Study and Analysis on the Characteristics of Intestinal Microorganisms and Serum Metabolites in Patients With Acute Pancreatitis Complicated With COVID-19

Acute pancreatitis (AP) is a common gastrointestinal disease. In recent years, the hospitalization rate and related costs of AP have increased significantly. About 15% - 20% of patients will develop acute severe pancreatitis, namely SAP. SAP is a serious abdominal disease with many complications and high mortality. The global average annual incidence rate is about 6.75 cases/100000 people. Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and sepsis are often associated with it. SIRS and MODS may be caused by the release of inflammatory cytokines in the early stage of AP, and intestinal dysfunction and pancreatic necrosis in the later stage. Some studies have shown that 59% of AP patients are accompanied by intestinal barrier injury, and increased permeability of intestinal mucosa, resulting in intestinal bacterial translocation, pancreatic tissue necrosis and infection, and multiple organ dysfunction syndrome. Most of the bacteria causing necrotic infection of pancreatic tissue to come from intestinal flora, such as Escherichia coli and Enterococcus. Therefore, intestinal flora may play an important role in the occurrence and development of AP.

As the largest organ of the human body, the gastrointestinal tract provides a broad colonization surface for biological flora. Intestinal bacteria present in the human gastrointestinal tract are essential components for the development of the mucosal immune system, the promotion of food digestion and absorption, and the regulation of glucose metabolism. In addition, it also has the function of protecting the intestinal barrier and mediating host immunity and metabolism. The host and microbe reach the micro-ecological balance in the state of health, which is called internal environment stability, and the host maintains normal physiological functions. However, external factors (such as infection, toxin, diet change, disease, etc.) may change or destroy the balance between them, and the disorder of intestinal flora will in turn induce or accelerate the disease's progress. As one of the research hotspots in recent years, the imbalance of intestinal flora has always attracted people's attention. The current study found that the ecological imbalance of intestinal microbiota during AP was defined as the decrease of intestinal microbial diversity and the change of the balance between symbiotic microbiota and pathogenic microbiota. The change of intestinal flora occurred in the early stage of AP, which may be involved in the aggravation of the disease. Not only that but also early intestinal flora disorder was found in SAP research. In addition to intestinal bacteria, their metabolites such as short-chain fatty acids (SCFAs) also affect the progress of AP. Moreover, more and more studies have found that changes in intestinal flora during the development of AP may be related to the severity of the disease. In the process of AP occurrence and development, the abnormal secretion of trypsin and the destruction of pancreatic structure leads to the abnormal secretion of the pancreas, which can cause changes in intestinal homeostasis and intestinal flora. In addition, the study also found that intestinal microbiota is an important medium during AP, and its imbalance is closely related to the severity of AP. At present, many experimental data have shown that the diversity of intestinal microorganisms and the relative abundance of specific bacterial groups have changed during the AP process.

Based on the relationship between intestinal flora imbalance and the occurrence and development of AP, the possible mechanisms of intestinal microbial imbalance in AP are mainly as follows: (1) intestinal motility disorder: gastrointestinal motility disorder often exists in AP and plays a role in disease progression. Intestinal motility disorder can also lead to the accumulation of harmful substances and inhibit the growth of probiotics. (2) Ischemia-reperfusion injury (IRI): pro-inflammatory cytokines such as TNF- α during AP, the release of insulin can cause intestinal mucosal IRI and disrupt intestinal microcirculation. One of the main causes of intestinal microcirculation damage is the destruction of sugar calyx. (3) Oxidative stress: severe oxidative stress and intestinal-activated caspase-3 pathway was found during AP. Oxidative stress not only accelerates the disorder of intestinal barrier function but also participates in the disorder of intestinal microbiota. (4) Immune dysfunction: intestinal immunosuppression can be observed in the early stage of acute pancreatitis, which is related to the damage of the clearance of proliferative pathogens.

In AP, the change of intestinal microflora is closely related to its occurrence and development, and the metabolites of intestinal microflora will also affect the serum metabolic indicators of AP patients. Intestinal microflora has high metabolic activity and can transform host sources and dietary components into different metabolites. Some metabolites are beneficial and some are harmful. Metabolites beneficial to the host include lactic acid, bile acid (BA), SCFA, and bacteriocin. These substances are generally considered antibacterial factors and play a key role in the prevention of pathogenic infection. In addition, there are also related intestinal flora and several specific products produced that may have a certain impact on SAP. In human intestines, bifidobacteria and lactobacillus are probiotics that can stimulate anti-tumor properties and immunity. The main products of bifidobacterium metabolism are lactic acid and acetic acid, which reduce the pH value in the intestine and inhibit the growth of harmful microorganisms. This mechanism is particularly evident in the cecum and ascending colon.

At present, the continuous pandemic of coronavirus disease (COVID-19) in 2019 caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) poses a serious threat to global public health, and millions of people in more and more countries are at risk. This pandemic has not only affected the medical system but also affected the global socioeconomic balance. COVID-19 was soon designated as a global pandemic by the World Health Organization, because as of January 2021, there were about 98 million confirmed cases and about 2 million confirmed deaths. Nevertheless, since the outbreak of COVID-19, our understanding of it has increased significantly, and a variety of treatment methods and drug interventions have been tested or are currently being developed to reduce its risk factors. Recently, some candidate vaccines have shown about 95% clinical efficacy and are currently being approved for emergency use in different countries. Therefore, vaccination as one of the effective means of protection is worth promoting worldwide. Some studies have confirmed that several intestinal microflorae have the potential to improve the immune response and reduce adverse events after COVID-19 vaccination and that intestinal microflora has the potential to supplement the effectiveness of the vaccine. Combined with several recent studies, intestinal flora plays a key role in regulating the immune response to vaccination and is related to the severity of COVID-19 patients. However, the comprehensive evaluation of host response, especially the role of intestinal flora in antibody production, is limited. Therefore, the specific role of intestinal flora in the development of COVID-19 needs further study.