Review Article A Review on Role of Microbiome in Obesity and Antiobesity Properties of Probiotic Supplements

Hindawi
BioMed Research International
Volume 2019, Article ID 3291367, 20 pages
https://doi.org/10.1155/2019/3291367

Review Article
A Review on Role of Microbiome in Obesity
and Antiobesity Properties of Probiotic Supplements

 Bhagavathi Sundaram Sivamaruthi ,1 Periyanaina Kesika ,1
 Natarajan Suganthy ,2 and Chaiyavat Chaiyasut 1
 1
 Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University,
 Chiang Mai- 50200, Thailand
 2
 Department of Nanoscience and Technology, Alagappa University, Karaikudi, India

 Correspondence should be addressed to Chaiyavat Chaiyasut; chaiyavat@gmail.com

 Received 21 March 2019; Accepted 16 April 2019; Published 9 May 2019

 Academic Editor: Koichiro Wada

 Copyright © 2019 Bhagavathi Sundaram Sivamaruthi et al. This is an open access article distributed under the Creative Commons
 Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
 properly cited.

 Probiotics are now recognized for several health benefits and they have been recommended as a complementary therapeutic agent
 for metabolic disorders. Obesity is an altered health condition, which is a resultant of irregular energy intake and energy balance,
 changes in gut microbiota, and improper diet with the influence of genetic makeup and environmental factors. Several studies
 revealed the influence of probiotic supplementation on obesity-associated consequences in vitro, in vivo, and in human clinical
 studies. The current manuscript discussed the factors influencing the occurrence of obesity, the interplay between microbiome
 and obesity, the effect of the probiotic intervention on the health status of obese people, and possible mechanism of antiobesity
 activity of probiotics. The literature survey revealed that the antiobese activity of probiotics might be associated with their ability
 to alter the intestinal microbiota, remodeling of energy metabolism, alter the expression of genes related to thermogenesis, glucose
 metabolism, and lipid metabolism, and change the parasympathetic nerve activity. Further intense research is necessary to figure
 out the best probiotic or synbiotic mixture and optimum dosage and duration of the intervention to reduce obesity and prevent the
 recurring of obese condition.

1. Introduction GM can be positively altered by the supplementation of
 probiotics, a group of beneficial microbes that confers health
Food habits and lifestyle greatly influence the quality of the benefits when consumed in an adequate amount [5]. Probi-
life and health status of humans. The improper diet and otic intervention has been recognized for the treatment or
lifestyle are associated with several metabolic disorders and betterment of several ill-health conditions such as diarrhea,
are the greatest global health issues [1]. The environmental allergy, gastrointestinal disorders, and metabolic syndromes
factors, maternal health, and host genetic makeup are also [6–11]. The probiotic supplementation also slows down the
involved in the development of metabolic disorders and aging-associated health issues by positive regulation of GM
diseases. The composition of gut microbiota (GM) and its [12, 13].
function is altered due to the consumption of improper Obesity is an altered health condition, which is a resultant
diet, which affects the health status of the host, specifically of irregular energy intake and energy balance, changes in GM,
associated with the development of obesity. GM is involved and improper diet with the influence of genetic makeup and
in the energy balancing, intestinal integrity, and immunity environmental factors. Obesity is defined as an accumulation
against invading pathogens; thereby GM controls the overall of excessive fat that impairs health status [14]. The obesity
health status of the host [2–4]. rate is drastically increased over the last decades [15], and

2 BioMed Research International

it has been estimated that about 1.9 billion adults were B (neurotrophic receptor expressed in neuronal and non-
overweight and, among them, 650 million adults are obese neuronal tissues and associated with several physiological
in 2016 [16]. The overweight with some ill-health conditions regulations and processes such as synaptic plasticity and
such as diabetes, hypertension, and cardiovascular diseases is hyperphagia), brain-derived neurotrophic factor (involved
considered as morbid obesity [14, 17]. in neuronal plasticity and cognitive function and acting
 GM is one of the influencing environmental factors as modulator of neurotransmitter), kinase suppressor of
involved in the initiation of obesity mainly by disturbing Ras 2 (molecular scaffold expressing majorly in brain), and
the food intake and energy balance. Though some of the tubby bipartite transcription factor were associated with
in vivo studies demonstrated the role of GM in the onset obesity [60–65] (Figure 1). The mutations or alterations in
of obesity, the exact etiology of obesity has not yet been the genes associated with obesity were linked to several
explained [2, 14, 18, 19]. As mentioned earlier, probiotic is clinical consequences such as the defective immune system,
a feasible way to regulate and improve the GM. In recent low blood pressure, cognitive deficiency, hypopigmentation,
decades, several studies have focused on the influence of insulin resistance, and metabolic dysfunction [65].
probiotic supplementation on the health improvement of Heymsfield and Wadden [65] have reviewed the patho-
obese people, and the results were found to be controver- physiological consequences of obesity in detail. The lethal
sial. The current manuscript summarizes and discusses the obese condition accelerates the incidence of type 2 diabetes
outcome of clinical trials conducted to evaluate the probiotic (T2D) via increased adipokine, proinflammatory cytokines
based supplementation on the health status of obese people. synthesis, and impaired insulin signaling and increased
The published scientific documents have been searched and insulin resistance. The increased lipid production in obese
retrieved from Scopus, Web of Science, PubMed, and Google condition releases free fatty acids, which cause lipotoxicity
Scholar using the search terms “Probiotic” and “obesity.” The and chronic diseases like T2D [66] and other disease condi-
relevant scientific documents in English have been selected tions such as cirrhosis, fatty liver, steatohepatitis, stroke, and
without any chronological restrictions for the preparation of heart failure [67]. Also, the accelerated sympathetic nervous
the current manuscript. system and renin-angiotensin-aldosterone system cause sys-
 temic hypertension, which ends up with several chronic and
 heart diseases [68]. Due to the overweight, internal organs
2. Obesity: Influencing Factors and of obese people become damaged by mechanical stress that
 Consequences causes overload on joints, and increased intra-abdominal
 tension leads to the development of osteoarthritis and gas-
Several factors are associated with the development of obesity. troesophageal reflux disease [69, 70]. Obesity also leads to
Use of high-calorie fast-foods, high consumption rate, less obstructive sleep apnea, which is due to the obstructions of
physical powered occupations, lack of physical activities, the upper airway during sleep [71] (Figure 2).
insufficient sleep, side effects from the medicines like topira-
mate, olanzapine, and pioglitazone, and other environmental,
genetic, and socioeconomic factors are closely related to the 3. Microbiome
onset of obesity [20–23]. GM represents densely populated microorganism such as
 Energy imbalance, environmental factors, and genetic bacteria, fungi, Archaea, protozoa, and viruses, which col-
makeup are significantly connected to a network that reg- onizes the human gastrointestinal tract. Approximately 100
ulates several physiological functions. The neuronal system trillion microbes colonize the human gut, which exhibits a
regulates the energy expenditure through the stimulants from symbiotic relationship with the host [72]. Each individual has
the gastrointestinal tract in the form of neurotransmitters unique GM composition influenced by several endogenous
and other neuropeptides produced by GM. The regulatory and exogenous factors such as gestational age, mode of
molecules released by the microbiota influence the brain delivery, breastfeeding, antibiotic exposure, diet, and lifestyle
regions, which is responsible for cognitive functions, emo- [73]. The colonization of GM is not uniform throughout
tions, and food consumption. The negative energy balance the gastrointestinal tract with limited distribution in stom-
(due to increased physical activity or reduced food consump- ach and small intestine followed by a dense and diverse
tion or both) plays a vital role in obesity in association with population in the colon due to the absence of digestive
energy expenditure, physical and metabolic activities, and secretion, slow peristalsis, and rich nutrient supply [74].
orexigenic signals [55–59]. These microbes play a significant role in maintaining host
 Pigeyre et al. [59] reviewed the genes associated with body homeostasis by participating in the digestive process
monogenic obesity in humans. The mutation in leptin and energy production, hampering pathogen colonization,
(leptin is an adipocyte-specific secreted protein associ- and modulating the immune system.
ated with energy expenditure and appetite), leptin recep- Gut microbiome influences the individual’s metabolic
tor, melanocortin 4 receptor (a G-protein-coupled receptor ability such as caloric extraction from indigestible dietary
implicated in energy homeostasis), and prohormone con- substance and its storage in adipose tissue, which predisposes
vertase 1 (involved in managing prohormones), defects in an individual to obesity. Studies in germ-free and conven-
proopiomelanocortin precursor (precursor of adrenocorti- tional mice showed alteration in kidney, liver, and intestinal
cotrophin, melanocyte-stimulating hormones, and opioid- homeostasis in germ-free mice depicting the fact that gut
receptor ligand beta-endorphin), tyrosine receptor kinase microbiome influences the whole body metabolism [75–77].

