ArticlePDF AvailableLiterature Review


Obesity is characterized by low-grade inflammation and a number of metabolic disorders. Distal gut microbes' content (microbiota) is not yet fully understood but evidence shows that it is influenced by internal and external factors that modulate its composition and function. The evidence that gut microbiota composition can differ between healthy and obese individuals, as well as for those who maintain specific dietary habits, has led to the study of this environmental factor as a key link between the pathophysiology of obesity and gut microbiota. Data obtained about the role of anthocyanins (ACNs) in microbiota may lead to different strategies to manipulate bacterial populations and promote health. Anthocyanins have been identified as modulators of gut microbiota that contribute to obesity control and these bioactive compounds should be considered to have a prebiotic action. This review addresses the relevance of knowledge about the influence of anthocyanins-rich food consumption on microbiota, and their health-promoting potential in the pathophysiology of obesity. © 2017 BioFactors, 2017.
Review Article
Contribution of anthocyanin-rich foods in
obesity control through gut microbiota
Giovana Jamar
ebora Estadella
Luciana Pellegrini Pisani*
Department of Biosciences, Federal University of S~
ao Paulo – UNIFESP,
Santos, S~
ao Paulo, Brazil
Obesity is characterized by low-grade inflammation and a
number of metabolic disorders. Distal gut microbes’ content
(microbiota) is not yet fully understood but evidence shows
that it is influenced by internal and external factors that modu-
late its composition and function. The evidence that gut micro-
biota composition can differ between healthy and obese
individuals, as well as for those who maintain specific dietary
habits, has led to the study of this environmental factor as a
key link between the pathophysiology of obesity and gut
microbiota. Data obtained about the role of anthocyanins
(ACNs) in microbiota may lead to different strategies to
manipulate bacterial populations and promote health. Antho-
cyanins have been identified as modulators of gut microbiota
that contribute to obesity control and these bioactive com-
pounds should be considered to have a prebiotic action. This
review addresses the relevance of knowledge about the influ-
ence of anthocyanins-rich food consumption on microbiota,
and their health-promoting potential in the pathophysiology of
C2017 BioFactors, 00(00):000–000, 2017
Keywords: obesity; microbiota; anthocyanins; nutrition; diet
1. Introduction
Obesity is recognized as an inflammatory disease, and hyper-
trophy of the adipose tissue leads to metabolic and hemody-
namic dysfunction through the production of adipokines [1].
Changes in lifestyle and diet in the post-industrialized/wester-
nized era have been argued to contribute to the increasing
global incidence of obesity by altering the genetic composition
and metabolic activity of intestinal bacteria, thereby leading to
significant consequences in local and systemic health [2]. In
this context, there is increasing interest in understanding the
role of gut microbiota as an intermediary factor between
environmental and food behavior and its impact on the central
nervous system [3]. Microorganisms in the large intestine play
an important physiological role in vital processes such as
digestion, vitamin synthesis, and metabolism [4]. The complex
interaction between diet and gut microbiota may contribute to
an individual’s overall health and the incidence of chronic dis-
orders such as obesity [5]. Dietary composition, for example,
fatty acids, consumption of artificial sweeteners, and dietary
emulsifiers alters microbiota composition and can contribute
to inflammatory processes, weight gain, adiposity, and meta-
bolic disorders [6].
On the other hand, fruit and vegetable-based diets with anti-
oxidant, anti-inflammatory, anticarcinogenic, anti-adipogenic,
and antidiabetic activity, particularly anthocyanin (ACNs)-rich
diets, have been recommended to reduce the potential develop-
ment of chronic diseases. ACNs are flavonoids in fruits and vege-
tables that render them vivid red to blue in color and they are
abundant in the human diet. With more than 700 ACNs already
identified in nature, they are the primary polyphenols in berries,
such as blackcurrants, black elderberries, blackberries, bilber-
ries, whortleberries, blueberries, ac¸ai berries, and juc¸ara berries
[7–10]. ACN derivatives have differing aglycone (anthocyanidin,
i.e., cyanidin, delphinidin, malvidin, peonidin, pelargonidin, and
C2017 International Union of Biochemistry and Molecular Biology
Volume 00, Number 00, Month/Month 2017, Pages 00–00
*Address for correspondence: Luciana Pellegrini Pisani, Ph.D., Rua Silva
Jardim, 136, Vila Mathias, Santos, S~
ao Paulo, Brazil, C
odigo Postal: 11015-
020. Tel.: 155 13 38783700; Fax: 155 13 32232592; E-mail: lucianapi-
Received 23 December 2016; accepted 12 April 2017
DOI 10.1002/biof.1365
Published online 00 Month 2017 in Wiley Online Library
BioFactors 1
petunidin) and glycone moieties (attaches to sugar residues, such
as glucose, xylose, galactose, arabinose, and rhamnose) [11].
There are also differences in the position and number of hydroxyl
groups, degree of methylation, and type and number of aliphatic
or aromatic acids (p-coumaric, caffeic, and ferulic acid) [12], with
cyanidin-3-glucoside (Cy-3-glu) being the most abundant ACN in
plants [11].
Because of their healthy biological effects, it has been
demonstrated that ACNs and their metabolites have preventive
properties against body fat accumulation [13] and are potent
modulators of inflammatory processes that seem to attenuate
the lipopolysaccharides (LPS)-induced nuclear factor-kappa B
(NF-jB) translocation to the nucleus cellular and mediate
inflammatory responses [14–16]. ACNs are associated with
beneficial changes in the gut microbiota as they might promote
intestinal colonization by specific groups of bacteria, particu-
larly Bifidobacterium spp., Lactobacillus spp., and Akkerman-
sia muciniphila [10,17–20]. These bacteria contribute to the
overall health of an individual as they participate in the activa-
tion and absorption of provitamins and phenolic compounds,
enhance gut barrier function, increase mucus secretion, and
modulate lipid metabolism and intestinal immune response
through cytokine stimulus [21,22]. These evidences confer a
prebiotic action to ACNs [10,23].
This review summarizes the current knowledge concerning
health benefits and obesity control characteristics associated
with the consumption of ACNs and microbiota interactions.
2. Anthocyanins and Gut Microbiota
Different polyphenols have been suggested to affect the viabil-
ity of colonic bacterial groups, implying that dietary modula-
tion with polyphenols may play a role in reshaping the gut
microbial community and enhance host/microbe interaction to
provide beneficial effects such as weight loss [10]. There is
broad agreement that dietary polyphenols, in particular ACNs,
have the ability to modulate colonic bacteria growth [24],
which may play a role in the control of several parameters
involved in the development of metabolic diseases associated
with obesity [25].
Several studies have shown evidence of a wide range of
health-promoting characteristics of ACN-rich foods, including
protection against weight gain and metabolic disorders
observed with a high-fat diet [15,23,26,27]; reduction in the
risk of several chronic diseases, such as type 2 diabetes and
cardiovascular diseases [15]; improvement in lipid profiles,
inflammatory markers, and immunoregulatory cytokines; and
reduction in the membrane component of gram-negative bac-
teria, such as lipopolysaccharides (LPS) which induce NF-jB
transactivation in humans and animals [28–32].
To achieve these health benefits, ACN–gut microbiota
interactions should be considered to understand their biologi-
cal functions. The dichotomy between the biotransformation of
ACNs into a potentially more bioactive, low molecular weight
metabolite [33], and modulation of the gut microbiota compo-
sition by ACNs contributes to positive health outcomes [34].
ACNs have a low bioavailability, and it is estimated that
only 5%–10% of the total polyphenol intake is absorbed in the
small intestine [22]. The food matrix can also influence pheno-
lic compound bioavailability during digestion [35]. Moreover,
most dietary ACNs arrive intact at the colon and may interact
with the microbiota to be biotransformed and metabolized
before being absorbed across the intestinal mucosa [10]. This
interaction can involve hydrolysis, demethylation, reduction,
decarboxylation, dehydroxylation, or isomerization of these
compounds into simpler components that modulate absorption
and biological activity [33]. The first step in ACN bacterial
hydrolysis involves cleavage of the sugar moiety leading to the
formation of ACN aglycon, and the second phase includes
degradation into simple phenolic acids by the activities of two
bacterial enzymes, in particular a-L-rhamnosidase and b-D-
glucosidase, in the small intestine [36,37].
The degradation of phenolic acids by enteric bacterial or
chemical conversions may produce other metabolites, includ-
ing protocatechuic acid, syringic acid, vanillic acid, phloroglu-
cinol aldehyde, phloroglucinol acid, and gallic acid [31,37].
These acidic metabolites are probably absorbed through
monocarboxylic acids transported by epithelial cells [10]. The
low level of oxygen in the small and particularly, the large
intestine should also be considered because low oxygen may
protect the ACN structure. The concentration of bacteria in the
small intestine can be expected to increase distally, thus
increasing the susceptibility of microbial-mediated catabolism
of ACNs [38].
It is considered that gut microbiota can increase the bioa-
vailability of the phenolic content of food and quadruple its
antioxidant activity [22,39]. ACNs and metabolites concur-
rently formed in the intestine have the ability to promote and
inhibit the growth of bacterial groups [18]. ACNs can exert an
antimicrobial activity with inhibitory effects on the growth of a
wide range of human pathogenic bacteria, both gram-negative
(Citrobacter freundii,Escherichia coli,Pseudomonas aerugi-
nosa, and Salmonella enterica ser. typhimurium) and gram-
positive (Listeria monocytogenes,Staphylococcus aureus,
Bacillus subtilis, and Enterococcus faecalis). Mechanisms
underlying ACN activity include both membrane and intracel-
lular interactions of these compounds [40], such as inducing
the release of LPS molecules from the outer membrane of
gram-negative bacteria [10].
ACNs are generally active by different microbes; however,
gram-positive bacteria are usually more susceptible to the
action of ACNs than gram-negative bacteria [41]. Nonetheless,
only a few bacterial genera (e.g., Bifidobacterium,Lactobacil-
lus,Akkermansia,Bacteroides, and Eubacterium), which cata-
lyze the metabolism of phenolics, have been described as con-
tributing to the health benefits of the host [20,41].
