Gut microbiota to counteract metabolic disorders and neuroinflammation : Impact of dietary factors and their potential to prevent Alzheimer’s disease
Author
Summary, in English
Studies included in this thesis aimed to evaluate whether the gut microbiota may have influences on AD risk factors and how a healthy gut microbiota, amending gut-brain interaction, may be composed. The shifts of gut microbiota upon dietary changes, and their relation to neurodegenerative and metabolic disturbances in rodents and humans were investigated.
The results showed that a mouse model of cerebral amyloidosis (APPPS1) displayed a distinct gut microbiota profile, as compared to that of healthy wild-type (WT) mice. Absence of the gut microbiota (germ-free, GF) in APPPS1 mice resulted in reduction of amyloid-beta (Aβ) deposition. Colonization of GF mice with the gut microbiota from APPPS1 mice resulted in increased Aβ pathology, relative to that seen with colonization of WT microbiota. Increased influx of inflammatory components seemed to be associated with Aβ pathology. A study in a neonatal rat model showed that dietary disturbances before weaning period affected the normal establishment of the gut microbiota, as well as gut barrier and blood-brain barrier (BBB) functions. Such disruption of a normal establishment of the gut microbiota early in life may have potential long-term adverse consequences. In human adults, whose gut microbial community has already established, a short-term dietary intervention with a multifunctional diet (MFD), including several active ingredients that may serve as substrates for the gut microbiota, seemed to be insufficient to produce a broad switch in the gut microbiota composition. Yet specific gut microbial genera that associated with the positive impact of the diet were identified. Studies in apolipoprotien E knockout (ApoE-/-) mice showed that high-fat (HF) feedings with inclusion of dietary fibres from lingonberries (Vaccinium vítis-idaéa) affect the gut microbiota, associated with the lingonberries’ positive effects to counteract the impaired metabolic functions induced by HF diets. Inclusion of lingonberries also decreased levels of gut- and neuro-inflammation and increased synaptic density in the hippocampus of mice fed HF diets.
The results of these studies suggest that the gut microbiota may be involved in the progression of AD by triggering systemic inflammatory responses. Chronic inflammation and ageing have been shown to increase vulnerability of the BBB. Inclusion of lingonberries in HF diets counteracted negative effects of the HF diets on metabolic and neuroinflammatory markers. Therefore, lingonberries may be included as a part of a functional diet to target specific gut microbiota associated with improved risk factors for developing AD or even other neurogenerative diseases.
Department/s
- Division of Food and Pharma
- Food for Health Science Centre
Publishing year
2018
Language
English
Full text
Document type
Dissertation
Publisher
Department of Food Technology, Lund University
Topic
- Nutrition and Dietetics
- Engineering and Technology
Keywords
- Alzheimer’s disease
- gut microbiota
- metabolic disorders
- inflammation
- neuroinflammation
- lingonberries
- dietary fibre
- gut barrier
- blood-brain barrier
Status
Published
Project
- ANTIDIABETIC FOOD CENTRE
ISBN/ISSN/Other
- ISBN: 978-91-7753-628-4
- ISBN: 978-91-7753-627-7
Defence date
20 April 2018
Defence time
09:15
Defence place
lecture hall KC:C, Kemicentrum, Naturvetarvägen 14, Lund University, Faculty of Engineering LTH, Lund
Opponent
- John F Cryan (Professor)