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The role of probiotics on each component of the metabolic syndrome and other cardiovascular risks

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Introduction: Probiotics are defined as live microorganisms that when administered in adequate amounts confer health benefits to the host. The consumption of probiotics has gained increasing recognition from the scientific community due to the promising effects on metabolic health through gut microbiota modulation. Areas covered: This article presents a review of scientific studies investigating probiotic species and their effects on different risk factors of the metabolic syndrome (MetS). This article also presents a summary of the major mechanisms involved with gut microbiota and the components of the MetS and raises the key issues to be considered by scientists in search of probiotics species for treatment of patients suffering from this metabolic disorder. Expert opinion: Probiotics may confer numerous health benefits to the host through positive gut microbiota modulation. The strain selection is the most important factor for determining health effects. Further studies may consider gut microbiota as a novel target for prevention and management of MetS components and other cardiovascular risks.
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1. Introduction
2. Dysbiosis and the components
of the MetS
3. Probiotics and intestinal
microbiota modulation
4. Microbiota modulation with
probiotics and the components
of the MetS
5. Conclusion
6. Expert opinion
Review
The role of probiotics on each
component of the metabolic
syndrome and other
cardiovascular risks
Bruna Miglioranza Scavuzzi, Lucia Helena da Silva Miglioranza,
Fernanda Carla Henrique, Thanise Pitelli Paroschi,
Marcell Alysson Batisti Lozovoy, Andrea Name Colado Sima
˜o&
Isaias Dichi
University of Londrina, Department of Internal Medicine, Parana
´, Brazil
Introduction: Probiotics are defined as live microorganisms that when
administered in adequate amounts confer health benefits to the host. The
consumption of probiotics has gained increasing recognition from the scien-
tific community due to the promising effects on metabolic health through
gut microbiota modulation.
Areas covered: This article presents a review of scientific studies investigating
probiotic species and their effects on different risk factors of the metabolic
syndrome (MetS). This article also presents a summary of the major mecha-
nisms involved with gut microbiota and the components of the MetS and
raises the key issues to be considered by scientists in search of probiotics
species for treatment of patients suffering from this metabolic disorder.
Expert opinion: Probiotics may confer numerous health benefits to the host
through positive gut microbiota modulation. The strain selection is the most
important factor for determining health effects. Further studies may consider
gut microbiota as a novel target for prevention and management of MetS
components and other cardiovascular risks.
Keywords: dysbiosis, dyslipidemia, gut microbiota, inflammation, insulin resistance, obesity
Expert Opin. Ther. Targets [Early Online]
1. Introduction
Metabolic syndrome (MetS) is a complex disorder represented by a cluster of car-
diovascular risk factors associated with central fat deposition, abnormal plasma lipid
levels, elevated blood pressure (BP), insulin resistance (IR), a low-grade inflamma-
tory state and possibly intestinal dysbiosis [1-3]. Changes in eating habits and lifestyle
are undoubtedly the most important non-pharmacological factors for the preven-
tion and treatment of MetS and various nutritional therapies have been researched.
Among nutritional therapies to prevent MetS, the scientific literature has pointed
out the consumption of probiotic, prebiotic and symbiotic products.
The gastrointestinal tract is composed of several connected organs, which are
involved in nutrient conversion. This complex system has a well-known anatomical
architecture that is ~7 m long, comprising 300 m
2
surface area in adults. The
human large intestine has a bacterial flora with total numbers of 10
14
cells (ten times
the number of cells in the human body) and > 1000 species [4-6]. The main
functions of gut microbiota are metabolic, protective and trophic [7].
From the mouth to the colon, there is a complex microbiota, which is formed by
facultative and strict anaerobes, including streptococci, bacteroides, lactobacilli and
yeasts. The microbiome comprises nearly two million genes, making the collective
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bacterial genome vastly greater than the human genome. The
advent of high-throughput methodologies and the elaboration
of sophisticated analytic systems have facilitated the detailed
description of the microbial constituents of the human gut
as never before and are now enabling comparisons to be
performed between health and various disease states [5].
The intestinal mucosa forms a biochemical and physical
barrier between the host and the intestinal lumen. The intes-
tinal mucosa is composed of a mucous layer, a single layer of
intestinal epithelial cells (IECs) connected by adhesive struc-
tures known as tight junctions, as well as the lamina propria
and two thin layers of muscle tissue -- the muscularis mucosae.
The loss of the barrier function may lead to a systemic
immune activation [8].
Currently, it has also been recognized that this dynamic yet
stable ecosystem plays a role in conditions such as obesity and
type two diabetes (T2D) from infancy to ageing and that early
differences in fecal microbiota composition in children may
predict obesity in their adulthood [4,9-13]. The literature has
demonstrated different gut microbial compositions between
non-diabetics and adults with T2D, as well as between lean
and obese individuals, suggesting that gut microbial composi-
tion may affect the metabolism and energy storage [4,14-16].
A consensus definition of the term ‘probiotics’ was adopted
after a joint Food and Agricultural Organization of the
United Nations and World Health Organization expert con-
sultation. In October 2001, the Organization experts defined
probiotics as ‘live micro-organisms which, when administered
in adequate amounts, confer a health benefit on the host.’ The
original idea of the prebiotic concept (that can be translated in
‘prebiotic effects’) was defined as: ‘the selective stimulation of
growth and/or activity (ies) of one or a limited number of
microbial genus (era)/species in the gut microbiota that
confer(s) health benefits to the host.’ When probiotics and
prebiotics are used in combination, they are known as
symbiotics [17].
The consumption of probiotics has gained recognition
from the scientific community due to the promising health
effects and well-documented history of safe use. Thus, the
present review gathers recent and relevant literature involving
the consumption of probiotics and the components of the
MetS in humans.
The articles included in this review were found in at least
130 Databases included in the Brazilian National Electronic
Library Consortium for Science and Technology and that
were published from 1998 to 2014. Studies were included if
they met the following criteria: 1) randomized, controlled
intervention trials with humans; 2) studied the effect of probi-
otics on waist circumference and/or body mass index, glucose
metabolism, blood lipids, BP, markers of inflammation and
other cardiovascular risk factors; 3) considered probiotic
products with a known amount of live bacteria from a given
strain. There were no restriction groups, but searches have
focused on texts written in English.
2. Dysbiosis and the components of the MetS
An alteration of gut microbial diversity and an imbalance
between the potentially harmful and beneficial intestinal
bacteria (e.g., increase in Firmicutes and reduction in the
abundance of Bacteroidetes), known as dysbiosis, has been
associated with several components of MetS, such as obesity
and IR, via modulation of inflammatory pathways [18-20].
The mechanisms linking these gut microbiota alterations
and metabolic changes are still a matter of debate; however,
it likely involves gut barrier alterations and low-grade inflam-
mation. High-fat, low-fiber and high-sugar diets have been
associated with a negative impact in gut activity and composi-
tion with a subsequent decrease in the barrier function [21-25].
Long-term overnutrition with macronutrients such as
saturated fats and carbohydrates can induce inflammation
through activation of toll-like receptor 4 (TLR-4) expressed
in the membrane of the IECs. Dietary products that are rich
in saturated fats, such as meats, contain significant amounts
of lipopolysaccharide (LPS), a major component from the
outer membrane of gram-negative bacteria that is known to
induce TLR-4 activation. TLR-4 stimulation induces
NF-kB-mediated inflammation, which has been related to
the development of IR [26].
Cani et al. [16] first demonstrated increased gut permeability
in mice after 4 weeks of a high-fat diet. This barrier disruption
is characterized by alteration of mucous thickness or tight
junction function and may allow the passage of microbial
components such as LPS to the systemic circulation, resulting
in metabolic endotoxemia and low-grade chronic inflamma-
tion that characterizes the MetS [18]. Elegant studies have
demonstrated that dietary fats may facilitate intestinal absorp-
tion of LPS. The mechanisms involved in LPS absorption
probably include paracellular leakage due to compromised
barrier function caused possibly by the saturated fats and
internalization by IECs and subsequent chylomicron
formation [27].
