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Volume X Issue X (2025) 1 doi: 10.36922/ejmo.8318
REVIEW ARTICLE
The role of gut microbiome in obesity and
metabolic dysfunctions: Insights and therapeutic
potential
Siham El Moussaoui1*, Touria Derkaoui1,2 , Fatima Zahrae Alaoui Ismaili1,
Nezha Tawq3, Mohammed El Mzibri4, Abdelilah Laraqui5,
Mohamed Mansouri1,6, Amina Barakat1, Naima Ghailani Nourouti1,
Maria Paz Weisshaar7 and Mohcine Bennani Mechita1
1Intelligent Automation and BioMed Genomics Laboratory, Faculty of Sciences and Techniques of
Tangier, Abdelmalek Essaâdi University, Tétouan, Morocco
2Higher Institute of Nursing Professions and Health Techniques of Tangier, Ministry of Health,Tangier,
Morocco
3Mohammed VI Center for Cancer Treatment, Ibn Rochd University Hospital, Hassan II University,
Casablanca, Morocco
4Biology and Medical Research Unit, National Centre for Energy, Nuclear Sciences and Techniques
(CNESTEN), Rabat, Morocco
5Sequencing Unit, Center of Virology, Infectious and Tropical Diseases, Mohammed V Military
Teaching Hospital, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
6Oncology Clinic, Al Amal of Tangier, Morocco
7Department of Natural Sciences, University of Applied Sciences Bonn-Rhein-Sieg, Rheinbach,
Germany
Abstract
Obesity is a chronic inammatory disease dened by an excessive accumulation of
body fat. The human gut microbiota (GM) is an intricate ecosystem of microorganisms
living symbiotically within the gastrointestinal tract and has emerged as a key player
in health and metabolic diseases. Recently, several studies have increasingly revolved
around understanding the specic compositions and strains of GM and their potential
impact on obesity. This review provides a summary of the most recent ndings
regarding obesity and newly developed therapies that show exceptional ecacy in
treating this condition. In addition, it explores dierent GM strains that may contribute
to the progression and development of obesity. This article summarizes the molecular
insights involved in the relationship between obesity and GM, the characteristics
of this ecosystem, and its involvement in human metabolism, energy balance, and
inammation leading to obesity. Furthermore, it examines the bacteria most engaged
in managing obesity. These ndings contribute to a better understanding of this
signicant and intricate relationship, ultimately aiding in obesity prevention.
Keywords: Microbiota; Weight loss; Weight gain; Obesity; Diversity; Gut microbiome
1. Introduction
Obesity is a condition linked to an abnormal accumulation of body fat. It involves
various intricate mechanisms. e buildup of fat, a process called adipogenesis, can
*Corresponding author:
Siham El Moussaoui
(siham.elmoussaoui1@etu.uae.
ac.ma)
Citation: El Moussaoui S,
DerkaouiT,IsmailiFZA,TawqN,
ElMzibriM,LaraquiA,et al. The
role of gut microbiome in obesity
and metabolic dysfunctions: Insights
and therapeutic potential. Eurasian
J Med Oncol.
doi: 10.36922/ejmo.8318
Received: December 31, 2024
Revised: January 28, 2025
Accepted: February 18, 2025
Published Online: March 24, 2025
Copyright: © 2025 Author(s).
This is an Open Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional
aliations.
Eurasian Journal of Medicine
and Oncology
Volume X Issue X (2025) 2 doi: 10.36922/ejmo.8318
Gut microbiome eects on obesity
Eurasian Journal of
Medicine and Oncology
manifest as hypertrophy, where adipocytes increase in size,
or as formation of new fat cells, a mechanism known as
hyperplasia.1,2 is pathogenesis can trigger inammation,
dyslipidemia, insulin resistance, hypertension, and
vascular endothelium dysfunction and is associated with
serious health conditions such as cardiovascular diseases,
non-alcoholic fatty liver disease, type2 diabetes mellitus
(T2DM), and cancers.3
e gut microbiota (GM) is made up of over
1500 species from y distinct phyla. Among them,
Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria,
and Verrucomicrobia are the dominant types. Firmicutes
and Bacteroidetes are the most abundant, making up at
least 90% of the human gut microbial population.4 is
complex ecosystem plays an essential role in monitoring
the progression of various human diseases. Moreover,
the role of GM in numerous health conditions has been
increasingly elucidated through the extensive application
of deep sequencing technologies.5
In recent years, increased investigations have suggested
that an imbalance in the GM could be a contributing factor
to obesity.6-11 Low-grade inammation present in obesity
is a consequence of GM alterations, which are, in turn,
linked to disorders in numerous metabolic pathways and
molecules.12,13 Together, obesity and gut dysbiosis can lead
to the alteration of metabolic pathways.14
2. Obesity
Obesity has been presented as an abnormal fat
accumulation according to the World Health Organization
(WHO). e pathogenesis of obesity involves various
intricate mechanisms. e buildup of fat, a process
called adipogenesis, can manifest as hypertrophy, where
adipocytes increase in size, or through the formation of
new fat cells, a mechanism known as hyperplasia.1,2 Body
mass index (BMI) is a commonly used metric to estimate
total body fat, calculated as weight in kilograms divided
by the square of height in meters. It serves as an eective
indicator of the risk of diseases associated with overweight
and obesity. Recently, waist circumference (WC) has
emerged as a potentially more accurate measure of obesity.15
e Global Burden of Disease study armed that, since
the 1980s, the occurrence of obesity has expanded rapidly
in over seventy countries, with a continuous upward trend
observed in the majority of other nations.16(p25) In 2013,
the American Medical Association ocially recognized
obesity as a disease requiring medical treatment and
follow-up.17 Health risks linked to this disease have
escalated to alarming levels, making obesity a major global
concern.18 In 2022, data showed that more than 1 billion
individuals worldwide were living with obesity and 43%
of them were adults.19 By 2035, it is projected that 51% of
the global population will be classied as either overweight
or obese,20 prompting WHO member states to agree on a
global plan to accelerate the response to obesity by 2030.21
Further data from the WHO European Region reclaim
that obesity is prevalent in nearly 60% of adults, aecting
one in three children, with prevalence rates of 27% among
girls and 29% among boys.22 Furthermore, the current
evidence indicates that obesity now exceeds underweight
in prevalence across all regions except sub-Saharan
Africa and Asia. Previously correlated with high-income
countries, obesity has become increasingly prevalent in
middle-and low-income countries, where its incidence has
been dramatically increasing.23
Obesity is linked to a multitude of serious health
conditions and non-communicable diseases, including
type 2 diabetes (T2D), cardiovascular diseases, chronic
kidney disease, as well as certain types of cancer.3,24
In addition, it is linked to other health risks such as
inammation, dyslipidemia, insulin resistance, and
hypertension.3 A systematic review and meta-analysis
of almost 1 million participants identied a signicant
association between obesity and T2D, as well as coronary
artery disease (CAD).25 CAD is a type of heart disease
characterized by the narrowing or blockage of the coronary
arteries, primarily due to the accumulation of cholesterol
and fatty deposits within the arterial walls, leading to
plaque formation.26 Other study has demonstrated high
levels of liver fat fractions in patient aected by T2DM and
morbid obesity. e ndings showed that hepatic steatosis
was associated with dierent measures of insulin sensitivity
in patients suering from T2DM and severe obesity.27
2.1. Common risk factors of obesity
Obesity and overweight can be attributed to a multitude of
factors, including unhealthy lifestyle habits such as poor
dietary patterns, physical inactivity, or insucient sleep, in
addition to certain medications, genetic predispositions,
or family history. e pathophysiological mechanisms of
obesity are complex, encompassing numerous overlapping
genetic and environmental factors.28 e main cause of
overweight and obesity is an energy imbalance between
caloric intake and energy expenditure, aected by some
genetic predisposition, feeding behavior, and lifestyle
factors.29
A familial history of obesity is a signicant risk factor
for both obesity and its early onset in childhood. In
addition, it is associated with the severity of obesity.30,31
Previous research has shown a signicant relationship