An increase in Bifidobacterium is favored in the presence
of carbohydrates, non-digestible carbohydrates, and ACNs
2Anthocyanin-Rich Foods in Obesity Control
[42], and it is recognized as one of the most important bacte-
rial groups associated with human health [19]. Among its ben-
efits, studies have reported anti-obesity effects [43] and choles-
terol regulation [44]. An increase in the expression of zonula
occludens-1 (ZO-1) has also been reported [45]; ZO-1 is a
peripheral membrane protein involved in the regulation of
paracellular permeability that is associated with a complex of
proteins localized at the apical side of epithelial cell mem-
branes–claudin and occludin–that form a tight junction barrier
in the lumen against microorganisms and food antigens [46].
Studies have already shown a role of ACNs in the bifido-
genic effect by a reduction in inflammatory markers and bene-
ficial changes in gut microbiota by competition for a growth
substrate in vitro [47], in humans [48], and in animals [49].
Previous data by our research group using a metabolic
programming model revealed that supplementing the diet of
pregnant rats with juc¸ara berries (262.4 mg ACN/100 g fresh
matter) reduced metabolic and inflammatory markers and
increased Lactobacillus and Bifidobacterium spp. expression of
genomic DNA and ZO-1 gene in their offspring, demonstrating
that phenolic compounds present in this fruit contribute to the
control of inflammation and prevention of the development of
chronic diseases through the intestinal pathway up until adult-
hood [50,51].
Recently, Guergoletto et al. [52] reported the potential pre-
biotic effect of juc¸ara berries by modulating the colonic micro-
biome in vitro. They found that it promoted bifidogenic effects,
including the antimicrobial effect on pathogenic microorgan-
isms by increasing the production of short-chain fatty acids
(SCFAs), acetate, and propionate.
The dietary administration of dealcoholized red wine
extract for 16 weeks to rats changed their intestinal micro-
biota populations from a predominance of Bacteroides,Clos-
tridium, and Propionibacterium spp. to a predominance of Lac-
tobacillus,Bifidobacterium spp., and Bacteroides, showing that
the role of ACNs in intestinal modulation favors an increase in
beneficial bacteria [42].
Supplementing diet-induced obese mice with cranberry
and grape extracts resulted in lower intestinal and systemic
inflammation, improved metabolic features, and increased the
abundance of A.muciniphila in their gut microbiota with a
prebiotic effect [20,53]. A.muciniphila inhabits the mucus
layer and is one of the most abundant members of the human
gut microbiota, comprising between 1% and 5% of our intesti-
nal microbes [20]. It is associated with increased mucus layer
thickness, improved glucose homeostasis, alleviated metabolic
endotoxemia, and improved cardiometabolic parameters in
obese individuals undergoing caloric restriction [20,54]. Cur-
rently, A.muciniphila has been considered as a therapeutic
option to target human obesity and associated disorders [54].
Recently, several studies have considered ACN benefits
after degradation by colonic microbiota. These metabolites
may contribute to the bioavailability of ACNs [37] and may be
responsible for antioxidant [55] and protective effects as nitric
oxide production increases [56]; they inhibit angiotensin-
converting enzymes to improve blood pressure [47]; minimize
weight gain and improve glucose metabolism [31]; improve the
plasma lipid profile and inflammation [57]; positively modulate
the intestinal bacterial population by enhancing the growth of
Bifidobacterium spp., Lactobacillus spp., and Enterococcus
spp.; and reduce Clostridium histolyticum, a potentially harm-
ful bacterium [47].
Therefore, there is a broad consensus that ACNs have pre-
biotic effects similar to the modulation of gut microbiota com-
position [18,24]. This benefits bacteria that are linked to
reducing LPS levels [57] and selective antimicrobial activities
against pathogenic gut bacteria [22] (Fig. 1), contributing to
chronic disease control even though the mechanisms have not
yet been elucidated [57].
3. Anthocyanins in Obesity and
Interplay with Gut Microbiota
The Western diet has altered the genetic composition and met-
abolic activity of our resident microorganisms (the human gut
microbiome). Such diet-induced changes in gut-associated
microbial communities are now suspected of contributing to
growing epidemics of chronic disease, including obesity, in the
developed world [58].
Normal weight and obese individuals have a different
microbiota composition. Emerging data have suggested that
obese individuals have a higher ratio Firmicutes/Bacteroidetes
than normal weight controls. Moreover, when they lose
weight, Firmicutes abundance decreases and becomes more
similar to that in lean subjects [59], reinforcing the hypothesis
that specific bacteria genera and species participate in the
regulation of energy homeostasis, modulation of energy bal-
ance, expansion of the adipose tissue, and glucose metabolism,
leading to a chronic inflammatory state [60–64] (Fig. 2).
Although different therapies have been suggested to
attenuate obesity including appetite or food control, chemically
manufactured medicines, different herbal drugs, and physical
exercise, obesity management remains a critical issue because
of its drastic outcomes. ACNs are valuable compounds that
play an important role in maintaining human health as they
can be used prophylactically and therapeutically owing to sev-
eral properties [11,13,65]. Besides that, ACNs can normalize
the ratio between beneficial and pathogenic bacteria and
plasma endotoxemia and reduce the impact of a high-fat diet
on the host’s metabolism [66]. Early reports suggested that
antioxidant properties alone are responsible for ACNs health-
promoting effects; however, it is now appreciated that ACNs
act beyond their antioxidant properties and likely influence an
array of cell signaling, anti-inflammatory, and gene expression
pathways [39].
ACNs have been shown to exert different degrees of anti-
oxidant and anti-inflammatory activities, depending on their
chemical structure [12]; therefore, the effects of diverse ACN-
rich berries have been tested. Recently, a study on three
Jamar et al. 3
prospective human cohorts demonstrated that a higher intake
of flavonoid-rich foods, mainly ACNs, may contribute to weight
maintenance in adulthood and may help in refining dietary
recommendations for the prevention of obesity and its poten-
tial consequences [67].
Basu et al. [68] found that ingestion of 742 mg of blue-
berry ACNs for 8 weeks significantly improved blood pressure
and oxidized low-density lipoprotein (LDL)-cholesterol levels,
whereas blood glucose levels, body weight, and waist circum-
ference were not improved in obese individuals. Similarly,
other researchers have not shown alterations in body weight
gain and white adipose tissue weight in mice fed a high-fat
diet after the ingestion of blueberry juice (1887 mg/mL ACN) in
place of drinking water over a period of 72 days [65]. How-
ever, consumption of high doses (200 mg/kg) of blueberry
ACNs by high-fat diet induced obese male mice over 8 weeks
reduced their body weight by 19.4%; decreased serum glucose
levels; attenuated epididymal tissue; improved lipid profiles;
and significantly down-regulated tumor necrosis factor alfa
(TNFa), interleukin 6, peroxisome proliferator-activated recep-
tors (PPARc), and fatty acid synthesis (FAS) gene expression
levels [69].
These studies highlight the potential of ACNs in weight
control and/or metabolic disorders related to overweight. How-
ever, the results depend of the dose and species of fruit or
compound administered. Nonetheless, how microbial pathways
influence weight gain and how ACNs affect obesity remains
uncertain. Next, we summarize the mechanisms involved in
the relationship between gut microbiota and obesity and ACNs
role in these processes.
The potential prebiotic effect of anthocyanins on gut microbiota and obesity. SCFA: short-chain fatty acids; FIAF: fasting-
induced adipose factor; LPS: lipopolysaccharide; ZO-1: zonula occludens-1; IR: insulin resistance. Anthocyanins and metabolites
formed in the intestine change the composition of the gut microbiota. This is associated with restored tight-junction protein
(ZO-1 and Occludin) distribution and localization. Hence, the gut permeability is decreased and plasma lipopolysaccharide
(LPS) levels (metabolic endotoxemia) are lowered, improving low-grade inflammation and obesity-related comorbidities. Antho-
cyanins decrease the activity of transcription factor NF-jB in the cell nucleus by decreasing gene expression of inflammatory
cytokines; exerting its anti-inflammatory action. Anthocyanins have the ability to promote the growth of Bifidobacterium spp.,
which increases the intestinal production of FIAF that inhibits fat storage in the host. Bifidobacterium spp. degrades SCFA; pro-
pionate stimulates mucus secretion and contributes to thickening of the mucus layer. While reduced mucus layer thickness
favors microbiota encroachment.
4Anthocyanin-Rich Foods in Obesity Control
3.1. Lipogenesis
The mechanisms of the apparent weight gain implied an
increase in the intestinal glucose absorption, energy extraction
from non-digestible food component, and concomitant higher
glycemia and insulinemia, two key metabolic factors regulating
lipogenesis [70]. Moreover, glucose and insulin are also known
to promote hepatic de novo lipogenesis by the expression of sev-
eral key enzymes, such as acetyl-CoA carboxylase (ACC) and
fatty acid synthase (FAS), which are controlled by carbohydrate-
responsive element-binding protein (ChREBP) and sterol-
responsive element-binding protein (SREBP-1) [71]. Germ-free
mice exhibited decreased hepatic ChREBP and SREBP-1 mRNA
levels by modulation of lipogenesis by energy extraction from
SCFAs [72]. These data provide evidence that the digestion of
polysaccharides by microbial enzymes and increase in saccha-
ride delivery to the liver participate in higher lipogenesis.
