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Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders


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Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual's quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, β-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area.
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Probiotics and Prebiotics: Present Status and Future
Perspectives on Metabolic Disorders
Ji Youn Yoo
and Sung Soo Kim
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea;
Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive
Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University,
Seoul 02447, Korea
* Correspondence:; Tel.: +82-2-961-0524
Received: 24 December 2015; Accepted: 11 March 2016; Published: 18 March 2016
Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD),
present an increasing public health concern and can significantly undermine an individual’s quality
of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times
higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic
disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle
changes over recent decades. Recently, the scientific community has considered alteration in gut
microbiota composition to constitute one of the most probable factors in the development of metabolic
disorders. The altered gut microbiota composition is strongly conducive to increased adiposity,
dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and
prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn
leads to insulin-signaling stimulation and cholesterol-lowering effects. We analyze the currently
available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the
treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current
paper explores the relevant contemporary scientific literature to assist in the derivation of a general
perspective of this broad area.
metabolic disorders; type 2 diabetes (T2DM); cardiovascular diseases (CVD); gut
microbiota; probiotics; prebiotics
1. Introduction
Metabolic diseases, such as type 2 diabetes (T2DM) and cardiovascular diseases (CVD), present an
important social problem, considering the increasing morbidity rate in both developing and developed
countries. Over the last decade, dynamic changes in dietary macronutrient ingestion and lifestyle have
rapidly increased the prevalence of metabolic disorders. T2DM patients have a higher risk of CVD, the
primary cause of death. Recently, scientists and nutritionists have proposed that metabolic disorders
might result from an alteration in gut microbiota composition [
]. Bacteroidetes and Firmicutes
are dominant (>90% of the total microbial population) in human intestine and play a significant
role in nutrient absorption, mucosal barrier fortification, xenobiotic metabolism, angiogenesis, and
postnatal intestinal maturation. Diet controls the composition of these bacteria, which are crucial in
the development of metabolic disorders [37].
The term “probiotic” originates from the Greek word meaning “for life” [
]. In 1989, Fuller
defined the term probiotic as “a live microbial feed supplement which beneficially affects the host
animal by improving its intestinal balance” [
]. In 1995, Gibson et al. defined prebiotics, on the other
hand, as “a non-digestible food ingredient that beneficially affects the host by selectively stimulating
Nutrients 2016, 8, 173; doi:10.3390/nu8030173
Nutrients 2016, 8, 173 2 of 20
the growth and/or activity of one or a limited number of bacteria in the colon” [
]. A long history of
human consumption of probiotics (particularly lactic acid bacteria and bifidobacteria) and prebiotics exists,
either as natural components of food or as fermented foods. In 76 B.C., the Roman historian Plinius
recommended the ingestion of fermented milk products to a patient who had gastroenteritis [
Probiotics and prebiotics began to blossom in the late 1800s and early 1900s. Subsequently, Metchnikoff
noticed health effects stemming from the alteration of the intestinal microbial balance, and he
proposed that the consumption of yogurt containing Lactobacillus would result in a decrease in
toxin-producing bacteria in the gut and an increase in the longevity of the host [
]. In 1900,
Tissier recommended the addition of bifidobacteria to the diet of infants suffering from diarrhea,
claiming that bifidobacteria superseded the putrefactive bacteria that caused the condition [
]. Since
then, numerous scientists have noticed that bacteria in the colon produce many different types of
compounds that maintain both positive and negative effects on gut physiology, as well as other systemic
influences [
]. As an example, short-chain fatty acids (SCFAs) are produced by the fermentation
of bacteria, when the bacteria in the colon metabolize proteins and complex carbohydrates. These
SCFAs may decrease the risk of developing metabolic disorders due to the increasing demand of
cholesterol for de novo synthesis of bile acids [
]. Probiotics and prebiotics are considered to be
alternative supplements against metabolic disorders, as the manner of their action is thought to be
based largely on a modulation of the composition and function of the intestinal microbiota. Several
studies have shown that probiotics and prebiotics play an important role in the amelioration of T2DM
and CVD [
]. A number of researchers studied the potential of food-grade bacteria for treating
or preventing diabetes. The studies indicated that certain probiotics (L. lactis, bifidobacteria) secrete an
insulin analog and promote the expected biological effect on target adipocytes both in human and
in animal subjects [
]. Accumulating evidence suggests that supplementation of probiotics and
prebiotics could have preventative and therapeutic effects on CVD due to a reduction in total serum
cholesterol, low-density lipoprotein (LDL-cholesterol), and inflammation [
]. This highlights a
growing recognition of the role of probiotics and prebiotics in modulating the metabolic activities of
the human gut microbiota and regulating the immune system, in turn improving the host’s health.
We analyze the current knowledge of the molecular mechanisms by which probiotics and
prebiotics participate in host functions that affect the prevention and treatment of metabolic disorders,
including T2DM, CVD, and obesity. The current review focuses on the important functions of probiotics
and prebiotics through relevant contemporary studies to assist in the derivation of a general perspective
of this broad area.
2. Gut Microbiota Compositions and Metabolic Disorders
Interactions between the gut microbiota and the host’s overall health begin at birth, and the nature
of microbial diversity changes throughout the host’s life. The interaction of gut epithelial cells with
microbes and their metabolites is a key mediator of the cross-talk between the gut epithelium and other
cell types [
]. Additionally, this interaction assists in maturation of the intestinal epithelial layer, the
enteric nervous system, the intestinal vascular system, and the mucosal innate immune system. Human
gut microbiota are strongly involved in diverse metabolic, nutritional, physiological, and immunological
processes, and changes in the composition of the gut microbiota directly influence the host’s health [
Although early intestinal microbiota studies focused on only a minority of bacteria species and their
functions, recent researchers have discovered more than 1100 bacteria species and were able to analyse
their functional properties as related to certain disease states, such as T2DM, CVD, obesity and cancer,
because of the development of advanced techniques, such as DNA-based analyses [
]. In particular,
changes of gut microbiota composition are strongly associated with increased adiposity,
-cell dysfunction,
metabolic endotoxemia, systemic inflammation, and oxidative stress associated with T2DM [28].
Intestinal microbiota can affect host adiposity and regulate fat storage which, in some cases,
can contribute to obesity [
]. The change in intestinal microbiota and the reduced bacterial
diversity were also observed in obese conditions. For example, Ley et al. demonstrated a significant
Nutrients 2016, 8, 173 3 of 20
relationship between gut microbiota composition and obesity. This study showed that the number
of Firmicutes increased while the number of Bacteroidetes decreased in obese mice compared to lean
mice [
]. Furthermore, other studies revealed that transplantation of microbiota from obese mice
into germ-free mice, despite reduced food intake, significantly increased adipose tissues compared to
transplantation of microbiota from lean mice [
]. Larsen et al. also demonstrated that the proportions
of Bacteroidetes to Firmicuteswere significantly and positively associated with reduction of glucose
tolerance. They showed that microbiome diversity was not different between T2DM and non-DM
patients, but the composition and function were different, including butyrate-producing bacteria
and opportunistic pathogens [
]. The change of these bacteria compositions increases susceptibility
to infections, immune disorders, inflammation, oxidative stress and insulin resistance, events that
are mediated by metabolic endotoxemia, which involves exposure to noxious intestinal products,
particularly lipopolysaccharides (LPS) [
]. LPS is a component of the gram-negative bacteria’s cell
wall. LPS binds to toll-like receptor-4 (TLR4) on endothelial cells, monocytes,and macrophages.