BioMed Research International 3

 Environmental and Personal factors
 Large portion of palatable foods
 Lack of physical activities
 Side effects from some medicines
 Inadequate sleep

 Obesity
 Genetic factors
 Epigenetic
 Defects in LEP, LEPR, MC4R, POMC,
 PCSK1, TUB, SH2B1, BDNF, NTRK2.

 Dysregulation of energy balance

 Gut microbiota

 Figure 1: The factors influencing the incidence and development of obesity.

 Obesity

 Compromised Insulin signaling
 Increased insulin resistance
 Increased lipid production
 Lipotoxicity
 Dyslipidemia
 Increased neuronal activation
 Mechanical stress

 Type 2 diabetes, Heart and
 Kidney diseases, Cirrhosis,
 Stroke, Fatty liver,
 Hypertension, Osteoarthritis
 Steatohepatitis

 Figure 2: The major consequences of obesity.

GM has received much attention related to human health and metabolic function in the human body, which cannot
and disease status in the recent decade. Conventionally, be performed in its absence. In healthy adult individuals,
the interrelation between genetic and environmental factors the microbiota of the gut is in a symbiotic relationship with
such as high-calorie diet and lack of physical activity was the host, which depends on host lifestyle, diet, and antibi-
considered as main contributor to obesity. However, recent otics, while in elderly people the composition of microbiota
scientific investigations have shown that GM has emerged as changes depending upon the alteration in digestive physiol-
a prime endogenous factor influencing obesity [78, 79]. ogy and diet [81]. GM belongs to the phyla Bacteroidetes,
 Firmicutes, Actinobacteria, Proteobacteria, and Verrucomi-
3.1. Development and Composition of Gut Microbiota. Emerg- crobia among which, Bacteroidetes and Firmicutes account
ing studies showed that prenatal gut microbiome represents for 90% of the total bacterial species [82]. Type and density
the maternal microbes transmitted to the fetus through pla- of the bacterial population in gastrointestinal (GI) tract
cental circulation and its composition acts as a determining depend on environmental variation such as pH, oxygen
factor for offspring microbial composition. Maternal obesity level, and nutrient availability. Recent findings in animal and
during pregnancy together with GM dysbiosis reflects in human models revealed that the GM plays a key role in
offspring microbiota leading to offspring metabolic disorders. nutrient acquirement, energy harvest, and host metabolic
GM of the newborn is also influenced by the factors like mode pathways, which are interrelated and are responsible for
of birth, antibiotic treatment, feeding type, and sanitation the development of obesity [83, 84]. Healthy human GM is
[80]. In the first year of child life, the microbial composition characterized by a high ratio of Bacteroidetes to Firmicutes,
varies according to developmental changes, host genotype, while in obese individuals inverse ratio is observed with a
and food intake, which stabilizes similar to adult microbiota high prevalence of Firmicutes [85]. In addition, the elevated
by the age of 3 years. The adult human gut is colonized by 1014 level of Lactobacillus species with a relatively low level of
bacteria with billions of genes exceeding the human genome Bacteroides vulgatus was observed in obese individuals [86].
content. These microbial factories contribute to biochemical Metagenomic analysis and clinical studies on GM of lean