ACNs can reduce the expression of PPARc, FAS, and
ChREBP [69,73], and differentiation of preadipocytes from the
Dietary contribution in changes in gut microbiota, fat storage, and development of metabolic disorders via LPS-induced. SCFA:
short-chain fatty acids; ACC: acetyl-CoA carboxylase; FAS: fatty acid synthase (FAS); ChREBP: Carbohydrate responsive
element-binding protein; SREBP-1: Sterol responsive element-binding protein; FIAF: fasting-induced adipose factor; LPL: lipo-
protein lipase; LPS: lipopolysaccharide; TLR-4: toll like receptor 4; GLP-1: glucagon-like peptide-1; PYY: peptide YY. Gut micro-
biota might be involved in energy storage. Environmental factor such as gut microbiota may regulate energy storage by
providing lipogenic substrates (SCFA, monosaccharides) to the liver, increasing hepatic lipogenesis and/or by suppressing the
FIAF in the gut, which increase LPL. It contributes to the release of fatty acids and triacylglycerol from circulating lipoproteins
in adipose tissue. Consumption of the Western diet (high in saturated/trans fat and simple sugars and low in fibers) is one of
the leading causes of obesity worldwide. Obesity-linked dysbiosis is associated with disrupted intestinal barrier. Western diet
causes changes in gut microbiota by specifically decreases Bifidobacterium spp. It is associated with a higher gut permeability
leading to higher plasma LPS levels (metabolic endotoxemia) that promotes low-grade inflammation-induced metabolic disor-
ders (insulin resistance, diabetes, obesity, steatosis, adipose tissue macrophages infiltration). Prebiotics increase Bifidobacte-
rium spp., decrease plasma LPS levels and normalized low-grade inflammation (decreased endotoxemia and proinflammatory
cytokines). This modulation is associated with changes in the plasma gut peptides levels (enhanced GLP-1 and PYY, and
reduced ghrelin). These effects are associated with satiety, weight loss, increase in insulin sensitivity, reduction in fat mass,
and low-grade inflammation characterizing obesity.
Jamar et al. 5
subcutaneous and visceral adipose tissue, suggesting inhibitory
effects on adipogenesis in the white adipose tissue. Recently,
You et al. [74] demonstrated that Cy-3-glu may act in brown
adipogenesis increasing the number of mitochondria.
Ac¸ai seed extract reduces lipogenesis and glucose levels
because of reduced expressions of SREBP-1c and the enzyme
HMG-CoA reductase and increased expressions of AMP-
activated protein kinase (AMPK) in mice that were fed a high-
fat diet [8]. AMPK plays an important role in the regulation of
fatty acids and glucose metabolism, favoring weight control as
well as appetite regulation. The activity of this enzyme is ana-
bolic when inhibited, blocking catabolic processes. The diver-
sity of the microorganisms in the gut can suppress fatty acid
oxidation in the muscle via mechanisms involving inhibition of
AMPK and favor adiposity and insulin resistance [71,75].
The activation of AMPK and fasting-induced adipose factor
(FIAF) lead to an inhibition of lipoprotein lipase (LPL), an
enzyme that regulates triacylglycerol metabolism and that can
be modulated by the microbiota [72]. FIAF participation in
lipid metabolism was reinforced when it was shown that
germ-free FIAF
mice were not protected from diet-induced
obesity and they demonstrated increased weight gain, intra-
abdominal adiposity, and higher leptin and insulin levels,
despite similar food intake, comparing with FIAF
mice [75].
This set of experiments demonstrated, for the first time, that
an environmental factor, such as gut microbiota, may regulate
energy storage [71].
A new insight demonstrated that gut microbiota plays an
unexpectedly important role in post-dieting weight regain, and
it could have been avoided or treated by altering microbiome
function or composition. In addition, flavonoid-based “post-
biotic” intervention ameliorates excessive secondary weight
gain. The possible mechanism for this action is that flavonoids
impact energy expenditure by induction of the major thermo-
genic factor uncoupling protein-1 in the brown adipose
tissue [76].
These evidences indicate a beneficial role of dietary ACNs
in preventing weight gain. The underlying mechanisms have
been hypothesized to involve factors including, but not
restricted to, suppression of fat absorption from the gut, adipo-
cyte differentiation, fatty oxidation, and sympathetic activation
of thermogenesis [77].
3.2. Energy Homeostasis Mechanism
The energy balance is regulated via neuronal and hormonal
signals. There is equilibrium between orexigenic and anorexi-
genic neuropeptides in the hypothalamus and brain stem to
regulate food intake, body weight, and energy homeostasis. In
obesity, there is a complex disorder involving an imbalance in
orexigenic and anorexigenic circuits and stimulation of the
intracellular neuropeptide Y (NPY), which further effects food
intake and lipid accumulation [78]. Neurons of the arcuate
nucleus that produce NPY exhibit enhanced expression of
gamma-aminobutyric acid (GABA), a G-protein coupled recep-
tor (GPR) and main inhibitory neurotransmitter in the central
nervous system. Thus, GABA can inhibit a tonic restraint to
elicit a feeding response directly or in conjunction with NPY
and other orexigenic signals [79].
Recently, Badshah et al. [78] demonstrated an efficient
anti-obesity capacity of black soybean ACNs via regulating the
expression of NPY and GABA in the hypothalamus. The exact
mechanism underlying these modifications by this ACNs treat-
ment is unclear. However, GABA may be an intermediate
influence on the microbiota in the gut–brain axis. It is located
throughout the gastrointestinal tract and is found in enteric
nerves as well as in endocrine-like cells, implicating GABA as
both a neurotransmitter and an endocrine mediator influenc-
ing gastrointestinal function. Experimental fecal extraction
studies revealed that GABA was increased following Roux-en-
Y gastric bypass surgery and that it could have been derived
from the microbial processing of putrescine [80,81]. Increased
expression of fecal GABA is consistent with the well-defined
increase of glucagon-like peptide 1 (GLP-1), an anorexigenic
gut hormone. Furthermore, ACNs may induce GLP-1 secretion
and contribute to energy homeostasis [82].
The activation of GLP-1 receptors, mainly GPR43 and 41
(also called free fatty acid receptors 2 and 3, respectively),
induce the secretion of peptide YY (PYY) and leptin, hormones
that influence intestinal function and appetite regulation by
inhibiting orexigenic neurons of the arcuate nucleus [43–45].
PYY favors the reduction of gut motility and increased energy
harvest from the diet, in particular SCFAs, which are sub-
strates for hepatic lipogenesis. Therefore, gut microbiota may
interfere with the central nervous system based on the pres-
ence or absence GPR41, thereby influencing the central regu-
lation of appetite and satiety [45] through the modulation of
PYY and SCFA absorption [43,44].
Access to the central nervous system is tightly controlled
by the blood–brain barrier (BBB); it is likely that a small and
specific set of bacterial metabolites modulate brain morphol-
ogy. The gut microbiota is also crucially involved in modulat-
ing BBB [83] as germ-free mice have a more permeable BBB
than conventional mice [84]. ACN gut microbiota metabolites
can cross BBB and be allocated to various brain regions, sug-
gesting that these compounds may deliver their antioxidants
and centrally signal and modify capabilities [85,86], although
the mechanisms remain unclear. However, it is worth high-
lighting that ACNs have a prebiotic effect that contributes to
the modulation of gut peptides, inducing effects on satiety and
food intake [87].
3.3 Obesity Inflammation Pathway
Obesity is characterized by the massive expansion of adipose tissues
and is associated with inflammatory complications. LPS was identi-
edasatriggerfactorfortheearly development of inflammation
and metabolic diseases. High LPS levels form a complex containing
LPS-binding proteins and the CD14 co-receptor that is recognized
by Toll-like receptor 4, a transmembrane receptors, triggering an
inflammatory response through the complex signaling pathways
6Anthocyanin-Rich Foods in Obesity Control
with NF-jB activation and the subsequent expression of pro-
inflammatory cytokines [60].
The activated NF-jB pathway may also impair insulin sig-
naling, which can lead to insulin resistance. LPS has been
found at a significantly higher level in the serum of obese than
lean individuals, and it is associated with a high-fat diet, par-
ticularly containing saturated fatty acids [6,88,89]. It creates a
metabolic endotoxemia that causes alterations in bacterial
diversity and microbiota balance (dysbiosis), damage to the
mucosal integrity, and dramatically increases intestinal per-
meability, reducing the expression of epithelial tight junction
proteins [60,88,90]. It is even questionable as to whether LPS
induces weight gain or only enhances subclinical inflammation
and contributes to metabolic changes, such as insulin resist-
ance, regardless of adiposity induction [88].
Changes in the number and size of adipocytes affect the
microenvironment of expanded fat tissues and are accompa-
nied by alterations in adipokine secretion, adipocyte death,
local hypoxia, and fatty acid fluxes. Chronic over-nutrition trig-
gers uncontrolled inflammatory responses, leading to systemic
low-grade inflammation and metabolic disorders, such as insu-
lin resistance [91].
ACNs act on the adipose tissue, inducing changes in adipo-
kine expression levels, as adiponectin, which enhances insulin
sensitivity, in rat [92] and human adipocytes [93]. Adiponectin
also lowers muscle triglyceride levels by increasing the influx
and combustion of free fatty acids resulting in decreased
hepatic level of triglycerides [65]. It has recently been reported
that a diet supplemented with wild blueberry powder signifi-
cantly increased blood adiponectin levels and decreased
inflammatory marker levels in the white adipose tissue [94],
including those related to cardiovascular risk (C-reactive pro-
tein (CRP), interleukins, TNFa, and Vascular cell adhesion pro-
tein 1 (VCAM-1)) [95]; decreased NF-jB activity [96] and serum
LPS levels [97]; and ameliorated dyslipidemia [98], showing
the anti-inflammatory effects of the different ACNs present in
the fruit [31].
4. Concluding Remarks and Future
ACNs seem to have an anti-obesity effect with properties that
prevent body fat accumulation, insulin resistance, dyslipide-
mia, and inflammation while contributing to energy homeosta-
sis and satiety. The exact molecular mechanism of their anti-
obesity effects should be clarified; their benefits may be linked
to ACN microbiota modulation.