The reaction initiates an inflammatory response and oxidative stress, leading to the activation of
B and AP-1. These activations produce pro- inflammatory cytokines, chemokines, adhesion
molecules and reactive oxygen species (ROS), which can cause endothelial damage and dysfunction.
For example, trimethylamine N-oxide (TMAO) contributesto the development and progression of
cardiovascular disease and the early detection of myocardial injury [
]. TMAO, an oxidation product
of trimethylamine (TMA), is a relatively common metabolite of choline in animals [
]. Tang et al.
validated that increased TMAO levels are associated with increased risk of incidence of major adverse
cardiovascular events in a large independent clinical cohort (n = 4007). According to the study, people
in the highest quartile of circulating TMAO levels had a 2.5-fold increased risk of having a major
adverse cardiac event, when compared to those in the lowest quartile [
]. Furthermore, TMAO levels
were dose-dependently related to obesity and insulin resistance in animal studies [
]. Although the
mechanisms by which circulating TMAO promotes CVD are currently unclear, there is a possible
hypothesis of cardiovascular physiology. Expression of scavenger receptors (CD36 and SR-A1) on
macrophages and foam cell formation were increased by supplementation of TMAO in normal chow
diet mice [
]. Furthermore, supplementation of TMAO reduces reverse cholesterol transport in
macrophage, which would be predicted to advance atherosclerosis [
]. Although supplementation
of TMAO clearly influences multiple steps of both forward and reverse cholesterol transport, the
underlying molecular mechanisms behind these observations remain unclear. Therefore, further
study should be performed to elucidate how circulating TMAO levels are sensed to elicit pathological
responses and to explain mechanisms by which TMAO promotes CVD.
Numerous studies also support the theory that gut microbiota can influence host immune
functions. Gut microbiota cooperate with the host immune system through an extensive array of
signalling pathways, which involve many different classes of molecules and extend beyond the
immune system. These immune-mediated signalling processes are directly associated with chemical
interactions between the microbe and the host.
3. Probiotics
The definition of a probiotic is “a live microbial feed supplement which beneficially affects the host
animal by improving its intestinal balance” [
]. The initial concept of probiotics originated from the
work of Metchnikoff at the beginning of the 20th century. Subsequently, Shaper et al. (1963) and later
Mann (1974) observed a reduction in serum cholesterol after consumption of copious amounts of milk
fermented with wild Lactobacillus and/or Bifidobacterium [
]. Probiotics have been investigated as a
potential dietary supplement that can positively contribute to an individual’s health [
]. These health
benefits are not limited to the intestinal tract, but also include amelioration of systemic metabolic
disorders, such as T2DM and CVD.
Since probiotics have been recognized as a key health promoter thought to stem from the
modulation of host immune responses [
], earlier studies have mainly focused on the relationship
Nutrients 2016, 8, 173 4 of 20
between probiotics and immune diseases, such as atopic dermatitis and inflammatory bowel disease.
Intestinal bacteria, including Lactobacilli and Bifidobacterium, can cross the intestinal mucous layer
and stimulate phagocytic activities in the spleen or in other organs for many days [
]. Proliferative
responses of spleen cells to concanavalin A (a T-cell mitogen) and lipopolysaccharide (a B-cell mitogen)
were significantly enhanced in mice supplied with Lactobacillus rhamnosus, Lactobacillus acidophilus, or
Bifidobacterium. Despite administration of these probiotics, the mice did not exhibit any significant
increase in interleukin-4 production by spleen cells nor peripheral blood leucocytes. Instead, spleen
cells from mice that consumed these probiotics produced significantly higher amounts of interferon-
response to stimulation with concanavalin A, compared to cells from the control animals [46].
Several studies have demonstrated that patients with T2DM have a significantly lower number of
bacteria that produce butyrate when compared to healthy people. Larsen et al. showed an association
between T2DM and compositional changes in the intestinal microflora. In particular, they demonstrated
a considerably lower proportion of phylum Firmicutes and bifidobacteria in T2DM patients than
in non-diabetic individuals [
]. Interestingly, several studies have revealed that probiotics
and prebiotics might maintain the potential to improve lipid profiles, including the reduction of
LDL-cholesterol, serum/plasma total cholesterol, and triglycerides or increment of high-density
lipoprotein (HDL-cholesterol) in the context of treating CVD [
]. Previous studies have
proven that the administration of certain probiotics can promote short-chain fatty acids (SCFAs) that
alter secretion of incretin hormones and attenuate cholesterol synthesis [53].
4. Prebiotics
A prebiotic was first defined as “a non-digestible food ingredient that beneficially affects the host
by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon,
and thus improves host health” [
]. Subsequently, Roberfroid stated that “A prebiotic is a selectively
fermented ingredient that allows specific changes, both in the composition and/or activity in the
gastrointestinal microflora that confers benefits upon host well-being and health.” [
]. Gibson et al.
examined three criteria, namely: (a) resistance to gastric acidity, hydrolysis by mammalian enzymes,
and gastrointestinal absorption; (b) fermentation by intestinal microflora; and (c) selective stimulation
of the growth and/or activity of intestinal bacteria associated with health and well-being [
]. Currently,
the prebiotics that fulfill these three criteria are fructooligosaccharides, galactooligosaccharides, lactulose,
and non-digestible carbohydrates. The non-digestible carbohydrates include large polysaccharides (inulin,
resistant starches, cellulose, hemicellulose, pectins, and gums), some oligosaccharides that escape digestion,
and unabsorbed sugars and alcohols. Most prebiotics, including fructooligosaccharides and inulin, are
digested by bifidobacteria and stimulate the growth of their colonies. These bacteria influence homeostasis
of intestinal cells and inhibit the growth of pathogenic bacteria [5658].
SCFAs, such as acetic acid, propionic acid, and butyric acid, are the essential end-products of
carbohydrate metabolism. Fermentation of carbohydrates represents a major source of energy for epithelial
cells in the colon [
]. SCFAs reduce the development of gastrointestinal disorders, cardiovascular
diseases, and cancers by inducing apoptosis (programmed cell death) [
]. Furthermore, prebiotics
could stimulate the immune system, produce Vitamin B, inhibit pathogen growth, and lower blood
ammonia. They also appear instrumental in promoting cell differentiation, cell-cycle arrest, and apoptosis
of transformed colonocytes by inhibiting the enzyme histone deacetylase and decreasing the transformation
of primary to secondary bile acids [
]. Moreover, SCFAs decrease glucagon levels in a dose-dependent
manner, improve glucose tolerance, and activate glucagon-like peptide1 (GLP-1), which can stimulate the
elevation of insulin production and increase insulin sensitivity [
]. Thus, administration of prebiotics
probably plays a regulatory role in modulating endogenous metabolism.
5. Effects of Probiotics and Prebiotics on T2DM
Over recent decades, an abundance of evidence has emerged to suggest a close link between T2DM,
CVD, and inflammation. Insulin plays an important role in the regulation of glucose homoeostasis
Nutrients 2016, 8, 173 5 of 20
and lipid metabolism. The failure of target organs to respond to the normal action of insulin is termed
insulin resistance, which in turn often results in compensatory hyperinsulinemia. This hyperinsulinemia
leads to an array of metabolic abnormalities thought to constitute the pathophysiologic basis of
metabolic syndrome which can lead to CVD and coronaryheart disease [63].
