Critical Reviews in Food Science and Nutrition

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The impact of probiotics, prebiotics, and synbiotics

on the biochemical, clinical, and immunological
markers, as well as on the gut microbiota of obese
hosts

Tatiane Ferreira da Silva, Sabrina Neves Casarotti, Gislane Lelis Vilela de

Oliveira & Ana Lúcia Barretto Penna

To cite this article: Tatiane Ferreira da Silva, Sabrina Neves Casarotti, Gislane Lelis Vilela de
Oliveira & Ana Lúcia Barretto Penna (2020): The impact of probiotics, prebiotics, and synbiotics
on the biochemical, clinical, and immunological markers, as well as on the gut microbiota of obese
hosts, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2020.1733483

To link to this article: https://doi.org/10.1080/10408398.2020.1733483

Published online: 10 Mar 2020.

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CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
https://doi.org/10.1080/10408398.2020.1733483

REVIEW

The impact of probiotics, prebiotics, and synbiotics on the biochemical, clinical,

and immunological markers, as well as on the gut microbiota of obese hosts

cia Barretto
Tatiane Ferreira da Silvaa, Sabrina Neves Casarottib, Gislane Lelis Vilela de Oliveirac, and Ana Lu
Pennaa
a
Departamento de Engenharia e Tecnologia de Alimentos, Universidade Estadual Paulista (UNESP), S~ao Jos
e do Rio Preto, Brazil; bInstituto
de Ci^encias Naturais e Exatas, Universidade Federal de Rondon
opolis (UFR), Rondon
opolis, Brazil; cBrigham and Women’s Hospital, Harvard
Medical School, Boston, Massachusetts, USA

ABSTRACT KEYWORDS
Obesity is currently considered a global epidemic and it leads to several alterations on the human functional food; dysbiosis;
body and its metabolism. There are evidences showing that the intestinal microbiota can influence obesity; intestinal health
on the pathogenesis of obesity. Microbiota plays a vital role not only in the digestion and absorp-
tion of nutrients, but also in the homeostatic maintenance of host immunity, metabolism, and gut
barrier. Its dietary alteration is an important target in the treatment of obesity. Emerging evidence
suggests that modifying the composition of the gut microbiota through probiotic, prebiotic, and
synbiotic supplementation may be a viable adjuvant treatment option for obese individuals. In
this review, the impact of probiotics, prebiotics, and synbiotics on the anthropometric profile, bio-
chemical regulation, clinical, and immunological markers, as well as on the gut microbiota of
obese hosts is described. It also emphasizes how changes in the composition and/or metabolic
activity of the gut microbiota through the administration of nutrients with probiotic, prebiotic, or
synbiotic properties can modulate the host’s gene expression and metabolism, and thereby posi-
tively influence on the host’s adipose tissue development and related metabolic disorders. The
beneficial effects on the host’s metabolism promoted by prebiotics, probiotics, and synbiotics
have been successfully demonstrated by several studies. However, further investigation is needed
to fully explain the cellular mechanisms of action of probiotics and prebiotics on human health,
and also to elucidate the relationship between microbiota and obesity etiology, using well-
designed, long-term, and large-scale clinical interventions.

Introduction highly dynamic metabolism (Delgado and Tamashiro 2018).

According to the literature, over the last 40 years,
overweight, obesity, and its complications have stood out
extraordinarily. The period goes from 1975 to 2016, when
there was a dramatic increase in obesity according to data
compiled by the World Health Organization (WHO).
The data describe about 1.9 billion people aged 18 years or
older who are at least overweight (body mass index or
BMI > 25 kg/m2); among them, around 650 million are diag-
nosed with obesity (BMI > 30 kg/m2). Thus, 3 years ago, 39%
and 13% of people worldwide were overweight or obese,
respectively. Overweight and obesity are increasingly worrying
in both low- and middle-income countries, especially in urban
areas (WHO 2018). This expansion is expressed by the set of
biological, behavioral, and environmental processes that still
need further studies (Rastelli, Knauf, and Cani 2018).
According to the WHO, the diagnosis of obesity is body
fat that poses a health risk (WHO 2018). Thus, there is an
accumulation of adipose cells (adipocytes), which signal the
increase or the deficiency of total body energy. The adipo-
cyte set builds adipose tissue, an endocrine organ with
Due to the complexity of obesity, a single solution against
this growing epidemic has not been disclosed in studies
published in scientific circles. Hence, individualized cautious
procedures should be studied in order to prevent and treat
overweight and obesity (Borgeraas et al. 2018).
It is also known that obesity is directly related to other
complications, including metabolic syndrome, hypertension,
type 2 diabetes, dyslipidemia, coronary artery disease, stroke,
asthma, arthritis, sleep apnea, some types of cancer, and
inflammation-related pathologies (Torres-Fuentes et al. 2015;
Seganfredo et al. 2017). Thus, there is a growing demand for
scientific studies with nutritional strategies to promote
health (Bailey and Holscher 2018).
The disproportionate relationship between overeating and
energy expenditures is one of the reasons of energy imbal-
ance known as obesity. After the ingestion of food, each
organism performs different weight-regulating mechanisms,
such as peripheral and central signs of hunger and satiety,
and response of the gastrointestinal tract organs; these
mechanisms are known to be individualized. Obesity is also

CONTACT Ana L
ucia B. Penna ana.lb.penna@unesp.br Department of Food Engineering and Technology, Universidade Estadual Paulista (UNESP), Rua
Crist
ov~ao Colombo, 2265. 15054-000 S~ao Jos
e do Rio Preto, Brazil.
ß 2020 Taylor & Francis Group, LLC
2 T. F. DA SILVA ET AL.
characterized by complex genetic interactions among genes,
environmental factors (diet, food components) and lifestyle
(sedentary or not), as well as imbalance of the intestinal
microbiota, which negatively affects this process (Gomes
et al. 2017; Kobyliak et al. 2018).
Studies have shown that obesity and its complications are
accompanied by changes in the intestinal microbiota (Al-
Assal et al. 2018). Nonetheless, appetite can be reduced and
satiety increased, according to the product generated from
the bacterial fermentation process and by modulation of bile
acid metabolism; an increase in energy expenditure modu-
lated by the microbiota can occur and thus inhibit diet-
induced obesity (Cani and Delzenne 2009; Watanabe et al.
2012; Sayin et al. 2013).
There are three ways in which the intestinal microbiota
can modulate the mechanisms of obesity: i) effect on energy
extraction and absorption - the fermentation of indigestible
fibers increases energy extraction from the diet, while the
microbiota also facilitates nutrient absorption; ii) induction
or prevention metabolic endotoxemia through changes in
intestinal permeability - obese microbiota can increase intes-
tinal inflammation, intestinal permeability and subsequently
systemic inflammation by increasing the tumor necrosis fac-
tor alpha (TNF-a) and interleukin 1beta (IL-1b) production
by peritoneal macrophages; iii) regulation and secretion of
intestinal metabolites – the short chain fatty acids (SCFAs)
produced by intestinal microbiota activate specific receptors
for nutrients that stimulate the intestinal release of the sati-
ety-inducing hormones peptide YY and glucagon-like pep-
tide-1 (GLP-1), by decreasing systemic inflammation or by
signaling to the brain. SCFAs also target adipocytes, where
they increase lipolysis and leptin release. Additionally, these
mechanisms of action can work simultaneously or be con-
nected (Mulders et al. 2018).
The intestinal microbial modification through feeding
mainly occurs with the ingestion of probiotic, prebiotics,
and synbiotics. Thus, the influence on the intestinal micro-
biota through feeding becomes attractive in the fight
against obesity. Probiotics are “live microorganisms that,
when administered in adequate amounts, confer a health
benefit on the host” (Hill et al. 2014). The benefits can be
either directly or through interactions with other microor-
ganisms (John et al. 2018). It is important to stand out that
the potential beneficial effects are strain and not species
specific. Prebiotics are generally carbohydrate-based, select-
ively fermented by the host’s microbiota, and are noted for
their beneficial effect on health (Gibson et al. 2017). The
synbiotic term is used when combining probiotic strains
and prebiotic substrates (John et al. 2018). In this sense,
probiotic strains, prebiotics, and synbiotics are used in
food production or used as supplements to positively mod-
ify the host’s microbiota, and thus possibly aid the clinical
treatment against obesity and malnutrition (Dror et al.
2017). The gut microbiota of obese individuals and the
impact of probiotics and prebiotics on the hosts are sum-
marized in Figure 1.
This review focused on highlighting the current state of
knowledge on the potential role of prebiotics, probiotics,
and synbiotics on the biochemical, clinical, and immuno-
logical markers, as well as on the gut microbiota of obese
hosts. Additionally, it aimed to clarify questions about cur-
rent knowledge, to suggest future studies and dietary inter-
ventions to improve obese patients’ health.
Effects of probiotics, prebiotics, and synbiotics on
clinical parameters of obesity
The literature has shown that eating habits positively correl-
ate with the human intestinal microbiota, since dietary
changes can alter its diversity and composition. Short-term
changes in diet profile can change the gut microbiota and
could be a key alternative in the treatment of obesity. One
of the ways to do so is by consuming probiotics, prebiotics,
and synbiotics aiming at improving the host’s health (Al-
Assal et al. 2018; John et al. 2018). Many studies are avail-
able in the literature.
Dewulf et al. (2013) and Salazar et al. (2015) had been
pioneers in testing the impact of inulin-type fructans (ITF)
as prebiotic in obese women and their effects in gut micro-
biota composition and metabolic activity. Dewulf et al.
(2013) reported that prebiotics were correlated with bacter-
ial-related metabolites (phosphatidylcholine, lactate, hippur-
ate) and with serum lipopolysaccharide (LPS) levels, despite
a lack of significant effect on body weight. Salazar et al.
(2015) observed that prebiotic consumption resulted in sig-
nificantly lower total SCFAs, acetate and propionate, which
positively correlated with BMI, fasting insulinemia and
homeostasis model assessment (HOMA) (p < 0.05), com-
pared to the placebo group after the treatment period.
Bernini et al. (2016) observed that a daily intake (80 mL)
of the probiotic Bifidobacterium lactis HN019 correlated
negatively with the side effects of the metabolic syndrome
(MS) and the cardiovascular risks. They observed that BMI,
total cholesterol (TC), and low-density lipoprotein choles-
terol (LDL) decreased compared with the control group after
the consumption of probiotic fermented milk.
In other study, Madjd et al. (2016) selected 89 overweight
and obese women who had the habit of eating traditional
low-fat (LF) yogurt and they were randomly asked to con-
sume probiotic (PY) or LF yogurt. Compared to baseline, in
both groups, there were lower anthropometric measures and
positive changes in cardiometabolic risk characteristics.
Compared to LF group, the PY group stood out by decreas-
ing TC, LDL-cholesterol, 2-h postprandial glycemia, homeo-
stasis model assessment of insulin resistance (HOMA-IR),
and fasting insulin concentration. Hence, in an intervention
focused on weight loss, the ingestion of PY improved the
lipid profiles and insulin sensitivity.
Gomes et al. (2017) recruited overweight or obese women
who were divided into 2 groups: one who received a pro-
biotic mix (PM - Lactobacillus acidophilus and casei;
Lactococcus lactis; B. bifidum and B. lactis; 2
1010 CFU/
day) and the other received placebo. Both groups received a
dietary prescription. The PM group had a greater reduction
in waist circumference, waist-height ratio, plasma polyunsat-
urated fatty acids, and increased glutathione peroxidase
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 3