There is an insufficient understanding about the difference
in ACN metabolism and biotransformation in the gastrointesti-
nal tract of normal weight versus obese individuals as well as
the role of intact versus disrupted gut microbiomes in these
The literature shows that a wide variety of results and
techniques were employed in the studies, such as different
ACN sources and the biotransformation of ACNs in either a
food matrix or isolated. This makes it difficult to understand
the exact mechanism of each individual compound. Neverthe-
less, there is broad agreement that ACNs have health-
promoting effects, have the ability to modulate colonic bacte-
rial growth, improve chronic low-grade inflammation, and
may indeed exert a prebiotic activity. It is crucial to emphasize
the benefits for bioavailability and/or bioactivity from ACN
metabolites that are synthesized by colonic microbiota.
Thus, microbiota modulation through dietary interventions
with ACN-rich foods may offer new directions for the preven-
tion and/or treatment of obesity. Future studies are still
required to understand these mechanisms and to be able to
specifically understand the interaction between the type of
bacteria and different metabolites derived from the degrada-
tion of ACNs.
Conflicts of Interest
There is no conflict interest.
[1] Tchernof, A. and Despr
es, J. P. (2013) Pathophysiology of human
visceral obesity: an update. Physiol. Rev. 93, 359–404. doi: 10.1152/physrev.
[2] Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A.,
et al. (2009) A core gut microbiome in obese and lean twins. Nature 457,
480–484. doi: 10.1038/nature07540.
[3] Moraes, A. C. F., Silva, I. T., Almeida-Pititto, B., and Ferreira, S. R. (2014)
Intestinal microbiota and cardiometabolic risk: mechanisms and diet modula-
tion. Arq. Bras. Endocrinol. Metab. 58, 317–327.
[4] Baothman, O. A., Zamzami, M. A., Taher, I., Abubaker, J., and Abu-Farha, M.
(2016) The role of gut microbiota in the development of obesity and diabetes.
Lipids Health Dis. 15, 108. doi: 10.1186/s12944-016-0278-4.
[5] Sekirov, I., Russell, S. L., Antunes, L. C., and Finlay, B. B. (2010) Gut micro-
biota in health and disease. Physiol. Rev. 90, 859–904. doi: 10.1152/physrev.
[6] Ding, S., Chi, M. M., Scull, B. P., Rigby, R., Schwerbrock, N. M., et al. (2010)
High-fat diet: bacteria interactions promote intestinal inflammation which
precedes and correlates with obesity and insulin resistance in mouse. PLoS
One 5, e12191. doi: 10.1371/journal.pone.0012191.
[7] Zanotti, I., Dall’Asta, M., Mena, P., Mele, L., Bruni, R., et al. (2015) Atheropro-
tective effects of (poly)phenols: A focus on cell cholesterol metabolism. Food
Funct. 6, 13–31.
[8] de Oliveira, P. R., da Costa, C. A., de Bem, G. F., Cordeiro, V. S., Santos, I. B.,
et al. (2015) Euterpe oleracea Mart.-derived polyphenols protect mice from
diet-induced obesity and fatty liver by regulating hepatic lipogenesis and cho-
lesterol excretion. PLoS One 10, e0143721. doi:10.1371/journal.pone.0143721.
[9] Azevedo da Silva, N., Rodrigues, E., Mercadante, A. Z., and de Rosso, V. V.
(2014) Phenolic compounds and carotenoids from four fruits native from the
Brazilian Atlantic forest. J. Agric. Food Chem. 62, 5072–5084.
[10] Faria, A., Fernandes, I., Norberto, S., Mateus, N., and Calhau, C. (2014) Inter-
play between anthocyanins and gut microbiota. J. Agric. Food Chem. 62,
6898–6902. doi: 10.1021/jf501808a.
[11] He, J., and Giusti, M. M. (2010) Anthocyanins: natural colorants with health-
promoting properties. Ann. Rev. Food Sci. Technol. 1, 163–187. doi:
[12] Vendrame, S., Del Bo, C., Ciappellano, S., Riso, P., and Klimis-Zacas, D.
(2016) Berry fruit consumption and metabolic syndrome. Antioxidants
(Basel) 5, pii: E34.
Jamar et al. 7
[13] Tsuda, T. (2016) Recent progress in anti-obesity and anti-diabetes effect of
berries. Antioxidants (Basel), 6, pii: E13. doi: 10.3390/antiox5020013.
[14] Lee, S. G., Kim, B., Yang, Y., Pham, T. X., Park, Y. K., et al. (2014) Berry
anthocyanins suppress the expression and secretion of proinflammatory
mediators in macrophages by inhibiting nuclear translocation of NF-jB
independent of NRF2-mediated mechanism. J. Nutr. Biochem. 25, 404–411.
doi: 10.1016/j.jnutbio.2013.12.001.
[15] Wu, T., Tang, Q., Yu, Z., Gao, Z., Hu, H., et al. (2014) Inhibitory effects of
sweet cherry anthocyanins on the obesity development in C57BL/6 mice.
Int. J. Food Sci. Nutr. 65, 351–359. doi: 10.3109/09637486.2013.854749.
[16] Noratto, G. D., Angel-Morales, G., Talcott, S. T., and Mertens-Talcott, S. U.
(2011) Polyphenolics from ac¸ai(Euterpe oleracea Mart.) and red muscadine
grape (Vitis rotundifolia) protect human umbilical vascular endothelial cells
(HUVEC) from glucose- and lipopolysaccharide (LPS)-induced inflammation
and target microRNA-126. J. Agric. Food Chem. 59, 7999–8012. doi: 10.1021/
[17] Morais, C. A., de Rosso, V. V., Estadella, D., and Pisani, L. P. (2016) Antho-
cyanins as inflammatory modulators and the role of the gut microbiota. J.
Nutr. Biochem. 33, 1–7. doi: 10.1016/j.jnutbio.2015.11.008.
[18] Boto-Ord
nez, M., Urpi-Sarda, M., Queipo-Ortu~
no, M. I., Tulipani, S.,
Tinahones, F. J., and Andres-Lacueva, C. (2014) High levels of Bifidobacteria
are associated with increased levels of anthocyanin microbial metabolites: a
randomized clinical trial. Food Funct. 5, 1932. doi: 10.1039/c4fo00029c.
[19] Hidalgo, M., Oruna-Concha, M. J., Kolida, S., Walton, G. E., Kallithraka, S.,
et al. (2012) Metabolism of anthocyanins by human gut microflora and their
influence on gut bacterial growth. J. Agric. Food Chem. 60, 3882–3890. doi:
[20] Anh^
e, F. F., Roy, D., Pilon, G., Dudonn
e, S., Matamoros, S., et al. (2015) A
polyphenol-rich cranberry extract protects from diet-induced obesity, insulin
resistance and intestinal inflammation in association with increased Akker-
mansia spp. population in the gut microbiota of mice. Gut 64, 872–883. doi:
[21] Gibson, G. R. (2008) Prebiotics as gut microflora management tools. J. Clin.
Gastroenterol. 42, S75–S79. doi: 10.1097/MCG.0b013e31815ed097.
[22] Cardona, F., Andr
es-Lacueva, C., Tulipani, S., Tinahones, F. J., and Queipo-
no, M. I. (2013) Benefits of polyphenols on gut microbiota and implica-
tions in human health. J. Nutr. Biochem. 24, 1415–1422. doi: 10.1016/j.
[23] Tsuda, T. (2012) Dietary anthocyanin-rich plants: biochemical basis and
recent progress in health benefits studies. Mol. Nutr. Food Res. 56,
1592170. doi: 10.1002/mnfr.201100526.
[24] Parkar, S. G., Trower, T. M., and Stevenson, D. E. (2013) Fecal microbial
metabolism of polyphenols and its effects on human gut microbiota. Anae-
robe 23, 12219. doi: 10.1016/j.anaerobe.2013.07.009.
[25] Cani, P. D., and Delzenne, N. M. (2009) Interplay between obesity and asso-
ciated metabolic disorders: new insights into the gut microbiota. Curr. Opin.
Pharmacol. 9, 737–743. doi: 10.1016/j.coph.2009.06.016.
[26] Kwon, S. H., Ahn, I. S., Kim, S. O., Kong, C. S., Chung, H. Y., et al. (2007)
Anti-obesity and hypolipidemic effects of black soybean anthocyanins. J.
Med. Food 10, 5522556.
[27] Benn, T., Kim , B., Park, Y. K., Wegner, C. J., Harness, E., et al. (2014)
Polyphenol-rich black currant extract prevents inflammation in diet-
induced obese mice. J. Nutr. Biochem. 25, 1019–1025. doi: 10.1016/j.
jnutbio.20 14.05.008.
[28] van Dam, R. M., Naidoo, N., and Landberg, R. (2013) Dietary flavonoids
and the development of type 2 diabetes and cardiovascular diseases:
review of recent findings. Curr. Opin. Lipidol. 24, 25–33. doi: 10.1097/MOL.
[29] Giordano, L., Coletta, W., Tamburrelli, C., D’Imperio, M., Crescente, M.,
et al. (2012) Four-week ingestion of blood orange juice results in measura-
ble anthocyanin urinary levels but does not affect cellular markers related
to cardiovascular risk: a randomized cross-over study in healthy volunteers.
Eur. J. Nutr. 51, 541–548. doi: 10.1007/s00394-011-0237-9.
[30] Wright, O. R., Netzel, G. A., and Sakzewski, A. R. (2013) A randomized,
double-blind, placebo-controlled trial of the effect of dried purple carrot on
body mass, lipids, blood pressure, body composition, and inflammatory
markers in overweight and obese adults: the QUENCH trial. Can. J. Physiol.
Pharmacol. 91, 480–488. doi: 10.1139/cjpp-2012-0349.
[31] Esposito, D., Damsud, T., Wilson, M., Grace, M. H., Strauch, R., et al. (2015)
Black currant anthocyanins attenuate weight gain and improve glucose
metabolism in diet-induced obese mice with intact, but not disrupted, gut
microbiome. J. Agric. Food Chem. 63, 6172–6180. doi:10.1021/acs.jafc.