High LPS concentrations have been strongly associated
with the components of the MetS [28]. The lipopolysaccha-
ride-binding protein (LBP) is known to reflect LPS levels
Article highlights.
.Metabolic syndrome (MetS) has been associated with
intestinal dysbiosis.
.Probiotics may normalize intestinal microbiota
composition and improve gut barrier function.
.Microbiota modulation with probiotic strains have
shown to improve the components of the MetS.
.The physiological effects of probiotics are highly
strain-dependent.
.Probiotics consumed within fermented milk products
may have additional health benefits.
This box summarizes key points contained in the article.
B. M. Scavuzzi et al.
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and activity and is considered a marker of subclinical endotox-
emia. Accordingly, elevated LBP concentrations have also
been was associated with obesity, MetS and T2D. LBP is a
protein that is involved in the transfer of the LPS molecule
to CD14, a protein found in the surface of most TLR-4-
expressing cells and that is required for TLR4 endocytosis [29].
It has been hypothesized that CD14 could modulate insulin
sensitivity in physiological conditions possibly via modulation
of inflammatory pathways. Correspondingly, CD14 knock-
out mice were remarkably resistant to inflammation induced
by LPS administration and high-fat feeding [30,31].
2.1 Inflammation and IR
There is evidence that chronic inflammation is triggered by
the binding of LPS and bacterial lipopeptides to toll-like
receptors, such as TLR-4 and that it negatively affects glucose
homeostasis [18,32,33]. In obese individuals, circulating fatty
acids (FA) concentration is frequently elevated. Under such
conditions, saturated FAs may also bind to and activate
TLR-4 [34,35]. These bound molecules may activate the c-Jun
NH2-terminal kinase (JNK) or the IkB kinase (IKK)/
NF-kB pathways and result in IR [33].
In a study to investigate the effects of Lactobacillus acidoph-
ilus NCFM on insulin sensitivity and LPS-induced inflamma-
tory response in human subjects, the authors found that LPS
triggered a systemic, though reversible, inflammatory response
that included an increase of TNF-a, IL-6 and IL-1 receptor
antagonist [36].
In early studies, Hotamisligil et al. [29] showed that TNF-a
could induce IR. Later investigations demonstrated the
involvement of other proinflammatory cytokines (e.g., IL-6),
chemokines (e.g., monocyte chemoattractant protein 1) and
several bioactive substances (e.g., leptin, resistin) on the
pathogenesis of IR [33]. Additionally, increased adiposity and
TNF-alevels decrease the expression of adiponectin, an
adipocyte-derived hormone with antiatherogenic, anti-
inflammatory and antioxidant capacity [36-41]. The decrease
of this adipokyne also correlates with IR [42].
2.2 Obesity and lipid metabolism
Backhed et al. [14] demonstrated that after conventionalization
of germ-free mice with a normal microbiota, there was an
increase in fat mass by 60% and IR, despite energy intake
reduction, and suggested that the gut microbiota affected
energy harvest from the diet and energy storage in the
host [14]. The authors also reported an increase in leptin levels
upon colonization and found it to be proportional to the
increase in body fat. After these findings, numerous studies
of human gut microbiome reported evidence of core differen-
ces between lean and obese individuals, reduced diversity of
microbiota in obese individuals and suggested that gut micro-
bial composition may affect metabolism and fat
storage [16,43,44].
Turnbaugh et al. [45] colonized the gut of germ-free mice
with microbiota from either obese or lean animals. The
authors demonstrated that animals colonized with obese
microbiota had an increased capacity to store energy from
the diet. Obesity was associated with higher proportion of
Firmicutes, whereas lean animals had a greater abundance of
Bacteroidetes. The authors also found that cecal concentra-
tions of short chain FAs (SCFAs) were lower in lean compared
to obese animals [45].
SCFAs are produced by intestinal fermentation of indigest-
ible carbohydrates and the main SCFAs are acetate, propio-
nate and butyrate. These substrates are absorbed and used as
an energy source to the host. SCFAs are also known to play
an important role in metabolism regulation; therefore, SCFAs
can act both as an energy substrate and as a metabolic
regulator [46,47].
SCFAs are converted to triacylglicerol, which is later stored
in adipocytes, through hepatic de novo lipogenesis. Several
mechanisms to explain the increased fat storage have been
postulated and they include: i) the suppression of the
fasting-induced adipose factor, also known as angiopoietin-
like protein 4, by gut microbiota results in an increase of
lipoprotein lipase activity, which enhances the storage of
triacylglicerol in adipocytes; ii) the inhibition of AMPK activ-
ity in the muscle, leading to reduction of mitochondrial FA
oxidation, which predisposes to obesity; and iii) SCFAs also
influence energy intake through the binding to G-protein
coupled receptors (free FA receptors 2 and 3) and leads to
modulation of glucagon-like peptides (GLP) and peptide-YY
(PYY). In turn, GLP-1 and PYY modulate the production
and release of digestive hormones that are responsible for
satiety [46,48-53].
Although the etiology of dyslipidemia is mostly genetic or
related to lifestyle (sedentary lifestyle with excessive intake of
saturated FA, trans FA and cholesterol), SCFAs produced by
microbiota fermentation may also play a role in the regulation
of blood lipids. The SCFA acetate is known to be a substrate
for cholesterol synthesis and could have the potential to
increase plasma cholesterol. Accordingly, Jenkins et al. [54]
studied the effect of colonic fermentation of a 25 g/day of
lactulose supplementation on serum lipids. After 2 weeks of
treatments, a significant increase of fasting serum total
cholesterol (TC), low-density lipoprotein (LDL) and apolipo-
proteins B was reported. The authors suggested that the
lipid-raising effect occurred due to an increase of serum
acetate concentrations. The effects of SCFAs on blood lipids
are still a matter of debate, but it is likely that the effect is
dependent on the propionate to acetate ratio.
2.3 Blood pressure
The number of studies linking gut dysbiosis and increase in
BP are very limited. However, BP may increase indirectly
due to obesity, elevated blood lipids and IR [55-58].
The main mechanisms linking dysbiosis and all the compo-
nents of MetS described in this topic have been summarized
and illustrated in Figure 1.
The role of probiotics on each component of the MetS and other cardiovascular risks
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3. Probiotics and intestinal microbiota
modulation
The modulation of the intestinal microbiota is one of the
potential beneficial health effects of probiotics, and numerous
research studies have documented that probiotics can alter gut
microbiota. The mechanisms and efficiency of probiotic
effects depend primarily on the interactions between the pro-
biotic microorganisms and either the microbiota of the host
or the immunocompetent cells of the intestinal mucosa [59,60].
Dysbiosis of intestinal microbiota has been associated with
a growing number of diseases. Recently, fecal microbiota
transplant from non-diabetic donors infused into the
duodenum of patients with the MetS improved their insulin
sensitivity, highlighting the broad potential of this interven-
tion [61]. Since modulation of the composition of intestinal
microbiota by probiotics was demonstrated to be possible,
this intervention could have the potential to counterbalance
intestinal dysbiosis and thus restore health.
Probiotics may play a beneficial role in several medical
conditions, including diarrhea, gastroenteritis, irritable bowel
syndrome, inflammatory bowel disease, cancer, infant
allergies, failure-to-thrive, hyperlipidemia, hepatic diseases,
Helicobacter pylori infections, and others [62].
Probiotics such as Lactobacilli and Bifidobacterium are mor-
phologically defined as Gram-positive, non-spore-forming,
anaerobic, aciduric, acidogenic, homofermentative or
heterofermentative microorganisms that have complex
nutritional requirements (carbohydrates, amino acids, pepti-
des, FA, salts, nucleic acids and vitamins) [63]. Even within
the same species of microorganisms, the physiological effects
of probiotics are highly strain-dependent. The variations in
outcomes between different studies appear to be due to choice
of probiotic strain, number of colony-forming units (CFU)
and length of the study.