Moreover, an excess accumulation of visceral fat leads to insulin resistance. In addition, this
excess causes a chronic low-grade inflammation characterized by increased macrophage infiltration and
pro-inflammatory adipokine production. Pro-inflammatory adipokines obstruct the insulin-signaling
pathway in peripheral tissues and promote the development of insulin resistance [
]. These data
indicate that T2DM is associated with a state of chronic low-level inflammation that leads to the
development of CVD. The molecular and cellular underpinnings of obesity-induced inflammation and
the signaling pathways at the intersection of metabolism and inflammation contribute to T2DM and
CVD [51,52,65].
SCFAs maintain important functions in T2DM patients. Interestingly, some studies have found
that the number of SCFAs producing bacteria were significantly lower in people with T2DM. These
SCFAs not only bind to G-protein coupled receptors (GPCRs), but also cause the exhibition of various
biological effects. For example, SCFAs promote secretion of GLP-1, one of the major incretin hormones
primarily synthesized by entero-endocrine L-cells. This hormone inhibits glucagon secretion, decreases
hepatic gluconeogenesis, improves insulin sensitivity, and enhances central satiety, resulting in
weight loss [
]. Furthermore, some evidence indicates that SCFAs may directly prevent low-grade
inflammatory response, as bacteria actively translocate from the intestines into the mesenteric
adipose tissue (MAT) and the blood. Amar et al. proved that certain probiotics (e.g., Bifidobacterium
animalis subsp. lactis 420) could reverse the low-grade inflammatory response by reducing mucosal
adherence and bacterial translocation of gram-negative bacteria from the Enterobacteriaceae. As a result,
probiotics may attenuate adipose tissue inflammation and several features of T2DM [48]. Asemi et al.
demonstrated the effects of oral supplements of probiotics on metabolic profiles, high sensitivity
C-reactive protein (hs-CRP), and oxidative stress in T2DM. In this randomized, placebo-controlled, and
parallel designed study, they utilized an oral supplement comprising seven viable and freeze-dried
strains: Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus bulgaricus,
Bifidobacterium breve, Bifidobacterium longum, and Streptococcus thermophilus. The test subjects ingested
the supplement for eight weeks. The results indicated that the consumption of multi-probiotics led to
a meaningful reduction in fasting plasma glucose compared to the placebo group [67].
Additionally, probiotics could promote antioxidation in T2DM patients. Erythrocyte superoxide
dismutase, glutathione peroxidase activities, and total antioxidants increased in the group
supplemented with probiotic yogurt compared to the control group [
]. Administration of Lactobacillus
acidophilus and Lactobacillus casei with dahi (yogurt in the Indian subcontinent) significantly suppressed
streptozotocin (STZ)-induced oxidative damage in pancreatic tissues by inhibiting the lipid peroxidation
and nitric-oxide formation [
]. Yadav et al. also demonstrated that administration of the probiotic dahi
in the diet significantly delayed the onset of glucose intolerance, hyperglycemia, hyperinsulinemia, and
dyslipidemia, and decreased oxidative stress in high fructose-induced diabetic rates [70].
In contrast, few papers demonstrated that probiotics fail to maintain significant effects on the lipid
profiles of T2DM patients. One of these studies concluded that supplementation of probiotics failed to
cause significant changes in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (TG),
TG/LDL, or LDL/HDL ratios, following eight weeks of intervention [
]. Additionally, Lewis et al.
showed that lactobacillus acidophilus administered to 80 hypercholesteraemic volunteers for six weeks
failed to produce any significant effects of probiotics on serum blood lipid [
]. Although some
studies showed no benefits of probiotics on serum lipids, numerous animal or human studies have
demonstrated the benefits of probiotics and prebiotics. Hence, further studies are required to improve
our knowledge of, and eliminate uncertainties regarding, probioticsand prebiotics (Tables 1 and 2).
Nutrients 2016, 8, 173 6 of 20
Table 1. Characteristics of the included animal studies.
Intervention Type
Name of
Pro/Prebiotic Strains
Study Type
Pro/Prebiotic Type
and Dose (Per Day)
Duration of
without Change
Rice bran (10
30 g/kg
4 weeks
Decreased serum total cholesterol
Increase 6-desaturase activity and
serum arachidonic acid
Fukushima et al.,
1999 [74]
B. lactis Bb-12,
B. longum Bb-46
Buffalo milk yoghurt
and soy-yoghurt
4 weeks
Decreased total cholesterol
and LDL-C
Increasedfecal excretions of bile acids
Abd El-Gawad et al.,
2005 [75]
Probiotics L. plantarum PH04 Mice
Human isolate
14 days
Decreased total cholesterol and TG
Increased fecal lactic acid bacteria
Nguyen et al.,
2007 [76]
L. acidophilus,
L. casei,
L. lactis biovar
Rats Dahi 15% (150g/kg) 8 weeks
Decreased glucose intolerance,
hyperglycemia, hyperinsulinemia,
dyslipidemia and oxidative stress
Yadav et al.,
2007 [70]
L. acidophilus NCDC14,
L. casei NCDC19
(73 ˆ 10
28 days
Inhibition of insulin depletion, lipid
peroxidation and nitrite formation
Yadav et al.,
2008 [69]
Probiotics B. animalis lactis 420 Mice
6 weeks
Decreased glucose intolerance, tissue
inflammation, insulin resistance and
secondarily glycaemia
Amar et al., 2011 [
Prebiotics Inulin Rats 5% 4 weeks
Decrease LDL-C, total cholesterol,
Liver lipid and TG concentrations
Increased HDL-C, and faecal
excretions of bile acids
Kim et al., 1998 [77]
Abbreviations: Bifidobacterium (B), lactobacillus (L), streptococcus (S), colony forming units (CFU), tab (tablet), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
(HDL-C), triglycerides (TG).
Nutrients 2016, 8, 173 7 of 20
Table 2. Characteristics of the included human studies.
Intervention Type
Name of
Pro/Prebiotic Strains
Study Type
Pro/Prebiotic Type
and Dose (Per Day)
Duration of
Parameter without
Probiotics L. acidophilus L1, Human
Fermented milk
200 mL/day
4 weeks Decreased total cholesterol
Anderson et al.,
1999 [78]
Probiotics B. longum BL1 Human/Rats
Fermented milk
100 mL/3 ˆday
4 weeks
Decreased total cholesterol,
LDL-C and TG
Xiao et al.,
2003 [79]
Probiotics L. acidophilus LA-1 Human
Two tablet/day
(3 ˆ 10
6 weeks
Total cholesterol,
Lewis et al.,
2005 [73]
Probiotics L. fermentum Human
Freeze-dried Two
tablet/2 ˆ day
(2 ˆ 10
10 weeks
Total cholesterol,
liver enzymes
Simons et al.,
2006 [80]
Probiotics L. casei subsp. casei. Human
Yogurt 100 g/day and
200 g/day
6 weeks
Decreased total cholesterol
and LDL-C
Increased HDL-C
Fabian et al.,
2006 [81]
L. rhamnosus LC705,
shermaniistrain JS
Two tablet/day
(2 ˆ 10
4 weeks
Total cholesterol,
Hatakka et al.,
2008 [82]
L. acidophilus La5,
B. lactis Bb12
Yogurt 300 g/day
(2 ˆ 10
6 weeks
Decreased total cholesterol
and LDL-C
Ejtahed et al.,
2011 [22]
L. acidophilus La5,
B. lactis Bb12
Yogurt containing
300 g/day
(2 ˆ 10
6 weeks
Decreased fasting blood
glucose levels and HbA
Increased erythrocyte
superoxide dismutase,
glutathione peroxidase
activities and total
Insulin concentration
Ejtahed et al.,
2012 [68]
L. acidophilus,
L. casei,
L. rhamnosus,
L. bulgaricus,
B. breve,
B. longum,
S. thermophiles
One tablet/day
(14 ˆ 10
8 weeks
Decreased serum hs-CRP
Increased plasma total GSH
Prevention of a rise in
fasting plasma glucose
Asemi et al.,
2013 [67]
Nutrients 2016, 8, 173 8 of 20
Table 2. Cont.