between maternal pre-pregnancy obesity and childhood
obesity, including overweight and obesity combined, as
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well as overweight alone.32 Accordingly, sleeping <7h has
been positively associated with an increase in BMI and
the development of obesity, compared to individuals who
attain an adequate and healthy amount of sleep.33
Eating habits play a signicant role in the management
of metabolic disorders and obesity. In this context, mindful
eating has been demonstrated to be eective in reducing
uncontrolled and emotional eating behaviors. However,
when combined with caloric restriction, weight loss was
not signicantly greater than with either approach alone.34
On the other hand, intermittent fasting, such as the 16:8 or
14:10 approach, has demonstrated a signicant reduction
in body weight (BW) while also improving glycemic and
lipid proles in obese patients with T2D. Experimental
ndings have shown an advantage for the 16:8 approach.35
Regarding time-restricted feeding, Xie et al.36 discovered
that eating meals early in the day increased insulin
sensitivity, reduced body mass, and lowered inammation
more signicantly than diets restricted to the middle of
the day. However, in the context of constant caloric intake,
a time-restricted diet failed to signicantly decrease
weight or enhance glycemic markers when compared
to a standard diet, indicating that the benecial eects
observed in other studies may be related to overall caloric
reduction.37 Furthermore, the order of food consumption
has been explored: eating vegetables rst, regardless of
meal speed, signicantly decreased postprandial glucose
and insulin peaks, indicating that this simple method
may provide metabolic benets.38 Pharmacologically, the
use of glucagon-like peptide-1 receptor agonist (GLP-
1RA), such as exenatide, has shown that adolescents
with lower postprandial leptin responses are better at
maintaining weight loss.39 In the same context, Libyan
health professionals have highlighted that some changes in
lifestyle of young people, including sleeping late, waking
up late, and skipping breakfast, are closely related to the
development of overweight and obesity.40
Zheng et al.41 conrmed through a systematic review
the existence of a relationship between rapid weight gain
(RWG) and obesity. Fieen studies indicated that RWG
in infancy is linked to overweight and obesity in both
childhood and adulthood, rearming that RWG at an
early age is a signicant predictor of obesity later in life.41 A
list of medications associated with signicant weight gain
among Canadian individuals has been dened, including
antipsychotics, antidepressants, antihyperglycemics,
and other medications that contribute to this issue.42
Accordingly, there is an urgent need in implementing new
pharmacotherapies that have fewer negative impacts on
weight. Psoriasis, a chronic autoimmune skin condition,
is linked to obesity, which aggravates its progression and
complicates treatment. Conversely, psoriasis can also
impact the development of obesity. e treatment of this
disease highlights the considerable inuence of weight loss
on symptom severity.43
Dysfunction in the thyroid is linked to changes in BW,
uctuations in body temperature, and alterations in both
total and resting energy expenditure, regardless of physical
activity levels. In addition, weight gain frequently occurs
following the treatment of thyroid dysfunction.44 yroid
hormones and body composition are closely interlinked.
Hypothyroidism, a condition in which the thyroid gland
fails to produce an adequate amount of thyroid hormones,
is linked to reduced thermogenesis, a lower metabolic rate.
It has been demonstrated to be positively related to both an
elevated BMI and a higher prevalence of obesity.45 Clinical
evidence suggests that even mild thyroid dysfunction,
such as subclinical hypothyroidism, can cause signicant
alterations in BW, representing a risk factor for overweight
and obesity.45 Furthermore, research has demonstrated a
negative association between BMI and serum-free T4 (FT4)
levels.46 Fat accumulation has been linked to lower FT4
levels46,47 and increased thyroid-stimulating hormones levels
in individuals who are slightly overweight but euthyroid.47,48
2.2. Protective factors against obesity
A literature review conducted on individuals with obesity
has highlighted dierent physiological advantages
associated with increased physical activity. As an
illustrative example, the ndings underscore its potential
for promoting weight loss.49 Moreover, as a part of a clinical
trial, obese individuals aiming to lose weight participated
in an 8-week stress management program while following
diet restrictions to maintain a healthy lifestyle. e
intervention group, in particular, experienced a notable
decline in BMI in comparison to the control group and
improvements in anxiety and depression scores.50
As is widely recognized, diet plays a crucial role
in managing obesity. A meta-analysis of randomized
controlled trials has identied a protective eect of high
dietary ber intake. Dietary ber plays a crucial role
in maintaining a healthy BW.51 It is associated with the
production of benecial metabolites, the amelioration
of obesity, and improved immune responses.52,53 In this
context, another type of dietary ber, resistant starch
(RS), has been used as a dietary supplement to aect
obesity-related outcomes. An 8-week RS supplementation
was found to contribute to body mass reduction (mean:
2.8 kg) and improve insulin resistance in individuals with
overweight or obesity.54
Tea is a common beverage consumed daily, and it
contains natural compounds with many health benets,
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including polyphenols. One of their main roles is to
prevent the digestion fats and carbohydrates from food.
is is due to their ability to block some digestive enzymes
responsible for breaking down nutrients, such as pancreatic
lipase, which helps digest fats, and amylases, which break
down carbohydrates into sugars that the body can absorb.55
During Ramadan, dietary habits and fasting programs
change. Ramadan intermittent fasting (RIF) aects gut
hormones, including leptin, and ghrelin, GLP-1. RIF has
proven to be an eective strategy to modulate appetite-
regulating hormones, resulting in improved body
composition indices and a reduction in obesity.56
Certain bioactive compounds, including curcumin and
zinc, have shown promising eects in obesity management.
Curcumin has demonstrated strong anti-inammatory
eects related to obesity. An umbrella review indicated
that curcumin intake could reduce WC, BMI, and BW.57
Moreover, the intake of curcumin, curcuminoids, or
turmeric has demonstrated notable anti-inammatory
properties. Individuals consuming dierent amounts of
these three compounds exhibited reductions in C-reactive
protein (CRP), tumor necrosis factor-alpha (TNF-α), and
interleukin (IL)-6.58 Furthermore, zinc and resveratrol
have shown promising potential in modulating leptin
levels and glucose signaling, which may have benecial
eects on energy regulation in obese individuals and
cardiovascular health. However, a longer exposure time is
suggested to be necessary to fully assess their impact on
energy homeostasis.59
Obesity is one of the major metabolic syndromes
(MetSyn).7 Signicant weight loss is considered the
primary and only curative treatment to address MetSyn,
as it can inuence many of its components. In addition to
high-dose GPL-1RAs, new medical treatment options are
being developed to manage MetSyn. ese include dual
or triple hormonal agonists targeting the GLP-1, glucose-
dependent insulinotropic polypeptide (GIP), and glucagon
receptors. GLP-1 plays a role in controlling blood sugar
and appetite, while GIP works alongside GLP-1 to enhance
insulin sensitivity, and glucagon helps regulate blood sugar
levels.60,61 In addition, leptin, a key hormone in appetite
regulation, plays an essential role in regulating appetite
and energy balance, which can inuence BW and obesity.62
In this regard, researchers have investigated the eects
of various medications on weight loss. Levothyroxine, a
medication used as a substitute for thyroid hormones,63 is
administered to restore hormonal balance.64 Results have
shown that aer 6 months of levothyroxine treatment
in individuals with hypothyroidism, resting energy
expenditure increased, which suggests that bodies are
burning more calories. is resulted in weight loss due
to a decrease in fat-free mass (0.8kg). However, fat mass
remained unchanged.65 e mechanisms underlying
this association remain unclear and require further
clarication.