4 BioMed Research International

and obese individuals exhibited diminished proportion of decrease in ghrelin leading to increased satiety and reduced
Bacteroidetes and increased level of Actinobacteria with no food intake [100]. Butyrate and propionate also reduce the
significant difference in Firmicutes revealing the fact that appetite by
ratio of Firmicutes to Bacteroidetes acts as a biomarker of
obesity susceptibility [87, 88]. These data strongly link that (i) inducing the expression of leptin in adipocytes and
certain bacterial phyla/class/species colonized in the gut acts regulating body weight and energy homeostasis by
as a driving force leading to the onset of obesity. reducing food intake and increasing energy expendi-
 ture [101]
3.2. Host-Gut Microbiota Metabolite Interaction. Mounting (ii) inducing the expression of intestinal gluconeogenesis
evidence revealed that metabolites derived by fermentation of gene promoting gluconeogenesis [102]
food by GM play a vital role in regulating the host metabolism (iii) inhibiting histone acetyltransferase and deacetylases
with perspective to obesity. Clostridium and Eubacterium exhibiting anti-inflammatory phenotype, epigeneti-
belonging to GM convert bile acid in the intestine to its sec- cally inducing the immune cell proliferation and dif-
ondary forms such as deoxycholic acid and lithocholic acid ferentiation, and upregulating adiponectin mediated
which binds to TGR5 receptor (G-protein-coupled receptor) AMPK pathway promoting mitochondrial biogenesis
and stimulates the secretion of incretin hormone GLP-1 and and fatty acid oxidation [103]
insulin, thereby promoting the energy expenditure [89]. Long
chain fatty acid such as linoleic acid derived by the GM SCF derived from GM regulates host metabolism by inter-
modulates the lipid profile leading to adiposity [90]. Another action with complex metabolic pathways intertwined with
important by-product of gut microbial fermentation is short the nervous, endocrine, and immune system. In healthy
chain fatty acids (SCFs) formed by the gut microbial diges- individuals SCF modulates the gut integrity, gut hormone
tion of indigestible poly- and oligosaccharides that escape production, and immune function, while in diseased state
from the digestion and absorption in the proximal jejunum SCF exhibits a protective effect against diabetes, ulcerative
[91]. SCFs primarily acetate and propionate produced by colitis, colorectal cancer, and neurodegenerative disorders
Bacteroidetes and butyrate contributed by Firmicutes reg- [94, 104]. Understanding the mechanism of interaction of
ulate the host metabolism by influencing energy harvest, SCFs with its receptor will help in exploring the therapeutic
fat accumulation, and appetite [92]. SCF in the GI tract way for the treatment of obesity and health-related disorders.
reduces the luminal pH enhancing the nutrient absorption
and also acts as a carbon source for GM [93]. Butyrate, the 3.3. Gut Microbiota and Obesity. The interrelation between
prime energy source for colonocytes, promotes proliferation GM and host obesity was first reported by Wostmann et al.
and maturation of colonocytes maintaining colon healthy. [105] based on their studies in germ-free (GF) rodents, i.e.,
In addition, butyrate protects the colon by enhancing the animals devoid of bacteria and conventional ones. However,
expression of mucin 2 and modulating immune response the mechanism behind the report was elucidated by Jeffery
[94]. Acetate and propionate cross the epithelium to the Gordon and his colleagues [2] who observed an increase
liver, where the propionate gets metabolized, while acetate in total body and gonadal fat in conventional mice when
alone remains in the peripheral circulation [95]. SCF plays a compared to GF mice consuming more food. Colonization of
significant role in maintaining the epithelial barrier integrity GF mice with cecum-derived microbiota showed an increase
by regulating the tight junction protein (claudin-1, occludin, in body fat mass together with insulin resistance, adipocyte
and Zonula Occludens-1), while downregulation of these hypertrophy, and enhanced level of circulating leptin and
proteins leads to translocation of bacteria and LPS triggering glucose level. The possible mechanism involved might be (1)
an inflammatory response [96]. So apart from the energy degradation of indigestible polysaccharide by GM increasing
source, SCF modulates host biological response such as hepatic lipogenesis in the host and (2) suppressing intestinal
inflammation, oxidative stress, and immune response to fight expression of angiopoietin-like 4 (ANGPTL4), the inhibitor
against intestinal diseases such as Crohn’s disease, ulcerative of lipoprotein lipase (LPL) thereby blocking the fatty acid
colitis, and colorectal cancer [97, 98]. metabolism leading to increased cellular uptake of fatty acids
 SCFs influence the host metabolism either by direct acti- and adipocyte triglycerides accumulation [2, 106, 107]. GF
vation of G-coupled receptors such as free fatty acid receptors mice fed with high fat and sugar diet exhibited lean pheno-
2 and 3 (FFAR2/GPR41 and FFAR3/GPR41) expressed pri- type while conventional mice fed with the same diet were
marily in the gut epithelial cells or by inhibiting nuclear class I observed to be obese. GF mice showed enhanced sensitivity
histone deacetylases (HDACs) within the epithelial cells [97]. to insulin improving glucose tolerance and exhibited altered
Acetate binds to FFAR2 while butyrate and propionate bind cholesterol metabolism reducing the storage and enhancing
to FFAR3 receptor regulating the level of satiety hormones fecal excretion of cholesterol.
ghrelin (orexigenic peptide), peptide-1 (GLP-1), and peptide GM leads to host obesity through various routes such as
YY (PYY) (anorexigenic peptide) [99]. Ghrelin is secreted by altering the intestinal permeability leading to endotox-
before a meal, while GLP-1 and PYY are released into emia, enhanced calorie provision, and endocannabinoid sys-
circulation after meals, which stimulates insulin secretion tem (eCB) stimulation and by regulating the lipid metabolism
by pancreatic cells, reduces food intake, and normalizes by enhancing lipoprotein lipase activity and lipogenesis.
weight loss and energy intake. Increased production of SCFs Experimental studies in animals and human volunteers
increases the gut peptide PYY and GLP-1 together with a revealed that increased production of SCFs by GM provides

