Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats

Abstract

Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P = .010, .044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated eNOS was downregulated. Portosystemic shunts determined by splenorenal shunt flow decreased in both transplantation groups (P = .037, .032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared to sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.

Synthesis, characterization, and biological verification of asialoglycoprotein receptor-targeted lipopolysaccharide-encapsulated PLGA nanoparticles for the establishment of a liver fibrosis animal model

“…The situation in which fibrotic bands and regeneration nodules compress the hepatic vasculature may cause abnormal vessel structures, while irregular vasoconstriction hinders blood flow. 40,41 Based on the significantly enhanced AST and total bilirubin expressions in plasma (Fig. 2b and 2c), we speculated that the increased hepatic vascular resistance in the ALPND-treated group was attributed to enhanced liver injury of the setting.…”

Spontaneous remission of hepatic myelopathy in a patient with alcoholic cirrhosis: A case report

“…Based on this, Sun et al [ 24 ] reported a case of HM in a patient who received FMT, and neurological function improved after three repetitions of FMT. More studies have revealed that repairing gut microbiota may decrease portal hypertension and repair the blood-brain barrier[ 25 , 26 ]. Further, there is increasing data to demonstrate the usefulness of FMT for improving HE[ 27 , 28 ].…”

Contribution of gut microbiota toward renal function in sepsis

“… Traykova et al (2017) reported that when bacterial translocation occurred, the number of bacterial species and the total bacterial DNA were positively correlated with the serum nitric oxide level [odds ratio (OR): 0.64, 95% confidence interval (CI): 0.247–0.852, P = 0.0041 and OR: 0.62, 95% CI: 0.216–0.842, P = 0.0062, respectively] and were inversely correlated with systemic vascular resistance (OR: −0.593, 95% CI: −0.83 to −0.175, P = 0.0095 and OR: −0.621, 95% CI: −0.843 to −0.218, P = 0.0060, respectively). Huang et al (2021) also found that fecal microbiota transplantation (FMT) restored the normal gut microbiota composition and downregulated phosphorylated endothelial nitric oxide synthase, leading to improved vasodilation. Therefore, we speculated that the gut microbiota in sepsis patients may promote increased renal blood flow by participating in the SIRS response, leading to ARC.…”

“…However, relevant research has not directly reached this conclusion. Although studies have shown that the gut microbiota affected nitric oxide expression, these reports experimented with cirrhosis, and it is unclear whether the underlying disease affected this process ( Traykova et al, 2017 ; Huang et al, 2021 ).…”