New medications have recently emerged to treat obesity
and promote weight loss. Semaglutide and tirzepatide are
two well-known drugs currently used to treat obesity.
Semaglutide, a GLP‐1 analog, imitates the eects of native
GLP‐1, improving glycemic control and promoting weight
loss by decreasing caloric intake, reducing hunger, and
increasing satiety and satiation.66 In patients suering
from obesity-related heart failure with preserved ejection
fraction and T2D, semaglutide resulted in greater declines
in heart failure symptoms and signicant weight loss
than the placebo aer 1year.67 Another study found that
participants receiving 2.4 mg of semaglutide per week
experienced an average BW reduction of 15.3kg.68
Similarly, the eects of tirzepatide have been
investigated. A recent systematic review and meta-
analysis of randomized controlled trials discovered the
positive eect of tirzepatide. e weekly treatment with
tirzepatide resulted in signicant increase in BW and lower
hemoglobin A1C levels, without a signicant increase in
serious or life-threatening adverse events.69
Colchicine is another pharmaceutical drug known
to reduce inammation in multiple diseases. It has the
ability to reduce inammatory markers, including CRP,
glycoprotein acetylation, and certain inammatory
cytokine serum concentrations.70-72 In the context of
obesity, colchicine has shown a considerable eect on
leukocyte populations implicated in both innate and
adaptive immune responses.73
To enhance nutrition and public health, more than
45 countries have imposed taxes on sugar-sweetened
beverages.74 In several nations, these taxes have been related
to higher pricing and reduced sales and consumption of
taxed beverages.75 A signicant decrease in the purchase
of these beverages and obesity rates has been observed
in middle- and upper-middle-income countries. ese
ndings conrm that imposing high taxes on SBBs could
be an eective solution to combat obesity and related
health risks.76
3. GM
e GM consists of a community of microorganisms,
including viruses, bacteria, archaea, and fungi, residing
within the gastrointestinal tract (GIT), with bacteria
reign over this niche.77,78 Most of these microorganisms
predominantly inhabit the large intestine.79,80 e most
dominant and prevalent bacterial phyla within the gut
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are Bacillota and Bacteroidota.81 Until recent years, the
majority of gut microorganisms remained unidentied,
mainly due to their anerobic nature, which made them
dicult to cultivate.82 e advent of the polymerase chain
reaction targeting the 16S rRNA gene, coupled with next-
generation sequencing and advanced bioinformatics tools,
has facilitated the precise identication of various bacterial
strains and the functional attributes of GM.83,84
Many factors, including nutritional, chemical, and
immunological gradients along the gut, can aect
the composition and density of GM. Indeed, it varies
according to dierent intestinal regions, where pH levels,
oxygen tension, host secretions, and substrate availability
uctuate.85
In the small intestine, transit time is short, with generally
elevated levels of acids, oxygen, and antimicrobials.86 ese
properties hinder bacterial proliferation, allowing only
facultative anerobes characterized by rapid growth and
adherence to epithelia or mucus to survive.86
Meanwhile, the colon provides dierent conditions that
support a diverse bacterial community, mainly anerobes
capable of metabolizing complex carbohydrates that go
through incomplete digestion in the small intestine.87 It
has been shown that Firmicutes (60 – 80%), Bacteroidetes
(20 – 40%), the Verrucomicrobia, the Actinobacteria, and a
reduced presence of Proteobacteria are ve predominantly
phyla of bacteria in the normal human GM.88
3.1. GM: Coevolution with human life
e human fetus has long been considered microbiologically
sterile. e predominant assumption suggests that the rst
human encounter and interaction with bacteria occur
at birth when the newborn comes into contact with the
surrounding environment.89,90 However, some studies
suggest that the human GM is generally established before
birth.91
is exposure to microbiota is highly benecial and
plays a critical role in programming the maturation of
an infant’s immunity during fetal life. Bacterial DNA is a
key factor in this process.92 Other research indicates that
contact with maternal microbiota through the placenta has
been associated with adverse outcomes, including preterm
birth, spontaneous abortion, and intrauterine infections,
as observed in cases of listeriosis throughout pregnancy.93
e mode of delivery is a key factor shaping the
composition of an infant’s microbiota.94,95 Infants delivered
by cesarean section (C-section) have a dierent GM
composition and colonization timeline compared to
those delivered vaginally.95,96 e colonization of bacteria
in an infant’s gut occurs gradually, beginning with the
rst contact with the maternal microbiota during birth
and culminating in a highly dense and diverse microbial
community.97 It has been shown that facultative anerobic
bacteria are usually the rst colonizers, followed by strictly
anerobic genera, including Bacteroides, Bidobacterium,
Eubacterium, and Clostridium.98,99
Breast milk also has a potential role in GM development.
Astudy of 94 premature mother-child dyads found that 30
– 40% of the bacteria present in an infant’s gut were also
found in breast milk, suggesting bacterial transfer. ese
interactions were inuenced by dietary practices and
antibiotic use.100
e GM of a newborn takes around 2 – 3years to develop
and stabilize into a prole similar to that of an adult.101 In
normal and healthy individuals, the GM is principally
dominated by Firmicutes, Bacteroidetes, Proteobacteria,
and Actinobacteria.102 An analysis of GM in Moroccan
residents showed a large percentage of Bacteroides (62.6%).
In addition, the genera Prevotella, Prevotella copri, and
Prevotella stercorea, as well as Fecalibacterium prosnitzi,
were signicantly dominant in these samples.103
roughout life, human GM undergoes multiple
changes related to lifestyle. Ahigh-ber diet increases the
abundance of benecial bacteria such as Lactobacillus,
Akkermansia, and Bidobacterium while reducing
opportunistic pathogenic bacteria such as Desulfovibrio
and Klebsiella.104 In 2010, researchers compared the GM
of European children to that of children living in a rural
village of Burkina Faso, where a ber-rich diet is common.
e results have showed signicant dierences in microbial
composition. Burkinabe children had a high abundance
of Bacteroides and a clear reduction in Firmicutes, with
increased Prevotella and Xylanibacter, both adapted to ber
degradation, and higher short-chain fatty acid (SCFA)
levels (P < 0.001). Moreover, pathogenic bacteria such us
Shigella and Escherichia were signicantly less common in
these children than in European children.105
Poor sleep also aects GM, as shown by the critical role
of the brain-gut-microbiota axis in sleep intensication.