Intervention Type
Name of
Pro/Prebiotic Strains
Study Type
Pro/Prebiotic Type
and Dose (Per Day)
Duration of
Parameter without
L. casei,
L. acidophilus,
L. rhamnosus,
L. bulgaricus,
B. breve,
B. longum,
S. thermophiles,
One tablet/day
500 mg/tab
8 weeks
Positive effects on systolic
blood pressure
Total cholesterol,
TG/LDL and
LDL/HDL ratios
Mahboobi et al.,
2014 [71]
Prebiotics Inulin Human
cereal (18%)
4 weeks
Decreased total cholesterol
and TG
Increased breath H2
excretion and fecal
lactic acid
Brighenti et al.,
1995 [83]
Prebiotics Inulin Human
One pint of vanilla ice
cream (20 g/pint)
3 weeks
Decreased total cholesterol
and TG
Causey et al.,
2004 [84]
Abbreviations: Bifidobacterium (B), lactobacillus (L), streptococcus (S), colony forming units (CFU), tab (tablet), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
(HDL-C), triglycerides (TG).
Nutrients 2016, 8, 173 9 of 20
6. Effect of Probiotics and Prebiotics on CVD
Cardiovascular disease (CVD) affects blood vessels and/or the heart. CVD primarily stems
from hypercholesterolemia and dyslipidemia. Particularly, a high level of LDL-cholesterol is most
commonly associated with CVD. CVD represents the most prevalent cause of death in T2DM patients.
The relative risk of CVD is two to four times higher in T2DM patients than in non-diabetic people.
The most common lipid pattern in people with CVD consists of increased triglyceride-rich lipoproteins,
high levels of LDL-cholesterol, and low levels of HDL-cholesterol.
Healthy nutrition and lifestyle intervention constitute important parts of managing CVD.
Hypercholesterolemia patients may avoid the use of cholesterol-lowering drugs by practicing dietary
control or through administration of probiotics and/or prebiotics. Health food supplements, such
as probiotics and prebiotics, can modulate gut health and regulate the immune system through gut
microbiota. Persuasive studies have shown that well-established probiotics and/or prebiotics possess
hypocholesterolaemic effects in humans and animals. Nguyen et al. demonstrated that total serum
cholesterol and triglycerides were significantly reduced in hypercholesterolaemic mice that ingested
Lactobacillus plantarum PH04 [
]. Moreover, some studies supportedthatbuffalo milk yogurt and
soymilk yogurt containing Bifidobacterium Bb-12 or Bifidobacterium longum Bb-46 were highly effective in
decreasing the concentration of total cholesterol by 50.3%, LDL- cholesterol by 56.3%, and triglycerides
by 51.2% compared to the levels of the control group [
]. Anderson et al. completed a similar
study, but they utilized a different probiotic called Lactobacillus acidophilus L1. They showed that daily
consumption of 200 g of yogurt containing Lactobacillus acidophilus after each dinner contributed to a
significant reduction in serum cholesterol concentration compared to the placebo group [
]. Another
study indicated that the combination of bacteria strains more effectively reduced total cholesterol and
liver cholesterol compared to individual bacteria strains. The supplied mixed-bacteria and Lactobacillus
acidophilus groups exhibited a 23%–57% decrease of cholesterol concentrations in the liver compared to
the control group. Additionally, cholesterol concentration in the supplied mixed-bacteria group was
lower than in single-bacteria supplemented groups [74].
Prebiotics may lead to hypocholesterolemia via two different mechanisms. First, lower cholesterol
absorption is caused by enhanced cholesterol excretion via feces. The other mechanism is the
production of SCFAs upon selective fermentation by intestinal bacterial microflora [
]. Causey et al.
concluded that a daily intake of 20 g of inulin (longer-chain prebiotics, containing 9–64 links per
saccharide molecule, fermented more slowly) significantly reduced serum triglycerides compared to
the control group. They also found that serum LDL-cholesterol decreased and serum HDL-cholesterol
increased following the administration of inulin compared to the control group [
]. Another study
showed that when normolipidemic individuals consumed 18% of inulin on a daily basis without any
other dietary restrictions, total plasma cholesterol and triacylglycerols decreased by
7.9% ˘ 5.4%
7.8%, respectively. Glucose tolerance tests demonstrated that inulin significantly enhanced
breath H2 excretion (IAUC test 280
40; placebo 78
26 ppm
h), as well as fecal concentration
of Lactobacillus-lactate [
]. Thus, inulin may possess lipid-lowering potential in normolipidemic
people, possibly mediated by mechanisms related to colonic fermentation. The addition of inulin
in the diet of rats induced higher excretions of fecal lipids and cholesterol compared to that of
rats in the control group. This increased level of excretion is attributed primarily to reduced
cholesterol absorption [
]. Other prebiotics, such as oligodextrans, lactose, resistant starches and their
derivatives, lactoferrin-derived peptides, and N-acetylchitooligosaccharides have also been identified
as maintaining hypocholesterolaemic effects in people with T2DM who are at high risk of developing
CVD [55].
Although numerous studies have documented the cholesterol-lowering effects of probiotics
and/or prebiotics in both
in vitro
in vivo
experiments, the effects remain controversial. Hatakka et al.
refuted the purported hypocholesterolaemic effect of probiotics, and reported that the administration
of Lactobacillus rhamnosus LC705 failed to influence blood lipid profiles in 38 men with mean cholesterol
levels of 6.2 mmol/L after a four-week treatment period [
]. Lewis et al. argued that the administration
Nutrients 2016, 8, 173 10 of 20
of Lactobacillus acidophilus failed to affect any serum lipid changes [
]. Furthermore, Simonsa et al.
showed that a supplement of Lactobacillus fermentum failed to significantly change plasma total
cholesterol, LDL-cholesterol, HDL-cholesterol, or triglycerides [
]. Although many studies suggest
that probiotics can favorably alter serum lipids, some human studies examining the benefits of
probiotics on serum lipids have shown conflicting results. This may bedue to the possibility that
different delivery systems may affect the experiment result. The human studies, which used capsules
probiotics, did not show significant changes inserum lipids compared to fermented bacteria product.
A study assumed that sufficient time was not available for the freeze-dried probiotic capsule to become
metabolically fully activated before being flushed into the colon. They thought that fermented dairy
products can be metabolically active when ingested, whereas freeze-dried probiotic capsules cannot
because the small intestinal transit is relatively short [
]. Furthermore, during the intervention,
the human studies could not control for an individual’s life style, including dietary intake, whereas
animal studies could, which may be one of the possible reasons for the apparent lack of effect.
Therefore, further researches are required to unequivocally establish the potential role ofprobiotics in
the management of metabolic disorder (Tables 1 and 2).
