Biotechnology

Vesicles produced by intestinal bacteria cause cycles of malignancy

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Niigata, Japan – Researchers from Niigata University and Kyoto Prefectural University have revealed that small vesicles, about 100 nm in size, secreted by gut bacteria induce immune activation and development of liver cirrhosis, as well as a decrease in serum albumin levels, which then leads to edema. and ascites.

Niigata, Japan – Researchers from Niigata University and Kyoto Prefectural University have revealed that small vesicles, about 100 nm in size, secreted by gut bacteria induce immune activation and development of liver cirrhosis, as well as a decrease in serum albumin levels, which then leads to edema. and ascites.

The global prevalence of cirrhosis is high and can be fatal when it progresses to the final stages. The development of cirrhosis produces a variety of symptoms including jaundice, ascites, rupture of varices, and hepatocellular carcinoma. Often, even if the root causes, such as viral hepatitis, alcohol, and lifestyle factors, are resolved, cirrhosis of the liver has limited regenerative capacity and fibrosis continues without improvement; this state is called the “point of no return”. Intestinal bacteria are considered as one of the important culprits that lead to this condition. According to previous reports and clinical observations, it has been found that during cirrhosis, the intestine is vulnerable to intestinal bacterial invasion, due to several factors such as edematous mucosa and decreased intestinal bacterial diversity, intestinal motility, mucus production, epithelial barrier function, and immune capacity. Researchers have recently studied the possibility that invasion of very small (about 100 nm) vesicles, originating from certain gut bacteria, has an adverse effect on the liver without invasion of the bacteria itself.

In their experiments, the effects on liver cells and a rat model of cirrhosis were analyzed when small vesicles were released by Escherichia coli (E.coli), which has been detected when the pathological state of cirrhosis worsens.

The results showed that the vesicles originate from E. coli induced inflammation involving macrophages and neutrophils, and increased expression Clec4E genes (macrophage-induced C-type lectin: Mincle) in cells. In addition, hepatocytes, which are the most important liver cells and responsible for most liver functions, were found to undergo important changes when exposed to vesicles, including decreased production of albumin, which is produced by hepatocytes and released into the blood.

Furthermore, the provision of vesicles originating from E. coli for cirrhotic rat models, induced liver inflammation, worsening fibrosis, and decreased serum albumin levels. In addition, this state of active inflammation and worsening of fibrosis was reduced by administration of albumin to mice. Also found that Clec4e genes are upregulated in macrophages that have migrated from outside the liver.

The investigators also reported that vesicles of intestinal bacterial origin and multiple antibodies against various bacterial antigens were detected in ascites and sera of patients with decompensated cirrhosis, respectively. Under experimental surveillance, the presence of these vesicles suggests the possibility that they have caused increased hepatic inflammation, worsened fibrosis, and decreased albumin production, leading to critical effects in these patients.

The results of this study reveal the mechanism by which patients with advanced cirrhosis develop chronic inflammation induced by bacterial vesicles and other agents, resulting in hepatic and systemic damage. This phenomenon may be related to the mild inflammation and fever seen routinely in cirrhotic patients. In an interview, Dr. Atsunori Tsuchiya from the Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Future Medical Research Center for Exosome and Designer Cell (F-EDC), Niigata University, who led the project said, “We will try to investigate the possibility of developing a therapeutic novelty, for example, to strengthen the gut barrier of patients with cirrhosis.”


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