Recent research has explored the impact of sleep disorders
such as fragmentation, sleep deprivation, obstructive sleep
apnea, insomnia, and circadian rhythm sleep disorders on
GM composition.106 Similarly, physical activity could aect
GM by increasing benecial bacteria, while a healthy GM
may, in turn, improve exercise performance.107
e GM presents diurnal oscillations on a global scale,
with its levels and rhythms uctuating in accordance with
a 24-h cycle. Using cosinor-based rhythmometry, diurnal
signals were detected across dierent taxonomic levels
of the GM, with 57% of phyla following a 24-h rhythmic
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cycle.108 On the other hand, microbiome seasonal variations
are widespread. It has been shown that some bacteria
follow two distinct proles or patterns, which have been
detected in many regions around the world.108
Among Ukrainian individuals, gut bacterial
composition uctuates with the seasons. Actinobacteria
abundance and the Firmicutes-to-Bacteroidetes ratio were
higher in samples collected during summer compared
to other seasons. In the contrary, Bacteroidetes were less
abundant during the summer.109
In healthy conditions, Firmicutes, Bacteroidetes, and
Actinobacteria are the three major microbial phyla in the
GM.110,111 However, in cases of intestinal inammation,
there is a notable increase in Proteobacteria, particularly
within the Enterobacteriaceae family, accompanied by
a decline in strict anerobes.112 A study evaluating the
impact of seasonal uctuations in vitamin D levels on
the composition of GM among Caucasians patients with
chronic inammatory bowel disease (IBD) found that
low vitamin D levels were associated with an increased
abundance of bacteria associated with inammation,
such as Proteobacteria (including Helicobacter spp.),
Actinobacteria, and Fusobacteria. However, it was noted
that low Vitamin D levels did not always correlate with
severe dysbiosis. In some ulcerative colitis samples,
an increased abundance of benecial bacteria, such as
Faecalibacterium prausnitzii, was detected, along with
a lower abundance of Escherichia/Shigella, which is
commonly associated with inammation. On the other
hand, it was demonstrated that high level of Vitamin D
in autumn and summer was associated with a decrease
in bacteria linked to inammation and an increased
presence of potentially benecial or anti-inammatory
bacteria, such as Pediococcus spp., Clostridium spp., and
Escherichia/Shigella spp.113 Another study found signicant
changes in GM composition at the genus level, including
an increase in Lachnospira, a genus associated with anti-
inammatory eects among Vitamin D-supplemented
individuals. However, no changes were noted in alpha
diversity between the study groups, nor were there notable
variations in community composition between samples.114
ese ndings suggest that diurnal and seasonal
variations could signicantly inuence gut microbial
proles, potentially inuencing the interpretation of
microbiome analyses and making the denition of normal
GM very challenging.108
e seasonal oscillations of some gastrointestinal
pathogens are now become registrable through syndromic
diagnostic platforms such as Biore Syndromic Trends by
Biomerieux, which is designed to rapidly detect and identify
infectious diseases, including gastrointestinal infections
caused by multiple viruses (e.g., rotavirus and norovirus)
and bacteria (e.g., Salmonella and Escherichia coli). For
example, rotavirus infections are more prevalent in the
winter.115 However, in 2023 and 2024, the Biore platform
has registered high levels of diarrheagenic infection caused
by E. coli or Shigella throughout the summer.116 is
platform has become essential for the rapid identication
of epidemics and for adapting prevention and treatment
strategies accordingly.117
Dysbiosis of GM is an alteration in the microbial
composition resulting from various factors, including
infections, diet, drugs, antibiotics, and small bacterial
overgrowth.118 Furthermore, numerous studies have
validated the implication of gut dysbiosis and various
pathological conditions, such as cardiovascular disease,119
hypertension,120 cancer,121 and chronic kidney disease.122
A growing body of scientic evidence supports a causal
link between GM and dermatological disorders, namely
atopic dermatitis, acne, psoriasis, and alopecia areata.
Nevertheless, further eorts are required to prioritize the
functional features of this relationship.123 Besides dysbiosis,
bariatric surgery has also been shown to inuence GM,
leading to microbial changes that may contribute to the
metabolic benets observed aer surgery.124
Meanwhile, recent research suggests that dysbiosis
originates from changes in the host environment. It occurs
when the host loses the ability to control oxygen levels and
certain electron acceptors, leading to increased oxygen
diusion into the colonic lumen. is promotes the growth
of facultative anerobic bacteria. Some researchers argue
that modications in GM are a consequence rather than
the primary cause of dysbiosis.125
e symbiosis between the intestinal microbiota and its
host is critical for maintaining physiological balance and
shaping host-microbe interactions. In a gnotobiotic bee
model, researcher employed the mutagenesis atmospheric
and room-temperature plasma approach to induce
bacterial mutations and identify those that enhance survive
in a host. eir investigation into the genetic mechanisms
promoting Snodgrassella bacterial adaptation to non-native
hosts revealed that mutations in the mglB gene, which
regulates bacterial motility through typeIV pili, provided
a competitive advantage for colonizing honeybee guts
(Apis mellifera). ese ndings underline the importance
of bacterial mobility in symbiosis and provide new avenues
for investigating host-microbe interactions using novel
experimental paradigms.126
Based on the ndings presented, it is evident that
numerous variables aect microbiota composition,
complicating the interpretation of results. e overall
composition of the microbiota is inuenced by various
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factors, including the analytical techniques used, sampling
location (biopsies or stools), inammatory state (inamed
or non-inamed sites), disease activity, and individual
characteristics such as age and lifestyle.127
3.2. Fecal transplantation: Transferring features and
characteristics
Fecal microbial transplantation (FMT) is a promising
intervention to reshape GM, oering potential treatment
for metabolic dysfunction and autoimmune diseases.128
It has been investigated in various contexts, including
MetSyn, non-alcoholic fatty liver disease, and obesity in
both animal and human studies.129 Patients with reduced
GM diversity have shown a signicant increase in
microbial diversity aer receiving fecal transplants from
lean and healthy donors.130 In addition, FMT has shown
promising results in slowing the progression of chronic
kidney disease122 and in the treatment of Parkinson’s
disease.131
Germ-free (GF) mice are animals derived from other
animals that are delivered through aseptic C-section. ese
rodents remained completely devoid of microorganisms
from birth throughout their entire lifespan. ey are
characterized by lower BW and notable variations in
immune system, metabolism, and neurodevelopment.132-134
Animal studies have demonstrated that fat accumulation
and insulin resistance levels can be inuenced through
FMT. It was demonstrated that FMT can modify the GM.135
Bäckhed et al.136 showed that adipose tissue accumulation
occurs in GF mice when they are colonized with the GM
of conventional mice, leading to an increase in adipose
tissue mass, fat content, and insulin resistance levels.136
In addition, Turnbaugh et al.137 conducted an experiment
in which GM from obese mice was transplanted into GF
mice, resulting in signicant weight gain and increased fat
accumulation in the recipients. ese ndings conrm that
GM dysbiosis can lead to obesity. ese results have been
further conrmed by recent research.138
FMT from lean donors to individuals with severe
obesity did not demonstrate any signicant changes in
insulin resistance or other primary metabolic variables
between the groups. Meanwhile, the allogenic FMT group
experienced benecial changes in metabolic pathways,
appetite regulation, and GM, with potential implications
for low-density lipoprotein levels.139
e eects of FMT combined with ber
supplementation in obese patients with MetSyn were also
assessed. Among the four study groups, only the group
treated with FMT and low-fermentable (LF) ber showed
a signicant improvement in insulin sensitivity aer
6weeks. e GM composition also showed favorable and
long-lasting alterations in this group, with an increase in
benecial bacteria, including Bacteroides and Akkermansia
muciniphila.140 ese ndings suggest that the combination
of FMT and LF ber represents a safe and eective strategy
to address metabolic dysfunction and modify GM over
time.
A critical question that arises is why certain individuals
exhibit a more favorable response to FMT than others.
