Involvement of the gut microbiota in the development of low grade inflammation
associated with obesity : focus on this neglected partner
P.D. Cani, N.M. Delzenne
Université catholique de Louvain, Louvain Drug Research Institute, Metabolism and Nutrition Research Group, Brussels, Belgium.
Nowadays, the literature provides evidence that obesity, type 2
diabetes and insulin resistance are characterized by a low grade
inflammation. Among the environmental factors involved in such
diseases, the gut microbiota has been proposed as a key player. This
neglected “organ” has been found to be different between healthy
and or obese and type 2 diabetic patients. For example, recent data
have proposed that dysbiosis of gut microbiota (at phyla, genus, or
species level) affects host metabolism and energy storage. Among
the mechanisms, metabolic endotoxemia (higher plasma LPS
levels), gut permeability and the modulation of gut peptides
(GLP-1 and GLP-2) have been proposed as putative targets. Here
we discuss 1° the specific modulation of the gut microbiota
composition by using prebiotics and 2° the novel findings that may
explain how gut microbiota can be involved in the development or
in the control of obesity and associated low-grade inflammation.
(Acta gastro enterol. belg., 2010, 73, 267-269).
Key words : obesity, gut microbiota, inflammation, LPS, endotoxemia,
adipose tissue, GLP-2.
Obesity is classically associated with a cluster of meta-
bolic diseases including glucose homeostasis alteration
(insulin resistance, glucose intolerance, type 2 diabetes)
and cardiovascular diseases (and/or risk factors such as
hypertension, fibrinolysis disorders, dyslipidaemia, ...).
Now, epidemiological, clinical and or experimental stud-
ies have causally linked a tight relationship between the-
ses diseases and the development of a low grade inflam-
mation (1). However, the mechanisms linking a low
inflammatory tone and the onset of metabolic diseases
are poorly defined. Along this line, we have discovered
that the gut microbiota initiates inflammatory disorders
associated with obesity and type 2 diabetes. In that
context, experimental evidence highlights potential
mechanisms connecting gut microbiota to host metabo-
lism (2,3). Until the recent development of powerful
molecular biology methods and gnotobiotic animals the
role of the gut microbiota was limited to the investigation
of specific pathogens or infectious diseases. However,
more studies are becoming essential to unravel whether
specific and selective modulation of the gut microbiota
may have an impact on the development of obesity and
related metabolic alterations. Among the potential tools
to target the gut microbiota, probiotic and prebiotic (4)
approaches appear as interesting treatments to reverse
host metabolic disorders linked to gut microbiota dys -
Obesity and related disorders : an inflammatory
state directly linked with changes in gut micro-
biota composition ?
Over the last years, we have demonstrated that both
nutritional and genetic obese mice models are character-
ized by a significant increase in plasma lipopolysaccha-
ride (LPS), defined as “metabolic endotoxemia” (7-10).
This constituent of the Gram negative bacteria present
within the gut is transported from the gut lumen towards
target tissues by a mechanism facilitated by the chylo -
microns freshly synthesized from epithelial intestinal
cells in response to fat feeding (11,12). We and others,
have confirmed these data in human subjects, hence, this
phenomenon could participate to the higher plasma LPS
levels and low grade inflammation found following high
fat diet feeding (7,13-15). However, we may not exclude
that these specific changes occur only at the level of fat
absorption, since, genetic obese models fed with a nor-
mal chow diet are also stigmatized by a higher plasma
LPS levels (10,16). Hence, we hypothesized that meta-
bolic endotoxemia could also bring about a modulation
in the gut microbiota. Therefore, we characterized and
quantified several bacterial families and demonstrated
for the first time that high-fat diet-induced obesity was
associated with changes in the gut microbiota (7,8).
More specifically, we found, that diet-induced obesity
strongly altered gut microbiota composition with
reduced Bifidobacterium spp. and Bacteroides-related
bacteria, Eubacterium rectale-Clostridium coccoides
group content (7,8).
To decipher the role of the metabolic endotoxemia in
the onset of insulin resistance and metabolic disorders
associated with obesity, we used a model of specific
alteration in the host-gut microbiota interaction such as
genetic invalidation of the LPS co-receptor CD14
(CD14/TLR4 receptor complex). In this model, we
found that LPS plays a key role in driving insulin resist-
ance, systemic inflammation, fat mass development and
steatosis because CD14-receptor knock out animals
completely resist to the high-fat diet induced metabolic
Correspondence to : Prof. P.D. Cani, UCL, LDRI, Av. E. Mounier, PMNT73/69,
B-1200 Brussels, Belgium. E-mail : email@example.com
Submission date : 31/03/2010
Acceptance date : 26/04/2010
Acta Gastro-Enterologica Belgica, Vol. LXXIII, April-June 2010
P.D. Cani, N.M. Delzenne
microbiota (9,10). In accordance with this hypothesis,
we found that selective modulation of the gut micro biota
by using prebiotics improves gut barrier, reduces meta-
bolic endotoxemia, lowers inflammatory and glucose
Among the mechanisms, we found that the selective
change in gut microbiota increases endogenous
glucagon-like peptides production (GLP-1 and GLP-2),
involved in glucose homeostasis and gut barrier function
respectively, both peptides being important in the meta-
bolic effects occurring upon prebiotics-induced modula-
tion of the gut microbiota (8,10,25-29). In obese ob/ob
mice, we further defined the GLP-2 has a key hormone
explaining the metabolic effects of prebiotics such as the
improvement of gut barrier, the decreased plasma LPS
levels, as well as systemic and hepatic inflammation.
Indeed, GLP-2 receptor antagonist has been shown to
completely abolish the positive effect of prebiotics (10).
Altogether, these data are in favour of a role played by
the gut peptide GLP-2 and appear as a novel mechanism
contributing to the decrease in inflammation and meta-
bolic disorders during obesity and diabetes.
Finally, in addition to the modifications of inflamma-
tory tone, several studies have also proposed that the gut
microbiota participate in the control of food intake and
fat mass development via several mechanisms including
endogenous gut peptides production involved in food
intake and energy homeostasis (5,6,30,31). Therefore,
we may not exclude the potential involvement of such
mechanisms in the development of obesity and related
disorders. Nevertheless, both experimental and human
data support the hypothesis that specific change in the
gut microbiota (with prebiotics) may participate in the
control of glucose tolerance and the development of
metabolic diseases associated with obesity. Thus, it
would be useful to decipher specific strategies aiming at
modifying gut microbiota in order to impact on the
occurrence of metabolic diseases.
PDC is research associate from the FRS-FNRS
(Fonds de la recherche scientifique, Belgium). PDC is
recipient of grants from the SFD (Société francophone
du diabète, France) and FRS-FNRS.
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low grade inflammation and obesity, recent results
obtained both in rodents and humans, have suggested
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mechanisms including tight-junction proteins (ZO-1 and
Occludin), a phenomenon directly dependent of the gut
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