BioMed Research International 5

additional calories to host leading weight gain [108]. Binding endogenous lipid with cannabinoid receptor (CB1 and CB2)
of these SCFs to GPR induces the secretion of peptide activates adenylate cyclase and also stimulates secondary
hormone PYY, which reduces the intestinal transit time messenger involved in MAPK, ERK, and NF- B pathway,
increasing the nutrient absorption in the intestinal lumen promoting inflammation and insulin resistance, ultimately
leading to weight gain [109]. Feces of obese individuals leading to obesity [115]. Experimental studies showed an
showed an increased level of SCF when compared to lean increased concentration of AEA, NAPE-PLD, and CB1 and
individuals. However, Ibrügger et al. [110] illustrated that low expression of FAAH in the adipose tissue, while the
consumption of food rich in dietary fibers increases the reverse was observed in prebiotic treated animals revealing
SCF production, thereby significantly reducing the weight in the fact that eCB activation leads to obesity and intervention
contradiction to the previous hypothesis, which makes the of eCB upregulation is beneficial [114, 116]. Overall the studies
role of SCF in obesity a puzzle. reveal that GM activates the eCB system, which increases
 Microbiota influences the LPL activity by altering the intestinal permeability promoting LPS migration into the cir-
expression of fasting-induced adipose factor (FIAF), the culatory system causing endotoxemia. Increased LPS, in turn,
inhibitor of LPL activity causing accumulation of triglyc- alters the tight junction integrity of the intestinal membrane
erides (TG) in adipocytes [2]. Increased level of TG in adipose enhancing increased release of LPS into circulation creating
tissue causes hypertrophy leading to chronic inflammation, virtuous circle promoting adipogenesis.
preventing further deposition of TG in adipose tissue and Although research on human GM has succeeded loga-
thereby promoting ectopic accumulation of TG in other rithmically, still this field remains a puzzle and is emerging
organs developing insulin resistance [111]. which needs to be explored. The gut microbiome is a complex
 Lipopolysaccharides (LPS), the cell membrane compo- microbial world having both beneficial and harmful microbes
nent of Gram-negative bacteria, act as triggering factors and manipulation of these microbes for the therapeutic
leading to low-grade chronic inflammation followed by the purpose is possible only if the precise role of each and every
development of insulin resistance (IR). LPS formed in the individual microbe is known. GM, its metabolite, and host are
gastrointestinal tract reach the circulation via direct diffusion interplaying systems; therefore integration of this system will
by enhancing the intestinal permeability or through absorp- give us a comprehensive idea of the function of each building
tion and incorporation with chylomicron [112]. Enhanced block of this system [117, 118].
level of LPS in circulation is called endotoxemia where diet
plays a key role. High fat intake inhibits the expression of
tight junction proteins zonulin and occludin, thereby increas- 4. Influence of Probiotic Supplementation on
ing intestinal permeability of LPS, the causative factor for Health Status of Obese People
endotoxemia. LPS interact with toll-like receptors TLR-4 in
immune cells and target organs like liver and adipose tissue. Intervention of calorie restricted diet (1500 kcal per day)
LPS interaction with TLR-4 induces conformational change supplemented with cheese (50 g per day) containing probi-
promoting the recruitment of adapter molecules like MyD88 otic (Lactobacillus plantarum TENSIA; 8.7 log CFU per g)
protein, IRAK, TRAF6, and NIK to intracellular domain, for three weeks significantly reduced the body mass index
thereby stimulating the phosphorylation and degradation (BMI) in patients with obese and hypertension compared
of IKKB, the NF- B inhibitors. Translocation of active NF- to the control group (patients fed calorie restricted diet
 B to the nucleus activates the expression of inflammatory supplemented with control cheese). The reduced morning
proteins and also triggers signaling pathways like JNK, p38 systolic blood pressure was also observed in the patients
MAPK, and ERK which induces insulin resistance leading of both groups treated with calorie restricted diet along
to obesity (Figure 3). Administration of Bifidobacterium with the aid of antihypertension drugs irrespective of the
infantis in mice reduced colonic permeability attenuating cheese (probiotic cheese or control cheese) consumption. The
inflammation revealing that gut microbial composition also urinary putrescine content and BMI changes were associated
plays a role together with diet in altering the intestinal with the lactobacilli load in the intervention group. The study
permeability. Excess dietary lipid intake not only increases suggested that supplementation of probiotic cheese with a
systemic exposure to potentially proinflammatory free fatty calorie restriction diet reduces the BMI and hypertension in
acids and their derivatives but more specifically facilitates the study subjects [24].
absorption of endotoxins, leading to higher plasma LPS level Overweight or obese adults were supplemented with
termed as “metabolic endotoxemia” [113, 114]. L. gasseri BNR17 (1010 CFU per capsule; 6 capsules per
 eCB modulates the food intake by regulating the expres- day) (a probiotic strain isolated from human breast milk)
sion of anorexigenic and orexigenic mediators such as for 12 weeks and the changes in body mass, body fat,
endocannabinoids (endogenous lipids like N-arachidonyl behavior, and biochemical parameters were assessed at four
ethanolamine (AEA) and glycerol 2-arachidonoyl (2-AG) and different intervals (0, 4, 8, and 12th week of intervention).
cannabinoid receptor (CB1 and CB2) coupled with G2 pro- The results suggested that the supplementation of BNR17
tein). AEA and 2-AG were synthesized using phospholipase D reduced body weight, hip, and waist circumferences com-
enzyme (NAPE-PLD) and sn-1-diacylglycerol lipase selective pared to the placebo group. Other tested parameters such as
(DAG lipase) dependent on phospholipids and are metabo- gastrointestinal, genital, endocrine, respiratory, and diabetic
lized into inactive compounds by fatty acid amide hydrolase associated parameters were not found to be changed during
(FAAH) and monoacylglycerol lipase (MGL). Interaction of the study among the study subjects. The supplementation

6 BioMed Research International

 Modulation in intestinal Low grade
 Enhanced calorie production Modulates the colon gene Modulation in
 cell integrity inflammation
 expression released bioactive molecule

 Enteroendocrine cells

 Specific bacteria Bacterial component
 Firmicutes/Bacteroidetes Microbial dysbiosis

 LPS SCF
 SCF LPS UB Ethanol Choline Neuroactives SCF Lactate LPS
 SCF

 Enteroendocrine cells
 ZO1
 Occludin Fiaf

 Vagal
 Afferent
 TMAO neurons
 GLP-1
 CD14 TLR4
 Gut-liver axis

 Gut-neuronal axis
 LPS rich PYY
 Microbiota fat signaling axis

 Immune lipoprotein
 cells FXR CCK
 AMPK Choline deficiency
 LPL
 LPL
 MYD88 CHREBP
 TRAF-6 BA metabolism Neuro-
 Inflammation NF-B SREBP-1
 NIK inflammation
 Translocase FFA
 GPR43 TG
 Inflammatory MAPK, JNK,
 GPR41 cytokines P38 IR Change in
 Adipose tissue appetite
 Inflammation IR 1
 NAFLD

 Liver
 • Inhibits lipolysis Brain
 Adiposity • Adipocyte differentiation

Figure 3: Gut microbial communication with immune cells and cells of target organs, pathways leading to obesity. Microbiota adipose tissue
axis: metabolites of gut microbiota promote adipogenesis by triggering LPS based inflammation and SCF induced adipocyte differentiation.
Gut-liver axis: microbiota dysbiosis alters the gut permeability enhancing the release of bacteria derived bioactive molecules in the liver. LPS
interacts with TLR4 of the Kupffer cells enhancing the recruitment of MyD88 protein, IRAK, TRAF6, and NIK which promotes activation
of MAPK, JNK, p38, and NF- B signaling pathways leading to inflammation and insulin resistance ultimately causing nonalcohol fatty liver
(NAFLD). Metabolites like bile acid, SCF, and choline play a vital role in causing NAFLD. Gut-brain axis: neuroactive peptides, lactate, SCF,
and LPS of gut microbiota activate vagal afferent neurons and gut hormones leading to alteration in appetite and neuroinflammation.

of BNR17 has not influenced the behavior pattern of the CFU per g), is necessary to reduce the obesity-associated
subjects, and no adverse effects were observed. The study consequences [28].
suggested that the intervention of single strain probiotic The healthy overweight people were randomly divided
reduced the body weight in obese people, and further in- into different groups and were supplemented with VSL#3 (a
depth extended research is necessary to explain the health probiotic formulation containing three strains of Bifidobac-
benefits of the strain [25]. A recent study revealed that the terium and four strains of Lactobacillus; 112.5 × 109 CFU
supplementation of BNR17 (1010 CFU per day) significantly per capsule; one capsule per day) or omega 3 fatty acids
reduced the visceral adipose tissue and waist circumferences (180 mg EPA and 120 mg DHA per day) or both VSL#3
in obese adults [26]. and omega 3 fatty acids for 6 weeks. After 6 weeks of
 Visceral adiposity of the healthy volunteers (with the supplementation, total cholesterol, low-density lipids (LDL),
large visceral fat area) has been significantly reduced after very-low-density lipids (VLDL), TG, and high-sensitivity C-
12-week supplementation of fermented milk containing L. reactive protein (hsCRP) were observed to be significantly
gasseri SBT2055 (200 g per day; 106 or 107 or 108 CFU per reduced in VSL#3 supplemented group. Additionally, VSL#3
g of milk) compared to control group. Also, the notable supplementation improved the high-density lipids (HDL)
reduction was observed in body weight, BMI, and waist level and insulin sensitivity. The positive regulation of GM
and hip circumferences of people who had the probiotic was also observed in probiotic-supplemented groups. Omega
intervention [27, 28]. The intervention associated positive 3 fatty acids supplementation also showed improved insulin
changes were diminished after 4 weeks of cessation of sensitivity, a slight reduction in LDL and hsCRP levels, and
probiotic supplementation, which indicates that continuous no effect on the composition of the GM. The combination
ingestion of L. gasseri SBT2055, even at the low dose (106 of VSL#3 and omega 3 fatty acids showed more pronounced