Several strains of probiotics have been shown to improve
metabolic parameters such as hypertension, obesity, inflam-
mation, glucose homeostasis disorders and abnormal plasma
lipid levels, such as decrease of LDL concentration, reduction
of TC and an improvement in TC: high-density lipoprotein
(HDL) and LDL:HDL ratios [12,64-73]. The important
criteria, which have been put forward by FAO/WHO in the
selection of food probiotics include identification of strains
using state-of-the-art techniques, ability to tolerate gastric
juice and bile, maintenance of stability and, most impor-
tantly, proof to be safe and beneficial to the consumer.
A number of genera of bacteria are used as probiotics,
including Lactobacilli (L.), Bifidobacterium (B.), Pediococcus,
Leuconostoc and Enterococcus [74]. Amongst probiotics,
L. acidophilus NCFM/La5, L. casei subsp. casei,L. gasseri
SBT2055, L. helveticus, L. plantarum 299v, L. rhamnosus
GG, L. reuteri NCIMB, B. lactis Bb12 and others, have
human health efficacy data with desirable properties and
well-documented clinical effects on parameters of
MetS [36,67]. The main clinical effects of these strains were
Inadequate diet
( Fat, Sugar, Fiber)
Changes in gut microbiota
composition
(e.g., Bacteroites, Firmicutes)
Proportion of
proinflammatory bacteria
Passage of microbial products (e.g., LPS)
to systemic circulation
Gut permeability
Systemic and adipose tissue inflammation
Proinflammatory cytokynes
(TNF-α, IL-6, and IL-1)
Adiponectin expression
Leptin levels
Insulin resistance Blood pressure
Short chain
fatty acids
De novo
lipogenesis Obesity
Energy
Storage
GLP-1
PYY
Satiety
Appetite
FIAF suppression by
gut microbiota
LPL
activity
AMPK inhibition in
muscle
Fatty acid oxidation
Figure 1. Mechanisms linking dysbiosis and the components of the metabolic syndrome.
FIAF: Fasting-induced adipose factor; GLP-1: Glucagon-like peptide 1. LPL: Lipoprotein lipase; LPS: Lipopolysaccharide; PYY: Peptide-YY.
B. M. Scavuzzi et al.
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body mass index and abdominal adiposity reduction,
diminished LDL and TC levels and decrease in BP [65,69,75,76].
The effects of probiotics are mediated by their role in nor-
malization of intestinal microbiota composition, immunomo-
dulation, and maintenance of gut barrier function. Three
main mechanisms have been proposed to explain the action
of probiotics. The first is the suppression of viable counts of
the pathogenic bacteria, which can occur by competition for
attachment surface and nutrients, as well as by production
of antibacterial compounds, such as AMPs, anti-microbial
peptide human-bdefensin 2, bacteriocins, acetic and lactic
acids. The second mechanism is by alteration of microbial
enzyme activities. SCFA and bacteriocins may reduce luminal
and fecal pH and decrease the activity of undesirable bacterial
enzymes. The third mechanism is by stimulation of host
immunity by increasing antibody levels (e.g., Immunoglobu-
lin A), and leukocyte and macrophages activity. Probiotics
also increase barrier function, inhibiting the invasion of
pathogenic microbial products [8,77].
With advancing knowledge of how probiotics interact with
the gut microbiome, there is an increasing interest in explor-
ing the effect of probiotics on specific elements of MetS in
humans.
4. Microbiota modulation with probiotics and
the components of the MetS
4.1 Probiotics and body weight
Kadooka et al. [75] performed a 12-week intervention study
with fermented milk containing Lactobacillus gasseri strain
SBT2055 (LG2055) in adults with large visceral fat areas.
The subjects consumed 200 g of fermented milk/day contain-
ing either 10
7
,10
6
or 0 (control) CFU of LG2055/g. The
authors found visceral adiposity reduction with LG2055
intervention to be dose-dependent and the average reductions
in abdominal visceral fat areas were 8.5% in the 10
7
dose
group and 8.2% in the 10
6
dose group. The control group
did not reduce abdominal visceral fat. The authors suggested
that LG2055 could enhance anti-inflammatory and
integrity-maintaining mechanisms of IECs and thus, contrib-
ute to reduced abdominal adiposity [75].
Although only few studies have investigated the effect of
probiotic strains in abdominal adiposity, several studies have
recognized that the composition of the gut microbiota has
an impact on energy homeostasis and have suggested that pro-
biotics have positive results on weight loss. However, it is
important to reinforce that the physiological effects of probi-
otics are highly strain-dependent. Million et al. [78] conducted
a comparative meta-analysis of studies considering the
effect Lactobacillus species on body weight in humans and
animals. The authors found that the species L.fermentum
and L.ingluviei were associated with weight gain in animals,
L.plantarum was associated with weight loss in animals and
L. gasseri was associated with weight reduction in animals
and humans [59].
Sanchez et al. [64] performed a 24-week intervention study
to investigate the impact of Lactobacillus rhamnosus
CGMCC1.3724 (LPR) on weight loss and maintenance in
obese men and women. The participants consumed two
capsules a day of either a placebo or a LPR formulation
(1.6 10
8
CFU of LPR/capsule). The authors found that
L. rhamnosus CGMCC1.3724 was associated with a reduction
in the abundance of the Lachnospiraceae family (phylum
Firmicutes) in women. The Lachnospiraceae family is a group
that is more abundant in the obese microbiota. The women in
the intervention group had significant weight loss after
12 weeks with the association of probiotic supplementation
and an energy-restricted diet. The women who received the
probiotic supplementation continued to lose body weight
and fat mass during the 12 weeks weight-maintenance period
where there was no diet restriction. However, the placebo
group gained weight. These results suggest that changes in
gut microbiota composition may help to lose weight and
maintain weight loss. They also indicated that the health
effects are also influenced by the host gender [64].
The mechanisms involved in body weight reduction are
not clear, but studies point to the reduction of adipocyte
size, inhibition of adipogenesis and suppression of energy
intake [59-67,74,75,77-82].
4.2 Probiotics and blood lipids
Guo et al. [83] conducted a meta-analysis of randomized
controlled trials to evaluate the effects of probiotics on blood
lipids. The authors found evidence that probiotics decrease
concentrations in LDL and TC in subjects with normal,
borderline high and high cholesterol levels [83].
Although the mechanisms involved in the cholesterol-
lowering effect are not clearly understood, it is accepted that
blood lipids are affected by: i) probiotics containing bile salt
hydrolase (BSH) (e.g., lactobacilli and bifidobacteria) increase
bile acid deconjugation, which suppresses cholesterol absorp-
tion in the enterohepatic circulation. Inhibition of the enter-
ohepatic circulation leads to the synthesis of more bile acid,
which utilizes circulating cholesterol; ii) probiotics bind and
incorporate cholesterol to their cell membrane, decreasing
the intestinal cholesterol pool available for absorption; and
iii) probiotics produce SCFAs such as propionate, which
reduces cholesterol synthesis by inhibiting hydroxymethylglu-
taryl CoA reductase (HMG-CoA reductase), a rate-limiting
step of the cholesterol synthesis pathway [84-86].
One proposed mechanism to explain HDL increase after
probiotic treatment is the reduction in serum triglyceride
(TG) levels. In hypertriacylglycerolemic states, HDL particles
exchange cholesterol for TG with LDL and very LDL and
become TG-rich. The TG-rich HDL particles are more
rapidly catabolized in the liver than normal HDL particles.
Therefore, reduction in serum levels of TG often observed
in probiotic treatments may indirectly lead to an increase in
serum HDL levels [87].
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Besides the cholesterol-lowering effects caused by probiot-
ics, when probiotics are consumed through dairy products,
there can be an additional decrease in cholesterol levels,
probably due to the presence of milk matrix components
such as calcium and magnesium [12].
