is also affected, leading to translocation and direct invasion of the flora. These changes will cause harmful substances to accumulate in the intestine, directly stimulate the TLR4 receptor of the epithelial cells in the intestine, activate the relevant inflammatory response pathways and ultimately accelerate the destruction of pancreatic cells and aggravate AP. Some harmful substances may even enter the blood circulation directly and activate the body’s immune response, thus causing the development of AP.

Figure 2

Predictive value of gut microbiota in AP. The gut microbiome is not only predictive of AP but also the severity, prognosis and comorbidities of AP, and the associations between alterations in gut microbiome and disease prognosis have underlying molecular biological mechanisms.