Figure 1. The impact of probiotics, prebiotics, synbiotics and obesity on host’s gut microbiota. AMPs -Antimicrobial proteins, DC - Dendritic cell, GLP-1 - Glucagon-
like peptide-1, GLP-2 - Glucagon-like peptide-2, IFNc - Interferon gamma, IL-10 - Interleukin – 10, IL-17 - Interleukin - 17, LPS - Lipopolysaccharide, M cells -
Microfold cells, PYY - Peptide YY, SCFAs - Short-chain fatty acids, sIgA - Secretory Ig A, TGF-b, Transforming growth factor b, Th1 - T helper 1 cells, Th17 - T helper
17 cells, and ZO-1 - Zonula occludens-1.

activity. In this sense, the probiotic supplementation had a
positive effect when compared to the dietary prescrip-
tion alone.
The effect of probiotic and synbiotic consumption on
fasting blood glucose (FBG) levels in adults was evaluated
by Nikbakht et al. (2018). None of the groups showed posi-
tive results; however, when FBG is highly unbalanced
(7 mmol/L), the use of probiotics has proved to be effect-
ive, and that multispecies probiotics may have more impact
on FBG than single species.
4 T. F. DA SILVA ET AL.
In that same year, the potential probiotic benefits were
published; Borgeraas et al. (2018) recruited 957 subjects,
either overweight or obese, and a high reduction in body
weight, BMI, and fat percentage was observed in comparison
with the placebo group; however, the effect level was low.
Its effect was not significant at the fat mass level either. In
this sense, the effects of probiotic supplementation on
anthropometric measurements should be further explored in
long-term research.
The positive modification of the intestinal microbiota
through the intake of prebiotics has been reported by
Kellow, Coughlan, and Reid (2014), who evaluated the
impact of a prebiotic supplementation through 26 random-
ized clinical trials involving 831 participants with metabolic
abnormalities. The authors found evidence supporting
a dietary intake of prebiotics for appetite regulation and
reduction of circulating postprandial glucose and insulin
concentrations; however, there is insufficient evidence at
present to recommend dietary prebiotics for reducing total
energy intake, body weight, peptide YY, glucagon-like
peptide-1 (GLP-1) concentrations, gastric emptying times,
insulin sensitivity, lipids, inflammatory markers, and
immune function. Such contradiction may be because the
research was short-term (3-8 weeks). Therefore, longer-term
(12-17 weeks), more participants, and larger-scale studies are
important and necessary to evaluate the modification of the
intestinal microbiota and its primary metabolic outcome.
The clinical study performed by Beserra et al. (2015)
demonstrated that a dietary intake of prebiotics decreased
plasma cholesterol and LDL-cholesterol levels in the overall
analysis, besides decreasing triglyceride levels and increased
HDL-cholesterol levels in diabetic research, while a synbiotic
food intake decreased levels of insulin and triglycerides.
The results support that a dietary intake of prebiotics and
synbiotics can be considered a positive alternative regarding
complications related to obesity, such as dyslipidemia and
insulin resistance.
The food intake of probiotic and prebiotic impact on
serum lipid profile and insulin resistance in 84 participants
with nonalcoholic fatty liver disease (NAFLD) was studied
as follows: (i) probiotic capsules (B. longum and L. acidoph-
ilus: 2
107 CFU/d) and placebo of prebiotic (maltodextrin
powder); (ii) sachet of prebiotic (inulin HP: 10 g/d) and pla-
cebo of probiotic (fat- and lactose-free milk capsules); (iii)
probiotic and prebiotic; and (iv) placebo of probiotic and
prebiotic. Probiotic was able to decrease BMI and weight in
all treatments in comparison to the placebo. The serum lev-
els of HDL- and LDL-cholesterol differed significantly in the
probiotic (i) and the pro- and prebiotic (iii) groups when
compared to the placebo group. Food intake of probiotic
and prebiotic may be beneficial to enhance the serum qual-
ity of lipid profile and insulin resistance markers in NAFLD
participants (Javadi et al. 2017).
Several clinical studies dedicated to evaluating the effect
of probiotic supplementation on clinical parameters of obes-
ity. In the study of Yan et al. (2019), a comprehensive
search across multiple databases was performed to identify
studies that focused on the effects of probiotics on blood
lipid levels in overweight or obese subjects. Their search
resulted in 6162 articles; however, only 12 articles met the
inclusion criteria for meta-analysis. These articles included a
total of 767 samples, with 391 treatments and 376 controls.
The results showed that obese or overweight participants
receiving probiotic supplementation had significantly larger
reductions in TC and LDL-cholesterol concentrations than
the control subjects. Even though the mode of action
has not yet been understood, it has been postulated that
probiotics can help the elimination of cholesterol and bile
acid by changes in cholesterol esters pathways and lipopro-
tein transporters, without affecting the synthesis of hepatic
cholesterol.
A systematic review and meta-analysis of clinical trials of
synbiotic supplementation in obesity treatment was recently
published by Hadi et al. (2020). In the study, it was identi-
fied 12057 articles, 7992 were screened, 50 full-text articles
were accessed, and 23 articles were included in meta-
analysis. The data analyses revealed that symbiotic supple-
mentation might have modest effects on body weight and
waist circumference through modulation of gut microbiota
composition.
Additional studies related to the impact of probiotic,
prebiotic, or synbiotic on the human obese gut microbiota
and on clinical parameters of obesity are summarized
in Table 1. Some studies using animal models are shown on
Table 2. According to the aforementioned studies, the food
intake of probiotic and prebiotic for positive modification
of the intestinal microbiome is a tool that stands out in
the fight against obesity and leads to reductions in
anthropometric measurements when compared to the pla-
cebo. Although such findings are promising, more research
is fundamental to establish the ideal formulation and to
verify the benefits regarding the time of consumption, in
order to evaluate if obese and overweight patients would
benefit from intestinal microbiome modification, in addition
to assessing the durability of these effects.
Effects of probiotics, prebiotics, and synbiotics on
satiety hormones regulation
The gut-brain axis is a complex network composed of
numerous systems, including the enteric nervous system
(ENS), the central nervous system, the autonomic nervous
system, the sympathetic, and the parasympathetic branches,
the neuroendocrine and the immunological systems, which
are important for metabolic homeostasis (Bliss and
Whiteside 2018). Several neurons and neurotransmitters,
which are part of the enteric nervous system, are responsible
for the communication between brain and gut; they send
information to the brain through spinal and vagal afferent
nerves (Rastelli, Knauf, and Cani 2018).
Changes in the communication between the gut and the
brain axis are closely related to the difficulty in controlling
the appetite and to a disturbed perception of satiety (Lam
et al. 2017). Food ingestion and body’s energy homeostasis
are modulated by gut hormones released along the intestinal
tract by enteroendocrine cells (EECs) and their concentrations