7. Others (Obesity)
Obesity causes low-grade inflammation and an altered composition of the gut microbiota.
Some studies have attempted to identify correlations between the composition of the microbiota
and the occurrence of inflammation and metabolic alterations in individuals with obesity [
The low-grade systemic inflammation in the obese phenotype is attenuated by peptides produced in
the gut. The composition of gut microbiota affects synthesis of these peptides. One such protein is
the serum amyloid A3 protein (SAA3). The gut microbiota serve to regulate SAA3 expression in the
adipose tissue [
]. Expression of this peptide was considerably higher in the adipose tissue and
colon of mice colonized with a normal gut microbiota from a healthy wild-type mouse when compared
with germ-free mice [
]. Collectively, these findings suggest that the gut microbiota modulate the
biological systems that regulate the availability of nutrients, energy storage, fat mass development, and
inflammation in the host, each of which is associated with the obese phenotype [
]. Significantly, the
number of bifidobacteria is inversely correlated with fat mass, glucose intolerance, and LPS level [
Furthermore, inulin-type fructans affect gut ecology and stimulate immune cell activity. They also
decrease weight gain and fat mass in obese individuals [9698].
8. Molecular Mechanisms of Action
Several hypotheses have been presented to explain how the mechanistic actions of probiotics and
prebiotics, including the improvement of gut microbiota, the stimulation of insulin signaling, and the
lowering of cholesterol, ameliorate the T2DM and CVD condition. Among the molecular mechanisms,
the current paper focuses on SCFA receptors and bile-salt hydrolase (BSH) that are associated with
regulation of insulin secretion, fat accumulation, and cholesterol levels.
Recently, two orphan GPCRs, GPR41 (known as FFAR3) and GPR43 (known as FFAR2), were
found to be receptors for SCFAs, including acetate, propionate, and butyrate. FFAR2 is primarily
activated by acetate and propionate, whereas FFAR3 is more often activated by propionate and
butyrate [
]. Both receptors are mainly expressed in L cells, which are located along the length of
the intestinal epithelium and respond directly to luminal signals [
]. FFAR2 and FFAR3 stimulate
the release of GLP-1 and peptide YY (PYY), which improve insulin secretion. The expression levels of
GLP-1 and PYY are often reduced in individuals with T2DM. Therefore, enhancement of GLP-1 and
PYY secretion from intestinal L cells could result in beneficial effects in people with T2DM.
Several studies have shown that a deficiency of FFAR2 decreases SCFA-induced secretion of GLP-1
in vitro
in vivo
, and enhances insulin resistance. The injectable GLP-1 mimetics are associated
with good blood glucose control and a decreased incidence of hypoglycemia [
]. In addition,
FFAR2 regulates energy metabolism via promotion ofleptin secretion, adipogenesis, and inhibition of
Nutrients 2016, 8, 173 11 of 20
lipolysis in adipose tissue and adipocytes [
]. Obesity is frequently observed in FFAR2-deficient
mice on a normal diet, while overexpressed FFAR2 in adipose tissue mice remain lean, even though the
mice are fed a high-fat diet. Isoproterenol-induced lipolysis is inhibited by SCFSs in a dose-dependent
manner in mouse 3T3-L1 derived adipocytes [
]. Kimura et al. concluded that FFAR2 activation
by SCFAs suppressed adipose-specific insulin signaling in white adipose tissues, and thus led to the
inhibition of fat accumulation [105].
Similarly, Samuel et al. demonstrated that germ-free mice with or without FFAR3 were colonized
by specific microbes. The results showed that PYY levels were decreased in FFAR3-deficient mice,
indicating that the secretion of PYY from the intestine was regulated by SCFA-induced FFAR3
Moreover, FFAR3 is abundantly expressed in sympathetic ganglia. Inoue et al. showed that
SCFA-induced FFAR3 activation resulted in increased heart rate and energy expenditure through
sympathetic activation. Notably, the effects were not observed in FFAR3-deficient mice. FFAR3
also directly promotes noradrenalin release from sympathetic neurons [
]. In contrast, FFAR3
suppresses energy expenditure and produces
-hydroxybutyrate in the liver during starvation. Thus,
sympathetic activity is regulated by SCFA-induced FFAR3, thereby maintaining energy balance.
Additional research has indicated that SCFAs are involved in the regulation of hepatic cholesterol
synthesis [
], as demonstrated via
in vitro
experiments of the liver of germ-free mice. The liver
metabolism of germ-free and colonized mice differs considerably, possibly due to the increased influx
of SCFAs into the liver of colonized mice [
]. The increased levels of stored triglycerides in the
liver and the increased production of the triglyceride transporters were observed in colonized mice.
Increased triglyceride synthesis in the liver of colonized mice was associated with reduced expression
of fasting-induced adipose factors, or angiopoietin-like 4 (ANGPTL4), in the small intestine. ANGPTL4
inhibits circulating lipoprotein lipase (LPL), which regulates the cellular uptake of triglycerides
in adipocytes [
]. ANGPTL4 is also a downstream target gene of peroxisome proliferator
activated receptors (PPARs), the agonists of which are widely utilized for the treatment of T2DM
and CVD [
]. PPAR-
mainly plays an important role in hepatic fatty acid oxidation, whereas
constitutes the master regulator of adipogenesis [
]. Moreover, research has indicated that
overexpression of ANGPTL4 in the liver leads to decreased activation of LPL and increased plasma
triglyceride levels [
]. Interestingly, ANGPTL4 is susceptible to regulation by the gut microbiota [
Germ-free ANGPTL4-deficient mice gained considerably more fat mass and body weight compared
to colonized mice during high-fat feeding, indicating that ANGPTL4 directly mediates microbial
regulation of adiposity in mice [
]. Thus, ingestion of SCFAs-producing probiotics could increase
influx of SCFAs into the liver, leading to regulation of ANGPTL4 (Figure 1).
SCFA-producing bacteria primarily produce acetate, butyrate, and propionate, which leads to
increased FFAR2 and FFAR3 activation. These enhancements of FFAR2 and FFAR3 not only promote
noradrenalin release, but also increase heart rate and energy expenditure for energy homeostasis.
SCFAs are involved in increased leptin secretion, adipogenesis, and the inhibition of lipolysis in
adipose tissues. In the intestine, SCFAs enhance the secretion of PPY and GLP-1. Moreover, an
improvement of triglyceride synthesis occurs due to an influx of SCFAs into the liver, which leads to
decreased ANGPTL4 activation in the intestines. In addition, SCFA-producing bacteria regulate the
suppression of ANGPTL4, an inhibitor of LPL, which promotes increased lipid clearance.
Enzymatic deconjugation of bile acids by bile-salt hydrolase (BSH) has been proposed as
an important molecular mechanism in cholesterol-lowering effects. Researchers evaluated BSH’s
cholesterol-lowering effect utilizing Lactobacillus plantarum 80 and Lactobacillus reuteri, whereupon it
was shown that the enzyme responsible for bile-salt deconjugation in enterohepatic circulation can
be detected in probiotics indigenous to the gastrointestinal tract [
]. Bile consists of conjugated
bile acids, cholesterol, phospholipids, bile pigment, and electrolytes. Synthesized in the liver, bile
is stored at high concentrations in the gallbladder between meals. After food intake, it is released
into the duodenum. Bile works as a biological detergent that emulsifies and solubilizes lipids for
digestion. BSH catalyzes the hydrolysis of glycine or taurine conjugated primary bile acids to create
Nutrients 2016, 8, 173 12 of 20
deconjugated bile acids. The deconjugated bile acids are less soluble and less efficiently reabsorbed
than their conjugated counterparts, leading to their elimination in the feces [
]. Deconjugation of
bile salts can lead to a reduction in serum cholesterol either by increasing the demand for cholesterol
for de novo synthesis of bile acids to replace those lost in feces or by reducing cholesterol solubility
and, thereby, absorption of cholesterol through the intestinal lumen [
]. Figure 2 shows the
mechanism of enzymatic deconjugation of bile acids by bile-salt hydrolase (BSH).
