Over the past decades the potential role of the gut microbiome and bile acids in type 2 diabetes mellitus (T2DM) has been revealed, with a special reference to low bacterial alpha diversity. Certain bile acid effects on gut bacteria concern cytotoxicity, or in the case of the microbiome, bacteriotoxicity. Reciprocally, the gut microbiome plays a key role in regulating the bile acid pool by influencing the conversion and (de)conjugation of primary bile acids into secondary bile acids. Three main groups of bacterial enzymes responsible for the conversion of bile acids are bile salt hydrolases (BSHs), hydroxysteroid dehydrogenases (HSDHs) and enzymes encoded in the bile acid inducible (Bai) operon genes. Interventions such as probiotics, antibiotics and fecal microbiome transplantation can impact bile acids levels. Further evidence of the reciprocal interaction between gut microbiota and bile acids comes from a multitude of nutritional interventions including macronutrients, fibers, prebiotics, specific individual products or diets. Finally, anatomical changes after bariatric surgery are important because of their metabolic effects. The heterogeneity of studies, diseases, bacterial species and (epi)genetic influences such as nutrition may challenge establishing specific and detailed interventions that aim to tackle the gut microbiome and bile acids.

Ageing changes the impact of nutrition, whereby inflammation has been suggested to play a role in age-related disabilities such as diabetes and cardiovascular disease. The aim of this study was to investigate differences in postprandial bile-acid response and its effect on energy metabolism between young and elderly people. Nine young, healthy men and nine elderly, healthy men underwent a liquid mixed-meal test. Postprandial bile-acid levels, insulin, glucose, GLP-1, C4, FGF19 and lipids were measured. Appetite, body composition, energy expenditure and gut microbiome were also measured. The elderly population showed lower glycine conjugated CDCA and UDCA levels and higher abundances of Ruminiclostridium, Marvinbryantia and Catenibacterium, but lower food intake, decreased fat free mass and increased cholesterol levels. Aging is associated with changes in postprandial bile-acid composition and microbiome, diminished hunger and changes in body composition and lipid levels. Further studies are needed to determine if these changes may contribute to malnutrition and sarcopenia in elderly.

Cerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7α-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls. Seven patients and seven age, gender and body mass index matched controls were included and subjected to a 4 h mixed meal test with regular blood sampling. CTX patients withdrew from chenodeoxycholic acid (CDCA) and statin therapy three weeks prior to the test. Postprandial levels of total bile acids were significantly lower in CTX patients and consisted of residual CDCA with low amounts of ursodeoxycholic acid (UDCA). The postprandial plasma glucose peak concentration occurred later in CTX patients compared to controls, and patients’ insulin levels remained elevated for a longer time. Postprandial GLP-1 levels were slightly higher in CTX subjects whereas postprandial FGF19 levels were lower in CTX subjects. This novel characterization of CTX patients reveals very low circulating bile acid levels and FGF19 levels, aberrant postprandial glucose and insulin profiles, and elevated postprandial GLP-1 responses.

Purpose: The Amsterdam UMC pharmacy has been compounding chenodeoxycholic acid (CDCA) capsules for Dutch cerebrotendinous xanthomatosis patients since 2018. However, limited data are available on the pharmacokinetics and bioequivalence of therapeutic CDCA formulations. Methods: An open-label, single-center, randomized, two-period, two-sequence, cross-over study was conducted in 12 healthy volunteers to compare the pharmacokinetic profile of pharmacy-compounded CDCA capsules to that of the authorized CDCA product. Results: Both formulations reached peak plasma concentrations (t_max) at approximately 1 h post-dose. The mean AUC_(0–6h) values were 262.4 (±69.4) µmol∙min/L for the compounded capsules and 248.0 (±78.1) µmol∙min/L for the authorized capsules, with a 90% confidence interval (CI) for the AUC_(0–6h) ratio of 0.89–1.30, exceeding the accepted bioequivalence range of 0.80–1.25. The mean C_max for the compounded formulation (2.96 ± 0.91 µmol/L) was significantly lower than that of the comparator product (4.42 ± 1.36 µmol/L; p = 0.0040), with a 90% CI for the C_max ratio of 0.57–0.80, also outside the bioequivalence range. Conclusions: Overall, the pharmacy-compounded and authorized capsules demonstrate a comparable AUC_(0–6h) and t_max. Bioequivalence could not be demonstrated, primarily due to high variation, a significantly lower C_max, and an AUC_(0–6h) ratio outside the accepted limits. These findings indicate that the compounded formulation results in reduced systemic peak exposure compared with the authorized product. However, given the high variation, a larger sample size would be needed to further investigate bioequivalence in future studies.