[32] Karlsen, A., Retterstol, L., Laake, P., Paur, I., Bohn, S. K., et al. (2007) Antho-
cyanins inhibit nuclear factor-jB activation in monocytes and reduce plasma
concentrations of proinflammatory mediators in healthy adults. J. Nutr. 137,
[33] Selma, M. V., Esp
ın, J. C., and Tom
an, F. A. (2009) Interaction
between phenolics and gut microbiota: role in human health. J. Agric. Food
Chem. 57, 6485–6501. doi: 10.1021/jf902107d.
[34] Queipo-Ortu~
no, M. I., Boto-Ord
nez, M., Murri, M., Gomez-Zumaquero, J.
M., Clemente-Postigo, M., et al. (2012) Influence of red wine polyphenols
and ethanol on the gut microbiota ecology and biochemical biomarkers.
Am. J. Clin. Nutr. 95, 1323–1334. doi: 10.3945/ajcn.111.027847.
[35] Sengul, H., Surek, E., and Nilufer-Erdil, D. (2014) Investigating the effects of
food matrix and food components on bioaccessibility of pomegranate (Punica
granatum) phenolics and anthocyanins using an in-vitro gastrointestinal diges-
tion model. Food Res. Int. 62, 1069–1079. doi:10.1016/j.foodres.2014.05.055.
[36] Fleschhut, J., Kratzer, F., Rechkemmer, G., and Kulling, S. E. (2006) Stability
and biotransformation of various dietary anthocyanins in vitro. Eur. J. Nutr.
45, 7–18.
[37] Pojer, E., Mattivi, F., Johnson, D., and Stockley, C. S. (2013) The case for
anthocyanin consumption to promote human health: A review. Compr. Rev.
Food Sci. Food Saf. 12, 483–508.
[38] Lila, M. A., Burton-Freeman, B., Grace, M., and Kalt, W. (2016) Unraveling
anthocyanin bioavailability for human health. Ann. Rev. Food Sci. Technol.
7, 375–393. doi: 10.1146/annurev-food-041715-033346.
[39] Meydani, M., and Hasan, S. T. (2010) Dietary polyphenols and obesity.
Nutrients, 2, 737–751. doi:10.3390/nu2070737.
[40] Cisowska, A., Wojnicz, D., and Hendrich, A. B. (2011) Anthocyanins as anti-
microbial agents of natural plant origin. Nat. Prod. Commun. 6, 149–156.
[41] Kutschera, M., Engst, W., Blaut, M., and Braune, A. (2011) Isolation of
catechin-converting human intestinal bacteria. J. Appl. Microbiol. 111, 165–
175. doi: 10.1111/j.1365-2672.2011.05025.x.
[42] Dolara, P., Luceri, C., De Filippo, C., Femia, A. P., Giovannelli, L., et al.
(2005) Red wine polyphenols influence carcinogenesis, intestinal microflora,
oxidative damage and gene expression profiles of colonic mucosa in F344
rats. Mutat. Res. 591, 237–246.
[43] An, H. M., Park, S. Y., Lee, D. K., Kim, J. R., Cha, M. K., et al. (2011) Antiobe-
sity and lipid-lowering effects of Bifidobacterium spp. in high fat
diet-induced obese rats. Lipids Health Dis. 10, 116. doi: 10.1186/1476-511X-
[44] Pereira, D. I., and Gibson, G. R. (2002) Cholesterol assimilation by lactic acid
bacteria and bifidobacteria isolated from the human gut. Appl. Environ.
Microbiol. 68, 4689–4693.
[45] Caricilli, A. M., Picardi, P. K., de Abreu, L. L., Ueno, M., Prada, P. O., et al.
(2011) Gut microbiota is a key modulator of insulin resistance in TLR 2
knockout mice. PLoS Biol. 9, e1001212. doi: 10.1371/journal.pbio.1001212.
[46] M
enard, S., Cerf-Bensussan, N., and Heyman, M. (2010) Multiple facets of
intestinal permeability and epithelial handling of dietary antigens. Mucosal
Immunol. 3, 247–259.
[47] Hidalgo, M., Martin-Santamaria, S., Recio, I., Sanchez-Moreno, C., de
Pascual-Teresa, B., et al. (2012) Potential anti-inflammatory, anti-adhesive,
anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of
anthocyanins and their gut metabolites. Genes Nutr. 7, 295–306. doi:
[48] Guglielmetti, S., Fracassetti, D., Taverniti, V., Del Bo, C., Vendrame, S., et al.
(2013) Differential modulation of human intestinal bifidobacterium popula-
tions after consumption of a wild blueberry (Vaccinium angustifolium) drink.
J. Agric. Food Chem. 61, 8134–8140. doi: 10.1021/jf402495k.
8Anthocyanin-Rich Foods in Obesity Control
[49] Espley, R. V., Butts, C. A., Laing, W. A., Martell, S., Smith, H., et al. (2014)
Dietary flavonoids from modified apple reduce inflammation markers and
modulate gut microbiota in mice. J. Nutr. 144, 146–154. doi: 10.3945/jn.113.
[50] Almeida Morais, C., Oya ma, L. M., de Oliveira, J. L., Carvalho Garcia, M.,
deRosso,V.V.,etal.(2014)Jussara(Euterpe edulis Mart.) supplementa-
tion during pregnancy and lactation modulates the gene and protein
expression of inflammation biomarkers induced by trans-fatty acids in the
colon of offspring. Mediators Inflamm. 2014, 987927. doi: 10.115 5/2014/
[51] Morais, C. A., Oyama, L. M., Conrado, R. M., de Rosso, V. V., Nascimento,
C. O., et al. (2015) Polyphenols-rich fruit in maternal diet modulates inflam-
matory markers and the gut microbiota and improves colonic expression of
ZO-1 in offspring. Food Res. Int. 77, 186–193.
[52] Guergoletto, K. B., Costabile, A., Flores, G., Garcia, S., and Gibson, G. R.
(2016) In vitro fermentation of juc¸ara pulp (Euterpe edulis) by human colonic
microbiota. Food Chem. 196, 251–258. doi: 10.1016/j.foodchem.2015.09.048.
[53] Roopchand, D. E., Carmody, R. N., Kuhn, P., Moskal, K., Rojas-Silva, P.,
et al. (2015) Dietary polyphenols promote growth of the gut bacterium
Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syn-
drome. Diabetes 64, 2847–2858. doi: 10.2337/db14-1916.
[54] Plovier, H., Everard, A., Druart, C., Depommier, C., Van Hul, M., et al. (2016)
A purified membrane protein from Akkermansia muciniphila or the pasteur-
ized bacterium improves metabolism in obese and diabetic mice. Nat. Med.,
(in press).
[55] Tsuda, T., Kato, Y., and Osawa, T. (2000) Mechanism for the peroxynitrite
scavenging activity by anthocyanins. FEBS Lett. 484, 207–210.
[56] Simoncini, T., Lenzi, E., Z
ochling, A., Gopal, S., Goglia, L., et al. (2011) Estro-
gen-like effects of wine extracts on nitric oxide synthesis in human endothe-
lial cells. Maturitas 70, 169–175. doi: 10.1016/j.maturitas.2011.07.004.
[57] Clemente-Postigo, M., Queipo-Ortu~
no, M. I., Boto-Ordo~
nez, M., Coin-
uez, L., Roca-Rodriguez, M. M., et al. (2013) Effect of acute and chronic
red wine consumption on lipopolysaccharide concentrations. Am. J. Clin.
Nutr. 97, 1053–1061. doi: 10.3945/ajcn.112.051128.
[58] David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E.,
et al. (2014) Diet rapidly and reproducibly alters the human gut microbiome.
Nature 23, 559–563.
[59] Ley, R. E., Turnbaugh, P. J., Klein, S., and Gordon, J. I. (2006) Microbial
ecology: human gut microbes associated with obesity. Nature 444, 1022–
[60] Ley, R. E., B
ackhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., and
Gordon, J. I. (2005) Obesity alters gut microbial ecology. Proc. Natl. Acad.
Sci. USA 102, 11070–11075.
[61] Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R.,
and Gordon, J. I. (2006) An obesity-associated gut microbiome with
increased capacity for energy harvest. Nature 444, 1027–1031.
[62] Cani, P. D. (2013) Gut microbiota and obesity: lessons from the microbiome.
Brief Funct. Genomics 12, 381–387. doi: 10.1093/bfgp/elt014.
[63] Turnbaugh, P. J., B
ackhed, F., Fulton, L., and Gordon, J. I. (2008) Diet-
induced obesity is linked to marked but reversible alterations in the mouse
distal gut microbiome. Cell Host Microbe 3, 213–223. doi: 10.1016/
[64] Million, M., Angelakis, E., Paul, M., Armougom, F., Leibovici, L., and Raoult,
D. (2012) Comparative meta-analysis of the effect of Lactobacillus species
on weight gain in humans and animals. Microb. Pathog. 53, 100–108. doi:
[65] Prior, R. L., Wilkes, S. E., Rogers, T. R., Khanal, R. C., Wu, X., and Howard,
L. R. (2010) Purified blueberry anthocyanins and blueberry juice alter devel-
opment of obesity in mice fed an obesogenic high-fat diet. J. Agric. Food
Chem. 58, 3970–3976. doi: 10.1021/jf902852d.
[66] Delzenne, N. M., and Cani, P. D. (2011) Interaction between obesity and the
gut microbiota: relevance in nutrition. Ann. Rev. Nutr. 31, 15–31. doi:
[67] Bertoia, M. L., Rimm, E. B., Mukamal, K. J., Hu, F. B., Willett, W. C., and
Cassidy, A. (2016) Dietary flavonoid intake and weight maintenance: three
prospective cohorts of 124,086 US men and women followed for up to 24
years. Bmj 28, 352:i17. doi:10.1136/bmj.i17.
[68] Basu, A., Du, M., Leyva, M. J., Sanchez, K., Betts, N. M., et al. (2010) Blue-
berries decrease cardiovascular risk factors in obese men and women with
metabolic syndrome. J. Nutr. 140, 1582–1587. doi: 10.3945/jn.110.124701.