BioMed Research International 7

effects. The high hsCRP levels and low HDL level were fat, carbohydrate, and protein, respectively, and it provides
correlated with the high concentration of Bacteroides and low extra ∼1000 kcal per day) and VSL#3 (4.5 × 1010 CFU per day)
Bifidobacterium and Lactobacillus content in study subjects for four weeks and the changes in body mass and fat content
[29]. were measured. The results revealed that the supplementation
 The obese pregnant women were supplemented with a of VSL#3 significantly prevents the development of excess
single probiotic strain of L. salivarius UCC118 (109 CFU body and fat mass in the subjects compared to the placebo
per capsule; one capsule per day) for four weeks from the control group [35].
24th week of gestation. The results suggested that UCC118 The supplementation of B. animalis ssp. lactis 420 (B420)
supplementation reduced the BMI of obese pregnant women (1010 CFU per day) with or without fiber (Litesse Ultra poly-
compared to placebo control, but no changes were observed dextrose; 12 g per day) for six months significantly reduced
in impaired glycemia incidences, metabolic profile, and preg- the fat mass in overweight and obese adults. The fat mass in
nancy outcomes [30]. In another study, the obese pregnant the abdominal region and waist circumference was reduced
women were supplemented with Vivomixx (a mixture of predominantly after B420 supplementation. The intervention
Bifidobacterium longum DSM 24736, B. breve DSM 24732, B. of fiber alone showed no positive changes in the subjects. The
infantis DSM 24737, Streptococcus thermophilus DSM 24731, reduction of blood hsCRP and zonulin level was related to
L. delbrueckii subsp. bulgaricus DSM 24734, L. acidophilus the changes in trunk fat mass. The study results revealed that
DSM 24735, L. paracasei DSM 24733, and L. plantarum supplementation of B420 alone was enough to reduce the fat
DSM 24730; 4.5 × 1010 CFU in total) from 14-20 weeks of mass in studied subjects [36].
gestation until the delivery of the baby. After the detailed The influence of supplementation of probiotic yogurt
analysis of blood, urine, fecal samples, and diet profile and (PY) and regular low-fat yogurt (LFY) on weight loss pro-
weight gain, it has been proved that the supplementation of gram has been studied in obese and overweight women.
Vivomixx significantly reduced the weight gain during the The consumption of PY (containing B. lactis BB12 and L.
pregnancy period and reduced the pregnancy complications acidophilus LA5; 107 CFU per day) for 12 weeks significantly
via positive alteration of GM of obese pregnant women reduced the total cholesterol, LDL, and insulin resistance
[31]. whereas no notable changes were observed in body mass,
 The supplementation of L. paracasei F19 (9.4 × 1010 CFU HDL, fasting plasma glucose, and TG level. The results
 suggested that the consumption of PY along with regular diet
per day) for six weeks had no effect on the GM and metabolic
 had not greatly influenced weight reduction, but it improves
profile of obese postmenopausal women. However, the inter-
 the lipid profile and insulin sensitivity in the obese and
vention of flaxseed mucilage (10 g per day) for six weeks
 overweight women [37].
reduced the serum C-peptide, increased the insulin sensi-
 The supplementation of probiotic mix (L. rhamnosus
tivity, and altered the abundance of about 33 metagenomic
 DSMZ 21690 (2 × 109 CFU), L. acidophilus ATCCB3208
species in obese postmenopausal women. The improved (3 × 109 CFU), B. bifidum ATCC SD6576 (2 × 109 CFU),
insulin sensitivity is not associated with altered microbiome
 and B. lactis DSMZ 32269 (6 × 109 CFU) per day) for 12
[32]. Likewise, the supplementation of low (2.5 × 109 CFU weeks improved the liver profile in obese children and adults
per day) and high dose (1× 1010 CFU per day) of multistrain with nonalcoholic fatty liver disease. After the probiotic
probiotic preparation Ecologic (B. bifidum W23, L. salivar- supplementation, the level of alanine aminotransferase and
ius W24, L. acidophilus W37, B. lactis W51, B. lactis W52, L. aspartate aminotransferase was decreased significantly in
casei W56, L. brevis W63, Lactococcus lactis W19, and L. lactis the probiotic group. The cholesterol, LDL, TG, and waist
W58) for 12 weeks showed a health improvement in obese circumference were also reduced with notable level while
postmenopausal women. Intake of a high dose of probiotic body weight, BMI, and fat mass were not changed. And
reduced the lipopolysaccharide, fat mass, glucose, HOMA-IR based on the sonography results, the study suggested that the
index, LDL, subcutaneous fat, total cholesterol, TG, insulin, supplementation of probiotic improved the liver conditions
uric acid, and waist circumference in the studied subjects. The in the subjects [38].
results claimed that supplementation of multistrain probiotic The supplementation of the probiotic mix (Danisco; B.
preparations improved the cardiometabolic parameters and lactis, B. bifidum, L. casei, L. acidophilus, and Lactococcus
intestinal permeability in obese postmenopausal women lactis; 2 × 1010 CFU per day) and/or controlled diet for 8 weeks
[33]. significantly reduced the polyunsaturated fatty acids level,
 The overweight adults were supplemented with B. breve conicity index, waist-height ratio, and waist circumference
B-3 (5 × 1010 CFU per day) for 12 weeks and the metabolic and increased the glutathione peroxidase activity in obese
parameters and adiposity level were measured. The results or overweight women. The results suggested that the sup-
indicated that B-3 supplementation reduced the fat mass in plementation of probiotic mix and controlled diet improved
subjects and also improved the blood parameters associated the antioxidant system of the subjects and effectively reduced
with liver function and inflammatory system in the studied the obesity-associated consequences compared to that of the
overweight adults [34]. intervention of controlled diet (without a probiotic mix) in
 The influence of VSL#3 on a high-fat diet (HFD) induced the placebo group [39].
obesity has been assessed. The healthy nonobese adults were The overweight people were supplemented with probiotic
supplemented with HFD (diet containing 55, 30, and 15% of preparation containing L. plantarum KY1032 and L. curvatus