4.3 Probiotics, glucose homeostasis and
inflammation
Firouzi et al. [88] conducted a review of studies in animals
and humans that considered the impact of probiotics on
parameters of glucose homeostasis. Sixteen out of seventeen
studies in animals, and three out of four studies in humans,
found significant improvements in at least one glucose
homeostasis-related parameter [88].
The mechanism by which gut microbiota modulation
improves IR has been associated to an increase in hepatic
natural killer T-cell number and a reduction in inflammatory
signaling [89]. One of the possible mechanisms to induce a
decrease in inflammatory signaling is through PPARgagonist
activation. Conjugated linoleic acid is produced by some
species of Lactobacilli (e.g., acidophillus, plantarum, paracasei
and casei) and has the potential to act as a PPARgagonist,
which up-regulates adiponectin, down-regulating inflamma-
tion, adiposity and improving IR by blocking suppression of
glucose transporter type 4 [26].
Studies evaluating probiotic intake and markers of inflam-
mation are scarce and the results are controversial. Gøbel et al.
[10] investigated the effect of L. salivarius Ls-33 on a series of
biomarkers related to inflammation and MetS. High-
sensitivity C-reactive protein (hs-CRP), IL-6 and TNF-a
were evaluated. The authors found no evidence of any benefi-
cial effect on inflammatory markers [10]. Andreasen et al. [32]
studied the effect of L. acidophilus NCFM on the systemic
inflammatory response. The authors found that this probiotic
strain did not affect the systemic inflammatory response
(C-reactive protein, TNF-a, IL-6 and IL-1 receptor antago-
nist) [36]. In contrast, Asemi et al. [90] studied the effect of a
multispecies probiotic supplement containing L. acidophilus,
L. casei, L. rhamnosus, L. bulgaricus, Bifidobacterium breve,
Bifidobacterium longum and Streptococcus thermophiles on hs-
CRP in diabetic patients. The authors found a significant
decrease in serum hs-CRP levels [90]. Barreto et al. [12]
performed a randomized controlled trial to compare the influ-
ence of fermented milk with L. plantarum and non-fermented
milk (control) on the classical parameters related to the MetS
and other parameters related to cardiovascular risk. The
authors found a significant decrease in IL-6 both in control
(p = 0.032) and intervention (p = 0.001) groups [12].
4.4 Probiotics and BP
In a recent systematic review and meta-analysis of randomized
controlled trials, Khalesi et al. [91] concluded that probiotics
moderately reduce BP. The authors found evidence that
BP reduction is greater when the intervention lasts
for > 8 weeks, when the daily dose of probiotic consumption
is greater than (or equal to) 10
11
CFU, and amongst individ-
uals with elevated BP. The study also suggests a greater
BP-lowering effect when multiple species of probiotics are
consumed [91].
Although the number of studies investigating the role of
gut microbiome on BP regulation is sparse, some authors
have demonstrated an influence of SCFAs on BP.
Mortensen et al. [92] found that SCFA acetate, propionate
and butyrate could produce a vasorelaxant effect in isolated
human colonic resistance arteries [92]. More recently,
Pluznick et al. [93] documented an acute decrease in BP after
propionate administration on wild-type mice. The authors
found that olfactory receptor 78 (Olfr78), an Olfr expressed
in the kidney and short-chain FA receptor GPR-41 respond
to SCFA propionate. Propionate stimulates the expression of
Olfr78, which elevates BP mediated by renin secretion but
conversely, propionate also causes a decrease in BP through
GPR41. The authors concluded that SCFA affects BP
through both receptors [93].
When probiotics are consumed with dairy products, a sig-
nificant reduction of BP may occur [91]. The BP lowering
ability of dairy products has been related to the release of
bioactive peptides that have an ACE inhibitory effect.
Different strains of probiotic microorganisms release different
bioactive peptides, which can be either more potent or less
potent in the ACE inhibitory activity [94]. BP decrease may
also be a result of the reduction of blood lipids, body weight
and IR [55-58].
The main mechanisms associated with improvements of all
components of MetS through probiotic consumption
described in this topic have been summarized in Figure 2.
Table 1 summarizes examples of human trials considering
probiotic intake and its effects on components of the MetS.
4.5 Probiotics and other cardiovascular risk factors
Barreto et al. [12] performed a randomized controlled trial to
evaluate the influence of fermented milk with L. plantarum
in the classical parameters related to MetS and other
parameters related to cardiovascular risk. The authors found
a significant decrease in homocysteine levels and associated
it to increased folate intake, naturally present in milk, and
the capacity of L. plantarum to synthesize folate [12].
Bukowska et al. [95] also performed an intervention
study with L. plantarum. There was a significant decrease
in levels of TC, LDL and fibrinogen after 6 weeks of
intervention. The authors associated the reduction of
fibrinogen levels to the reduction in cholesterol levels and
hypothesized that it could be due to: i) modulation of
the immune response; and ii) suppression of hepatic
synthesis of fibrinogen by lowering serum levels of free
FA promoted by propionate production during intestinal
fermentation [95].
B. M. Scavuzzi et al.
6Expert Opin. Ther. Targets (2015) 19(8)
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5. Conclusion
Evidence is now accumulating that a diet rich in probiotics
might confer numerous benefits to the metabolic health of
the host through positive gut microbiota modulation and is
thus a novel target to be further studied and considered for
the prevention and management of all MetS components.
Considering that the effects of probiotics are strain-
dependent, the strains to be used for the management of the
MetS must be selected based on clinically established health
benefits and safety records. Overall, the studies show that
several probiotic strains have a favorable effect on at least
one component of the MetS in intervention studies.
6. Expert opinion
The connection between gut microbiota imbalance, inflam-
mation and its role in the pathogenesis of the components
of the MetS has been increasingly recognized. This interven-
tion is of particular interest since it has the potential to signif-
icantly improve all parameters of the MetS at once. However,
to date, the number of human intervention studies consider-
ing the effect of probiotics on every component of the MetS
is very limited and often contradictory. The conflicting results
may be due to differences in study design and probiotic strain
selected. Therefore, there is great research potential in this
field, as very little has been established specially regarding
the mechanisms of action involved and the information on
intervention characteristics such as effective probiotic strain,
duration, and dose required to achieve health benefits.
The key finding in this area is that microbiota modulation
with probiotics may improve metabolic parameters and that
the metabolic effects of probiotic are strain-dependent. There-
fore, when searching for a specific clinical response, the strain
should be carefully selected based upon scientific evidence of
efficacy. The strain selection is the most important factor for
determining the health effects, for example, when an addi-
tional reduction of cholesterol levels is needed, the strains
selected should be BSH-active.
The strain that has shown favorable and significant
improvements for most components of the MetS in the stud-
ies selected for this review was L. plantarum. However, most
studies considered only one metabolic parameter and there-
fore, it is very possible that other strains have a more favorable
impact on the metabolic risk factors overall. Therefore, more
in-depth studies are needed in order to conclude which strains
will be the most promising for metabolic improvements.
Unfortunately, the limited number of trials that consider
every component of the MetS and specific probiotic strains
make it difficult to suggest a microorganism (or a combina-
tion of strains) that is more likely to yield better clinical
improvements. This is also a promising field to be studied.
Lipogenesis
Microbiota modulation
with probiotics
Restore gut microbiota
composition balance
(e.g., Bacteroites, Firmicutes)
Proportion of
proinflammatory bacteria
Passage of microbial products
to systemic circulation
Gut permeability
Systemic and adipose tissue
inflammation Insulin resistance Blood pressure
Short chain fatty acids
(e.g., propionate)
Obesity
Energy
storage
GLP-1
PYY
Satiety
Appetite
Adipogenesis
Adipocytes size
Adipocytes number Blood lipids
Cholesterol binding/incorporation
to probiotic cells
Cholesterol
absorption
Bile acid
deconjugation
Bile acid synthesis using circulating cholesterol
Cholesterol
absorption
Figure 2. Mechanisms linking gut microbiota modulation with probiotics and improvements in components of the metabolic
syndrome.