Nutrients2016,8,173 12of20
increased FFAR2 and FFAR3 activation. These enhancements of FFAR2 and FFAR3 not only
promote noradrenalin release, but also increase heart rate and energy expenditure for energy
lipolysis in adipose tissues. In the intestine, SCFAs enhance the secretion of PPY and GLP1.
which leads to decreased ANGPTL4 activation in the intestines. In addition, SCFAproducing
Enzymaticdeconjugationofbile acids by bilesalthydrolase(BSH)hasbeenproposed as an
important molecular mechanism in cholesterollowering effects. Researchers evaluated BSH’s
the duodenum. Bile works as a biological detergent that emulsifies and solubilizes lipids for
counterparts,leadingtotheireliminationinthefeces [43,122].Deconjugation
of bile salts can lead to a reduction in serum cholesterol either by increasing the demand for
cholesterolfordenovosynthesisofbileacidstoreplacethoselostinfecesorby reducingcholesterol
solubility and, thereby, absorption ofcholesterol
through the intestinal lumen [121,123]. Figure 2
Figure 1. Molecular mechanisms of short-chain fatty acid (SCFA) receptors.
Nutrients2016,8,173 13of20
Cholesterol is utilized as the precursor for synthesis of new conjugated bile acids, and the
and/or prebiotics. Key issues in this field are safety and efficacy. Currently, some probiotics
secondary bile acids in the enterohepatic circulation, which in turn could increase the risk of
or colorectal cancer [125]. Lithocholic acid (LCA) is a secondary bile acid primarily
The genetic interactions between ingested probiotics and the native intestinalmicrobeshave
by DNA may be enhanced upon the ingestion of bacteria, leading to genetic rearrangements. In
Figure 2. bile-salt hydrolase (BSH) effects on lowering cholesterol by probiotics.
Nutrients 2016, 8, 173 13 of 20
Cholesterol is utilized as the precursor for synthesis of new conjugated bile acids, and the
activation of BSH by probiotics catalyzes primary bile acids to create deconjugated bile acids that are
less soluble and less efficiently reabsorbed in the intestine and liver. Decongugated bile acids also
contribute to the elimination of cholesterol in the feces.
9. Future Prospects
in vivo
in vitro
studies have been conducted utilizing an array of probiotics
and/or prebiotics. Key issues in this field are safety and efficacy. Currently, some probiotics
(Lactobacillus, Bifidobacterium) and prebiotics (inulin, oligofructose) do not require approval from
the FDA and are present in our daily dietary intake. Although the safety of probiotics and prebiotics
for food application has been confirmed by several legal authorities worldwide, few studies have been
conducted regarding incidences of bloating, flatulence, and high osmotic pressure, which can lead to
gastrointestinal discomfort [
]. Furthermore, the effects could vary depending on the individual
and the type of food containing the prebiotics or probiotics. Probiotics and prebiotics are believed to
be safe for oral consumption due to their relatively low capacity to cause adverse effects. However,
no standard safety guidelines currently exist for oral administration of probiotics and prebiotics in
human cases. Therefore, individual probiotics and prebiotics should be evaluated at specific dosages
to ascertain potential adverse reactions.
Although BSH was shown to be beneficial, it may lead to an increase in potentially cytotoxic
secondary bile acids in the enterohepatic circulation, which in turn could increase the risk of cholestasis
or colorectal cancer [
]. Lithocholic acid (LCA) is a secondary bile acid primarily formed in the
intestines by the bacteria. Trauner et al. and Beilke et al. showed that administration of LCA and its
conjugates to animals causes intrahepatic cholestasis. In humans, abnormal bile acid composition,
especially an increase in LCA, was found in patients suffering from chronic cholestatic liver disease or
cystic fibrosis [
]. However, most studies argued mainly for the benefits rather than the adverse
effects of BSH from probiotics and/or prebiotics.
The genetic interactions between ingested probiotics and the native intestinal microbes have also
constituted a topic of interest. The genetic materials can be exchanged via three mechanisms, including
transduction, conjugation, and transformation. The transformation of intestinal microflora by DNA
may be enhanced upon the ingestion of bacteria, leading to genetic rearrangements. In addition, the
transmission of antibiotic-resistantgenes among beneficial bacteria and harmful pathogens could be
associated with a complex microflora colony in the gastrointestinal tract. This transmission can, in
turn, lead to the evolution of antibiotic-resistant probiotics and the potential emergence of resistant
pathogens [128131].
10. Conclusions
Metabolic disorders are undoubtedly associated with an increased risk of morbidity and mortality.
In our study, we sought to evaluate the effect of probiotics and prebiotics in the context of metabolic
disorders. Intestinal microbiota may play an important role in the pathogenesis of T2DM and CVD by
influencing body weight, pro-inflammatory activity, and insulin resistance. The scientific community,
in general, accepts that the gut microbiota composition and function can be regulated via probiotics
and prebiotics. Numerous studies have indicated that probiotics and prebiotics affect T2DM and
CVD by changing gut microbiota, regulating insulin signaling, and lowering cholesterol. However,
elucidating the interactions between intestinal microbiota and ingested probiotics continues to present
a challenge.
Some of the proposed mechanisms and experimental evidence specifically targeting
cholesterol-lowering effects remain equivocal. Therefore, more specific and thoroughly designed
in vivo
trials are required to improve our knowledge and eliminate uncertainties. This will, in turn, provide
a deeper understanding of the underlying mechanisms and enable us to conduct a more optimal
safety assessment prior to the consumption of probiotics and prebiotics by humans. Moreover, no
Nutrients 2016, 8, 173 14 of 20
standard safety guidelines currently exist regarding the oral administration of probiotics and prebiotics
in human cases. Therefore, individual probiotics and prebiotics should be carefully evaluated in order
to determine potential adverse reactions. Future studies are required to increase our understanding of
the complex interplay between intestinal and ingested microbiota.
This work was supported by the National Research Foundation of Korea (NRF), and the
grant was provided by the Korean government (MEST) (No. 2011–0030072).
Author Contributions: Ji Youn Yoo and Sung Soo Kim conceived, designed, and drafted the manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
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... Ultimately, the reduction of GI symptoms with probiotic supplementation may lead to maintained or even improved athletic performance [17]. The intake of prebiotics, fermented food ingredients that can induce the activity of certain microorganisms, has also shown potential for modifying the microbiome [18]. Improved GI and immune system function but also improved mental health have been associated with prebiotics [4,18]. ...
... The intake of prebiotics, fermented food ingredients that can induce the activity of certain microorganisms, has also shown potential for modifying the microbiome [18]. Improved GI and immune system function but also improved mental health have been associated with prebiotics [4,18]. Therefore, the intake of both probiotics and prebiotics may benefit athletes [4,18]. ...