Addressing this question requires an exploration of
recipient-related factors. In this regard, a study showed
that recipients with greater baseline microbiome diversity
and a specic microbial composition, characterized
by low Prevotella levels, responded more eectively to
FMT. ese individuals exhibited greater improvements
in insulin sensitivity and a higher degree of donor
bacterial engrament, including Roseburia spp. and
Christensenellaceae spp. Meanwhile, other studies have
reported no notable eects of FMT on human metabolism
or weight in adults with obesity.141,142
Bäckhed et al.136 highlighted some dierences between
GF mice and conventional raised counterparts. e study
reported that GF mice display 42% less total body fat than
their conventional counterparts, despite ingesting 29%
more calories.136 Furthermore, when subjected to a high-
fat diet (HFD), GF mice experienced reduced weight
gain, oering a protection against diet-induced glucose
intolerance and the onset of insulin resistance.143-145 In
addition, the ability of microbiota to control the BW
was stated. rough colonizing GF mice with the GM of
conventionally raised mice, a subsequent increase in body
fat content and insulin resistance was observed.146 is
conrms the essential role of GM in BW regulation.
Furthermore, under typical conditions, mice are
coprophagic (i.e., consumption of feces). It has been
illustrated that obese mice were protected from further
weight gain by consuming microbiota from lean cage
mates. However, in the reverse scenario, where lean mice
consumed feces from obese mice, no signicant weight
gain was observed.147 Studies in human patients further
suggest that, when combined with lifestyle interventions,
FMT can induce benecial changes in lipid metabolism.148
Other research has investigated the role of the gut
virome in diabetes, revealing its unexpectedly and
remarkable eects. It was found that gut virome not only
stabilizes blood glucose levels and reduces host weight
but also capable of modifying the gut microbial prole
and inuencing the expression of genes related to glucose
metabolism, leptin signaling, and fat breakdown.149
Based on these ndings, GM contributes signicantly
to a range of physiological functions, and microbiota
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transplantation appears to be a viable approach for
transferring these characteristics.
4. Microbiota-mediated obesity: Molecular
insights
During the past decades, increasing evidence has
demonstrated that GM plays a signicant role in the
onset and development of obesity.150 Several studies have
analyzed the link between obesity and GM, highlighting
that an imbalance in GM can be a contributing factor to
obesity.151-153
4.1. SCFAs: Key players in the obesity development
GM has diverse functions, including the fermentation of
indigestible carbohydrates into metabolites, such as SCFAs,
which are the primary byproducts of bacterial fermentation
of dietary ber in the GIT.154 SCFAs encompass a range of
metabolites, with acetate, propionate, and butyrate being
the most prevalent in the human colon.155,156
Recently studies have conrmed that SCFAs play an
essential role in host health by acting at multiple levels, such
as cells, tissues, and organs, through mechanisms related to
glucose homeostasis, gut barrier function, and obesity.157
Furthermore, SCFAs are recognized for their role in
controlling obesity-associated health conditions across the
lifespan by managing energy balance, controlling appetite,
and increasing energy expenditure.158
Studies suggest that obese individuals show increased
levels of SCFA than lean individuals, suggesting a possible
role of SCFAs in the energy dynamics associated with
obesity, as they serve as energy-rich metabolites.159,160 Some
investigations propose that elevated SCFA levels in obese
individuals contribute to increased adiposity by providing
extra energy from dietary ber fermentation.161,162
Contradictory ndings indicate that SCFA levels are
notably decreased in obese individuals,163-165 highlighting
that the link between SCFAs and obesity remains
incompletely understood.
Butyrate and acetate serve as energy sources that the
liver relies on to generate energy through the tricarboxylic
acid cycle, a crucial pathway for metabolism that takes place
in mitochondria.166 However, they also alter liver function
and inuence adipose tissue metabolism by modifying
mitochondrial uncoupling protein 2 (UCP2) expression
through peroxisome proliferator-activated receptor gamma.
is mechanism increases the adenosine monophosphate
(AMP)/adenosine triphosphate (ATP) ratio, which
promotes aerobic metabolism through AMP-activated
protein kinase (AMPK) signaling. ese results suggest that
SCFAs may alleviate MetSyn by increasing energy utilization
and metabolic eciency.167 Moreover, SCFAs stimulate the
release of GLP-1, which improves insulin sensitivity and
inhibits glucagon production.168,169 ese studies emphasize
the multifaceted role of SCFAs in obesity, energy metabolism,
and overall health, as well as their regulatory eects on the
liver, adipose tissue, and intestinal health.
Breast milk contains small amounts of SCFAs,170 with
concentrations varying greatly between individuals.171 It
contains microbiota that interacts symbiotically with the
infant gut. Certain microbes are benecial for neonatal
health by producing breast milk butyrate acid (C4),
which plays an important role in enforcing immune and
metabolic development by inuencing the abundance of
the infant GM.172
SCFA production can be inuenced by both dietary
and genetic factors such as leptin resistance. In a recent
study, they have found that diet-induced obesity in mice
signicantly decreased SCFA production in the early stage
(day 14), with production dynamics diering distinctly
from those of control mice on a standard diet.173 In contrast,
genetic obesity caused by leptin resistance initially showed
SCFA production like controls, but a signicant reduction
occurred at the mid-stage (day 60). ese results suggest that
diet has a greater eect on the production of SCFAs, while
genetic factors like leptin resistance can also impact SCFA
production, though with a delayed and moderate eect.173
4.2. Conjugated linoleic acid (CLA)
Firmicutes and Actinobacteria, of particular interest, have
the ability to generate polyunsaturated omega-6 fatty
acids in addition to CLA. Modication in the synthesis of
this fatty acid is particularly related to obesity. CLA has
dierent features, including anti-obesity eects, such as
enhanced energy metabolism, increased lipolysis, as well
as reduced adipogenesis and lipogenesis.158 According to
a meta-analysis and systematic review, CLA signicantly
increases triglyceride levels and decreases total cholesterol
(TC) compared to placebo and olive oil. ey found
that in obese individuals (BMI ≥ 25) aged over 25years,
consuming more than 3mg/day of CLA for at least 8weeks
resulted in a signicant reduction in TC levels.174
In addition, numerous studies have demonstrated that
CLA reduces de novo lipid synthesis and triggers adipocyte
apoptosis.175 is apoptotic eect on adipose tissue is
associated with the activation of TNF-α and UCP2. UCP2
disrupts electron transfer across the inner membrane
of mitochondria, redirecting energy toward thermal
dissipation rather than its storage in the form of ATP.176
Furthermore, it has been revealed that certain strains of
Bidobacterium spp. and Lactobacillus spp. produce
benecial CLA, which enhances energy metabolism and
lipolysis, ultimately aecting BW.177
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To highlight CLA’s potential role in regulating
interactions between the GM, host metabolism, and
immunity in attenuating insulin resistance, a study
evaluated its eects in a mouse model of insulin resistance
induced by a HFD. CLA supplementation improved
hyperglycemia, hyperlipidemia, glucose intolerance, and
insulin resistance. It enhanced antioxidant capacity and
reduced fat deposits and inammation in adipose tissue.
