Pachikian, Barbara D.
[UCL]
(eng)
The prevalence of obesity is increasing worldwide. Among
environmental factors, involved in this phenomenon, the nutritional
dys-balance plays a major role. Surprisingly, the excess of calorie
intake is often associated with specific nutritional deficiencies.
Moreover, recent data suggest that the gut microbiota is a novel
partner to take into account when evaluating the regulation of host
energy metabolism by the nutrients provided in the diet.
In the context of this thesis, we have focused our work on the
assessment of two nutritional deficiencies often occurring in western
countries and which have been associated with diabetes, inflammation
and/or obesity: namely, magnesium (Mg) and n-3 polyunsaturated
fatty acid (PUFA) deficiencies. We have characterized the metabolic
alterations occurring in animal models mimicking those deficiencies
and we have tested the hypothesis that perturbations of the gut
microbiota contribute to the metabolic alterations occurring in
deficient mice.
We have shown for the first time that Mg deficiency, independent of
any other changes in nutrient intake, modulates the concentration of
bifidobacteria in the gut in a time dependent manner. A short term (4
days) Mg-deficiency leads to a drop of bifidobacteria, which is
associated with intestinal and hepatic inflammation and with a loss of
gut barrier integrity. A restoration of the gut microbial changes occurs
spontaneously after a few days (21 days), which allows to normalize
the metabolic alterations.
In the second part of the thesis, we have developed mouse models of
n-3 PUFA depletion: one long term (depletion installed for two
generations) and one short term (depletion installed for three months).
Both long-term and short-term n-3 PUFA depletions induce hepatic
steatosis, alterations in glucose metabolism and a metabolic stress in
the liver tissue. Moreover, mice depleted in n-3 PUFA for two
generations exhibit a lower body weight. A microarray analysis
performed in the liver of mice depleted in n-3 PUFA for three months
revealed a higher expression of several factors involved in fatty acid
and cholesterol synthesis and a lower expression of factors involved in
fatty acid oxidation. These metabolic alterations occur together with a
modification in the gut microbiota composition, characterized by a
lower content in lactobacilli and a higher content in bifidobacteria in
long-term depleted mice and characterized by a higher Roseburia spp.
content in short-term depleted mice.
Supplementation with a prebiotic called fructooligosaccharides (FOS)
leads to differential effects depending on the model of n-3 PUFA
depletion. In mice depleted for two generations, after FOS feeding, we
observed an increased body weight and an improvement of the
catabolic state, whereas there was no effect on hepatic steatosis. In
mice depleted for three months, FOS supplementation restored the
hepatic lipid deposition, mainly by activating fatty acid oxidative
pathways and by lessening cholesterol synthesis.
In conclusion, a nutritional deficiency in n-3 PUFA or in Mg
modulates the gut microbiota composition. In Mg deficiency, a
spontaneous adaptation of the gut microbiota composition is observed
progressively and is associated with a restoration of the inflammatory
state. In n-3 PUFA-depleted mice, changing the gut microbiota
composition by FOS supplementation leads to an improvement of
several metabolic alterations induced by the depletion.
These results support the idea that gut microbiota affects the health of
the host and should be taken into account in the treatment of
inflammatory conditions and hepatic steatosis.


Bibliographic reference |
Pachikian, Barbara D.. Metabolic disorders induced by nutritional deficiency in n-3 polyunsaturated fatty acid or magnesium : potential implication of the gut microbiota. Prom. : Delzenne, Nathalie |
Permanent URL |
http://hdl.handle.net/2078.1/93969 |