8 BioMed Research International

HY7601 at the concentration of each 2.5 × 109 CFU per day and inflammatory system significantly improved in OAGB-
for twelve weeks. The level of dodecenoylcarnitine, decanoyl- MGB patients without affecting the folate, vitamin B12 , and
carnitine, tetradecenoylcarnitine, and octanoylcarnitine was homocysteine levels. Further studies are required to confirm
found to be increased, while the body weight and fat mass the efficiency of the probiotic supplementation in detail [44].
were reduced in the probiotic-supplemented group. The study Healthy preobese people (BMI ≥ 25 kg/m2 but BMI <
claimed that the positive effect of probiotic intervention was 30 kg/m2 ) were supplemented with B. breve B-3 (2 × 1010
attributed to the increase in medium-chain acylcarnitines in CFU per day) for 12 weeks, and the changes in the baby fat
the studied overweight individuals [40]. mass, body weight, and blood parameters were measured. B.
 The supplementation of a mixture of probiotic strains (B. breve B-3 supplementation effectively reduced the body fat
bifidum, B. longum, B. infantis, L. acidophilus, L. casei, and L. mass and TG and improved the HDL level in preobese people
lactis; 3 ×1010 CFU per day) for four weeks had no significant compared to baseline. The study suggested that the regular
improvement in the waist circumference, body mass, blood supplementation of B. breve B-3 helps to reduce the body fat
 mass [45].
glucose level, and fecal short-chain fatty acid in the studied
 The supplementation of fortified yogurt (prepared with
overweight people. But the reduction in energy intake was
 S. thermophiles and L. bulgaricus as starter culture and
clearly noted in the probiotic-supplemented group compared enriched with 107 CFU of B. lactis Bb-12 per gram, inulin,
to baseline value. The study suggested that probiotic prepara- whey protein, vitamin D3 , and calcium) to obese individ-
tion can be used in diet management for weight loss program uals significantly improved the body composition (reduced
as an adjuvant [41]. the waist circumference, body fat percentage, body fat,
 A twelve-week supplementation of synbiotic preparation TG level, and Homoeostasis Model of Assessment-Insulin
(L. rhamnosus CGMCC1.3724 (3.24 ×108 CFU, 90 g inulin, Resistance (HOMA-IR) value and increased the HDL, 25-
and 210 g oligofructose per day)) effectively induced weight hydroxyvitamin D level, and Quantitative Insulin Sensitivity
loss in obese women. The disinhibition and hunger scores, Check Index (QUICKI)) and metabolic profile. The level of
Beck Depression Inventory score, and food craving were free fat mass was not reduced significantly in the fortified
reduced, while the satiety efficiency and Body Esteem Scale yogurt supplemented group compared to the low-fat plain
were increased in the studied obese women. The male yogurt (prepared with S. thermophiles and L. bulgaricus
subjects also displayed positive effects like fasting fullness and as starter culture) group. The positive effects of fortified
cognitive restraint. The study suggested that the supplemen- yogurt were associated with calorie restricted diet plan during
tation of synbiotics controls appetite and associated behavior the intervention period. The study suggested that regular
in obese people during weight management [42]. consumption of probiotic-enriched fortified yogurt along
 with a strict diet plan helps to reduce the body weight and
 The probiotic oral suspension (psychobiotics) was sup-
 to improve the metabolic status in obese people [46].
plemented to normal weight lean (BMI

Table 1: Influence of probiotic supplementation on obese people.
 Duration of
 BioMed Research International

Study subjects Intervention Dose Clinical outcomes Conclusions Ref.
 the study
 Calorie restriction and probiotic
 Hypocaloric diet ↓BMI
 Calorie restricted diet supplementation significantly
People with obesity (1500 kcal/d), and cheese BMI associated with lactobacilli
 and 50 g of cheese per 3 weeks reduced the BMI, and systolic BP [24]
and hypertension containing Lactobacillus load in the intestine.
 day in people with obesity and
 plantarum TENSIA ↓ Morning systolic BP.
 hypertension.
 Reduced the body weight, waist
Overweight or 6 capsules per day ↓ Weight, waist and hip
 L. gasseri BNR17 12 weeks and hip circumferences [25]
obese people (1010 CFU per capsule) circumferences.
 compared to baseline.
 The probiotic supplementation
 ↓ Visceral adipose tissue, waist reduced the visceral fat
Obese people L. gasseri BNR17 1010 CFU per day 12 weeks [26]
 circumferences. accumulation and waist
 circumference.
 Low concentration of SBT2055
 ↓ Abdominal visceral fat supplementation reduced the
Adults with L. gasseri SBT2055 200 g of FM per day (106
 ↓ Body weight, waist and hip obesity associated health
abdominal mediated fermented / 107 / 108 CFU per g of 12 weeks [27, 28]
 circumferences problems, but continuous
adiposity milk (FM) FM)
 ↓BMI consumption is needed to
 maintain the effect.
 VSL#3 alone or in combination
 of OFA supplementation:
 1 capsule per day (112.5 ×
 ↓ Total cholesterol, triglyceride,
Healthy 109 CFU per capsule); The combination of VSL#3 and
 VSL#3 and /or omega 3 LDL, VLDL, and hsCRP
Overweight 1 OFA capsule per day 6 weeks OFA showed more pronounced [29]
 fatty acid (OFA) ↑ HDL level, insulin sensitivity.
volunteers (180 mg EPA, and 120 mg effects.
 Altered the gut microbiota
 DHA)
 positively. OFA supplementation
 did not affect the microbiota.
 9

10

 Table 1: Continued.
 Duration of
Study subjects Intervention Dose Clinical outcomes Conclusions Ref.
 the study
 UCC118 supplementation had
 ↓BMI
Obese pregnant 1 capsule per day (109 not significantly affected the
 L. salivarius UCC118 4 weeks No changes in glycemia, and [30]
women CFU per capsule) metabolic profile, fasting glucose
 pregnancy outcomes
 level, and pregnancy outcomes.
 Altered the microbiota in a
 A mixture of probiotic
Obese pregnant ↓ weight gain and pregnancy positive way and reduced the
 Vivomixx strains (4.5 × 1010 CFU Depends∗ [31]
women consequences complications of pregnancy and
 per day)
 weight gain.
 FM intervention altered the
 microbiota and improves insulin
Obese
 L. paracasei F19 or 9.4 × 1010 CFU per day sensitivity. But F19 FM improved the health status of
postmenopausal 6 weeks [32]
 flaxseed mucilage (FM) or 10 g of FM supplementation had no effect on obese postmenopausal women
women
 the metabolic profile in the
 subjects
 Ecologic
 (Bifidobacterium bifidum Both high and low dose of
 Level of LPS, fat mass, glucose,
 W23, L. salivarius W24, 10 Ecologic supplementation
Obese High dose (1× 10 CFU HOMA-IR index, LDL,
 L. acidophilus W37, B. improved the cardiometabolic
postmenopausal per day); Low dose (2.5 12 weeks subcutaneous fat, total [33]
 lactis W51, B. lactis W52, parameters and intestinal
women × 109 CFU per day) cholesterol, TG, insulin, uric
 L. casei W56, L. brevis permeability in obese
 acid, waist circumference
 W63, Lactococcus lactis postmenopausal women.
 W19, and L. lactis W58)
 BioMed Research International