[69] Wu, T., Jiang, Z., Yin, J., Long, H., and Zheng, X. (2016) Anti-obesity effects
of artificial planting blueberry (Vaccinium ashei) anthocyanin in high-fat
diet-treated mice. Int. J. Food Sci. Nutr. 67, 257–264. doi: 10.3109/09637486.
[70] Denechaud, P. D., Dentin, R., Girard, J., and Postic, C. (2008) Role of
ChREBP in hepatic steatosis and insulin resistance. FEBS Lett. 582, 68–73.
[71] Cani, P. D., and Delzenne, N. M. (2009) The role of the gut microbiota in
energy metabolism and metabolic disease. Curr. Pharm. Des. 15, 1546–1558.
[72] Backhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., et al. (2004) The
gut microbiota as an environmental factor that regulates fat storage. Proc.
Natl. Acad. Sci. USA 101, 15718–15723.
[73] Pompei, A., Toniato, E., Innocenti, P. D., Alimonte, I., Cellini, C., et al. (2012)
Cyanidin reduces preadipocyte differentiation and relative ChREBP expres-
sion. J. Biol. Regul. Homeost. Agents 26, 253–264.
[74] You, Y., Yuan, X., Lee, H. J., Huang, W., Jin, W., and Zhan, J. (2015) Mul-
berry and mulberry wine extract increase the number of mitochondria dur-
ing brown adipogenesis. Food Funct. 2, 401–408.
[75] B
ackhed, F., Manchester, J. K., Semenkovich, C. F., and Gordon, J. I. (2007)
Mechanisms underlying the resistance to diet-induced obesity in germ-free
mice. Proc. Natl. Acad. Sci. USA 104, 979–984.
[76] Thaiss, C. A., Itav, S., Rothschild, D., Meijer, M., Levy, M., et al. (2016) Per-
sistent microbiome alterations modulate the rate of post-dieting weight
regain. Nature, (in press). doi: 10.1038/nature20796.
[77] Panikar, K. S. (2013) Effects of dietary polyphenols on neuroregulatory fac-
tors and pathways that mediate food intake and energy regulation in obe-
sity. Mol. Nutr. Food Res. 1, 34–47. doi: 10.1002/mnfr.201200431.
[78] Badshah, H., Ullah, I., Kim, S. E., Kim, T. H., Lee, H. Y., and Kim, M. O.
(2013) Anthocyanins attenuate body weight gain via modulating neuropep-
tide Y and GABAB1 receptor in rats hypothalamus. Neuropeptides 47, 347–
353. doi: 10.1016/j.npep.2013.06.001.
[79] Wang, H. X., and Wang, Y. P. (2016) Gut microbiota-brain axis. Chin. Med.
J. (Engl.) 129, 2373–2380. doi: 10.4103/0366-6999.190667.
[80] Li, J. V., Ashrafian, H., Bueter, M., Kinross, J., Sands, C., et al. (2011) Meta-
bolic surgery profoundly influences gut microbial-host metabolic cross-talk.
Gut 60, 1214–1223. doi: 10.1136/gut.2010.234708.
[81] Kurihara, S., Kato, K., Asada, K., Kumagai, H., and Suzuki, H. (2010) A
putrescine-inducible pathway comprising PuuE-YneI in which gamma-
aminobutyrate is degraded into succinate in Escherichia coli K-12. J. Bacter-
iol. 192, 4582–4591.
[82] Kato, M., Tani, T., Terahara, N., and Tsuda, T. (2015) The anthocyanin del-
phinidin 3-rutinoside Stimulates glucagon-like peptide-1 secretion in murine
GLUTag cell line via the Ca21/calmodulin-dependent kinase II pathway.
PLoS One 11, e0126157. doi: 10.1371/journal.pone.0126157.
[83] Schroeder, B. O., and B
ackhed, F. (2016) Signals from the gut microbiota to
distant organs in physiology and disease. Nat. Med. 22, 1079–1089. doi:
[84] Braniste, V., Al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., et al.
(2014) The gut microbiota influences blood-brain barrier permeability in
mice. Sci. Transl. Med. 6, 263ra158.
[85] Andres-Lacueva, C., Shukitt-Hale, B., Galli, R. L., Jauregui, O., Lamuela-
Raventos, R. M., and Joseph, J. A. (2005) Anthocyanins in aged blueberry-
fed rats are found centrally and may enhance memory. Nutr. Neurosci. 8,
[86] Passamonti, S., Vrhovsek, U., Vanzo, A., and Mattivi, F. (2005) Fast access
of some grape pigments to the brain. J. Agric. Food. Chem. 53, 7029–7034.
[87] Delzenne, N., and Reid, G. (2009) No causal link between obesity and probi-
otics. Nat. Rev. Microbiol. 7, 901. doi: 10.1038/nrmicro2209-c2.
[88] Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., et al. (2007) Meta-
bolic endotoxemia initiates obesity and insulin resistance. Diabetes 56,
Jamar et al. 9
[89] de La Serre, C. B., Ellis, C. L., Lee, J., Hartman, A. L., Rutledge, J. C., and
Raybould, H. E. (2010) Propensity to high-fat diet-induced obesity in rats is
associated with changes in the gut microbiota and gut inflammation. Am. J.
Physiol. Gastrointest. Liver Physiol. 299, G440–G448. doi: 10.1152/ajpgi.
[90] Barczynska, R., Bandurska, K., Slizewska, K., Litwin, M., Szalecki, M., et al.
(2015) Intestinal microbiota, obesity and prebiotics. Pol. J. Microbiol. 64, 93–
[91] Choe, S. S., Huh, J. Y., Hwang, I. J., Kim, J. I., and Kim, J. B. (2016) Adipose
tissue remodeling: its role in energy metabolism and metabolic disorders.
Front Endocrinol. (Lausanne) 7, 1–16. doi: 10.3389/fendo.2016.00030.
[92] Tsuda, T., Ueno, Y., Aoki, H., Koda, T., Horio, F., et al. (2004) Anthocyanin
enhances adipocytokine secretion and adipocyte-specific gene expression in
isolated rat adipocytes. Biochem. Biophys. Res. Commun. 316, 149–157. doi:
[93] Tsuda, T., Ueno, Y., Yoshikawa, T., Kojo, H., and Osawa, T. (2006) Microar-
ray profiling of gene expression in human adipocytes in response to antho-
cyanins. Biochem. Pharmacol. 71, 1184–1197. doi: 10.1016/j.bcp.2005.12.042.
[94] Vendrame, S., Daugherty, A., Kristo, A. S., Riso, P., and Klimis-Zacas, D.
(2013) Wild blueberry (Vaccinium angustifolium) consumption improves
inflammatory status in the obese Zucker rat model of the metabolic syn-
drome. J. Nutr. Biochem. 24, 1508–1512. doi: 10.1016/j.jnutbio.2012.12.010.
[95] Karlsen, A., Paur, I., Bøhn, S. K., Sakhi, A. K., Borge, G. I., et al. (2010) Bil-
berry juice modulates plasma concentration of NF-kB related inflammatory
markers in subjects at increased risk of CVD. Eur. J. Nutr. 49, 345–355.
[96] Seymour, E. M., Lewis, S. K., Urcuyo-Llanes, D. E., Tanone, I. I., Kirakosyan,
A., et al. (2009) Regular tart cherry intake alters abdominal adiposity, adi-
pose gene transcription, and inflammation in obesity-prone rats fed a high
fat diet. J. Med. Food 12, 935–942. doi: 10.1089/jmf.2008.0270.
[97] Kolehmainen, M., Mykk
anen, O., Kirjavainen, P. V., Lepp
anen, T., Moilanen,
E., et al. (2012) Bilberries reduce low-grade inflammation in individuals with
features of metabolic syndrome. Mol. Nutr. Food Res. 56, 1501–1510.
[98] Vendrame, S., Daugherty, A., Kristo, A. S., and Klimis-Zacas, D. (2014) Wild
blueberry (Vaccinium angustifolium)-enriched diet improves dyslipidaemia
and modulates the expression of genes related to lipid metabolism in obese
Zucker rats. Br. J. Nutr. 111, 194–200.
10 Anthocyanin-Rich Foods in Obesity Control
... The metabolism of anthocyanins by intestinal bacteria involves a sequence of chemical cleavages, initially the glycosidic bonds and then the breaking of the anthocyanidin heterocycle and the degradation to phloroglucinol derivatives and benzoic acids [103][104][105][106][107][108]. Absorption of intact anthocyanins is limited [94], and they are degraded by the action of α-rhamnosidase and β-glycosidase, which are needed to catalyze the reaction, releasing sugar moieties from the anthocyanin structure and transforming it into aglycone form (anthocyanidin) [109][110][111][112][113]. Several intestinal bacteria can metabolize anthocyanins, including Bifidobacterium spp. ...
... Other important factors resulting from the metabolism of anthocyanins by the microbiota are related to short-chain fatty-acid production. Acetate, propionate, and butyrate can serve as a substrate for intestinal epithelial-cell growth (favoring nutrient absorption), can decrease the intestinal pH, and also inhibit the growth of pathogenic bacteria [6,7,106]. Furthermore, anthocyanin supplementation can stimulate an increased number of goblet cells and tight junction proteins and improve villi in the intestine [6]. ...
Full-text available
Anthocyanins are an important group of phenolic compounds responsible for pigmentation in several plants. For humans, a regular intake is associated with a reduced risk of several diseases. However, molecular instability reduces the absorption and bioavailability of these compounds. Anthocyanins are degraded by external factors such as the presence of light, oxygen, temperature, and changes in pH ranges. In addition, the digestion process contributes to chemical degradation, mainly through the action of intestinal microbiota. The intestinal microbiota has a fundamental role in the biotransformation and metabolization of several dietary compounds, thus modifying the chemical structure, including anthocyanins. This biotransformation leads to low absorption of intact anthocyanins, and consequently, low bioavailability of these antioxidant compounds. Several studies have been conducted to seek alternatives to improve stability and protect against intestinal microbiota degradation. This comprehensive review aims to discuss the existing knowledge about the structure of anthocyanins while discussing human absorption, distribution, metabolism, and bioavailability after the oral consumption of anthocyanins. This review will highlight the use of nanotechnology systems to overcome anthocyanin biotransformation by the intestinal microbiota, pointing out the safety and effectiveness of nanostructures to maintain molecular stability.