... Improved GI and immune system function but also improved mental health have been associated with prebiotics [4,18]. Therefore, the intake of both probiotics and prebiotics may benefit athletes [4,18]. To our knowledge, no studies have been conducted on the effects of these supplements in wheelchair athletes. ...
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Background Gastrointestinal (GI) problems represent a health burden in Para athletes and can ultimately reduce athletic performance. This study aimed to evaluate the feasibility of a randomized controlled crossover trial (RCCT) assessing the effects of probiotic and prebiotic supplementation on the health of Swiss elite wheelchair athletes. Methods The RCCT was conducted between March 2021 and October 2021. Athletes were randomized to receive either a daily probiotic (3 g of probiotic preparation, including eight bacterial strains), or a daily prebiotic (5 g of oat bran) supplementation first. After the first supplementation phase (4 weeks), a washout period (4 weeks) and the second crossover supplementation phase (4 weeks) followed. Data were collected at four study visits (every 4 weeks) and included 3-day training and nutrition diaries, the Gastrointestinal Quality of Life Index (GIQLI) questionnaire, stool samples, and fasting blood samples. The study assessed the feasibility criteria such as recruitment rate, retention rate, success of data collection, adherence to the protocol, willingness to participate, and safety. Results This pilot study met the majority of the predefined minimum requirements for the feasibility criteria. Out of 43 invited elite wheelchair athletes, 14 (33%) consented (mean (standard deviation) age: 34 (9) years, eight females, 11 with a spinal cord injury). The desired sample size was not reached, but the achieved recruitment rate was modest, especially considering the population studied. All participating athletes completed the study. With the exception of one missing stool sample and two missing diaries, data were successfully collected for all athletes at all four visits. Most athletes adhered to the daily intake protocol for at least 80% of the days, both for probiotics (n = 12, 86%) and prebiotics (n = 11, 79%). Ten (71%) athletes would be willing to participate in a similar study again. No serious adverse events occurred. Conclusion Despite the limited number of elite wheelchair athletes in Switzerland and the modest recruitment rate, the implementation of a RCCT in elite wheelchair athletes is feasible. The data collected in this study provide essential information for the design of the subsequent study which will include a larger cohort of physically active wheelchair users. Trial registration Swiss Ethics Committee for Northwest/Central Switzerland (EKNZ), 2020–02337)., NCT04659408.
... Gut dysbiosis may provide a way for the pathogenesis of metabolic disorders such as obesity, diabetes mellitus type 2 (DM2), and cardiovascular diseases (Jin et al. 2019;Vallianou et al. 2019;Sikalidis and Maykish 2020). Dysbiosis of intestinal flora may result in βcell dysfunction, increased adiposity, oxidative stress, systemic inflammation, and metabolic endotoxemia (Yoo and Kim 2016). Probiotics are considered an effective alternative treatment for metabolic diseases as they modulate gut microbial modulation resulting in insulin signaling stimulation (Delzenne et al. 2011;Yoo and Kim 2016). ...
... Dysbiosis of intestinal flora may result in βcell dysfunction, increased adiposity, oxidative stress, systemic inflammation, and metabolic endotoxemia (Yoo and Kim 2016). Probiotics are considered an effective alternative treatment for metabolic diseases as they modulate gut microbial modulation resulting in insulin signaling stimulation (Delzenne et al. 2011;Yoo and Kim 2016). SCFAs, the end-products of carbohydrate metabolism help in improving glucose tolerance, decreasing glucagon levels in a dose-dependent manner and activating glucagon-like peptide (GLP), which, in turn, stimulates insulin production and enhances insulin sensitivity (Everard et al. 2011;Parnell and Reimer 2012). ...
... Therefore, the combined intake of probiotics-prebiotics enhances the composition of the intestinal microbiota and leads to the strengthening of the intestinal barrier and of the intestinal epithelium, a reduction in pathogens or harmful metabolic derivatives, the increased production of antibodies, and a competitive action against exogenous pathogens [5,40,245]. Consequently, probiotics-prebiotics can contribute significantly to the management of a variety of gastrointestinal and metabolic diseases, and also to some neurological and neuro-psychopathological disorders [1,41,233,[246][247][248]. ...
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Several studies have shown that the gut microbiota influences behavior and, in turn, changes in the immune system associated with symptoms of depression or anxiety disorder may be mirrored by corresponding changes in the gut microbiota. Although the composition/function of the intestinal microbiota appears to affect the central nervous system (CNS) activities through multiple mechanisms, accurate epidemiological evidence that clearly explains the connection between the CNS pathology and the intestinal dysbiosis is not yet available. The enteric nervous system (ENS) is a separate branch of the autonomic nervous system (ANS) and the largest part of the peripheral nervous system (PNS). It is composed of a vast and complex network of neurons which communicate via several neuromodulators and neurotransmitters, like those found in the CNS. Interestingly, despite its tight connections to both the PNS and ANS, the ENS is also capable of some independent activities. This concept, together with the suggested role played by intestinal microorganisms and the metabolome in the onset and progression of CNS neurological (neurodegenerative, autoimmune) and psychopathological (depression, anxiety disorders, autism) diseases, explains the large number of investigations exploring the functional role and the physiopathological implications of the gut microbiota/brain axis.
This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30‐day intermittent fasting (IF) program in 24‐month‐old male Sprague–Dawley rats. Rats underwent 18‐h daily fasting and received 1 × 10 ⁸ CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome‐stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm ⁻¹ ) and improved protein phosphorylation (A 1239 /A 2955 and A 1080 /A 1545 ) and carbonylation (A 1740 /A 1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw 2922 /Bw 2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.
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L’objectif de notre travail est de tester l’activité antibactérienne des huiles essentielles et des extraits aqueux de Thymus vulgaris et de Thymus serpyllum sur neuf (09) souches de bactéries pathogènes, et d’évaluer l’effet prébiotique de ces extraits sur les bactéries lactique du yaourt. Les résultats obtenus ont montrés que les deux huiles essentielles ont une très forte activité bactéricide sur toutes les souches pathogènes avec des diamètres d’inhibitions allant de 27.20 à 77.80 mm pour l’huile essentielle de Thymus vulgaris et de 37.80 à 63. 50 mm pour l'huile essentielle de Thymus serpyllum et des valeurs de la concentration minimale inhibitrice qui se situent ente 0.031 à 0.0009 % pour l’huile essentielle de T. vulgaris et de 0.015 à 0.0004 % pour l'huile essentielle de T. serpyllum. Cependant, la synergie de ces deux huiles essentielles a montré un effet potentialisateur de leur activité bactéricide (les diamètres varient de 48.70 à 84.00 mm). Il en est de même pour l’extrait aqueux de T. vulgaris avec des diamètres d’inhibition variant de 14.20 à 22.30 mm et des valeurs de 0.5 à 0.0009 % pour la concentration minimale inhibitrice. L’activité antibactérienne de l’extrait aqueux de T. serpyllum va d’un effet résistant à un effet bactériostatique. Toutefois, toutes les souches ont montrées des valeurs de CMI allant de 0.5 à 0.0625 % pour cet extrait. D'un autre côté, à l'exception de Pseudomonas aeruginosa, Salmonella typhimurium et Escherichia coli, le mélange des deux extraits aqueux a eu un effet synergétique modéré sur les six autres souches avec des diamètres variant de 14.80 à 20 mm. Par comparaison aux extraits étudiés, les antibiotiques n’étaient pas tous actifs contre les souches testées (diamètres d'inhibition varient de 13 à 23 mm pour la gentamicine et de 00 à 20 mm pour la pénicilline et une résistance totale à l'amoxicilline). Quant à l’activité prébiotique, les résultats ont mis en exergue la bonne croissance des bactéries lactiques en présence des huiles essentielles et des extraits aqueux des deux plantes étudiées. Mots clés : Thymus vulgaris, Thymus serpyllum, huile essentielle, extrait aqueux, activité antibactérienne, activité prébiotique.