GLP-1: Glucagon-like peptide 1; PYY: Peptide-YY.
The role of probiotics on each component of the MetS and other cardiovascular risks
Expert Opin. Ther. Targets (2015) 19(8) 7
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The majority of studies considering the effects of probiotics
on metabolic health are very recent, most of which started to
be published around 2005. Therefore, very little is known
about which strains produce more effects on the components
of the MetS, the dose needed for each strain and the mini-
mum treatment period, since alteration of the gut microbiota
composition is probably gradual. The health effects are also
likely affected by the host characteristics, such as ethnicity,
gender and age.
Most studies selected for this review reported a positive
impact on the components of the MetS. The overall daily
dose of probiotic bacteria ranged from 10
6
to 10
10
CFU
consumed in capsules or within fermented dairy products.
The intervention period ranged from 3 to 24 weeks. These
studies indicate that significant results can be achieved in a rel-
atively short period and without a major change in dietary
habits.
Additional health benefits may occur when probiotics are
consumed in fermented dairy products, as milk alone also
has the potential to improve the components of the MetS
due to its complex matrix. For example, microorganism-
fermented dairy products may contain ACE inhibitory
peptides that contribute to BP reduction by decreasing the
production of angiotensin II.
It is also important to mention that the improvements in
metabolic parameters are more significant when probiotic
consumption is made within a balanced diet. Considering
that a diet rich in fat and sugar, and poor in fiber leads to
an alteration of barrier function and of the gut microbiota
composition, the limitation of using probiotics is that
improvements will likely be maintained only if there is a life-
long adherence to a balanced diet or continuous probiotic
consumption.
Medical organizations such as the World Gastroenterology
Organization; the European Society for Pediatric Gastroenter-
ology, Hepatology and Nutrition; and the North American
Society for Pediatric Gastroenterology, Hepatology, and
Nutrition have begun to suggest probiotics for clinical use
in the treatment of various clinical conditions, such as
antibiotic-associated diarrhea and irritable bowel syndrome.
Therefore, it is likely that the scientific findings, which associ-
ate probiotics and metabolic health, will be translated into
clinical recommendations considering the history of safe use
of many strains and the increasing body of evidence of health
benefits.
A promising area to be studied is how early gut coloni-
zation affects metabolic diseases in adulthood and meta-
bolic health (e.g., detailed information on the impact of
Table 1. Examples of human studies considering probiotics and components of metabolic syndrome.
Study/strain Population Duration Daily intake Effect Ref.
A DB, RPCT to assess the
cholesterol-lowering clinical
efficacy and safety of
microencapsulated Lactobacillus
reuteri NCIMB 30242
supplemented in a yogurt
formulation
114 healthy hypercholesterol-
emic adult men and women,
18 -- 74 years
2-week
washout,
2-week
run-in,
6-week
treatment
1.15
10
CFU Microencapsulate L. reuteri
yoghurt consumption
decreased LDL, total cholesterol
and non-high-density
lipoprotein cholesterol
[65]
A multicenter, DB, RPCT to
evaluate the effects of the
probiotic L. gasseri
SBT2055 (LG2055) - originated
from the human gut - on
abdominal adiposity, body
weight and other body measures
87 healthy adults (59 men/
28 women) with BMI of
24.2 -- 30.7 kg/m
2
and
abdominal visceral fat area
(81.2 -- 78.5 cm
2
)
12 weeks 200 g of FM
containing
10
7
and 10
6
CFU of
LG2055/g
LG2055 consumption
promoted a significant
reduction in abdominal
adiposity, BMI, waist and hip
circumference
[75]
A DB, RPCT parallel pilot study
to evaluate the effects of a
hypocaloric diet supplemented
with a probiotic cheese with
L. plantarum on obese
hypertensive patients
25 obese hypertensive
patients
3 weeks 50 g cheese.
Containing
110
9
CFU/g
The hypocaloric diet
supplemented with a probiotic
cheese helped to reduce
arterial blood pressure
[76]
A randomized, prospective,
parallel-group intervention study
to investigate whether
supplementation of probiotics
(L. rhamnosus GG, ATCC 53
103 and Bifidobacterium lactis
Bb12) with dietary counseling
affects glucose metabolism
256 pregnant women (mean
age of 30 years)
Entire preg-
nancy and
12 months
postpartum
1 capsule
with 10
10
CFU/day
Combined dietary counselling
and probiotics intervention
yielded improved glucose
metabolism and insulin
sensitivity
[96]
BMI: Body mass index; CFU: Colony forming units; DB: Double blind; FM: Fermented milk; LDL: Low-density lipoprotein; RPCT: Randomized placebo controlled
trial; TC: Total cholesterol.
B. M. Scavuzzi et al.
8Expert Opin. Ther. Targets (2015) 19(8)
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formula milk on long-term gut composition) and how the
microbiota is altered due to ageing or to different diseases.
Studies comparing the effects of different strains and possi-
bly combining them for optimum results are warranted.
The mechanisms of action have mostly been demonstrated
in animal models and remain to be confirmed in human
trials. Thus, in the next few years, the role of the micro-
biota composition on overall health will hopefully become
clearer.
Future intervention studies should preferably include stool
analysis to verify changes in stool composition (e.g., choles-
terol, SCFA, microorganisms). Studies should also include
measures of circulating LPS and markers of inflammation,
which would help to explain results and make associations
with the mechanisms of action.
Currently available scientific evidence is sufficient to sup-
port the study of dietary intake of probiotics in patients
with the MetS and with a normal immune system. This inter-
vention may broaden the area of non-medication strategies to
be employed to ameliorate the components of the MetS,
which currently include healthy nutrition and regular physical
activity.
Declaration of interest
The authors have no relevant affiliations or financial involve-
ment with any organization or entity with a financial interest
in or financial conflict with the subject matter or materials
discussed in the manuscript. This includes employment, con-
sultancies, honoraria, stock ownership or options, expert testi-
mony, grants or patents received or pending, or royalties.
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2011;21:844-50
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Research Advances With Regards to
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Mechanisms of the Cholesterol-Lowering
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The role of probiotics on each component of the MetS and other cardiovascular risks
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Affiliation
Bruna Miglioranza Scavuzzi
1
MSc,
Lucia Helena da Silva Miglioranza
2
PhD,
Fernanda Carla Henrique
3
MSc,
Thanise Pitelli Paroschi
3
MSc,
Marcell Alysson Batisti Lozovoy
4
PhD,
Andrea Name Colado Sima
˜o
4
PhD &
Isaias Dichi
5
MD PhD
Author for correspondence
1
University of Londrina, Health Sciences
Graduate Department, Post Graduate Program in
Health Sciences, Rua Robert Koch n. 60,
Londrina, Parana
´, Brazil
2
University of Londrina, Department of Food
Science and Technology, Rodovia Celso Garcia
Cid (PR 445), Km 380, Londrina, Parana
´, Brazil
3
University of Londrina, Food Science and
Technology Graduate Department, Post
Graduate Program in Food Science, Rodovia
Celso Garcia Cid (PR 445), Km 380, Londrina,
Parana
´, Brazil
4
University of Londrina, Department of
Pathology, Clinical and Toxicological Analysis,
Rua Robert Koch n. 60, Londrina, Parana
´, Brazil
5
University of Londrina, Department of Internal
Medicine, Rua Robert Koch n. 60, Londrina,
Parana
´, Brazil
Tel: +55 43 33712332;
Fax: +55 43 33715100;
E-mail: dichi@sercomtel.com.br
B. M. Scavuzzi et al.
12 Expert Opin. Ther. Targets (2015) 19(8)
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... 16 In general, studies that evaluated the effects of different PROB in the prevention, control, and treatment of PE demonstrated that they can promote the reduction of periodontopathogens, improve periodontal clinical parameters, decrease salivary levels of prostaglandin E2, matrix metalloproteinases, and the levels of pro-inflammatory cytokines in the GCF, in addition to inhibiting the development of gingivitis and potentiating the effects of SRP. 17 The use of PROB can also be a promising alternative in the treatment and prevention of MS and can act on its main comorbidities, such as diabetes, TC and blood pressure, influencing OS, and systemic inflammation. 18 The probiotic strain Bifidobacterium animalis subsp. lactis HN019 (B. ...
