bims-liverm 2023-04-30 papers

Issue of 2023‒04‒30
three papers selected by
Marti Cadena Sandoval
Columbia University

Nutrients. 2023 Apr 12. pii: 1850. [Epub ahead of print]15(8):

Emerging Roles of Gut Microbial Modulation of Bile Acid Composition in the Etiology of Cardiovascular Diseases.

Tess Yntema, Debby P Y Koonen, Folkert Kuipers.

Despite advances in preventive measures and treatment options, cardiovascular disease (CVD) remains the number one cause of death globally. Recent research has challenged the traditional risk factor profile and highlights the potential contribution of non-traditional factors in CVD, such as the gut microbiota and its metabolites. Disturbances in the gut microbiota have been repeatedly associated with CVD, including atherosclerosis and hypertension. Mechanistic studies support a causal role of microbiota-derived metabolites in disease development, such as short-chain fatty acids, trimethylamine-N-oxide, and bile acids, with the latter being elaborately discussed in this review. Bile acids represent a class of cholesterol derivatives that is essential for intestinal absorption of lipids and fat-soluble vitamins, plays an important role in cholesterol turnover and, as more recently discovered, acts as a group of signaling molecules that exerts hormonal functions throughout the body. Studies have shown mediating roles of bile acids in the control of lipid metabolism, immunity, and heart function. Consequently, a picture has emerged of bile acids acting as integrators and modulators of cardiometabolic pathways, highlighting their potential as therapeutic targets in CVD. In this review, we provide an overview of alterations in the gut microbiota and bile acid metabolism found in CVD patients, describe the molecular mechanisms through which bile acids may modulate CVD risk, and discuss potential bile-acid-based treatment strategies in relation to CVD.

Keywords: atherosclerosis; bile acids; cardiovascular disease; gut microbiota

DOI: https://doi.org/10.3390/nu15081850

Genes (Basel). 2023 Mar 29. pii: 825. [Epub ahead of print]14(4):

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases.

Yoshimitsu Kiriyama, Hiromi Nochi.

Bile acids (BAs) are amphiphilic steroidal molecules generated from cholesterol in the liver and facilitate the digestion and absorption of fat-soluble substances in the gut. Some BAs in the intestine are modified by the gut microbiota. Because BAs are modified in a variety of ways by different types of bacteria present in the gut microbiota, changes in the gut microbiota can affect the metabolism of BAs in the host. Although most BAs absorbed from the gut are transferred to the liver, some are transferred to the systemic circulation. Furthermore, BAs have also been detected in the brain and are thought to migrate into the brain through the systemic circulation. Although BAs are known to affect a variety of physiological functions by acting as ligands for various nuclear and cell-surface receptors, BAs have also been found to act on mitochondria and autophagy in the cell. This review focuses on the BAs modified by the gut microbiota and their roles in intracellular organelles and neurodegenerative diseases.

Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; autophagy; bile acids; mitochondria; neurodegeneration; neurodegenerative disease

DOI: https://doi.org/10.3390/genes14040825

Aliment Pharmacol Ther. 2023 Apr 26.

Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis.

Signe Wiese, Karen V Danielsen, Troels Busk, Jens D Hove, Henriette Ytting, Svend Høime Hansen, Klaus Kaae Andersen, Andrei Voiosu, Søren Møller, Flemming Bendtsen.

BACKGROUND: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis.AIM: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis.
METHODS: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed.
RESULTS: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e', left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01).
CONCLUSIONS: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine-conjugated BA are associated with portal hypertension.

DOI: https://doi.org/10.1111/apt.17533