Table 1. Characteristics of human intervention studies with probiotics, prebiotics and synbiotics on microbiota.
Description
Prebiotic interventions
A double blind, placebo-
controlled intervention study
with ITF prebiotics (inulin/
oligofructose 50/50 mix) or
placebo (maltodextrin),
16 g/day.
Randomized, double blind,
parallel, placebo-controlled
trial, randomly assigned to
groups that received either
16 g/day ITF or
maltodextrin (placebo).
Treatment: GOS, 15 g.
Treatments: i) oligofructose-
enriched inulin (OI; 8 g/day);
ii) maltodextrin placebo
(isocaloric dose).
Treatments: i) 2 doses/day of
prebiotic bar with Inulin-type
fructans (ITF, 6 g oligofructose
þ 2 g inulin); ii) protein bar
(5 g WP); iii) combination bar
(8 g ITF þ 5 g WP).
Treatment: Oligofructose (8 g/day
for 12 wks þ 16 g/day for
24 wks).
Treatments: HFM: (i) 24 g inulin
of which 0.5 g was U-13C-
inulin; (ii) 24 g
maltodextrin placebo.
A double-blind, placebo-
controlled, randomized clinical
trial with bread containing 6 g
of barley beta glucans or
equal bread but without
beta glucans
Probiotic interventions
Treatments: two groups received
200 g/day of FM: (i) FM
containing 5
1010 CFU/100 g
L. gasseri SBT2055 LG2055: (ii)
FM without LG2055.
Lactobacillus casei Shirota,
6.5
109 CFU/dose.
Capsules of Lactobacillus gasseri
BNR17, 1
1010 CFU/dose.
Treatment: chewable tablets
with 10.6 log CFU L. casei
Zhang (LcZ) once daily
Duration (weeks) Subjects
12 N ¼ 30, obese women.
12 N ¼ 30, obese women.
12 N ¼ 44, overweight or
obese, prediabetic,
BMI ¼ 28-40 kg/m2.
16 N ¼ 42, children, 7-12
years old, overweight
or obese (> 85th
percentile of BMI) but
otherwise healthy.
12 N ¼ 125, overweight and
obese, healthy, BMI >
25 kg/m2.
36 N ¼ 14, NASH, NAS  5.
2 days of trial twice N ¼ 14, overweight to
and 5 days of obese, male,
washout period BMI ¼ 25–35 kg/m2.
in between.
4 N ¼ 43, with high risk for
metabolic syndrome
development or with
diagnosed
metabolic syndrome.
12 N ¼ 87 subjects,
BMI ¼ 24.2-30.7 Kg/m2.
12 N ¼ 28 patients,
overweight and obese,
MetS (13 patients/
probiotic group and 15/
control group) and 10
healthy controls
were included.
12 N ¼ 62, obese, BMI >
23 kg/m2.
4 N ¼ 24 Chinese subjects
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 5
Outcomes References
ITF treatment " Bifidobacterium and Dewulf et al. (2013)
Faecalibacterium prausnitzii and #
serum LPS levels. ITF also #
Bacteroides intestinalis, Bacteroides
vulgatus and Propionibacterium, and
slight # in fat mass, plasma lactate
and phosphatidylcholine levels.
Population of Bifidobacterium longum, Salazar et al. (2015)
Bifidobacterium pseudocatenulatum
and Bifidobacterium adolescentis " at
the end of the treatment in the
prebiotic group; B. longum
negatively correlated with serum
LPS endotoxin.
GOS " abundance of Bifidobacterium Canfora et al. (2017)
species in feces by 5-fold. Microbial
richness or diversity in fecal samples
were not affected, nor was the
insulin sensitivity or related
substrate and energy metabolism in
overweight or obese
prediabetic consumers.
OI treatment # BW z-score, # BF%, and Nicolucci et al. (2017)
# percent trunk fat, # serum
triglycerides compared to placebo, #
IL-6, " Bifidobacterium spp. and #
Bacteroides vulgatus.
WP # BF. Hunger, desire to eat and Reimer et al. (2017)
prospective food consumption were
all lower with all interventions
compared to the control. ITF and
ITF þ WP " Bifidobacterium sp.
Oligofructose supplementation Bomhof et al. (2018)
improved liver steatosis and overall
NAS score. Oligofructose "
Bifidobacterium and # Clostridium
cluster XI and I.
Inulin supplementation " fat oxidation Van Der Beek et al.
" plasma free fatty acids in the EPP (2018)
(0-3 h), # plasma glucose # Insulin
and " SCFA.
Bread with barley beta glucans # total Velikonja et al.
plasma cholesterol, # waist (2019)
circumference, " propionic acid and
# acetic acid in control group. A
significant # Clostridium leptum and
Collinsella aerofaciens, and #
Agathobacter rectalis after BGB
intervention. Beta glucan changed
the composition of gut microbiota,
lowering the diversity and richness
of the microbial populations.
Probiotic group # abdominal visceral Kadooka et al.
and # subcutaneous fat areas, # BW (2010)
and # BMI, and " serum adiponectin
levels compared to placebo.
Gut permeability of MetS patients was Leber et al. (2012)
increased significantly compared
with controls. L. casei Shirota
administration did not have any
influence in the LBP and sCD14
levels compared with
healthy controls.
The administration of BNR17 in Jung et al. (2013)
capsules reduced weight, waist, and
hip circumferences; however, there
were no significant differences
between the two groups.
LcZ significantly altered the Zhang et al. (2014)
composition of intestinal microbiota
and the gut microbiota diversity.
(continued)
6 T. F. DA SILVA ET AL.
Table 1. Continued.
Description
Probiotic intervention: 200 g/day
of yogurt containing L.
acidophilus La5, B. lactis Bb12,
and L. casei DN001 (1
107
CFU/mL).
Treatments 200 g/day of FM: i)
106 CFU/100 g L. gasseri
SBT2055 (LG2055); ii) 107
CFU/100 g L. gasseri
SBT2055(LG2055); iii) FM no
probiotic (control).
Treatments: i) hypocaloric diet þ
50 g/day of probiotic cheese
containing Lactobacillus
plantarum TENSIA (DSM
21380); ii) hypocaloric diet þ
50 g/day of probiotic-
free cheese.
Treatment: Bifidobacterium breve
B-3, 50
109 CFU/dose.
Treatments: i) Probiotic powder
with heat-killed Pediococcus
pentosaceus LP28, 100
109
CFU/dose; ii) alive Pediococcus
pentosaceus LP28, 100
109
CFU/dose.
Treatments: i) high-dose
probiotic (1
1010 CFU/twice
a day); ii) low-dose probiotic
(2.5
109 CFU/twice a day);
iii) placebo. Probiotic
intervention: B. bifidum W23,
B. lactis W51, B. lactis W52, L.
acidophilus W37, L. brevis
W63, L. casei W56, L. salivarius
W24, Lactococcus lactis W19,
and Lc. lactis W58.1.
A randomized, double-blind,
placebo-controlled study with
300 g/d of probiotic yogurt
containing Lactobacillus
bulgaricus, Streptococcus
thermophilus, 6.45
106 CFU/
g L. acidophilus La5 and
4.94
106 CFU/g B. lactis
Bb12 or regular
yogurt (placebo).
A randomized, crossover,
placebo-controlled, single-
center trial with a capsule
containing either the
probiotic L. reuteri V3401
(5
109 CFU) or a placebo.
Duration (weeks) Subjects Outcomes References
LcZ " Prevotella, Lactobacillus,
Faecalibacterium, Propionibacterium,
Bifidobacterium and an unidentified
genus from Bacteroidaceae and
Lachnospiraceae, and # Clostridium,
Phascolarctobacterium, Serratia,
Enterococcus, Shigella
and Shewanella.
8 N ¼ 75, overweight and Probiotic intervention # CRP, # TNF-a Zarrati et al. (2014)
obese individuals with/ and # IL-17 when compared to
without WLD. baseline in treated group.
Probiotic þ WLD resulted in
differences in thymus-specific
isoform of the retinoic acid
receptor-related orphan receptor
gamma (ROR-ct) gene expression, in
peripheral blood mononuclear cells.
Probiotic þ WLD had synergistic
impacts on immune inflammatory
markers in obesity.
12 N ¼ 210, healthy adults Probiotic FM # abdominal visceral fat Kadooka et al. (2013)
with large visceral fat areas, # BMI, # waist and hip
areas (80.2-187.8 cm2). circumferences and # BFM.
3 N ¼ 40, obese, MetS. Probiotic cheese # plasma triglycerides, Sharafedtinov
arterial BP and BMI and risk of et al. (2013)
metabolic syndrome.
12 N ¼ 44, BMI ¼ 24-30 kg/m2, Probiotic # BFM and improved blood Minami et al. (2015)
overweight, healthy. parameters related to liver functions
and inflammation, such as
c-glutamyltranspeptidase and high-
sensitivity CRP.
12 N ¼ 41, BMI ¼ 25-30 kg/m2, Fasting plasma glucose, HbA1c, fasting Higashikawa
overweight, healthy. insulin, HOMA-IR and serum lipid et al. (2016)
levels did not change by intaking
neither living LP28 nor heat-
killed LP28.
12 N ¼ 81, obese, The high-dose probiotic # metabolic
ska et al. (2018)
Szulin
postmenopausal female. endotoxemia, # LPS, # HOMA-IR,
and improved insulin resistance
index in the obese
postmenopausal women.
8 N ¼ 44 (22 men and 22 Probiotic yogurt # blood glucose level Rezazadeh et al. (2019)
women), MetS patients, and VCAM-1. Probiotic yogurt
20 to 65 years. promoted significant changes in
plasminogen activator inhibitor 1,
VCAM-1, insulin, HOMA-IR, and
insulin sensitivity were observed
after intervention compared
with baseline.
12 N ¼ 53 adults with MetS. L. reuteri V3401 # IL-6 and VCAM-1 Tenorio-Jim
enez
and " Verrucomicrobia phylum and et al. (2019)
Akkermansia genus.
(continued)