... In addition to the local effects on PE, probiotic strains can benefit the intestinal microbiota with different mechanisms of action, including host immune modulation, production of antimicrobial products, competition for pathogen binding sites, and increased function of the intestinal epithelial barrier. 18,43 Gatej et al. (2018) investigated the role of L. rhamnosus in alveolar bone loss and local and systemic inflammation in mice with PE. The authors demonstrated that the probiotic administration before the induction of PE via oral gavage or via oral inoculation significantly reduced alveolar bone loss and gingival inflammation, evidencing the action of PROB through both local and systemic pathways. ...
... The MSPEP group showed a reduction of 23% in serum TCH levels when compared with the MSPE group. These data corroborate the results of previous studies 18,49,50 and can be explained by the ability of some probiotic strains to incorporate cholesterol into their cell membrane, reducing the pool of intestinal cholesterol available for absorption. 18,50 It is also important to highlight that several studies have already demonstrated the systemic impact of probiotic strains on MS comorbidities and this is mainly because of the ability of probiotics to modulate the intestinal microbiota and the immune system, and also to its capacity to change the permeability of the intestinal barrier, influencing the entire metabolism of the host. ...
Article
Background: This study evaluated the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) in the development of periodontitis (PE), associated or not with metabolic syndrome, (MS) in rats. Methods: 96 rats were grouped according to a food protocol: high-fat diet for induction of MS or standard diet for the control groups (C). They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) probiotic (PROB): C -**, CP-*, PE+**, PEP+*, MS-**, MSP-*, MSPE+** and MSPEP+*. PROB administration started on the 8th week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular analyzes, immunoenzymatic assays, and microtomographic analyses were performed. The data obtained were analyzed statistically (p <0.05). Results: The PEP and MSPEP groups showed lower levels of alveolar bone loss when compared to the PE and MSPE groups, respectively (p <0.05). The immunoenzymatic analysis showed higher levels of interleukin (IL)-1β and a higher receptor activator of NF-kappaB ligand (RANKL)/ osteoprotegerin (OPG) ratio in the MSPE group when compared to the MSPEP group (p <0.05). The PEP group showed lower levels of tumor necrosis factor (TNF)-α and IL-6 when compared to the PE group. The use of PROB attenuated dyslipidemia parameters in animals with MS, with or without PE. Conclusion: B. lactis HN019 reduced more significantly the severity of PE in rats with MS, modulating both systemic metabolic and immunoinflammatory parameters in periodontal tissues. This article is protected by copyright. All rights reserved.
... The connection between gut microbiota imbalance, inflammation and its role in the pathogenesis of MetS components has recently been the focus of attention [10]. As a matter of fact, it is well known as the gut microbiota is the product of a complex interaction between host's genetics and environment [11]. ...
... Recently, a meta-analysis of 18 randomized clinical trials with 1544 included patients has concluded that probiotic foods and supplements with Lactobacillus and Bifidobacterium could be considered as interventions to improve anthropometric and biochemical outcomes in MetS [16]. However, to date the number of human intervention studies considering the effect of probiotics and synbiotics on every component of MetS is very limited and sometimes contradictory [10], especially in the elderly, though treating MetS would be particularly useful to prevent disability and promote a normal aging [17]. ...
... The tested formulation also exerted an anti-inflammatory effect by reducing hsCRP and TNF-alpha serum levels. For this reason, this intervention may broaden the area of non-medication strategies to be employed to ameliorate the components of MetS and insulin resistance, which currently include healthy nutrition (with large quantities of foods high in beneficial antioxidants and polyunsaturated fatty acids) and regular physical activity [10,33]. ...
Article
Full-text available
PurposeThe connection between gut microbiota imbalance, inflammation and its role in the pathogenesis of metabolic syndrome (MetS) clustering factors has been increasingly recognized. However, data on the efficacy of probiotics supplementation on MetS components are few and almost lacking in the elderly. To address this issue, we conducted a randomized, double-blind, placebo-controlled, parallel-group, clinical study on a large sample of MetS elderly patients. Methods After 14 days of diet and physical activity standardization, 60 elderly patients were randomized to treatment with a synbiotic formula of Lactobacillus plantarum PBS067, Lactobacillus acidophilus PBS066 and Lactobacillus reuteri PBS072 with active prebiotics or placebo. Patients were evaluated anamnestically and by the execution of a physical examination and laboratory and haemodynamic analyses at the baseline and after 60 days of treatment. At enrollment and at the end of the trial, all enrolled patients complete the EuroQol-5 Dimension (EQ-5D) questionnaire. ResultsThrough the 2-month period of treatment, patients who received active treatment experienced a statistically significant improvement in waist circumference and in fasting plasma insulin, total cholesterol, high-density lipoprotein cholesterol, non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and tumor necrosis factor alpha serum levels, compared both to the baseline and the control group. Visceral adiposity index improvement in the synbiotic treatment group was significantly greater than in placebo group. Compared to baseline, treatment with synbiotics also significantly reduced mean arterial pressure and fasting plasma glucose.All treatment groups demonstrated a significant decrease in TG. TG reduction in the synbiotic group was significantly greater than in the control group.The EQ-5D VAS questionnaire significantly improved only in probiotics-treated subjects.Conclusion Treatment with a synbiotic formula of L. plantarum PBS067, L. acidophilus PBS066 and L. reuteri PBS072 with active prebiotics decreased MetS syndrome prevalence, several cardiovascular risk factors and markers of insulin resistance in elderly patients.
... Selected microbial strains commonly known as probiotics have been documented to have a beneficial effect on glycaemic control in the blood (reviewed in [13,[24][25][26]). In addition, there is growing evidence that microorganisms play an important role in glucose homeostasis, particularly in metabolic conditions such as obesity and obesity-induced insulin resistance [14,15], metabolic syndrome [16,17], type 2 diabetes [18][19][20][21]27] and cardiovascular disorders [23,28]. ...
Article
Full-text available
The maintenance of a healthy status depends on the coexistence between the host organism and the microbiota. Early studies have already focused on the nutritional properties of probiotics, which may also contribute to the structural changes in the gut microbiota, thereby affecting host metabolism and homeostasis. Maintaining homeostasis in the body is therefore crucial and is reflected at all levels, including that of glucose, a simple sugar molecule that is an essential fuel for normal cellular function. Despite numerous clinical studies that have shown the effect of various probiotics on glucose and its homeostasis, knowledge about the exact function of their mechanism is still scarce. The aim of our review was to select in vivo and in vitro studies in English published in the last eleven years dealing with the effects of probiotics on glucose metabolism and its homeostasis. In this context, diverse probiotic effects at different organ levels were highlighted, summarizing their potential mechanisms to influence glucose metabolism and its homeostasis. Variations in results due to different methodological approaches were discussed, as well as limitations, especially in in vivo studies. Further studies on the interactions between probiotics, host microorganisms and their immunity are needed.
... It is considered pertinent at this point to make reference to probiotics, which are used in several patient groups with intestinal gut diseases as dietary supplements. There appears to be a growing literature highlighting the cardiovascular benefits of the use of probiotics and increasing data associating probiotics with a significant reduction of certain CV risk factors such as low-density lipoprotein cholesterol (LDL-C), total cholesterol, blood pressure, triglycerides, body mass index (BMI) and waist circumference [99][100][101][102][103][104][105]. Research also indicates that probiotics could potentially have a beneficial effect on IBD [106][107][108], yet more clinical trials are needed in this area [109][110][111]. ...