... and Lactobacillus spp., metabolize anthocyanins into small metabolites that may promote the colonization of beneficial bacteria like Lactobacillus spp., Bifidobacterium spp., and Akkermansia muciniphila spp. [45][46][47]. In both humans and rodents, various berries have been studied to determine whether there is an effect on markers of metabolic health and/or the composition of the microbiota. ...
Full-text available
Obesity in America is a public health crisis that will continue to impact the country at an individual, social, and economic level unless we address the disease with dietary modifications to reduce or prevent its development. Nutritional interventions designed for obesity treatment are constantly evolving. Berries, which are a rich source of polyphenols, have been suggested as a potential bioactive component, as they have been reported to have anti-obesity effects. Therefore, this review will provide an overview of epidemiological studies to introduce the idea of berries for health promotion. Studies conducted in both rodents and humans are summarized. This review includes an overview of the physiological responses associated with berry consumption, including the effects on the composition of the gut microbiota in humans and rodents, which demonstrate how berry consumption may provide a protective effect against obesity and its related comorbidities. However, these findings have yet to be translated into feasible, long-term nutrition intervention in humans. Future research into different berries and their components will identify effective, accessible functional food options that can augment nutritional interventions.
... In addition, the ratio of Firmicutes to Bacteroidota is considered to be closely related to obesity. Studies have shown that obese individuals have a higher ratio of Firmicutes/Bacteroidota than normal weight controls [25]. Zhang et al. reported that the relatively high level of Firmicutes and low level of Bacteroidota may lead to an increase in the ability of obese microbiota to obtain energy from the diet [26]. ...
Full-text available
Lyciumruthenicum Murray (L. ruthenicum) has been used both as traditional Chinese medicine and food. Recent studies indicated that anthocyanins are the most abundant bioactive compounds in the L. ruthenicum fruits. The purpose of this study was to investigate the preventive effects and the mechanism of the anthocycanins from the fruit of L. ruthenicum (ACN) in high-fat diet-induced obese mice. In total, 24 male C57BL/6J mice were divided into three groups: control group (fed a normal diet), high-fat diet group (fed a high-fat diet, HFD), and HFD +ACN group (fed a high-fat diet and drinking distilled water that contained 0.8% crude extract of ACN). The results showed that ACN could significantly reduce the body weight, inhibit lipid accumulation in liver and white adipose tissue, and lower the serum total cholesterol and low-density lipoprotein cholesterol levels compared to that of mice fed a high-fat diet. 16S rRNA gene sequencing of bacterial DNA demonstrated that ACN prevent obesity by enhancing the diversity of cecal bacterial communities, lowering the Firmicutes-to-Bacteroidota ratio, increasing the genera Akkermansia, and decreasing the genera Faecalibaculum. We also studied the inhibitory effect of ACN on pancreatic lipase. The results showed that ACN has a high affinity for pancreatic lipase and inhibits the activity of pancreatic lipase, with IC50 values of 1.80 (main compound anthocyanin) and 3.03 mg/mL (crude extract), in a competitive way. Furthermore, fluorescence spectroscopy studies showed that ACN can quench the intrinsic fluorescence of pancreatic lipase via a static mechanism. Taken together, these findings suggest that the anthocyanins from L. ruthenicum fruits could have preventive effects in high-fat-diet induced obese mice by regulating the intestinal microbiota and inhibiting the pancreatic lipase activity.
... For millennia, ancient cultures have harnessed their various pharmacological effects to foster and enhance health. In comparison, our understanding hence the perception of their activities has been very limited until recently ( Jamar et al., 2017 ;Bello et al., 2018 ). Polyphenols were not even treated so long ago as non-core anti-nutrients. ...
Full-text available
Background: As an antioxidant-rich plant foods, cereals can impede lipid and starch breakdown in the human body, are germane to diabetes management. Objective: We aim to identify newer sources of phytochemicals and health-promoting constituents with desirable antidiabetics and antioxidant functional properties. Methods: Three millet types i.e. fonio (Digitaria exilis), finger millet (Eleusine coracana), and pearl millet (Pennisetum glaucum) available locally were investigated for antioxidant ability employing these assays i.e. DPPH, ABTS, H2O2, antidiabetic ability employing these assays i.e. α-amylase, α-glucosidase and inhibitory property on glycosylation formation. Preliminary characterization tools were employed i.e. UV-Visible spectroscopy (UV-visible) and Fourier-Transform Infrared Spectroscopy (FTIR) for the polyphenolic confirmation. The absorbance intensity range 325–425 nm confirmed that polyphenolics are present in the three millet types; most of the biological results showed the activities are dose-dependent. Results: Fonio millet extract revealed the highest activity against haemoglobin glycosylation (29.469 ± 0.399 %) which compared favorably with the standard (acarbose) (29.354 ± 1.607 %). Fonio millet extract also showed the best antioxidant activity (significantly higher % inhibition value = 47.909 ± 3.472) and the pearl millet revealed the least antioxidant activity (significantly lower % inhibition value = 44.910 ± 3.597) both at a concentration of 500 mg/ml, though all the millet extracts showed activity towards this assay better than the standard (19.883 ± 2.485 %). Fonio millet extract displayed a significantly higher percentage inhibition of α-amylase and glucosidase (43.729 ± 0.410 % and 55.835 ± 2.198 %) than finger millet (39.002 ± 1.604 %; 43.971 ± 5.849 %) and pearl millet (33.223 ± 2.708 %; 30.845 ± 2.841 %), respectively. Conclusion: The polyphenolic extracts from these millet types have therapeutic potentials, which may play significant roles in type 2 diabetes prevention and management, and hence these millets, especially fonio and finger millet, have the potential to be utilized as functional foods.
... Berry polyphenols provide a wide range of protections for the human body including antigiardial (Anthony et al., 2011), antioxidant, anticancer, anti-inflammatory, antimicrobial, and antiobesogenic properties (Jamar et al., 2017) through prebiotic mechanisms. For a food ingredient to be considered as having a prebiotic effect, the effect must be demonstrated through an appropriate nutrition intervention trial using validated methods (FoodData Central, 1999). ...
Full-text available
Dark berry fruits are one of the top 10 richest sources of dietary polyphenols and have been examined for their pharmacokinetic benefits in the human body related to absorption, digestion, metabolism, and excretion (ADME). With the expansion of the world wide web and rise of discretionary income in Europe and North America impacting the global food trade during the 21st century, several species of berries have become available for general consumption that may have previously been out of reach of the average consumer. Compared to their commercial counterparts, these berries contain many of the same polyphenols, and the possibility exists for the discovery of novel phenolic compounds that may affect the ADME process in a host-beneficial way. Several species have demonstrated antioxidant, antiobesogenic, antimicrobial, and anti-inflammatory properties through in vitro, animal studies, and human clinical trials. This review examines the available chemical compositions of several dark berries and their effect on the ADME process, their implication in host health effects, and the potential of these emerging species to suggest areas for future research.
We explored the effect of phlorizin against cholinergic memory impairment and dysbacteriosis in D-galactose induced ICR mice. The control (CON) group, D-galactose model (DGM) group, and three groups (DG-PL, DG-PM, DG-PH) treated with phlorizin at 0.01%, 0.02%, and 0.04% (w/w) in diets were raised for 12 weeks. Supplementing with phlorizin reversed the loss of organ coefficient and body weight caused by D-galactose. The functional abilities of phlorizin on hippocampal-dependent spatial learning and memory, anti-oxidation, anti-inflammation were also observed. Meanwhile, phlorizin intervention upregulated the gene expression of Nrf2, GSH-PX, SOD1, decreased the gene expression of NF-κB, TLR-4, TNF-α, and IL-1β in the hippocampus, while enhanced the gene expression of JAM-A, Mucin2, Occludin in the caecum. Furthermore, a neurotransmitter of acetylcholine (ACh) was enhanced, while acetylcholinesterase (AChE) activity was inhibited by phlorizin administration. Moreover, phlorizin administration increased short-chain fatty acids (SCFAs) content, and reduced lipopolysaccharides (LPS) levels, which may relate to the rebuilding of gut microbiota homeostasis. Treatment with phlorizin may be an effective intervention for alleviating cognitive decline and gut microbiota dysbiosis.
Black corn (Zea mays L.) is a pigmented type of this cereal whose color of the kernels is attributed to the presence of the anthocyanins. In this study, we assessed the black corn soluble extract (BCSE) effects on the intestinal functionality, morphology, and microbiota composition using an in vivo model (Gallus gallus) by an intra-amniotic administration. The eggs were divided into four groups (n=6-10): (1) No Injection; (2) 18 MΩ H2O/cm; (3) 5% (5mg/mL) BCSE; (4) 15% (15mg/mL) BCSE. The BCSE showed anti-inflammatory effects by down regulating the gene expression of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL6), and the transcriptional nuclear factor kappa beta (NF-κB). Further, the BCSE increased the relative abundance of E. coli and Clostridium. 5% and 15% BCSE increased the hepatic glycogen and upregulated the gene expression of sodium-glucose transport protein (SGLT1). In the morphology, 5% and 15% BCSE increased the goblet cell (GC) number on the crypt, the GC size on the villi, Paneth cell number on the crypt, and the acid GC. Further, the BCSE strengthened the epithelial physical barrier through upregulating the intestinal biomarkers AMP- activated protein kinase (AMPK) and caudal-related homeobox transcriptional factor 2 (CDX2). The overall result suggests that the BCSE promotes intestinal anti-inflammatory effects as well as enhances the intestinal barrier function.
