Short chain fatty acids regulate hemodynamics in cirrhosis

• Author / Creator

  Alghbli, Salem

• Abstract
  Advanced cirrhosis is characterized by hemodynamic abnormali􀆟es, including increased portal pressure, and decreased arterial pressure, which contribute to the complica􀆟ons of the disease4. Short chain faty acids (SCFAs), produced by the gut microbiota through carbohydrate fermenta􀆟on, have been shown to regulate blood pressure by interac􀆟ng with the G-protein coupled receptor GPR4131. Impaired liver metabolism, along with dysbiosis in chronic liver disease, can result in elevated circula􀆟ng levels of SCFAs35-36. However, the precise role of SCFAs in cirrhosis-related hemodynamic changes remains unclear. This study aimed to inves􀆟gate the impact of SCFAs, such as propionate and acetate, on splanchnic vasodila􀆟on and hemodynamics in advanced cirrhosis, providing further insights into their poten􀆟al role in the pathophysiology of the disease.
  Methods: A rat model of cirrhosis was established using common bile duct ligation (CBDL), mimicking decompensated cirrhosis. Hemodynamic studies were performed four weeks post-surgery to evaluate mean arterial pressure (MAP), portal pressure (PP), and superior mesenteric artery blood flow (SMABF). The degree of portal systemic shunting (PSS) was determined using colored microspheres, as described by Abraldes et al.12. To assess the impact of increased SCFAs, propionate infusion was administered, while metronidazole was used to decrease SCFAs levels.
  The results showed that increasing plasma SCFAs through propionate infusion in control rats induced hypotension and splanchnic vasodilation, replicating some hemodynamic features of advanced cirrhosis. In CBDL rats, elevated plasma acetate and propionate levels were observed,
  II
  along with hemodynamic abnormalities. Furthermore, propionate infusion in CBDL rats exacerbated splanchnic vasodilation, arterial hypotension, and portal hypertension. To reduce plasma SCFAs, a subgroup of CBDL rats was treated with metronidazole, leading to improved hemodynamics. Specifically, the metronidazole-treated rats showed a significant 11% increase in mean arterial pressure (MAP), a 12% decrease in portal pressure, and a 36% decrease in superior mesenteric artery blood flow (SMABF). Measurements of SCFA concentration in cecal content revealed no significant differences between CBDL and sham rats, suggesting that elevated plasma levels were not solely attributed to increased colonic production. In conclusion, this study highlights the potential role of SCFAs in regulating splanchnic vasodilation and its impact on cirrhosis hemodynamics. Increasing circulating SCFAs replicated hemodynamic abnormalities in control rats, while CBDL rats exhibited elevated plasma SCFAs levels and worsened hemodynamics. Decreasing plasma SCFAs through antibiotic treatment improved cirrhosis hemodynamics. These findings contribute to understanding the complex interactions between gut microbiota-derived SCFAs and hemodynamic changes in cirrhosis. keywords: Short chain fatty acids, cirrhosis, hemodynamics, splanchnic vasodilation, portal hypertension, propionate, metronidazole, gut microbiota

• Subjects / Keywords

  • Short chain fatty acids
  • cirrhosis
  • hemodynamics
  • splanchnic vasodilation
  • portal hypertension
  • propionate
  • metronidazole
  • gut microbiota

• Graduation date

  Spring 2024

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-v0f8-ba46

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.