Article
Full-text available
Sixty inflammatory bowel disease (IBD) patients (45 Crohn disease and 15 ulcerative colitis, 40 ± 13 years, 53% male) were examined at baseline and 4 months after intervention (surgical (35 patients) or anti-TNFa treatment (25 patients)). IBD severity, using Mayo score, Harvey–Bradshaw Index (HBI) and biomarkers, was correlated with cardiovascular markers. At baseline, the disease severity, the white blood cells (WBC) values and the reducing power (RP) were significantly correlated with the aortic pulse wave velocity (PWV) (r = 0.4, r = 0.44 and r = 0.48, p < 0.05) and the lateral mitral E’ velocity (r = 0.35, p < 0.05 and r = 0.3, p < 0.05). Four months after intervention, there was a reduction of WBC (1962.8/mm3 ± 0.425/mm3, p < 0.001), C-reactive protein (CRP) (8.1 mg/L ± 1.7 mg/L, p < 0.001), malondialdehyde (MDA) (0.81 nmol/mg ± 0.37, p < 0.05) and glycocalyx perfused boundary region (PBR 5-25) (0.24 μm ± 0.05 μm, p < 0.01). Moreover, the brachial flow mediated dilatation (FMD), the coronary flow reserve (CFR) and the left ventricle global longitudinal strain (LV GLS) were significantly improved for both groups (4.5% ± 0.9%, 0.55 ± 0.08, 1.4% ± 0.35%, p < 0.01), while a more significant improvement of PWV/GLS was noticed in the anti-TNFa group. IBD severity is associated with vascular endothelial, cardiac diastolic, and coronary microcirculatory dysfunction. The systemic inflammatory inhibition and the local surgical intervention lead to significant improvement in endothelial function, coronary microcirculation and myocardial deformation.
... Scavuzzi Bruna Miglioranza [27] вивчала роль пробіотиків при кожному компоненті метаболічного синдрому (МС) та інших серцево-судинних ризиках . В даній статті представлений огляд наукових досліджень, присвячених вивченню видів пробіотиків і їх впливу на різні чинники ризику MС . ...
Article
Background: Prebiotics and probiotics may be effective dietary components that can alter the gut microbiota of the host and consequently overcome imbalances associated with obesity. This work aimed to evaluate the synergistic and isolated effects and mechanisms by which probiotic yogurt containing Bifidobacterium animalis and/or Lactobacillus acidophilus and yacon flour alter metabolic parameters and inflammatory and insulin signaling proteins in diet-induced obese mice. Swiss mice were fed a high-fat diet (n = 48) or a standard diet (control; n = 6) for 56 days. The 42 mice that gained the most weight were selected and divided into seven groups that received different combinations of probiotic yogurt and yacon flour. After 30 days, biochemical parameters (blood glucose, serum total cholesterol and triacylglycerols), crude fat excretion in feces, and periepididymal fat were assessed and an immunoblotting analysis of insulin signaling proteins and IL-1β was conducted. Results: The combination of yacon flour and a yogurt with two strains of probiotics exerted positive effects on the evaluated parameters, such as decreased body weight (-6.5%; p < 0.05), fasting glucose (-23.1%; p < 0.05), and triacylglycerol levels (-21.4%; p < 0.05) and decreased periepididymal fat accumulation (-44.2%; p < 0.05). There was a decrease in inflammatory markers (p < 0.001) and an improvement in insulin signaling (p < 0.001). Conclusions: The combination of a prebiotic with two strains of probiotics in a food matrix may exert a protective effect against obesity-associated inflammation, improving insulin resistance, even in the short term. This article is protected by copyright. All rights reserved.
Article
Aims We conducted a systematic review and meta-analysis to evaluate evidence from randomized controlled trials (RCTs) documenting the effectiveness of supplementation with pro-/synbiotics versus placebo controls on anthropometric and metabolic (glucoregulatory status, lipid profile) indices in adults with metabolic syndrome (MetS). Methods Databases of MEDLINE, Scopus, Embase, Web of Science, and Cochrane Library were searched through March 2020 to identify eligible RCTs evaluating the effects of pro-/synbiotic consumption in adults (≥18 years) with MetS. Mean differences (MDs) and 95% confidence intervals (CIs) were pooled using random-effects models. Results Ten eligible publications (9 RCTs, n=344 participants) were included. Supplementation with pro-/synbiotics reduced total cholesterol (TC) in adults with MetS versus placebo (MD: -6.66 mg/dL, 95% CI: -13.25 to -0.07, P=0.04, I²=28.8%, n=7), without affecting weight, body mass index, waist circumference, fasting blood sugar, homeostasis model assessment for insulin resistance, insulin, triglyceride, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol (P>0.05). Conclusions Pro-/synbiotic consumption may be beneficial in reducing TC levels in adults with MetS. However, our observations do not support the effectiveness of pro-/synbiotics consumption on other anthropometric or metabolic outcomes of MetS. Further investigations with larger sample sizes are required to confirm these findings.
Article
Objectives Previous clinical studies have shown controversial results regarding the effect of Lactobacillus supplementation on blood pressure (BP). The purpose of this systematic review and meta-analysis is to examine the effect of Lactobacillus consumption on BP. Methods Five electronic databases were searched for eligible randomized controlled trials (RCTs) until May 2020. In total, 18 studies were included in our meta-analysis. Quality of the selected studies was assessed, and a random-effects model was used to calculate the overall effect sizes of weighted mean differences (WMD). This systematic review was registered in PROSPERO with the number: CRD42019139294. Results Lactobacillus consumption significantly reduced systolic blood pressure (SBP) by −2.74 mmHg (95% confidence interval, −4.96 to −0.51) and diastolic blood pressure (DBP) by −1.50 mmHg (95% confidence interval, −2.44 to −0.56) when comparing with the control group. Subgroup analysis showed that type 2 diabetes mellitus (T2DM) patients, Asian individuals, or borderline hypertension participants were more sensitive to daily consumption of Lactobacillus. And the effect of Lactobacillus on BP reduction was more significant in capsule form, with the dose was above 5 × 10⁹ colony-forming unit (CFU)/day or lasted for more than 8 weeks. Conclusions Our present study suggests that Lactobacillus consumption in capsule form when the daily dose is above 5 × 10⁹ CFU for more than 8 weeks can decrease SBP or DBP in T2DM patients, borderline hypertension participants or Asian individuals.
Article
Introduction Metabolic syndrome comprises a set of risk factors for chronic diseases including abdominal obesity, increased fasting blood glucose (FBG), altered lipid profile and elevated blood pressure (BP). Due to high prevalence of metabolic syndrome and its complications in the military personnel, the relevant problems should be identified and controlled. Therefore, the present study was conducted to determine the effect of synbiotic supplements on the components of metabolic syndrome in the military personnel with metabolic syndrome. Methodology Sixty military personnel with metabolic syndrome were included in this double-blind randomised controlled clinical trial. During the intervention, they were asked to consume one capsule of synbiotic supplement or placebo per day for 8 weeks. Body Mass Index (BMI), waist circumference, BP, FBG and lipid profile were measured before and after the intervention. Results The results of the study showed that the synbiotic supplementation had a large significant adjusted effect on the BMI (Cohen’s d=0.82 (95% CI 0.29 to 1.34)). It also had a medium significant adjusted effect on the FBG (Cohen’s d=0.52 (95% CI 0.004 to 1.03)) as well as triglyceride (Cohen’s d=0.65 (95% CI 0.13 to 1.17)). Conclusion Findings of the study revealed that synbiotic supplementation may lead to a significant improvement in the BMI, triglyceride and FBG levels in the military personnel. Thus, consumption of synbiotic supplements is recommended as an adjuvant therapy in the military personnel with metabolic syndrome.
Article
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.