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Background Worldwide, diabetic retinopathy (DR) remains the leading cause of visual impairment that often leads to irreversible vision loss. Despite the screening programs and treatments, DR affects approximately 17.9% of type II diabetes patients in Egypt.AimTo assess the curative effect of intravitreally injected bone marrow mesenchymal stem cells on experimentally induced diabetic retinopathy.Methods Thirty adult female albino rats were randomized into 5 groups: group (I), received no treatment; group (II), received intravitreal injection of phosphate buffer saline; group (III), subjected to diabetes induction using intraperitoneal injection of streptozotocin; group (IV), received intravitreal injection of bone marrow mesenchymal stem cells (BM-MSCs); and group (V), received intravitreal injection of BM-MSCs post-diabetes induction. After 30 days, the right eyes were enucleated and prepared for histological stains (H&E and PTAH), histochemical stain (PAS), and immunohistochemical stains (anti-CD34, anti-caspase-3 active, and anti-fibronectin), and the left eyes of group (V) were prepared for PCR analysis.ResultsGroup (V) revealed preserved retinal tissue integrity, and the cellular organization appeared nearly normal in comparison to control groups. Less gliosis was seen in group (V) in comparison to group (III). Morphometric analysis of group (V) revealed a statistically significant increase in retinal thickness and decrease of the optical density of CD34 and fibronectin immunoreaction compared to group (III). PCR results revealed that all recipient rats contain SRY-positive gene.ConclusionBM-MSCs significantly reduced neurovascular retinal degeneration and gliosis within treated animals. BM-MSCs might be beneficial in preventing DR progression.Lay SummaryDiabetic retinopathy remains the leading cause of visual impairment which could progress up to visual loss. Vaso-regenerative stem cell therapy could be an effective therapeutic approach to prevent progression of retinal nerve cell damage in patients with ischemic retinopathies including diabetic retinopathy. In the present study, we investigated the therapeutic effect of intravitreally injected BM-MSCs in a short-term experimentally induced diabetic retinopathy. BM-MSCs could provide a partial curative effect on the retina through decreasing retinal nerve cell degeneration, microangiopathies, fibrosis, and gliosis.Further studies focusing on the quality and timing of stem cell injection in different diabetic retinopathy stages and effectiveness of cell therapy as well as the possible adverse effects are recommended.
Blood Oxidant Ties: The Evolving Concepts in Myocardial Injury and Cardiovascular Disease is an update on the recent advances in the development of antioxidant-based therapies. It starts with an overview of the mechanisms underlying the genesis of oxidative stress, summarizing the link between oxidative stress and a number of cardiovascular conditions. This is followed by an explanation of how oxidative stress interacts with lipid metabolism and the placental environment. Three chapters on the role of antioxidant-based therapy for cardiovascular diseases round up the book. Key Features - Outlines several cell-signaling pathways that are modulated by the interplay between reducing and oxidizing agents (redox status) and gene expression in the cardiovascular disease process - Brings information about maternal programming environment in the placenta - Covers development of novel nanotechnology-based antioxidant delivery systems for effective drug delivery - Includes references for further reading The book is aimed at a broad readership of scientific and medical professionals involved in research on cardiovascular diseases, pathophysiology, pharmacy, pharmaceutical science and life sciences. It also serves as a reference for scholars who want to understand the complex biochemical mechanisms of antioxidant agents.
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Consumption of lactic acid bacteria (LAB) has been suggested to confer a range of health benefits including stimulation of the immune system and increased resistance to malignancy and infectious illness. In the present study, the effects of feeding Lactobacillus rhamnosus(HN001, DR20(TM)),Lactobacillus acidophilus(HN017)and Bifidobacterium lactis(HN019, DR10(TM))on in vivo and in vitro indices of natural and acquired immunity in healthy mice were examined. Mice were fed daily with L. rhamnosus, L. acidophilusor B. lactis(10(9) colony forming units) and their immune function was assessed on day 10 or day 28. Supplementation with L. rhamnosus, L. acidophilusor B. lactis resulted in a significant increase in the phagocytic activity of peripheral blood leucocytes and peritoneal macrophages compared with the control mice. The proliferative responses of spleen cells to concanavalin A (a T-cell mitogen) and lipopolysaccharide (a B-cell mitogen) were also significantly enhanced in mice given different LAB. Spleen cells from mice given L. rhamnosus, L. acidophilusor B. lactis also produced significantly higher amounts of interferon-gamma in response to stimulation with concanavalin A than cells from the control mice. LAB feeding had no significant effect on interleukin-4 production by spleen cells or on the percentages of CD4(+), CD8(+) and CD40(+) cells in the blood. The serum antibody responses to orally and systemically administered antigens were also significantly enhanced by supplementation with L. rhamnosus, L. acidophilusor B. lactis. Together, these results suggest that supplementation of the diet with L. rhamnosus(HN001),L. acidophilus(HN017)or B. lactis(HN019)is able to enhance several indices of natural and acquired immunity in healthy mice.
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Microbes play an important role in human health and disease. In the setting of heart failure (HF), substantial hemodynamic changes such as hypoperfusion and congestion in the intestines can alter gut morphology, permeability, function, and possibly the growth and composition of gut microbiota. These changes can disrupt the barrier function of the intestines, and exacerbate systemic inflammation through microbial or endotoxin translocation into systemic circulation. Furthermore, cardio-renal alterations via metabolites derived from gut microbiota can potentially mediate or modulate HF pathophysiology. Recently, trimethylamine N-oxide (TMAO) has emerged as a key mediator which provides mechanistic link between gut microbiota and multiple cardiovascular diseases, including HF. Potential intervention strategies which may target this microbiota-driven pathology include dietary modification, prebiotics or probiotics, and selective binders of microbial enzymes or molecules - yet further investigations into their safety and efficacy are warranted.
This article provides an overview of how intestinal epithelial cells (IEC) recognize commensals and how they maintain host-bacterial symbiosis. Endocrine, goblet cells, and enterocytes of the intestinal epithelium express a range of pattern recognition receptors (PRR) to sense the presence of microbes. The best characterized are the Toll-like receptors (TLR) and nucleotide oligomerization domain-like receptors (NLR), which play a key role in pathogen recognition and the induction of innate effectors and inflammation. Several adaptations of PRR signaling have evolved in the gut to avoid uncontrolled and potentially destructive inflammatory responses toward the resident microbiota. PRR signaling in IEC serve to maintain the barrier functions of the epithelium, including the production of secretory IgA (sIgA). Additionally, IECs play a cardinal role in setting the immunosuppressive tone of the mucosa to inhibit overreaction against innocuous luminal antigens. This includes regulation of dendritic cells (DC), macrophage and lymphocyte functions by epithelial secreted cytokines. These immune mechanisms depend heavily on IEC recognition of microbes and are consistent with several studies in knockout mice that demonstrate TLR signaling in the epithelium has a profoundly beneficial role in maintaining homeostasis