Table 1: Continued.
 Duration of
Study subjects Intervention Dose Clinical outcomes Conclusions Ref.
 the study
 ↓ Fat mass B-3 supplementation improved
Overweight adults B. breve B-3 5 × 1010 CFU per day 12 weeks Improved the liver function, and the metabolic profile of [34]
 BioMed Research International

 inflammation system. overweight adults
 VSL#3 supplementation prevents
 Reduced the body mass and fat
Healthy non-obese the high-fat diet and induced fat
 VSL#3 and high fat diet 4.5 × 1010 CFU per day 4 weeks mass compared to placebo [35]
people and body mass increase in
 control
 healthy non-obese adults
 B. animalis ssp. lactis 420
 B420 supplementation reduced
Overweight and (B420) with/ without 1010 CFU per day; 12 g of ↓ Fat mass, waist circumference.
 6 months the fat mass in obese people with [36]
obese people Litesse Ultra LU per day ↓ Blood hsCRP, and zonulin level
 or without LU.
 polydextrose (LU)
 No significant change in body
 A mixture of probiotic Improved the insulin sensitivity,
Obese and mass, HDL, TG.
 Probiotic yogurt strains (107 CFU per 12 weeks and lipid profiles in the obese [37]
overweight women ↓ Total cholesterol, LDL, insulin
 day) and overweight women
 resistance.
 L. rhamnosus DSMZ
 21690 (2 × 109 CFU), L.
 acidophilus ATCCB3208 The probiotic supplementation
Obese children and (3 × 109 CFU), B. ↓ AsAT, AAT, cholesterol, LDL, improved the condition of
 Probiotic mix 12 weeks [38]
adults bifidum ATCC SD6576 TG, waist circumference nonalcoholic fatty liver disease in
 (2 × 109 CFU), B. lactis obese people
 DSMZ 32269 (6 × 109
 CFU) per day
 Dietary restriction along with
 B. lactis. B. bifidum, L. ↓ Polyunsaturated fatty acids
 Probiotic mix probiotic intervention effectively
Obese or casei, L. acidophilus, level conicity index, waist-height
 (Danisco) and 8 weeks reduced the obesity associated [39]
overweight women Lactococcus lactis, 2 × ratio, waist circumference.
 controlled diet consequences and improved the
 1010 CFU per day ↑ glutathione peroxidase activity
 antioxidant status of the subjects
 ↑ Dodecenoylcarnitine, Probiotic supplementation
 2 g of probiotic powder decanoylcarnitine, mediated weight loss is
 L. plantarum KY1032,
Overweight people (Each 2.5 ×109 CFU per 12 weeks tetradecenoylcarnitine, and associated with increased [40]
 and L. curvatus HY7601
 day) octanoylcarnitine level. medium-chain acylcarnitines in
 ↓body weight, body fat mass the overweight individuals.
 11

12

 Table 1: Continued.
 Duration of
Study subjects Intervention Dose Clinical outcomes Conclusions Ref.
 the study
 Probiotic supplementation
 Probiotic preparation (B.
 No changes in waist reduced the energy intake
 bifidum, B. longum, B.
Overweight people 3 ×1010 CFU per day 4 weeks circumference, body weight, compared to baseline. It can be [41]
 infantis, L. acidophilus,
 glucose level. ↓ Energy intake used as an adjuvant for the
 L. casei, L. lactis)
 weight loss program.
 The intervention of synbiotic
 Synbiotic formula (L. ↑ Weight loss in women.
 3.24 ×108 CFU per day; preparation influenced the
 rhamnosus ↑ Satiety efficiency↓
Obese people 90 g inulin, 210 g 12 weeks appetite control and associated [42]
 CGMCC1.3724, inulin, Disinhibition and hunger scores,
 oligofructose per day behavior in obese people during
 oligofructose) food craving.
 weight loss program
 Psychobiotics (B.
 bifidum SGB02, B.
 animalis subsp. lactis
 SGB06, Streptococcus ↓ BMI, Fat mass
 Psychobiotics supplementation
 thermophilus SGSt01, S. ↓ Psychopathological scores
Preobese-obese, improved the body composition,
 thermophiles, L. ↓ Bacterial overgrowth syndrome
normal weight Each 1.5 ×1010 CFU per reduced the dysbiosis, and
 plantarum SGL07, L. 3 weeks ↓ BUT GSI scale [43]
obese, and normal day reduced the psychopathological
 delbrueckii spp. ↑ Free fat mass
weight lean women scores in preobese-obese and
 bulgaricus DSM 20081, Improved the meteorism and
 normal weight obese people.
 L. reuteri SGL01, L. defecation frequency
 acidophilus SGL11,
 Lactococcus lactis subsp.
 lactis SGLc01)
 Familact
 L. casei (3.5 × 109 CFU),
 L. rhamnosus (7.5 × 108
 CFU), L. bulgaricus (108 4 weeks
 Improved the vitamin D status,
 CFU), L. acidophilus (109 before Familact supplementation
 inflammatory markers, lipid
Obese patients CFU), B. breve (1010 surgery and improved inflammatory markers
 One sachet per day profile, and glycemic indices. [44]
(OAGB-MGB) CFU), B. longum (3.5 × 12 weeks and promoted weight loss in
 No changes in folate, vitamin B12 ,
 109 CFU), and S. after OAGB-MGB patients.
 and homocysteine levels
 thermophilus (108 CFU), surgery
 and
 fructo-oligosaccharide
 (38.5 mg) in one sachet
 BioMed Research International