Table 1. Continued.
Description
Synbiotic interventions
Dietary supplement containing
phloridzin, isoflavones,
Lactobacillus casei,
Lactobacillus acidophilus,
7.5
108 CFU/dose.
Treatment: 2 capsules/day of LPR
(10 mg L. rhamnosus
CGMCC1.3724 providing
1.62
108 CFU, 300 mg of
oligofructose þ inulin mixture
[70:30, v/v] and 3 mg of
magnesium stearate).
Treatments: i) probiotics (5
109
CFU S. thermophilus KCTC
11870BP, L. plantarum KCTC
10782BP, L. acidophilus KCTC
11906BP, L. rhamnosus KCTC
12202BP, B. lactis KCTC
11904BP, B. longum KCTC
12200BP, and B. breve KCTC
12201BP) þ herbal medicine
BTS; ii) BTS þ placebo.
Treatments: (i) probiotic group
consumed 2 g probiotic
powder twice a day
containing 0.1 g of L. curvatus
HY7601, 0.1 g of L. plantarum
KY1032 (each at 2.5
109
CFU), 1.24 g of crystalline
cellulose, 0.5 g of lactose, and
0.06 g of blueberry-flavoring
agent; (ii) placebo group
consumed the same amount
of powder without
any probiotics.
Treatments: i) Microcrystalline
cellulose (MC), 12 g/day
(control); ii) LU, 12 g/day; iii)
B. animalis ssp. lactis 420
(B420), 1
1010 CFU/
dose þ MC; B. animalis ssp.
lactis 420, 1
1010
CFU/dose þ LU.
Treatments: (i) synbiotic group
(500 mg/day) ¼ probiotics
(Lactobacillus sp and
Bifidobacterium sp,
Streptococcus thermophilus),
prebiotics (FOS) and B group
vitamins (1 mg), lactose
(0.5 mg), maltodextrin,
magnesium saturate; (ii)
placebo group consumed the
same amount of product
without any probiotics
or prebiotics.
Treatment: i) symbiotic capsule
with 69 mg or 15
109 CFU
of Lactobacillus acidophilus
DDS-1, Bifidobacterium lactis
UABla-12, Bifidobacterium
longum UABl-14, and
Bifidobacterium bifidum UABb-
10 þ prebiotic component at
a dose of 5.5 g/d (2.75 g GOS
and the remainder simple
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 7
Duration (weeks) Subjects Outcomes References
13 N ¼ 40, obese. Phyto-supplement # BW, # BFM, and # Doria et al. (2013)
waist, thigh and buttock
circumference compared to the
control group.
12 N ¼ 125, BMI ¼ 29-41 kg/ Lactobacillus rhamnosus CGMCC1.3724 Sanchez et al. (2013)
m2, overweight and formulation helps obese women to
obese, healthy. achieve sustainable weight loss.
8 N ¼ 50, female, BMI > Probiotics and BTS, or BTS alone did Lee et al. (2014)
25 kg/m2 and waist not affect metabolic endotoxemia
circumference > 85 cm. and intestinal permeability
compared to baseline. B. breve in
obese patients # endotoxin
concentrations, weight, BMI, fat
mass, " Firmicutes phylum and S.
thermophilus, and # intestinal
permeability.
12 N ¼ 120, nondiabetic Probiotic group # BW, # BF%, # BFM, # Jung et al. (2015)
and overweight. ox-LDL, # Lp-PLA2 and " LDL
particle size.
24 N ¼ 225, BMI ¼ 28-34.9 kg/ LU þ B420 and B420 $ weight. Stenman et al. (2016)
m2, overweight and LU þ B420 # BFM, LU alone and
obese, healthy. B420 alone $ BFM. B420 and
LU þ B420 # energy intake
compared to placebo. LU þ B420 #
blood zonulin levels and # hsCRP
were associated with corresponding
# trunk fat mass. Probiotic
treatment with or without dietary
fiber $ BFM. B420 and LU þ B420
#waist circumference and # food
intake; LU alone had no effect on
the measured outcomes.
9 N ¼ 70, non-obese Synbiotic # FBG # HbA1c, $ Ebrahimi et al. (2017)
patients with T2D. lipid profiles.
12 N ¼ 20, male and female Synbiotic treatment $ body mass, Sergeev et al. (2020).
overweight/obese, BMI, body fat mass, body fat
BMI ¼ 33.5 kg/m2. percentage, body lean mass, and
bone mineral content. Synbiotic
supplementation " abundance and
richness gut microbiota associated
with positive health effects,
especially Bifidobacterium and
Lactobacillus. Bacteroides was the
most abundant genus in both
(continued)
8 T. F. DA SILVA ET AL.

Table 1. Continued.
Description Duration (weeks) Subjects Outcomes References
sugars); ii) placebo groups. Prevotella and Gardnerella
supplement was similar in genera were significantly decreased
appearance and energy after the synbiotic intervention.
content as the
synbiotic supplement.
The strains were not informed. AA – arachidonic acid; BF% – body fat percentage; BFM – body fat mass; BMI – body mass index; BP – blood pressure; BTS –
Bofu-tsusho-san; BW – body weight; CFU – colony forming units; CRP – C-reactive protein; DHA – docosahexaenoic acid; EPP – early postprandial phase; FBG –
fasting blood glucose; FM – fermented milk; FOS – fructooligosaccharide; GOS – galactooligosaccharide; HbA1c – glycated hemoglobin; HFM – high-fat
milkshake; HOMA-IR – homeostatic model assessment for insulin resistance; hsCRP – high-sensitivity C-reactive protein; IL – interleukin; ITF – Inulin-type
fructans; LBP – lipopolysaccharide-binding protein; LC-PUFA – long chain poly unsaturated fatty acids; LDL – low-density lipoprotein Lp-PLA2 – lipoprotein-
associated; LPS – lipopolysaccharide; MC – Microcrystalline cellulose; MetS – metabolic syndrome; ox-LDL – oxidized low-density lipoprotein; LU – Litesse
Ultra Polydextrose; NASH – non-alcoholic steatohepatitis; NAS – non-alcoholic fatty liver activity score; PBMCs – peripheral blood mononuclear cells; sCD14 –
soluble CD14; SCFA – short-chain fatty acids, and T2D – type 2 Diabetes; TNF-a – tumor necrosis factor – alfa; VCAM-1 - vascular cell adhesion molecule cell;
WLD – weight-loss diet; WP – whey protein.

vary after each meal. Among these hormones, there is ghrelin,
which stimulates appetite, and leptin, glucagon-like peptide
one and two (GLP-1 and 2), peptide YY (PYY), cholecysto-
kinin (CCK), and oxyntomodulin (OXM), which regulate
food ingestion and control body weight (Delgado and
Tamashiro 2018).
A large number of studies have been showing that gut
microbiota can affect behavior and core brain mechanisms,
including the production and release of hormones involved
in regulating appetite and satiety (Bliss and Whiteside 2018;
Cani and Delzenne 2009). For such reasons, shifting intes-
tinal microbiota composition into a more favorable profile
regarding the regulation of such hormones is an alternative
for the control of obesity, appetite, and their related meta-
bolic comorbidities (Falcinelli et al. 2018). In this context,
probiotics and prebiotics can be used successfully for this
purpose. Even though other benefits coming from the con-
sumption of such products have been extensively explored,
the therapeutic potential of prebiotic and probiotic con-
sumption on food intake regulation has started to gain
attention in the last two decades.
The major mechanism of action by which probiotics and
prebiotics exert control on appetite involves the production
of SCFAs (Dao and Clement 2018; Torres-Fuentes et al.
2017). Some probiotic strains have the capacity to produce
SCFAs (Chen et al. 2018) whilst prebiotics can be converted
into SCFAs by the gut microbiota. The main SCFAs pro-
duced through bacterial fermentation are acetate, propion-
ate, and butyrate, which will vary according to the
carbohydrate type, microbiota diversity, composition, activ-
ity, and gut transit time (Byrne et al. 2015).
Some early in vitro studies showed that SCFAs have cru-
cial functions in the gut-brain axis in the host, leading to
the stimulation of the secretion of satiety hormones (Karaki
et al. 2008; Tolhurst et al. 2012). These findings encouraged
further studies with animal and human subjects, even
though at the present moment data from animal studies are
more abundant compared to human trials, which makes it
difficult to establish a definitive explanation of the mecha-
nisms through which SCFAs control appetite.
The administration of a probiotic mixture VSL#3 (5 mg/
kg body weight) to mice receiving a high-fat diet (HFD) for
8 weeks increased the GLP-1 secretion and has been related
with the increase in production of butyrate (Yadav et al.
2013). Chen et al. (2018) reported that the probiotic L. mali
APS1 (5
108 CFU in saline through daily gavage) increased
the excretion of SCFAs and concomitantly increased the
expression of PYY and PP in mice receiving a HDF
for 6 weeks.
Besides stimulating the production of hormones through
SCFAs production, some bacteria can secret some neuro-
chemicals such as ghrelin, leptin, PYY, and neuropeptide Y,
which may have an effect on the vagus nerve activity and,
consequently, the host’s eating pattern (Nie, Luo, and Lin
2018). In this context, the search for probiotic strains with
this characteristic is desirable considering that they could be
used in functional food specifically for the control of
weight gain.
Regarding human trials, the consumption of a synbiotic
capsule (Protexin Balance, Probiotics International Limited,
Somerset, United Kingdom), containing the following pro-
biotic strains: L. casei PXN 37, L. rhamnosus PXN 54, L.
acidophilus PXN 35, L. bulgaricus PXN 35, S. thermophilus
PXN 66, B. breve PXN 25, and B. longum PXN 30, at
2
108 CFU and 125 mg of fructooligosaccharides (FOS)
significantly increased GLP-1 and PYY amounts in patients
with a metabolic syndrome (BMI  25 kg/m2) (Rabiei
et al. 2018).
Although there is evidence that shows the effect of
probiotic bacteria and prebiotics on gut hormone secretion,
further studies linking the probiotic and prebiotic consump-
tion with appetite are desirable. In this line, Forssten et al.
(2013) detected a trend for reduced food consumption
among mice groups receiving fermented milk (2.5 mL/day)
through a single oral gavage with the probiotic strains
L. rhamnosus MUH 142 and L. bulgaricus MUH 192;
such tendency was attributed to the high levels of hippuric
acid in the probiotic fermented milk when compared to the
treatment without any probiotic strains.
Another trial carried out by Sanchez et al. (2017) with
obese subjects demonstrated that a symbiotic capsule (con-
taining 1.62
108 CFU of L. rhamnosus CGMCC1.3724,
210 mg of oligofructose, and 90 mg of inulin) administered
for 12 weeks positively affected the appetite sensation and
eating patterns, as it contributed to an increased sense of
satiety in women. These outcomes support the assumption
that appetite regulation and associated behaviors in the
obesity treatment can be influenced by the gut-brain axis.