This study explored the advantageous effects of purple sweet potato anthocyanin extract (PSPAE) on redox state in obese mice. The normal chow diet (NCD) group, high‐fat/cholesterol diet (HCD) group, and three groups based on HCD and added with low, middle, and high dose of PSPAE (PAL, PAM, and PAH) were raised for 12 weeks. High dose of PSPAE treatment decreased the elevations of the body weight by 24.7%, serum total cholesterol by 48.3%, serum triglyceride by 42.4%, and elevated serum activities of glutathione peroxidase by 53.3%, superoxide dismutase by 57.8%, catalase by 75.4%, decreased serum contents of malondialdehyde by 27.1% and lipopolysaccharides by 40.5%, as well as increased caecal total short‐chain fatty acid by 2.05‐fold. Additionally, PSPAE depressed toll‐like receptor 4 (TLR‐4), nuclear factor kappa‐B (NF‐κB), interleukin 6, tumor necrosis factor α, and preserved nuclear factor erythroid‐2‐related factor 2 (Nrf2) gene expression. Similarly, the protein expression of Nrf2 was enhanced, while TLR‐4 and p‐NF‐κB/NF‐κB were depressed by PSPAE treatment. Moreover, PSPAE administration promoted the protection of intestinal barrier function and rebuilt gut microbiota homeostasis by blooming g_Akkermansia, g_Bifidobacterium, and g_Lactobacillus. Furthermore, antibiotic interference experiments showed that the gut microbiota was indispensable for preserving the redox state of PSPAE. These results suggested that PSPAE administration could be an opportunity for improving HCD‐induced obesity and the redox state related to gut dysbiosis. Purple sweet potato anthocyanin has diverse pharmacological properties. It is applicable for individuals to consume extracts (as pills or other forms) from raw purple sweet potato if they want to improve obesity or redox state.
Anthocyanins are the potential bioactive compounds that exerted a protective effect against metabolic disease. In this book chapter, we discussed the interplay between microbiota dysbiosis and metabolic disease as well as accumulated the recent updates of the metabolic modulatory effect of anthocyanins and anthocyanin-rich food. Based on our findings, anthocyanins showed metabolic modulatory effects via exerting antioxidant, anti-inflammatory, anti-apoptotic, pro-apoptotic, and autophagy effect. In addition, the modulatory effects of anthocyanins are partly attributed to gut microbiota communities. Further studies are warranted to understand the involvement of gut microbiota with anthocyanin effect. Thus, the consumption of anthocyanins is recommended to combat metabolic disease. Furthermore, intake of berry fruits is also suggested for preventing metabolic disease because of the rich source of anthocyanins.
Full-text available
Obesity is associated with alteration of the gut microbiota. In order to clarify the effect of Lactobacillus-containing probiotics (LCP) on weight we performed a meta-analysis of clinical studies and experimental models. We intended to assess effects by Lactobacillus species. A broad search with no date or language restriction was performed. We included randomized controlled trials (RCTs) and comparative clinical studies in humans and animals or experimental models assessing the effect of Lactobacillus-containing probiotics on weight. We primarily attempted to extract and use change from baseline values. Data were extracted independently by two authors. Results were pooled by host and by Lactobacillus species and are summarized in a meta-analysis of standardized difference in means (SMDs). We identified and included 17 RCTs in humans, 51 studies on farm animals and 14 experimental models. Lactobacillus acidophilus administration resulted in significant weight gain in humans and in animals (SMD 0.15; 95% confidence intervals 0.05-0.25). Results were consistent in humans and animals. Lactobacillus fermentum and Lactobacillus ingluviei were associated with weight gain in animals. Lactobacillus plantarum was associated with weight loss in animals and Lactobacillus gasseri was associated with weight loss both in obese humans and in animals. Different Lactobacillus species are associated different effects on weight change that are host-specific. Further studies are needed to clarify the role of Lactobacillus species in the human energy harvest and weight regulation. Attention should be drawn to the potential effects of commonly marketed lactobacillus-containing probiotics on weight gain.
Full-text available
Metabolic Syndrome is a cluster of risk factors which often includes central obesity, dyslipidemia, insulin resistance, glucose intolerance, hypertension, endothelial dysfunction, as well as a pro-inflammatory, pro-oxidant, and pro-thrombotic environment. This leads to a dramatically increased risk of developing type II diabetes mellitus and cardiovascular disease, which is the leading cause of death both in the United States and worldwide. Increasing evidence suggests that berry fruit consumption has a significant potential in the prevention and treatment of most risk factors associated with Metabolic Syndrome and its cardiovascular complications in the human population. This is likely due to the presence of polyphenols with known antioxidant and anti-inflammatory effects, such as anthocyanins and/or phenolic acids. The present review summarizes the findings of recent dietary interventions with berry fruits on human subjects with or at risk of Metabolic Syndrome. It also discusses the potential role of berries as part of a dietary strategy which could greatly reduce the need for pharmacotherapy, associated with potentially deleterious side effects and constituting a considerable financial burden.
Full-text available
Objective: To systematically review the updated information about the gut microbiota-brain axis. Data Sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. Results: It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota. Conclusions: Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future.
Full-text available
Obesity and its associated complications like type 2 diabetes (T2D) are reaching epidemic stages. Increased food intake and lack of exercise are two main contributing factors. Recent work has been highlighting an increasingly more important role of gut microbiota in metabolic disorders. It's well known that gut microbiota plays a major role in the development of food absorption and low grade inflammation, two key processes in obesity and diabetes. This review summarizes key discoveries during the past decade that established the role of gut microbiota in the development of obesity and diabetes. It will look at the role of key metabolites mainly the short chain fatty acids (SCFA) that are produced by gut microbiota and how they impact key metabolic pathways such as insulin signalling, incretin production as well as inflammation. It will further look at the possible ways to harness the beneficial aspects of the gut microbiota to combat these metabolic disorders and reduce their impact.
Full-text available
The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.
Full-text available
Berries are rich in polyphenols such as anthocyanins. Various favorable functions of berries cannot be explained by their anti-oxidant properties, and thus, berries are now receiving great interest as food ingredients with "beyond antioxidant" functions. In this review, we discuss the potential health benefits of anthocyanin-rich berries, with a focus on prevention and treatment of obesity and diabetes. To better understand the physiological functionality of berries, the exact molecular mechanism of their anti-obesity and anti-diabetes effect should be clarified. Additionally, the relationship of metabolites and degradation products with health benefits derived from anthocyanins needs to be elucidated. The preventive effects of berries and anthocyanin-containing foods on the metabolic syndrome are not always supported by findings of interventional studies in humans, and thus further studies are necessary. Use of standardized diets and conditions by all research groups may address this problem. Berries are tasty foods that are easy to consume, and thus, investigating their health benefits is critical for health promotion and disease prevention.
Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders.
In tackling the obesity pandemic, significant efforts are devoted to the development of effective weight reduction strategies, yet many dieting individuals fail to maintain a long-term weight reduction, and instead undergo excessive weight regain cycles. The mechanisms driving recurrent post-dieting obesity remain largely elusive. Here, we identify an intestinal microbiome signature that persists after successful dieting of obese mice, which contributes to faster weight regain and metabolic aberrations upon re-exposure to obesity-promoting conditions and transmits the accelerated weight regain phenotype upon inter-animal transfer. We develop a machine-learning algorithm that enables personalized microbiome-based prediction of the extent of post-dieting weight regain. Additionally, we find that the microbiome contributes to diminished post-dieting flavonoid levels and reduced energy expenditure, and demonstrate that flavonoid-based 'post-biotic' intervention ameliorates excessive secondary weight gain. Together, our data highlight a possible microbiome contribution to accelerated post-dieting weight regain, and suggest that microbiome-targeting approaches may help to diagnose and treat this common disorder.
The ecosystem of the human gut consists of trillions of bacteria forming a bioreactor that is fueled by dietary macronutrients to produce bioactive compounds. These microbiota-derived metabolites signal to distant organs in the body, which enables the gut bacteria to connect to the immune and hormone system, to the brain (the gut-brain axis) and to host metabolism, as well as other functions of the host. This microbe-host communication is essential to maintain vital functions of the healthy host. Recently, however, the gut microbiota has been associated with a number of diseases, ranging from obesity and inflammatory diseases to behavioral and physiological abnormalities associated with neurodevelopmental disorders. In this Review, we will discuss microbiota-host cross-talk and intestinal microbiome signaling to extraintestinal organs. We will review mechanisms of how this communication might contribute to host physiology and discuss how misconfigured signaling might contribute to different diseases.
Background Anthocyanins, which are found in high concentrations in fruit and vegetable, may play a beneficial role in retarding or reversing the course of chronic degenerative diseases. However, little is known about the biotransformation and the metabolism of anthocyanins so far. Aim of the study The aim of the study was to investigate possible transformation pathways of anthocyanins by human faecal microflora and by rat liver microsomes as a source of cytochrome P450 enzymes as well as of glucuronyltransferases. Methods Pure anthocyanins, an aqueous extract of red radish as well as the assumed degradation products were incubated with human faecal suspension. The incubation mixtures were purified by solid-phase extraction and analysed by HPLC/DAD/MS and GC/MS. Quantification was done by the external standard method. Furthermore the biotransformation of anthocyanins by incubation with rat liver microsomes in the presence of the cofactor NADPH (as a model for the phase I oxidation) and in the presence of activated glucuronic acid (as a model for the phase II glucuronidation) was investigated. Results Glycosylated and acylated anthocyanins were rapidly degraded by the intestinal microflora after anaerobic incubation with a human faecal suspension. The major stable products of anthocyanin degradation are the corresponding phenolic acids derived from the B-ring of the anthocyanin skeleton. Anthocyanins were not metabolised by cytochrome P450 enzymes, neither hydroxylated nor demethylated. However they were glucuronidated by rat liver microsomes to several products. Conclusions The gut microflora seem to play an important role in the biotransformation of anthocyanins. A rapid degradation could be one major reason for the poor bioavailability of anthocyanins in pharmacokinetic studies described so far in the literature. The formation of phenolic acids as the major stable degradation products gives an important hint to the fate of anthocyanins in vivo