Article
Full-text available
Background: Probiotic bacteria have been shown to have various effects on the microbiota; this may also affect appetite and may help promote weight loss and maintenance. Objective: This study was conducted to investigate the effect of Lactobacillus paracasei subsp paracasei L. casei W8 (L. casei W8) on glucagon-like peptide-1 (GLP-1) responses in an isolated pig intestine, in piglets and postprandially in humans. Additionally, the effect on subjective appetite, ad libitum energy intake, and glucose and insulin responses in humans was investigated. Design: Piglets were fed with probiotics for 2 weeks and the effect on glucagon encoding gene (GCG) was investigated. An isolated pig intestine was perfused with L. casei W8 and the GLP-1 response was measured. Twenty-one subjects completed a randomized, controlled, crossover study with three arms. Each participant completed 3 test days testing the effect of low dose (LD) (10(9) CFU), high dose (HD) (10(10) CFU) L. casei W8 or placebo capsule. Subjective appetite was assessed before an ad libitum lunch was served. GLP-1, insulin and glucose concentrations were analyzed. Results: Two weeks of treatment of piglets with L. casei W8 resulted in an increase in GCG expression compared to control animals (P<.05). L. casei W8 increased the GLP-1 response in the isolated pig intestine. In humans, L. casei W8 had an overall effect on energy intake (P=0.03), but no effects on subjective appetite sensation, overall glucose and insulin response and on GLP-1 release were observed (P>0.1). Conclusion: The probiotic bacteria L. casei W8 appears to lower food intake acutely, but the underlying mechanisms are not understood.
Article
Full-text available
To evaluate the effects of synbiotic supplementation on insulin resistance and lipid profile in individuals with the metabolic syndrome, we conducted a randomised, double-blind, placebo-controlled pilot study on thirty-eight subjects with the metabolic syndrome; they were supplemented with either synbiotic capsules containing 200 million of seven strains of friendly bacteria plus fructo-oligosaccharide or placebo capsules twice a day for 28 weeks. Both the synbiotic (G1) and the placebo (G2) groups were advised to follow an energy-balanced diet and physical activity recommendations. Parameters related to the metabolic syndrome and insulin resistance were measured every 7 weeks during the course of the study. After 28 weeks of treatment, the levels of fasting blood sugar and insulin resistance improved significantly in the G1 group (P< 0·001). Both the G1 and G2 groups exhibited significant reductions in TAG levels ( - 71·22 v. - 10·47 mg/dl ( - 0·80 v. - 0·12 mmol/l) respectively; P< 0·001) and total cholesterol levels ( - 21·93 v. - 14·2 mg/dl ( - 0·57 v. - 0·37 mmol/l) respectively; P= 0·01), as well as increases in HDL levels (+7·7 v. +0·05 mg/dl (+0·20 v. +>0·01 mmol/l) respectively; P< 0·001). The mean differences observed were greater in the G1 group. No significant changes were observed in LDL levels, waist circumference, BMI, metabolic equivalent of task and energy intake between the groups. The present results indicate that synbiotic supplementation increases the efficacy of diet therapy in the management of the metabolic syndrome and insulin resistance.
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Full-text available
The obesity epidemic has drastically impacted the state of health care in the United States. Aside from poor diet hygiene and genetics, there are many other factors thought to play a role in the emergence of obesity and the metabolic syndrome. There has been a paradigm shift toward further investigating the gut microbiota and its implications in the pathogenesis of a variety of disease states, including inflammatory bowel disease, Clostridium difficile, and most recently obesity and the metabolic syndrome. This article is intended to evaluate the role of gut microbiota in the pathogenesis of obesity and metabolic syndrome and its influence in future management.
Book
Since the publication of the first edition in 1999, the science of probiotics and prebiotics has matured greatly and garnered more interest. The first handbook on the market, Handbook of Probiotics and Prebiotics: Second Edition updates the data in its predecessor, and it also includes material topics not previously discussed in the first edition, including methods protocols, cell line and animal models, and coverage of prebiotics. The editors supplement their expertise by bringing in international experts to contribute chapters. This second edition brings together the information needed for the successful development of a pro- or prebiotic product from laboratory to market.
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Probiotics are living microorganisms that, upon ingestion in high amounts, exert health effects beyond inherent basic nutrition. To date, some studies have shown that dietary intake of probiotics is effective at lowering plasma cholesterol. The aim of this article is to summarize the current knowledge on the underlying mechanism(s) that affect(s) the cholesterol-lowering action of probiotics. The accepted mechanism responsible for the cholesterol-lowering effect of probiotics is the inhibition of intestinal cholesterol absorption and the suppression of bile acid reabsorption. Recent research has indicated that several sites within the cholesterol metabolism, such as the NPC1L1 protein, 3hydroxy3methylglutarylCoA reductase and 7α and 27αhydroxylase, have been suggested where regulation may take place after oral administration of probiotics, but these mechanisms are still imperfectly understood. Human metagenomic studies examining the possible mechanisms by which probiotic ingestion can be used to treat hypercholesterolemia should be carried out in the future.
Article
Abstract—Previous human clinical trials have shown that probiotic consumption may improve blood pressure (BP) control. The aim of the present systematic review was to clarify the effects of probiotics on BP using a meta-analysis of randomized, controlled trials. PubMed, Scopus, Cochrane Library (Central), Physiotherapy Evidence Database, and Clinicaltrial.gov databases were searched until January 2014 to identify eligible articles. Meta-analysis using a random-effects model was chosen to analyze the impact of combined trials. Nine trials were included. Probiotic consumption significantly changed systolic BP by −3.56 mm Hg (95% confidence interval, −6.46 to −0.66) and diastolic BP by −2.38 mm Hg (95% confidence interval, −2.38 to −0.93) compared with control groups. A greater reduction was found with multiple as compared with single species of probiotics, for both systolic and diastolic BP. Subgroup analysis of trials with baseline BP ≥130/85 mm Hg compared with <130/85 mm Hg found a more significant improvement in diastolic BP. Duration of intervention <8 weeks did not result in a significant reduction in systolic or diastolic BP. Furthermore, subgroup analysis of trials with daily dose of probiotics <1011 colony-forming units did not result in a significant meta-analysis effect. The present meta-analysis suggests that consuming probiotics may improve BP by a modest degree, with a potentially greater effect when baseline BP is elevated, multiple species of probiotics are consumed, the duration of intervention is ≥8 weeks, or daily consumption dose is ≥1011 colony-forming units.
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A new era in medical science has dawned with the realization of the critical role of the "forgotten organ," the gut micro-biota, in health and disease. Central to this beneficial interaction between the microbiota and host is the manner in which bacteria and most likely other microorganisms contained within the gut communicate with the host's immune system and participate in a variety of metabolic processes of mutual benefit to the host and the microbe. The advent of high-throughput methodologies and the elaboration of sophisticated analytic systems have facilitated the detailed description of the composition of the microbial constituents of the human gut, as never before, and are now enabling comparisons to be made between health and various disease states. Although the latter approach is still in its infancy, some important insights have already been gained about how the microbiota might influence a number of disease processes both within and distant from the gut. These discoveries also lay the groundwork for the development of therapeutic strategies that might modify the microbiota (eg, through the use of probiot-ics). Although this area holds much promise, more high-quality trials of probiotics, prebiotics, and other microbiota-modifying approaches in digestive disorders are needed, as well as laboratory investigations of their mechanisms of action.
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The abundance of innate and adaptive immune cells that reside together with trillions of beneficial commensal microorganisms in the mammalian gastrointestinal tract requires barrier and regulatory mechanisms that conserve host-microbial interactions and tissue homeostasis. This homeostasis depends on the diverse functions of intestinal epithelial cells (IECs), which include the physical segregation of commensal bacteria and the integration of microbial signals. Hence, IECs are crucial mediators of intestinal homeostasis that enable the establishment of an immunological environment permissive to colonization by commensal bacteria. In this Review, we provide a comprehensive overview of how IECs maintain host-commensal microbial relationships and immune cell homeostasis in the intestine.