Table 2. Characteristics of animal intervention studies with probiotics, prebiotics and synbiotics on microbiota.
Description
Prebiotic interventions
Treatments: i) standard diet
(control); ii) HFD containing
49.5% fat (g/100 g of total dry
diet) corresponding to 72% of
the total energy content; iii) a
mix of HFD þ OFS;
iv) HFD þ NFDF.
Treatments: i) control diet; ii)
prebiotic oligofructose and iii)
control
(microcrystalline cellulose).
Treatments: i) HFD (60% fat and
20% carbohydrates), PRE
(oligofructose, 0.3 g per
mouse/day), ii) HFD þ PRE,
and iii) CT groups.
Treatments: i) HFS ad libitum; ii)
HFS þ 10% wt/wt OFS ad
libitum; iii) weight matched to
the OFS group with WM; iv)
lean reference group was
maintained on control AIN-
93 diet.
Treatments: i) LFD; ii) HFD; iii)
HFD þ 150 mg
polymannuronic acid/kg
body weight.
Probiotic interventions
Probiotic treatment: B.
pseudocatenulatum
CECT 7765.
Probiotic treatment: 1
108
CFU/day of L. rhamnosus
GG (LGG).
Probiotic treatment: L. reuteri
ATCC 6475.
Duration (weeks) Subjects
14 N ¼ 8 per group, wild-type
mice, Murine model.
5 N ¼ 10/group, ob/ob mice
(C57BL/6 background;
Jackson Laboratory, Bar
Harbor, Maine, USA).
8 N ¼ 40; 10-week-old C57BL/
6J mice.
10 N ¼ 104; 12-week-old virgin
female Sprague-Dawley
rats. Rats (N ¼ 90) were
fed a high-fat/sucrose diet
(Diet #102412, Dyets, Inc)
ad libitum for 10 weeks to
induce obesity. The 42 rats
with the greatest weight
gain were allocated to one
of three groups
throughout gestation
and lactation.
22.5 N ¼ 15; C57BL/6J male mice.
7 N ¼ 4 groups (n  6 mice
per group), male wild-type
C57BL-6 mice. HFD B6
obese mice.
13 N ¼ 4 groups (7 or 8 mice
per group), male wild-type
C57BL/6J mice. B6
HFD mice.
12 N ¼ 10-30 mice per group
(each experiment included
5-15 animals per group
with two replications).
Western fast food-diet
Swiss mice.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 9
Outcomes References
HFD resulted in " Gram-negative gut Cani et al. (2007b)
microbes and # Gram-positive
bacteria (Eubacterium rectal,
Clostridium coccoides group and
Bifidobacterium). The LPS receptor
protein CD14 system was driving
the metabolic effects of the HFD in
the wild-type mice.
Treated animals showed # plasma LPS Cani et al. (2009a)
and cytokines, and # hepatic
expression of inflammatory and
oxidative stress markers. # intestinal
permeability and " tight-junction
integrity compared to controls and
" endocannabinoid signaling.
Prebiotic treatment " Reg3g expression Everard et al. (2014)
(by 50-fold), " intectin and
improved intestinal homeostasis.
The mice microbiome was greatly
dominated by the phyla Firmicutes
and Bacteroidetes. HFD treatment
profoundly affected the caecal
Firmicutes/Bacteroidetes ratio, and
the gut microbiota modulations
induced by prebiotics counteracted
HFD-induced inflammation.
The prebiotic intake during pregnancy Paul, Bomhof, Vogel,
and lactation improves maternal and Reimer (2016)
metabolism in diet-induced obese
rats (HFS) (# maternal energy
intake, # gestational weight gain),
and prevents increased adiposity in
dams and their offspring.
Polymannuronic acid # diet-induced Liu, Wang, Shi, Wang,
BW gain and blood TAG levels (P < Xue, and
005) and " glucose tolerance. PM # Tang (2017)
LPS in blood and ameliorated local
inflammation in the colon and the
epididymal adipose tissue. PM also
had a profound impact on the
microbial composition in the gut
microbiome and resulted in a
distinct microbiome structure. PM "
abundance of probiotic
Lactobacillus reuteri.
The probiotic CECT 7765 " insulin Cano, Santacruz, Trejo,
resistance and glucose tolerance, IL- and Sanz (2013)
4 levels, # serum concentrations of
leptin, IL-6, MCP-1 and recovered
the macrophage and dendritic cell
functions, cytokine secretion and
ability to induce T-cell activation
and proliferation.
Probiotic group # weight gain, " Kim, Park, Kim, Kim,
insulin sensitivity and " serum and Hyun, (2013)
adiponectin, which promotes an
anti-inflammatory state in
macrophage in adipose tissues.
Probiotic treated animals presented " Poutahidis et al. (2013)
serum anti-inflammatory IL-10. The
IL-10-deficient mice fed with
Western diet and probiotic became
obese and failed to respond for
probiotic treatment. Slim mice fed
with Western diet þ L. reuteri ATCC
(continued)
10 T. F. DA SILVA ET AL.
Table 2. Continued.
Description
Probiotic treatment: 1
108
CFU/day of L.
coryniformis CECT5711.
Treatment with L. rhamnosus
LMG S-28148 (1
109 CFU)
and B. animalis subsp. lactis
LMG P-28149 (1
109 CFU).
The animals received: i)
LFD þ probiotic; ii) only LFD;
iii) HFD þ probiotic; iv)
only HFD.
Mice were fed a HFD for 6
weeks, followed by
treatments: i) NDS; ii) normal
diet þ Lactobacillus mali APS1
(5
108 CFU/day) (NDAPS1).
Rats were subdivided into 4
groups: i) normal diet; ii)
normal diet plus probiotics (L.
paracasei HII01 - 1
108 CFU/
mL); iii) high-fat diet, and; iv)
high-fat diet plus probiotics
(L. paracasei HII01 - 1
108
CFU/mL).
Synbiotic interventions
Treatments: i) control, ii) 10%
oligofructose, iii)
Bifidobacterium Bb-12, and iv)
oligofructose þ Bb-12.
Treatments: i) AIN-93G
diet þ prebiotics (scGOS/
lcFOS); ii) AIN-93G
diet þ synbiotics (scGOS/lcFOS
with 109 CFU/g
Bifidobacterium breve M-16 V);
iii) AIN-93G diet þ a non-
active control component
(REF) and AIN-93G diet þ a
non-active control component
(CTRL): 2% w/w maltodextrin,
until post-natal day 42.
Thereafter CT, PRE, and SYN
animals received a WSD (40%
energy from fat) as a
challenge until sacrifice
on PN98.
AIN-93G diet –American Institute of Nutrition dietary standard 93; BW – body weight; COX-2 – cyclooxygenase-2; CFU – colony forming units; CTRL – control
component; F4/80þ macrophage – macrophage specific genes F4/80þ; GLP-1 – glucagon-like peptide-1; GLP-2 – glucagon-like peptide-2; HFD – high-fat diet;
HFS – high-fat-sucrose diet; IL – interleukin; JNK – c-Jun N-terminal kinase; LFD – low-fat and low-sucrose diet; LPS – lipopolysaccharide; MCP-1 – monocyte
chemotactic protein-1; mRNA – messenger ribonucleic acid; MSG – monosodium glutamate; NDS – normal diet þ saline; NF-jB – nuclear factor kappa-B; NFDF
– non-fermentable dietary fiber; OFS – oligofructose; PN42 – post-natal day 42; PN98 – post-natal day 98; PRE – prebiotic supplementation; Reg3g – regenerat-
ing islet-derived 3-gamma; PYY – peptide YY; SYN – synbiotic supplementation; TAG – triacylglycerol; TNF-a – tumor necrosis factor – alfa; Tregs cell – regula-
tory T cells; WM – limited oligofructose þ fat þ sucrose diet; WSD – Western-style diet.
Duration (weeks) Subjects
12 N ¼ 4 groups (n ¼ 10 mice
per group), male C57BL/6J
mice. Obesity induced by
HFD in B6 mice.
7 N ¼ 4 groups (5-15 mice per
group), male C57BL/6J
obese mice.
3 N ¼ 16, 7-week-old male
C57BL/6 J mice.
12 N ¼ 12, obese rats.
8 N ¼ 10 rats per group, male
Sprague-Dawley rats. Diet-
induced obese.
8 N ¼ 48, high-fat WSD.
Outcomes References
6475 had " Tregs and # IL-17A in
lymphoid tissues. Probiotic benefits
depend on interactions with
immune cells in the gut mucosa
through Tregs cell and oral
tolerance induction.
Probiotic ameliorates glucose Toral et al. (2014)
metabolism: # glycaemia, insulin
resistance, LPS plasma levels, TNF-a,
IL-10, JNK, and MCP-1 genes
expression in the liver, and " mRNA
of the anti-inflammatory
adiponectin in adipose tissue.
Probiotic administration # F4/80þ Alard et al. (2016)
macrophage accumulation, and
MCP-1 expression. In treated obese
mice # TNF-a, IL-1a, IL-6, and IL-17
gene expression.
Normal diet þ Lactobacillus mali APS1 Chen et al. (2018)
" BW loss and # caloric intake, and
# fat accumulation in obese mice.
Lactobacillus mali APS1 ameliorated
hepatic steatosis in preexisting
obese mice after dieting,
significantly " abundance of
Lactobacillus mali and # abundance
of the Streptococcaceae family and
Anaerotruncus genus; it also
manipulated the gut microbiome’s
obesity-associated metabolites,
followed by regulation of lipid
metabolism, enhancement of energy
expenditure and inhibition
of appetite.
The probiotic supplementation in Wanchai et al. (2018).
group iv # metabolic endotoxemia,
compared to group iii. The probiotic
administration # NF-jB
phosphorylation, # JNK protein, and
# kidney inflammation. The
probiotic administration $ COX-2
levels in renal tissue, # TNF-a, # IL-
1b, # IL-6 and # MCP-1.
Oligofructose " fasting portal plasma Bomhof, Saha, Reid,
GLP-1, " PYY, while probiotic " GLP- Paul, and
2 and ghrelin levels. Reimer (2014)
Early life synbiotics protected mice Mischke et al. (2018)
against WSD-induced excessive fat
accumulation throughout life. Adult
insulin sensitivity and dyslipidaemia
were improved and most
pronounced changes in gene
expression were observed in the
ileum. In early life and adulthood,
there were changes in faecal
microbiota composition, and "
abundance of Bifidobacterium. The
synbiotics-modified microbiota at
PN42 is not enough to transfer
long-lasting protection of metabolic
health status when transplanted in
germ-free recipients.