It also promotes fatty acid oxidation and insulin signaling
pathways.178 In addition, transcriptomic analysis revealed
that CLA inhibited inammatory signaling pathways while
activating several benecial metabolic pathways, including
phosphoinositide 3-kinase-Akt, AMPK, and insulin-
related pathways. It also regulated specic metabolic
processes, such as those related to arachidonic acid, linoleic
acid, arginine, and proline metabolism. In the same mice
model, CLA supplementation eectively reduced weight
gain, adipose tissue weight, and adipocyte size compared
to HFD-fed mice without supplementation.178
4.3. Bile acids metabolites
Bile acids are metabolites derived from cholesterol in the
liver and subsequently metabolized by gut bacteria in the
intestines. e decrease of both primary and secondary
bile acid subtypes aer the consumption of low-calorie
weight-loss diets has shown a prominent correlation
with improving adiposity, fat accumulation, and energy
metabolism. is suggests that specic subtypes of bile
acids could serve as potential biomarkers for predicting
long-term weight-loss success and an individual’s
response to dietary interventions.179 e GM assists in
bile acid metabolism by facilitating deconjugation and
dehydroxylation processes inside the intestinal lumen.
ese mechanisms convert primary bile acids into
secondary bile acids, such as cholate into deoxycholate
and chenodeoxycholate into lithocholate.180,181 is
process is promoted by bile salt hydrolase enzymes, which
mainly found in Firmicutes and Bacteroidetes, notably in
Clostridium genera clusters.182
Aer analyzing the postprandial responses of bile
acids, the bile acid synthesis marker C4, broblast growth
factor 19 (FGF19), and farnesoid X receptor (FXR)-
regulated FGF19 in obese patients before and aer surgery,
researchers observed a signicant increase in total plasma
bile acid levels, while fecal excretion of these molecules
decreased. Furthermore, FGF19 levels increased, whereas
C4 levels decreased, indicating enhanced FXR activity in
the gut. e increase in bile acid levels and the activation of
FXR may contribute to the observed metabolic benets.183
Understanding the role of these bacterial metabolites in
weight loss remains an active area of research.
4.4. Trimethylamine N-oxide (TMAO)
TMAO is a compound belonging to the amine oxides class,
chemically represented as (CH3)3NO. TMAO is produced
through the metabolism of dietary choline, L-carnitine, and
betaine by the intestinal microbiota.184,185 Specically, it is
derived from the oxidation of trimethylamine (TMA).186-188
Moreover, the dierentially expressed microbial genes
summarized in the Kyoto Encyclopedia of Genes and
Genomes Orthology (KO) suggest that these genes are
responsible for encoding the trimethyl N-oxide reductase
enzyme, which plays a crucial role in the conversion of
TMAO to TMA.189
TMAO levels increased in tandem with BMI, displaying
a positive association with both fatty liver index and visceral
adiposity index.190 A recent study revealed persuasive
results regarding the relationship between TMAO levels
and obesity, identifying that individuals in the highest
TMAO category exhibited an increase of 0.56 kg/m2 in
BMI. Furthermore, a dose-dependent association was
observed between circulating TMAO levels and obesity
in individuals categorized as apparently healthy. Notably,
this study represents the rst meta-analysis to unveil
these positive dose-dependent associations between
the concentration of circulating TMAO and obesity.191
In addition, patients with obesity and colorectal cancer
display distinct GM characteristics, including a reduced
abundance of butyrate-producing bacteria, accompanied
by increased TMAO levels, increased pro-inammatory
cytokine IL-1β, and enhanced intestinal permeability.192
On the other hand, there are viable solutions to
modulate TMAO levels. e Mediterranean diet, a high-
ber diet, and probiotics have demonstrated their ability
to reduce the eects of TMAO.193 A high-ber diet led to
an increase in the abundance of benecial bacteria such
as Lactobacillus, Akkermansia, and Bidobacterium while
reducing the opportunistic pathogenic bacteria such as
Desulfovibrio and Klebsiella.104
5. Bacteria taxa implicated in the control of
BW
Evidence from various studies consistently demonstrates
that certain gut bacteria signicantly inuence
obesity-related metrics, metabolic parameters, and fat
accumulation by impacting intestinal health. e following
table summarizes intestinal bacteria associated with
obesity based on studies conducted on mice and humans of
dierent ages and weights. Table1 compiles results derived
from several studies, highlighting the role of various GMs
in BW regulation. Each bacterium’s specic inuence is
examined individually.
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Table1. Correlation of bacterial taxa to BMI and obesity
Reference study Type (Animal/Human) Publication
year
Results
Tav ella et al. 194 Human (Italian elderly) 2021 e relative abundance of Christensenellaceae Porphyromonadaceae
and Rikenellaceae was inversely related to host BMI.
Alemán et al. 195 Human (Postmenopausal women) 2018 e relative abundance of Christensenellaceae was inversely related to
host BMI.
Depommier et al. 11 Human (Overweight/obese
insulin-resistant volunteers)
2019 Supplementation with Akkermansia muciniphila reduced body
weight, fat mass, and hip circumference.
Deng et al. 196 60 male age matched C57BL/6 mice 2020 Akkermansia muciniphila improved metabolic aspects related to
obesity and metabolic syndromes.
Everard et al. 197 10-week-old, C57BL/6 male mice 2013 Abundance of Akkermansia muciniphila decreased in obese mice.
Park et al. 198 4-week-old, C57BL/6J male mice 2017 Lactobacillus plantarum HAC01 led to a reduction in mesenteric
adipose tissue.
Mohd Hasali
etal. 199
7-week-old, 30 male C57BL/6 mice 2024 Lactobacillus brevis NJ42 reduced weight gain among the HFD-fed
group.
Yang et al. 200 6-week-old, 36 male C57BL/6 mice 2022 A mixture of Lactobacillus acidophilus and Clostridium cochlearium
showed lower body weight gain among the HFD-fed group.
Mu et al. 201 6-week-old, 60 specic pathogen-free
C57/BL6J mice (30 females, 30 males)
2020 Lactobacillus plantarum KFY02 showed a reduction in body weight
in mice.
Shirouchi et al. 202 4-week-old, 12 Sprague–Dawley rats 2016 Lactobacillus gasseri SBT2055 was linked to higher carbohydrate
oxidation, resulting in increased energy expenditure leading to body
weight reduction.
Schellekens et al. 203 5-week-old, 40 male C57BL/6 mice 2021 Bidobacterium longum APC1472 decreased body weight gain aer
een weeks of administration.
Solito et al. 204 Human (Children and adolescents) 2021 Bidobacterium breve BR03 and B. breve B632 showed improvements
in metabolic parameters and reduction in weight and Escherichia coli
levels.
Zhang et al. 205 Obese mice 2024 Bidobacterium adolescentis CCFM8630 showed anti-obesity eects
through modulation of tryptophan metabolism related to GM.
Yang et al. 206 7-week-old, 72 male C57BL/6 mice 2023 Faecalibacterium prausnitzii strains reduced body weight gain.
Navab-Moghadam
et al. 207
Human (Type 2 diabetes individuals/
healthy controls)
2017 Faecalibacterium prausnitzii was negatively correlated with BMI.
Yoshida et al. 208 Human (Obese individuals) and mice 2021 Bacteroides probiotics could be used for treating obesity.
Seong et al. 209 Human (Patients with metabolic
syndrome)
2021 Bacteroides spp. showed a negative correlation with BMI.
Luo et al. 210 10-week-old diabetic mice db/db. 2022 Bacteroides spp. exhibited an inverse correlation with BMI.
Yang et al. 211 C57BL/6 (B6), CD11c-Cre, Villine-Cre,
and LysM-Cre mice; Atg7f/f mice
2017 Bacteroides acidifaciens JCM10556 aids in the prevention of metabolic
disorders such as diabetes and obesity.
Cano et al. 212 6 – 8-week-old, 32 male wild-type
C57BL-6 mice
2012 Bacteroides uniformis CECT 7771 signicantly decreased body weight
gain in HFD‑fed mice.
You et al. 213 Human (Healthy Korean) 2023 Bacteroides vulgatus SNUG 40,005 was associated with a signicant
reduction in body weight.
Dong et al. 214 Human (Obese and non-obese) 2022 Obesity was linked to an increased P/B ratio.
Hjorth et al. 215 Human (Overweight participants) 2019 A high P/B ratio aids weight loss.
Hjorth et al. 216 Human (Participants with increased
waist circumference)
2020 Pre-treatment P/B ratio led to highly individualized weight loss.
Hjorth et al. 217 Human (Participants with increased
waist circumference)
2018 A higher P/B ratio was more likely to reduce body fat on diets rich in
whole grains and ber.
