Regulation of bile acids by prebiotic food components: Studies in rat caecum and in serum of mice and humans

Tannaz Ghaffarzadegan

Research output: ThesisDoctoral Thesis (compilation)

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Abstract

Bile acids (BA) are formed from cholesterol in the liver and, apart from being part of fat digestion, they also act as signalling molecules in several health-related physiological processes. BA composition is regulated by gut microbiota as well as dietary fibre (DF) and fat in the diet. This thesis describes how different types of DF and fat levels, can alter BA composition in the caecum/faeces and blood. One methodology for analysing BAs in caecum was developed, while another methodology was set up to analyse BAs in blood/serum samples. In the first study, the method developed for BA analysis in caecum materials was based on hollow-fibre liquid-phase microextraction followed by gas chromatography with flame ionization detector. The method was applied by analysing the caecum content of rats fed three diets containing fermentable DF: pectin, guar gum and a mixture of the two, and a fibre-free control diet. All diets containing DF increased the total amounts of BAs related to beneficial health effects and reduced the amounts of those connected to diseases and cancers. Furthermore, an in vivo study of rats given guar gum of three different viscosities and pectin with two different degrees of methoxylation in low-fat (LF) and high-fat (HF) settings was performed. Guar gum with medium viscosity showed the best BA profile, containing higher amounts of BAs connected to health, and lower amounts of BAs associated with disease. There was a strong correlation between the gut microbiota, BAs and caecal short-chain fatty acids (SCFAs). BAs with beneficial health properties and SCFAs, with the exception of valeric acid, correlated positively with Bifidobacterium and RF32 and they were higher in groups fed fibre. The amounts of BAs connected to diseases were positively correlated with Firmicutes and were higher in groups fed the fibre-free control diet. The pectins behaved similarly and their effects on BA compositions were less pronounced. In study III, two barley varieties with different levels of DF and β-glucan in LF and HF settings were evaluated. In the LF groups, the higher content of β-glucan showed higher amounts of the health-promoting BAs, while in the HF setting the group with medium β-glucan content and highest amounts of arabinoxylan showed an increase in these BAs. The arabinoxylan seemed to be more effective at reducing the levels of BAs connected with negative effects (than the β-glucan), both in LF and HF settings. The BAs with beneficial health effects were associated with Bifidobacterium and Lactobacillus and their abundance was higher in LF diets. In study IV, free and conjugated BAs in serum samples from hearts of mice were determined using simple protein precipitation followed by ultra-high-performance liquid chromatography–mass spectrometry. Different lingonberry samples, consisting of soluble, insoluble or whole lingonberry fractions in a HF diet or cellulose in LF and HF diets, were investigated. The whole lingonberries showed a healthier BA profile and a greater abundance of Bifidobacterium and Prevotella. In study V, postprandial serum concentrations of BAs in healthy subjects after consumption of a turmeric-based beverage prior to medium-fat and HF breakfasts were registered. Turmeric could modify the BA profile towards a healthier composition, with higher levels of free and conjugated forms of cholic and ursodeoxycholic acids as well as free and taurine-conjugated forms of chenodeoxycholic acid but lower levels of conjugated forms of deoxycholic acid. In conclusion, using the new set of methodologies, the BA composition in rat caecum and in mice and human serum could be studied after the intake of different diets. The type and functional properties of prebiotic chosen, and the amount of fat can affect the BA profile and gut microbiota composition. A HF diet increased the total amounts of BAs in blood and caecum, as usually assumed. Less well-known is that fermentable DF can also shape the BA profile. The results of this work may be the basis for development of prebiotic food products for the promotion of improved BA metabolism and overall health.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Food Technology, Engineering and Nutrition
Supervisors/Advisors
  • Nyman, Margareta, Supervisor
  • Hållenius, Frida, Supervisor
  • Sandahl, Margareta, Supervisor
Award date2018 Apr 27
Place of PublicationLund
Publisher
Print ISBNs978-91-7753-635-2
Electronic ISBNs978-91-7753-636-9
Publication statusPublished - 2018

Bibliographical note

Defence details
Date: 2018-04-27
Time: 13:15
Place: lecture hall F, Kemicentrum, Getingevägen 60, Lund University, Faculty of Engineering LTH, Lund
External reviewer
Name: Landberg, Rikard
Title: Professor
Affiliation: Chalmers University of Technology, Gothenburg, Sweden
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Subject classification (UKÄ)

  • Nutrition and Dietetics

Keywords

  • Bile acids
  • Dietary fibre
  • Fat
  • Pectin
  • Guar gum
  • Barley
  • Lingonberry
  • Turmeric
  • Short-chain fatty acids
  • Gut microbiota
  • Caecum
  • Serum
  • Rat
  • Mice
  • Humans
  • GC-FID
  • UHPLC-MS

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