The above-mentioned studies successfully proved that
probiotics and prebiotics influence on satiety hormones and
food ingestion. Nevertheless, the results concerning their
effects on these parameters are still discrepant. For instance,
Jones et al. (2018) reported no significant shift in gut hor-
mones as a consequence of receiving VSL#3 probiotic (three
packets/day) in a double-blind, randomized placebo-con-
trolled trial conducted with 19 obese Latin adolescents.
Another randomized placebo-controlled trial with over-
weight or obese individuals (n ¼ 20) aimed at determining
the effects of the daily consumption of a prebiotic powdered
ingredient mixture for 4 weeks (4 g inulin, blueberry extract,
and 2.5 g oat b-glucan) or a placebo product. Glucose, insu-
lin, glycosylated hemoglobin, HOMA-IR, triglycerides, and
cholesterol (TC, LDL and HDL), SCFAs produced by gut
microbiota, plasma satiety hormones (ghrelin and PYY), and
satiety perception were assessed. There was an increased
sense of satiety in the group that received the prebiotic mix-
ture; however, there was no significant difference in the
plasma satiety hormones (PYY and ghrelin) concentration
between both groups (Rebello et al. 2015).
Further research using human subjects is essential to
thoroughly explain the molecular mechanisms through
which SCFAs produce these effects and to make it feasible
to use these compounds in the clinical management of obes-
ity (Byrne et al. 2015). Furthermore, it is noteworthy that
the effect of prebiotics and probiotics on appetite regulation
will depend on intrinsic characteristics of the hosts, includ-
ing genetics, physiology, and lifestyle, as well as on prebiotic
and probiotic type and dose.
Probiotics, prebiotics, and synbiotics on
inflammatory markers
The association between intestinal dysbiosis and obesity
could be explained by the metabolic endotoxemia propos-
ition which connects alterations in the gut microbiota to
systemic inflammation and metabolic dysfunctions (Torres
et al. 2018; Sroka-Oleksiak et al. 2020). In animal and
human models, obesity and metabolic dysfunctions have
been correlated to an increased barrier permeability that
induces the bacterial translocation of endotoxins, particularly
of the Gram-negative bacterial membrane component, the
lipopolysaccharides (LPS), which activates innate immune
receptors and promote metabolic endotoxemia (Torres et al.
2018). Additionally, LPS has been identified as a trigger for
insulin resistance, because it affects the secretion of proin-
flammatory cytokines. In response to the LPS, the activated
toll-like receptor-4 (TLR-4) induces the inflammatory tran-
scription nuclear factor kappa B (NF-jB) in gastrointestinal
epithelial cells. The induced NF-jB can trigger a systemic
inflammation, classical activation of M1 macrophages, and
infiltration of the visceral adipose tissue, thus contributing
to an inflammatory state, with increased TNF-a, interleukin
(IL)1b, IL-6, leptin, resistin, and C-reactive protein (CRP),
and subsequent resistance against insulin (Neyrinck et al.
2016; Torres et al. 2018, Zhi et al. 2019).
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 11
Besides the effect of SCFAs on hormone regulation, as
previously described, butyrate in particular has exceptional
ability regarding immunoregulatory effects, such as leuko-
cytes activity, by recruiting them to inflammation sites, and
the secretion of TNF, IL-2, IL-6, IL-10, eicosanoids, and spe-
cific chemokines. Moreover, SCFAs are recognized for their
ability to suppress the progression of metabolic diseases
(Vinolo et al. 2011).
Studies performed with cell lines, by using adipocytes or
macrophages, both in HFD models and in human clinical
trials, reported that the administration of probiotics pro-
motes an anti-inflammatory state, decreasing the leptin/
resistin secretion, increasing M2 macrophages in adipose tis-
sue and anti-inflammatory molecules, such as IL-10 and adi-
ponectin (Kobyliak et al. 2016).
In the last decade, there has been significant increase in
studies evaluating the interaction between foods (including
probiotics and prebiotics), microbes, and their metabolites
with the mucosal and systemic immune systems (Clemente,
Manasson, and Scher 2018; Han and Xiao 2020), by using
human or animal models.
An important randomized clinical trial investigated the
effects of prebiotics on 42 overweight or obese children.
They received oligofructose-enriched inulin or maltodextrin
placebo. The group that received prebiotics experienced an
increase in Bifidobacterium species and a decrease in CRP
and IL-6 inflammatory cytokine, in comparison to the pla-
cebo group. However, there were no differences in LPS lev-
els between the two evaluated groups (Nicolucci et al. 2017).
Another randomized clinical trial assessed the effect of
administering probiotics with prebiotics (synbiotics) in 225
participants. The synbiotics preparation combined B. ani-
malis subsp. lactis 420 (109 CFU/per day) with ultra-poly-
dextrose, an undigested glucose polymer that favors the
Bifidobacteria proliferation in culture systems (Probert et al.
2004). In contrast, another randomized controlled clinical
trial using synbiotics to treat overweight men and women
observed no significant differences in inflammatory markers,
such as serum levels of CRP, LPS-binding protein (LBP),
and adiponectin. The intervention with two capsules/day
containing 10 mg of a L. rhamnosus CGMCC1.3724
(1.62
108 CFU) and 300 mg oligofructose and inulin
resulted in weight loss, besides decreased fat mass and leptin
levels in obese women (Sanchez et al. 2014). Furthermore, a
significant decrease in TNF and IL-6 was observed. B. lactis
HN019 demonstrated potential to reduce obesity, minimiz-
ing cardiovascular risks in patients with MetS (Bernini
et al. 2018).
Recently, Depommier et al. (2019) conducted a random-
ized, double-blinded, placebo-controlled clinical trial to
evaluate the effect of Akkermansia muciniphila supplementa-
tion in 32 overweight, obese, and insulin resistant patients.
Individuals were enrolled to receive daily oral administration
of placebo, alive A. muciniphila or pasteurized A. mucini-
phila (1010 CFU/per day), for three months. The supplemen-
tation was considered safe and well tolerated. Compared to
control group, pasteurized A. muciniphila reduced the levels
of relevant blood markers of hepatic and renal dysfunction
12 T. F. DA SILVA ET AL.
and inflammation (reduced LPS plasma levels, improved
insulin sensitivity, decreased insulinemia and plasma total
cholesterol). Moreover, after three months pasteurized
A. muciniphila improved metabolic parameters (reduced
body weight, fat mass, and hip circumference) when
compared with placebo group.
The probiotic L. gasseri SBT2055 (LG2055) have been
associated to anti-obesity effects in obese C57BL/6 mice,
induced through their diet (B6 mice) during a 24-week
treatment. Authors reported that LG2055 significantly
suppressed the inflammatory gene expression, including the
monocyte chemoattractant protein-1 (MCP-1) and the C-C
chemokine receptor type 2 (CCR2) in adipose tissues. They
hypothesized that the effects against obesity of L. gasseri
were associated with the modulation of immune system and
anti-inflammatory responses (Miyoshi et al. 2014).
Another study investigated the impacts of administering
L. rhamnosus, L. acidophilus, and B. bifidum to HFD Swiss
mice, for five weeks (Bagarolli et al. 2017). The HFD led to
leaky gut, LPS translocation, and systemic inflammation. By
administering probiotics to the obese animals, they could
recover the TLR-4 expression in muscle and liver to the
baseline, besides suppressing the TLR4 activation, c-Jun
N-terminal kinase (JNK), and the insulin receptor phosphor-
ylation. In the same way, TNF and IL-6 expressions were
significantly decreased in the treated mice’s livers and
muscles. The LPS levels in portal circulation, involved in
metabolic endotoxemia, were decreased in the probiotic
group. Furthermore, molecules involved in bacterial
translocation and gut inflammation, nucleotide-binding
oligomerization domain-containing protein 1 (NOD1), clus-
ter of differentiation 14 (CD14) decreased in the probiotic
group. Also, the probiotic administration decreased F4/80þ
macrophage infiltration in adipose tissues and crown-like
structures, prevalent in obese animals. The zonulin (ZO-1)
and occludin proteins, involved in intestinal permeability
integrity, were partially reestablished in the treated obese
animals (Bagarolli et al. 2017).
In HFD B6 mice, the administration of 5
109 CFU/day
of L. curvatus HY7601 and L. plantarum KY1032, resulted
in weight loss and reduced fat mass, leptin, and insulin lev-
els, and gene expression of inflammatory TNF, IL-6, IL-1b
and MCP-1 in adipose tissues. These probiotic strains were
reported to decrease adipogenesis in 3T3-L1 cell lines (Park
et al. 2013). Another study in HFD B6 mice, through oral
gavage with 5
108 CFU/day of Bacteroides uniformis CECT
7771, promoted a decrease in their body weight, serum con-
centrations of glucose, insulin and leptin, and enhanced
their oral tolerance to glucose and immune responses, such
as TNF secretion by macrophages and dendritic cells in
response to LPS stimulation. Obesity interferes in effective
immune responses and the probiotic administration reestab-
lishes the capacity of dendritic cells to activate naïve T lym-
phocytes in obese mice (Gauffin-Cano et al. 2012).
Metabolic endotoxemia, induced by bacterial translocation
and increased LPS plasma levels, is frequently correlated to
inflammation in adipose and hepatic tissues (Cani et al.
2007a; Toral et al. 2014).
The intestinal microbiota represents a strategic tool for
reducing metabolic endotoxemia, which has been linked
to inflammatory states during metabolic dysfunctions.
In obesity, the intestinal microbiota modulates energy
regulation and the fermentation of dietary fibers not
digested by humans, with the production of SCFAs (Bailey
and Holscher 2018).
The role of diet, prebiotics, and the intestinal microbiota
in metabolic endotoxemia is under investigation. Research
concerning the different types of dietary habits on the gut
microbiota, and their relationship with systemic inflamma-
tion is needed in order to determine the real role of the
efficacy of diet interventions to suppress metabolic endotox-
emia, inflammation, and metabolic dysfunctions (Bailey and
Holscher 2018).
Currently, studies have focused on the role of the intes-
tinal microbiota in obesity, metabolic syndrome, and T2D.
However, further studies in animal models are required to
explore the metabolites-immune system-gut barrier axis in
order to investigate how probiotic metabolites interact
with the mucosal immune system, and the impact of this
interaction on intestinal permeability, which is involved
in metabolic endotoxemia and obesity. In addition, clinical
trials are still scarce, and the number of subjects, strains
combination, doses, and administration duration need to be
better established.
Effect of probiotics, prebiotics, and synbiotics on obese
GI microbiota
The collective genomes of the human gut microorganisms
and their effect on both health and diseases have been the
focus of considerable studies. However, a deep understand-
ing of the role of the gut microbiota in the beginning of dis-
eases is still under investigation (Rastelli, Knauf, and Cani
2018; Clemente, Manasson, and Scher 2018).
Studies have shown which microbes are normally present
and how the relationship among them affects health and dis-
eases, besides their role in metabolism, immune system, and
human health (Patterson et al. 2016; Hugon et al. 2017).
Although most of the studies conducted on the human gut
microbiota concentrated on bacterial diversity, other prokar-
yotes (including archaea) and eukaryotic populations also
participate in other relationships in the gut ecosystem. This
microbiota is not fully characterized due to technical restric-
tions (Hugon et al. 2017).
The GI microbiota is susceptible to adaptations and
transformations, with important effects throughout the
human body, due to its ability to produce expressive bio-
active metabolites, such as exopolysaccharides, SCFAs, con-
jugated fatty acids, and neuroactive metabolites, such as
serotonin and c-aminobutyric acid (GABA), which are
transported via the circulatory system throughout the body
(Ross et al. 2010; Patterson et al. 2016). The GI microbiota
performs several critical roles in adults, such as ecology pro-
tection, metabolism of dietary components, immune system
modulation, intestinal motility, cholesterol metabolism, and
enterohepatic cycling of bile acids (Ross et al. 2010; Foxx-