Abbreviations: BMI; Body mass index; P/B ratio: Prevotella-to-Bacteroides ratio.
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e abundance of Porphyromonadaceae,
Christensenellaceae, and Rikenellaceae has been inversely
correlated with host BMI.194,195 A. muciniphila is linked
to the reduction of BW,11 and its abundance has been
shown to decrease in obese mice.196,197 Other experiments
conducted on mice and rats have demonstrated that
Lactobacillus species198-202 and Bidobacterium species203-205
show a revers correlation with BW gain, arming their
ability to improve metabolic parameters. Faecalibacterium
prausnitzii acts similarly, contributing to reduced BW
gain.206,207 Furthermore, Bacteroides species are also
inversely correlated with BMI208-210,212,213 and have been
shown to help prevent metabolic disorders including
diabetes and obesity.211 Notably, Bacteroides can be used
as probiotics in treating metabolic disorders.208 In addition
to the benecial eects of Bacteroides, the complex
interactions between dierent bacterial species in the GM
play a crucial role in regulating weight and metabolism.
Among these interactions, Prevotella-to-Bacteroides (P/B)
ratio has been particularly studied. Individuals with a high
P/B ratio before any treatment have been shown to achieve
greater weight loss on high-ber diets compared to those
with a lower P/B ratio.214-217
A detailed examination of each bacterium will now
follow.
5.1. Lactobacillus species
Lactobacillales are a phylogenetically diverse order of
lactic acid-producing organisms.218 Lactobacillus spp. is
Gram-positive, non-spore-forming rods that are catalase-
negative and facultatively anerobic, typically thriving in
environments with lower oxygen levels. Numerous studies
have highlighted the positive inuence of Lactobacillus
spp. in mitigating metabolic disorders, including obesity.219
Crovesy et al.220 provided a summary of the inuence
of Lactobacillus on BW among overweight individuals.
ey reported a negative correlation between Lactobacillus
paracasei and obesity. In addition, they also noted
signicant correlations between Limosilactobacillus reuteri
and Lactobacillus gasseri with obesity. Another study found
that the abundance of Lactobacillus spp. was higher in the
stool of obese patients and individuals with metabolic
diseases,221 identifying this species as an obesity-associated
taxon.221
Lactobacillus plantarum is a widespread member of the
genus Lactiplantibacillus. ere are divergent perspectives
on the impact of L. plantarum on obesity and weight
regulation.198 In this context, it has been observed that
the administration of L. plantarum, either alone or in
combination with inulin, may decrease food intake and
prevent weight loss in diabetic rats.202,222 Similarly, Shirouchi
et al.202 demonstrated that L. gasseri SBT2055 contributes
to BW reduction in rats by promoting higher carbohydrate
oxidation, resulting in increased energy expenditure.202
Despite that, no noticeable dierence in food intake was
observed between both groups in this study.202 A similar
pattern was observed with Lactobacillus brevis NJ42.199
Other results showed that administering Lactobacillus
fermentum and Lactobacillus ingluviei was related to
noticeable increase in weight, while administering
L. plantarum, Lactobacillus acidophilus, and L. gasseri
was coupled with weight loss in both obese humans and
animals.201-223
5.2. Faecalibacterium prausnitzii
F. prausnitzii is a Gram-positive bacterium that belongs
to Ruminococcaceae family224 and Firmicutes phylum.225 It
is one of the highly widespread anerobic bacteria in the
gut,202,226 constituting approximately 1 – 6% of the total
fecal microbiota.224,227 A reduction of F. prausnitzii has
been related to chronic inammation, a key manifestation
of obesity.228-230
ere have been conicting outcomes regarding the
relationship between F. prausnitzii abundance and obesity.
For instance, a Chinese study reported a decrease in the
abundance of F. prausnitzii, Bacteroides, and Akkermansia
among pre-diabetic obese patients.231 In contrast, another
study on obese adults in China found a positive correlation
between fasting glucose levels and F. prausnitzii in men.232
Similarly, an earlier study carried out in Southern India
discovered reduced abundance of F. prausnitzii in non-
obese children compared to obese children.233 Meanwhile,
numerous studies have reported opposing ndings.
A 2017 Iranian study has shown a negative correlation
between F. prausnitzii and BMI.207
Hippe et al.234 have demonstrated that aer weight loss,
patients suering from T2D exhibited increased levels of
F. prausnitzii. ey also revealed that samples from lean
individuals had a lower expression of F. prausnitzii genes
compared to obese individuals and those with T2D. In
addition, F. prausnitzii is being explored for its potential
in treating obesity and its related comorbidities. Mice on
HFD treated with F. prausnitzii twice a week showed a
notable decrease in adipocyte size and cell inltration of
adipose tissue compared to the control group.235 Another
study has identied F. prausnitzii as a species with lower
prevalence in obesity and associated disorders,236 which
lead to its proposal as a next-generation probiotics for
treating obesity and its related disorders.237
Butyrate, is a SCFA produced by bacterial fermentation
of indigestible bers in the colon.238 F. prausnitzii is
one of the bacteria that produce butyrate and bioactive
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anti-inammatory molecules similar to shikimic and
salicylic acids.239 It is considered one of the most important
butyrate producers in the human gut, capable of degrading
inulin and producing butyrate.240-242 Butyrate plays an
essential role in gut health, serving as the principal energy
source for colonocytes and exerting benecial eects on the
GM, ultimately contributing to overall human health.238,241
In addition, F. prausnitzii has demonstrated benecial
eects on the gastrointestinal health of obese patients.
e metabolites it produces, including butyrate, have
demonstrated good results in the treatment of obesity.243,244
F. prausnitzii’s supernatant has been observed to
regulate T helper 17/regulatory T cells dierentiation
by suppressing proinammatory pathways, including
signal transducer and activator of transcription 3/IL-17
and IL-6. is is accomplished through the targeting of
histone deacetylase 1.245,246 is proinammatory pathway
is implicated in obesity.234 Further observations found that
treatment of HDF-fed mice with F. prausnitzii reduced
inammation in adipose tissue, validating previously
reported results.235
5.3. A. muciniphila
A. muciniphila is among the bacterial species that inuence
BW. ese anaerobic bacteria which contribute to mucus
layer degradation, reside within the intestinal mucosa of
both humans and rodents.247 Analysis of stool microbiota
revealed a reduced concentration of A. muciniphila in obese
and overweight children compared to lean children.248
ese results were conrmed by other studies reporting
an inverse correlation between this bacterium and BW
in humans and rodents.11,197 ey have shown that A.
muciniphila abundance decreases in both obese and type2
diabetic mice.197 In addition, in a group of patients on a HFD
for 8weeks, Akkermansia bacteria increased signicantly.104
A. muciniphila has been shown to reduce fat mass, BW, and
hip circumference in obese or overweight insulin-resistant
volunteers11 while also improving metabolic aspects related
to obesity and other MetSyn.196
Moreover, several studies suggest the potential role of
A. muciniphila as a therapeutic option. Research has found
that A. muciniphila treatment has the ability to alleviate
BW gain and reverse HFD-induced metabolic disorders,
including metabolic endotoxemia, fat-mass gain, and
adipose tissue inammation.197,249 ese ndings suggest
that Akkermansia is oen associated with better weight
management and a reduced risk of obesity.250,251
5.4. Bidobacterium
Bidobacterial ora is among the rst microbes to colonize
the human GIT.252 Usually, colonization starts during the
rst few days aer delivery and can constitute up to almost
80% of the GM composition during infancy.253
Numerous Bidobacterial strains have been reported
to exert useful eects in dierent clinical conditions. e
eects of dierent Bidobacterium species have been
studied in diet-induced obesity (DIO) mouse models. In the
study, four Bidobacterial groups (B. FS31-12, B. M13-4, B.