Table 1: Continued.
 Duration of
 BioMed Research International

Study subjects Intervention Dose Clinical outcomes Conclusions Ref.
 the study
 B-3 supplementation reduced the
Healthy pre-obese ↓ Body fat mass, TG
 B. breve B-3 2 ×1010 CFU per day 12 weeks body fat effectively in pre-obese [45]
adults ↑ HDL
 subjects.
 Calorie restricted diet
 ↓ Body fat mass
 and fortified yogurt (S.
 ↓ Waist circumference, body fat
 thermophiles, L. Improved the body composition,
 500 g of fortified yogurt percentage, TG level, HOMA-IR
Obese people bulgaricus and B. lactis 10 weeks and metabolic profile in obese [46]
 per day value.
 Bb-12, inulin, whey people
 ↑ HDL, 25-hydroxyvitamin D
 protein, vitamin D3 ,
 level, QUICKI.
 calcium)
 ↓ BMI, visceral fat
 ↓ Conicity index
 CECT 8145 supplementation
 ↓ Waist circumference
Abdominally obese B. animalis subsp. lactis 10 effectively reduced the obesity
 10 CFU per day 12 weeks ↓ Waist circumference/ height [47]
people CECT 8145 associated consequences in
 ratio
 abdominally obese people
 ↑ Akkermansia spp. in the gut
 microbiota
 ↓ BMI, hsCRP, monocyte CECT 7765 supplementation
Insulin-resistant B. pseudocatenulatum 9-10 chemoattractant protein-1 improved the lipid profile and
 10 CFU per day 13 weeks [48]
obese children CECT 7765 ↑ Omentin-1, and HDL. inflammatory markers in obese
 ↑ Alistipes spp. children
∗Intervention starts from 14-20 weeks of the gestation and continued until delivery of the baby; ↓: Reduced; BMI: Body mass index; BP: Blood pressure; VSL#3: A probiotic formulation containing three strains
of Bifidobacterium and four strains of Lactobacillus; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; TG: Triglyceride; LDL: Low-density lipids; VLDL: Very-low-density lipids; HDL: High-density
lipids; hsCRP: High-sensitivity C-reactive protein; Vivomixx: A probiotic formulation containing eight bacterial strains; AAT: Alanine aminotransferase; AsAT: Aspartate aminotransferase; BUT GSI scale: Body
uneasiness test and global severity index; OAGB-MGB: Anastomosis Gastric Bypass-Mini Gastric Bypass; QUICKI: Quantitative Insulin Sensitivity Check Index; HOMA-IR: Homoeostasis Model of Assessment-
Insulin Resistance; LPS: Lipopolysaccharide.
 13

14 BioMed Research International

5. In Vivo Studies Using longum BG7, B. lactis BL3, and B. bifidum BF3) for 8 weeks sig-
 Laboratory Animal Models nificantly reduced the body weight and improved the serum
 level metabolic profile in the HFDO rat. The microbiota
The influence of supplementation of probiotic strain L. analysis showed that probiotic intervention increased the
rhamnosus PB01 (DSM 14870) on sperm kinetics in diet- amount of Lactobacillus, Bacteroidetes, and Bifidobacterium
induced obese mice has been reported by Dardmeh group. while it reduced the Firmicutes load in experimental animals
The study suggested that the supplementation of DSM 14870 [54] (Table 2).
(1 × 109 CFU per day for 4 weeks) effectively improved
the levels of serum testosterone, follicle-stimulating hor-
mone, and luteinizing hormone. The concentration of highly 6. Conclusion and Future Perspectives
active motile sperm was increased and a significant level of The detailed literature survey showed that the benefi-
reduction in nonmotile sperm count was observed in both cial impact of probiotic supplementation in obese peo-
obese and lean (normal weight) mice models. The sperm ple has been associated with several factors such as
kinetic measurements revealed that DSM 14870 intervention nature of the probiotic strain, composition of the probi-
remarkably increased the sperm kinetics in obese mice otic formula (single or multistrain; with or without prebi-
model compared to baseline values. The study suggested otics), duration of the intervention, dose, and other aided
that the supplementation of DSM 14870 improved the sperm activities like calorie/dietary restrictions and weight loss
motility, reproductive hormones levels, and weight loss in medications.
diet-induced obese mice model [49].
 A meta-analysis study reported that the probiotic supple-
 The combination of probiotic supplementation (L. rham- mentation was not associated with weight loss in obese peo-
nosus; 1 × 108 CFU per day) and ultrasound treatment ple, which may be due to the less number of articles (studies
(at acoustic pressure of 2 W/cm2 for 30 sec) for 8 weeks with clinical trials) chosen for the analysis based on the selec-
significantly reduced the body mass, total body fat mass, tion criteria (randomized controlled trials; supplementation
and thickness of the subcutaneous fat layer and improved of probiotic; control (placebo or no probiotic supplementa-
the plasma lipid profile in diet-induced obese mice model tion); results of body weight and BMI) of the study [119].
compared to baseline and single treatment groups (either Nevertheless, the subsequent report based on a meta-analysis
probiotic supplementation or ultrasound treatment) [50].
 of 25 clinical trials with 1931 obese subjects revealed that
 The supplementation of L. reuteri 263 (2.1 × 109 or 1.05 the probiotic supplementation effectively reduced the body
 10
×10 CFU per day for 8 weeks) altered the energy metabolism
 weight. The study also disclosed that a minimum of 8 weeks
in white adipose tissue of high-energy-diet-fed rat model. The
expression of genes associated with thermogenesis, glucose, of multistrain probiotic intervention reduced the body weight
and lipid metabolism has been altered significantly after the in obese subjects compared to single strain intervention and
intervention of L. reuteri 263. The level of proinflammatory fewer intervention periods [120]. A recent systemic review
markers and antioxidant system of the host has been modified and meta-analysis of fifteen clinical trial studies with 957 sub-
and confers the protection against the high-energy-diet- jects revealed that the intervention of probiotic supplementa-
induced consequences. The study revealed that the antiobe- tion for 3 to 12 weeks significantly reduced the body weight
sity activity of L. reuteri 263 was attributed to the ability of and fat mass in obese subjects compared to placebo group
remodeling of energy metabolism in white adipose tissue of [121].
high-energy-diet-fed rat model [51]. The antiobese activity of probiotic supplementation
 The supplementation of Lactobacillus strain (L. plan- may be associated with the ability to remodel the energy
tarum and/or L. fermentum; 1 × 108 CFU per day for 8 metabolism, alter the expression of genes related to ther-
weeks) improved the systemic immune status of the HFD mogenesis, glucose, and lipid metabolism genes, enhance
fed rat model. Fat vehicle sizes, liver steatosis, endotoxin, the intestinal permeability, reduce the release of endotox-
and IL-6 level were significantly reduced in the probiotic- ins, reduce the inflammation, and change the parasympa-
supplemented group compared to control. The microbiota thetic nerve activity. Most importantly probiotic interven-
analysis revealed that the supplementation of probiotics tion greatly modified the composition of intestinal micro-
notably improved Lactobacillus and Bifidobacterium content biota (increased the load of Bifidobacterium, Lactobacillus,
in an experimental model. The study claimed that the combi- Proteobacteria, Bacteroidetes, and Peptococcaceae members
nation of multiple strains of probiotics confers better health and reduced the amount of Firmicutes, Clostridium, and
benefits in obese experimental models via modulating the Actinobacteria), which accelerates the weight loss in obese
intestinal microbiota and immune system when compared to people [122] (Figure 4).
single strain intervention [52]. The supplementation of soy- Interrelationship between the dietary supplement and
based probiotic product (containing B. longum ATCC 15707 GM envisages the fact that “we are what we eat and what
and Enterococcus faecium CRL 183) altered the intestinal our gut microbiome is.” In the near future, several gut-
microbiota and immune profile in a positive way in HFD- microbiome based clinic will become prevalent where the
induced obese (HFDO) mice model [53]. Similarly, the individual’s GM will be used for diagnosis, prophylaxis, and
supplementation of a multistrain probiotic preparation (L. therapy of human health problems. In addition, analysis
rhamnosus LR5, L. acidophilus LA1, S. thermophilus ST3, B. of the infant’s gut microbial composition will help us to