Orenstein and Chey 2012). Thus, the intestinal microbiota
can affect the human health, though in particular situations;
imbalanced changes in microbiota profile (dysbiosis) can
happen and may pose the risk of developing diseases or syn-
dromes, including obesity and its related comorbidities,
which have been reported in both animals and humans (Al-
Assal et al. 2018; Makki et al. 2018; Rastelli, Knauf, and
Cani 2018). The gut microbiota is mostly composed of strict
anaerobes, facultative anaerobes, and aerobes; its compos-
ition varies widely among individuals because of a natural
selection at both microbial and host levels (Al-Assal et al.
2018; Nie, Luo, and Lin 2018).
Among Prokaryotes, most of the bacteria species har-
vested from the gut belong to the phyla Firmicutes,
Bacteroidetes, Actinobacteria, and Proteobacteria; the dom-
inant species belong to the families Bacillaceae,
Enterobacteriaceae, Corynebacteriaceae, and Bacteroidaceae
(Hugon et al. 2015). Genera from Archaea are also present,
such as Methanobrevibacter (Ross et al. 2010). Nevertheless,
when considered at the level of bacterial species, the vari-
ation in the composition of interindividual microbial com-
munities is considerably greater than that observed at the
phylum level. Moreover, many studies have shown that sev-
eral species considered to dominate the healthy gut micro-
biota belong to the genera Bacteroides, Bifidobacterium,
Clostridium, Eubacterium, Fusobacterium, Lactobacillus,
Peptococcus, Peptostreptococcus, Ruminococcus, and
Veillonella (Hugon et al. 2017).
The gut microbial community is incredibly dynamic, with
some autochthonous members (permanent residents), and
allochthonous ones (transient residents), deriving from the
hosts’ diet, water, and environment resources. Additionally,
diet plays a crucial role in the composition, diversity, and
richness of the intestinal microbiota (Ross et al. 2010). The
gut microbes, their composition and function, and the host-
microbe interactions are modulated by food type, quality,
and origin. Moreover, a diet rich in sugar and fat, and poor
in dietary fibers can contribute to the reduction of specific
bacteria in the gut (Makki et al. 2018).
Some research has demonstrated that obesity and related
diseases are linked to alterations in gut microbiota. Indeed,
a higher Firmicutes/Bacteroidetes ratio has been reported in
both obese humans and animals (Le Chatelier et al. 2013).
Several systems linking energy metabolism and gut micro-
biota in the host have been postulated, including the diet
energy, regulation of fat metabolism, and synthesis of gut
peptides involved in energy homeostasis (Cani and Delzenne
2009). However, disagreement exists regarding the
Firmicute/Bacteroidetes proportion to characterize the obese
phenotype, since more recent studies have not confirmed
this result. Differences may be associated with changes in
metabolic functions at the genus and species levels com-
pared to the phylum level (Bliss and Whiteside 2018).
Angelakis et al. (2012) reported that the relationship
between microbiota and obesity is probably more sophisti-
cated than Firmicutes/Bacteroidetes proportion at a phylum-
level. This suggests that differences in weight or BMI may
not be universally related to the intestinal microbiota
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 13
composition at the phylum level if compared to the genus
and species levels and may be associated with changes in
metabolic functions (Bliss and Whiteside 2018).
The genera Anaerostipes, Bacteroides, Campylobacter,
Dialister, Parabacteroides, Porphyromonas, Ruminococcus,
and Staphylococcus were prevalent in individuals with the
obese phenotype and low bacterial richness. They are char-
acterized by insulin resistance, more intense general adipos-
ity and dyslipidemia, and a more significant inflammatory
phenotype when compared with lean individuals, who pre-
sent high bacterial richness. Additionally, species of
Akkermansia, Alistipes, Bifidobacterium, Butyrivibrio,
Coprococcus, Faecalibacterium, Lactobacillus, and
Methanobrevibacter were more prevalent in individuals with
high bacterial richness and the lean phenotype.
Furthermore, the production of metabolites with possible
harmful effects on the host’s health (such as procarcinogens)
was significantly higher in low gene count participants, and
including modules for b-glucuronide degradation, aromatic
amino acids degradation, and dissimilatory nitrate reduction
(Le Chatelier et al. 2013; Al-Assal et al. 2018). Hence, the
metabolism of the intestinal microbiota and the metabolites
produced are also a subject to be further studied.
There are evidences showing that the loss of biodiversity
can be related to many diseases. People with intestinal dis-
eases, such as inflammatory bowel disorder (IBD), present a
lower diversity of species in their intestines, and the propor-
tion of the different types of bacteria in the microbiota dif-
fers from that of healthy people. Additionally, elderly
patients with inflammation and obese individuals also pre-
sent low richness of gut microbiota (Le Chatelier
et al. 2013).
Studies by Mulders et al. (2018) reported that HFD feed-
ing extensively modifies the composition of gut microbiota.
It is reported that A. muciniphila, Bifidobacterium spp., B.
uniformis, and C. coccoides can prevent obesity, based on
their associations with glycaemic control, leptin levels, and
adiposity. In contrast, Bilophila wadsworthia and
Oscillibacter spp. are indicated to contribute to the compli-
cations of obesity. Moreover, increased intestinal and serum
inflammation are linked to relative abundance of A. mucini-
phila, whereas multiple correlations between A. muciniphila,
Bifidobacterium spp. and decreased inflammation have
been reported.
The relationship between obesity and intestinal micro-
biota is well-known; however, more studies are necessary to
focus on the capacity of the intestinal microbiota and its
metabolites to target ENS, in order to suggest new
approaches for the treatment of obesity and its related
comorbidities: intestinal dysmotility disorder, increased food
intake, and T2D. Additionally, the influence of ENS on glu-
cose absorption is not completely understood (Rastelli,
Knauf, and Cani 2018).
HFD can affect the gut microbiome and intestinal physi-
ology under certain conditions which lead to metabolic dys-
functions (Bailey and Holscher 2018). Conversely, several
studies have shown that probiotics and prebiotics play a
14 T. F. DA SILVA ET AL.
crucial role in restoring the balance of the intestinal micro-
biota of obese human (Table 1) and animals (Table 2).
Bifidobacterium and Lactobacillus species are the most
studied ones to recover the GI balance. Bifidobacterium spe-
cies longum, animalis, bifidum and breve and Lactobacillus
species acidophilus, plantarum, rhamnosus, fermentum, reu-
teri, bulgaricus, lactis, casei, paracasei, curvatus and sakei are
generally recognized as safe (GRAS) for consumption by
humans by the United States Food and Drug
Administration (FDA) and have qualified presumption of
safety (QPS) status by the European Food Safety Authority
– EFSA (Ricci et al. 2017, FDA 2020).
More recently, A. muciniphila has gained special interest
to recover intestinal dysbiosis. A. muciniphila is a strict
anaerobe isolated from human feces which uses the mucin
as the sole sources of carbon and nitrogen elements. A.
muciniphila is known to have an essential role in improving
the host metabolic functions and immune responses. The
restoration of A. muciniphila has also been shown to
improve glucose tolerance and insulin action, and low abun-
dance of this bacterium was reported for obese individuals
(Zhi et al. 2019). The beneficial effects of A. muciniphila
include provision of nutrients (acetate and propionate) for
the growth of other bacteria and reduction of intestinal per-
meability via the upregulation of mucin. In contrast, the
genera Oscillibacter and Flavonifractor increase inflammation
via mechanisms that are poorly understood (Mulders et al.
2018; Zhang et al. 2019).
In a recent clinical study, the effects of daily oral supple-
mentation of 1010 bacteria either alive or pasteurized A.
muciniphila for 3 months was evaluated in overweight and
overweight/obese insulin resistant women volunteers
(N ¼ 32). It reduced the levels of liver dysfunction and
inflammation while the overall gut microbiome structure
was unaffected (Depommier et al. 2019).
The effectiveness of different bacteria strains in clinical
trials testing animals and humans are summarized in
Table 1. The outcomes of prebiotics and synbiotics on the
biochemical markers and gut microbiota have also been
evaluated. Recently, Crovesy et al. (2017) reviewed the
impact of Lactobacillus on body fat and weight in
overweight patients. They suggested that possible modes of
action include the anti-inflammatory ability of some strains
and the modulation of lipid metabolism parallel to increases
in Bifidobacterium spp.
The use of many natural products containing dietetic
fibers and probiotics has been potentially related to
improvements in intestinal microbiota. Such modulation
may occur through the regulation of cytokines activity, acti-
vation of nuclear receptor proteins, or production of SCFAs
(Daguet et al. 2016). Additionally, the concentrations of fecal
SCFAs (acetate, butyrate, and propionate, in a molar ratio of
approximately 60:20:20) are indicative of intestinal health.
Other SCFAs such as formate and valerate (pentanoate) as
well isobutyate and isovalerate (branched-chain fatty acids)
have been detected at much lower levels in the gut of
humans and rodents. Studies demonstrated that butyrate
promotes fatty acid oxidation and thermogenesis in brown
adipose tissues; it can differentially regulate genes involved
in gut integrity and apoptosis, which may be a system cap-
able of decreasing gut inflammation. Moreover, butyrate
exerts a trophic effect on the intestine, resulting in intestinal
morphology changes, such as increased villus height and
crypt depth and thickened mucosal layer, which contribute
to strengthen the intestinal barrier function, essential for
preventing the development of metabolic diseases. Butyrate
and propionate activate intestinal gluconeogenesis, thereby
promoting glucose control and metabolic benefits reflected
by body weight, while acetate reduces appetite by activating
the tricarboxylic acid cycle to alter the expression profile of
the hypothalamic appetite-regulating neuropeptide.
Moreover, acetate can be converted into butyrate by enzyme
butyryl-CoA producer microbes, such as Faecalibacterium
prausnitzii, Anaerostipes spp., Eubacterium spp., and
Roseburia spp., by using a mechanism known as cross-feed-
ing or cross-talk, when one species produces metabolites
that are utilized by another species. (Bailey and Holscher
2018; Luu and Visekruna 2019; Mulders et al. 2018; Zhi
et al. 2019).
Diet and particularly dietary fiber have a crucial effect on
the gut microbiota. There is evidence supporting that a
high-fiber diet presents many health benefits, such as
decreased incidence of coronary artery disease, diabetes, and
obesity. Higher microbial richness in terms of both tax-
onomy and gene expression has been associated with fiber-
rich, plant-based diets; in contrast, low microbial richness
has been associated with higher insulin resistance, adiposity,
inflammation, and dyslipidemia (Le Chatelier et al. 2013;
Bailey and Holscher 2018).
Additionally, an increase in the relative abundance of
Bifidobacterium, Eubacterium rectale, and C. coccoides was
shown with inulin supplementation, while decreased the
relative abundance of Roseburia (Mulders et al. 2018);
in contrast, oligofructose has been linked to increases in
A. muciniphilia, F. prausnitzii, Bifidobacterium, and
Lactobacillus (Cani et al. 2009b). Studies have demonstrated
that prebiotics, such as oligofructose and inulin, increase the
concentration of SCFAs, such as acetate and propionate,
have been reported to have a beneficial effect on host
metabolism and appetite; they improve gut-barrier function,
bring about weight-loss, and reduce food intake, by improv-
ing gut nutrient-sensing mechanisms; they also decrease
systemic inflammation and leptin resistance. The SCFAs
promote energy metabolism through their effects on
receptor mediated pathways of cellular metabolism. These
effects are associated with changes in the gut microbiota
composition (Bauer, Hamr, and Duca 2016; Mulders et al.
2018; Zhi et al. 2019).
Using an in vitro batch culture fermentation, Henrique-
Bana et al. (2020) evaluated the effect of synbiotic supple-
ments containing short chain FOS (1% w/v) combined with
either B. lactis Bb12 or B. lactis HN019 (106 CFU/mL).
Maltodextrin (1% w/v), FOS (1% w/v) and the probiotic
strains were also tested individually. FOS increased the
Atopobium cluster while maltodextrin increased the
Clostridium coccoides-Eubacterium rectale group. Additionally,