L75-4, and B. L66-5) were administered to mice on HFD,
with only Bidobacteria L66-5 demonstrating weight-loss
properties.254 Another study found that supplementation
with Bidobacterium adolescentis promoted weight loss
and improved steatosis and steatohepatitis, which are
fatty liver diseases related to excess fat buildup in the
liver. ese positive eects were observed in mouse
and rat models.205,255,256 Similar ndings were reported
in other studies. Aer 15 weeks of supplementation,
Bidobacterium longum APC1472 was shown to reduce
BW gain in mice.203 In addition, Bidobacterium breve
BR03 and B. breve B632 were associated with improvements
in metabolic parameters, decreased weight, and reduced
E. coli counts.204 Moreover, a reduction in visceral fat and
insulin resistance has been observed aer treatment with
other Bidobacterium strains in rodent models.257
5.5. Bacteroides and Prevotella
Bacteroides is a genus of Gram-negative, non-
spore-forming, and obligate anerobic bacteria258 that
predominantly inhabit the lower intestinal tract of
human.259 Bacteroides species have been inversely
correlated with BMI208-210,212,213 and play a role in preventing
metabolic disorders, including diabetes and obesity.211
Notably, they have also been it can be used as probiotics
treating metabolic disorders.208
Prevotella is a Gram-negative bacterium belonging to the
Bacteroidetes phylum. is genus is commonly associated
with carbohydrate-rich diets, such as plant-based foods. Its
ber fermentation activity could potentially play a role in
carbohydrate metabolism.105,260
Prevotella and Bacteroides constitute two of the largest
bacterial groups and are among the major microbial
populations found within sheep and cattle rumens across
multiple diet regimens.260 In addition, they represent two of
the most prevalent groups of anerobic bacteria within the
human colon.260,261 ey play an essential role in breaking
down and converting food components, with Bacteroides
spp. being particularly involved in metabolizing both
plant-derived and host-derived polysaccharides.261
Individuals with a high P/B ratio, compared to those
with a low (P/B) ratio, have been observed to experience
greater reductions in both body fat and BW. is
suggests that individuals with a high P/B ratio are more
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susceptible to weight loss following a ber-rich diet.215
Other eorts were made to describe the role of P/B ratio
in weight gain, indicating that individuals with a high
P/B ratio are more prone to weight regain than those
with a low P/B ratio.262 is eect becomes more crucial
and important when combined with low dietary ber
consumption and altered glucose metabolism.262 A high
P/B ratio has been associated with increased fermentation
of dietary bers, resulting in the production of SCFA,
which enhances energy metabolism and satiety. is
was demonstrated in a study showing that Prevotella is
highly ecient at metabolizing complex polysaccharides
found in dietary bers,263,264 which is benecial in the
context of caloric restriction. ese ndings align with
the previous research,215 where participants with a high
P/B ratio experienced greater weight loss on an HFD.
is demonstrates the signicance role of dietary ber
in enhancing the benecial eects of GM, particularly
Prevotella, by promoting the synthesis of benecial
SCFAs. As a result, ber intake could potentially lead to
an imbalance in microbial metabolic functions, which
might explain the observed dierences in individual
responses based on the P/B ratio.265
Furthermore, Kootte et al.266 showed that insulin
resistance may reduce the eectiveness of SCFAs in
enhancing insulin sensitivity, which might worsen fat
storage rather than promote fat oxidation. e metabolic
response appears to also depend on the baseline microbial
diversity of patients.266 Low microbial diversity that reects
an imbalance or functionally compromised microbiota
can justify this metabolic response. Patients with lower
microbial diversity are more likely to benet from the
good bacteria transplanted or introduced through FMT.
Conversely, patients with greater microbial diversity tend
to have a more stable GM which may limit the integration
and benecial eects of transplanted microbiota.
Further investigations214,267 support this notion, where
they found that higher Prevotella levels (P = 0.004) and
lower Bacteroides levels (P = 0.03) are linked to obesity.214
Interestingly, although their functional similarities and
ability to predominate the GM independently, they
rarely coexist in high relative abundance, suggesting a
co-exclusionary relationship.268
Another study has highlighted that the P/B ratio before
treatment is a notable indicator associated with changes in
body fat resulting from unrestricted high-ber diets. It has
been shown that obesity is linked to an increase in the P/B
ratio.214 However, it was demonstrated that individuals with
a higher P/B ratio responded more eectively to ber-and
whole grain-rich diets, exhibiting greater reductions in
body fat compared to those consuming an average Danish
diet. In contrast, individuals with a lower P/B ratio did not
show signicant dierences in body fat reduction.217
6. Conclusion
In summary, this review highlights the complex
relationship between GM strains and obesity. e evidence
shows an existing relationship between the composition
of GM and its role in regulating metabolism and overall
obesity. Interactions between GM and the host’s metabolic
processes reveal potential pathways for therapeutic
interventions aimed at treating and preventing the
development of obesity. e relationship between GM and
BW is inuenced by various factors, including physical
activity, diet, sleep, and medication, making it a complex
area of study that requires further studies. Standardizing
experimental conditions is essential to reduce bias and
ensure comparable results in GM studies. Given that
numerous factors aect GM composition, it is crucial to
consider variables such as patient age, diet, origin, and
temporal uctuations, including seasonal and circadian
variations. For instance, to prevent circadian variations in
the microbiota, fecal samples should ideally be collected
from each patient at a consistent time of day (morning or
evening). Similarly, because seasonal dierences aect the
microbial composition, investigations conducted in the
winter should be compared only to those conducted under
similar seasonal conditions.
Further research is needed to evaluate GM alterations
aer newly developed drug treatments or bariatric surgery,
especially involving patients who experience weight
regain. ese studies should take into account the host’s
environment, initial microbiota composition, and its role
in metabolic regulation. In addition, personalized medicine
should be considered as a solution for modulating GM, with
the goal of designing tailored probiotics for each patient to
prevent and treat obesity and its associated health eects.
Acknowledgments
None.
Funding
e authors would like to thank the Moroccan Ministry of
Higher Education, Scientic Research and Innovation, as
well as the OCP Foundation for funding this work through
the APRD Research Program. Dr.Siham El Moussaoui was
awarded a scholarship from Mohammed VI Polytechnic
University of Benguerir during the preparation of this
literature review. e scholarship provided nancial
support throughout the 3-year duration of the doctoral
studies, enabling the execution of the content or
interpretation of this review.
Volume X Issue X (2025) 14 doi: 10.36922/ejmo.8318
Gut microbiome eects on obesity
Eurasian Journal of
Medicine and Oncology
Conict of interest
e authors declare that they have no competing interests.
Author contributions
Conceptualization: Siham El Moussaoui, Touria Derkaoui,
Amina Barakat, Naima Ghailani Nourouti
Supervision: Mohcine Bennani Mechita
Writing–original dra: Siham El Moussaoui
Writing–review & editing: Touria Derkaoui, Fatima Zahrae
Alaoui Ismaili, Nezha Tawq, Mohammed El Mzibri,
Abdelilah Laraqui, Mohamed Mansouri, Maria Paz
Weisshaar
Ethics approval and consent to participate
e study was approved by the Ethics Committee of the
University Hospital in Tangier registered under number
AC13FV/2023.
Consent for publication
Not applicable.
Availability of data
Not applicable.
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