maltodextrin, FOS and synbiotics increased the production of
acetate and butyrate, compared to the negative control and
probiotics individually.
In healthy individuals, the SCFAs homeostasis requires
high abundance of SCFAs-producing bacteria in the gut
lumen and a continuous intake of non-digestible carbohy-
drates such as dietary fiber. In contrast, recent studies have
highlighted that restricted gut microbiota composition and
atypical production of SCFAs have been associated with
several autoimmune and inflammatory disorders, such as pro-
gressive intestinal inflammation and colitis-associated carcino-
genesis, multiple sclerosis, type 1 diabetes and rheumatoid
arthritis. Furthermore, SCFAs modulate the metabolic status
of T cells, thereby impacting on epigenetic modifications and
T cell function (Luu and Visekruna 2019).
In a clinical study, Salazar et al. (2015) treated 30 obese
women with 16 g/day inulin-type fructans (N ¼ 15) or malto-
dextrin (N ¼ 15) for 3 months and determined variations on
fecal SCFAs concentration and explored associations between
Bifidobacterium species, SCFAs and host biological markers of
metabolism. Changes in B. bifidum and B. adolescentis were
inversely associated with fat mass percentage whereas B. breve
negatively correlated with total cholesterol and LDL cholesterol.
Moreover B. longum negatively correlated with serum LPS.
Further investigations are desirable to deeply understand
the mode of action of probiotics and prebiotics on the
human health, using long-term and large-scale clinical inter-
ventions to elucidate how changes in the intestinal micro-
biota is linked to obesity development.
Final remarks and futures studies
Accumulated data about the impact of probiotic, prebiotic
and synbiotic food or supplements on obesity diseases are
encouraging. Many studies have successfully demonstrated
several beneficial effects on the host’s metabolism: enhanced
metabolism of dietary components, weight loss, decrease in
BMI and adiposity, enhanced body composition, hormone
regulation, decreased pro-inflammatory markers, improved
biochemical markers, and ecology protection.
Additionally, these foods or supplements play a crucial role in
composition, diversity, and richness of gut microbiota profile,
consequently, reducing the incidence of diseases, such as obesity
and its comorbidities. Moreover, there is a need to extend the
current knowledge about the role of bacteria involved in the
pathogenesis of obesity and how particular bacterial groups can
present therapeutic potential to avoid or treat obesity.
Disclosure statement
The authors declare that they have no conflict of interest.
Funding
This study was sponsored by The Brazilian National Council for
Scientific and Technological Development (CNPq - Project 307155/
2015-3). The authors would like to thank Vivian R. Diamantino for
preparing Figure 1.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 15
ORCID
Ana L

ucia Barretto Penna http://orcid.org/0000-0001-6715-9276
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