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V. BaradaranRahimi and V. R. Askari
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Herbal Medicines fortheManagement
https://t.me/medicina_free
ofIrritable Bowel Syndrome
andConstipation Problem
EswaraRaoPuppala, NeethuPrasad, MeenakshiSingh,
ArunN.Prakash, MdAbubakar, PriyankaAdhikari,
andV.G.M.Naidu
Abstract
Irritable bowel syndrome (IBS) is a serious digestive
disorder, which is mainly of two forms ulcerative colitis
(UC) and Crohn’s disease (CD). IBS is characterised by
abdominal pain, bloating, diarrhoea, and constipation
periods. Among these constipation is accompanied by a
number of bowel symptoms including difculty passing
stool, hard stool, and inadequate evacuation sensations.
Although the aetiology is unknown, it is widely thought
that diet and microbiota contribute to the development
of IBS. By targeting the various aetiological factors,
medical treatment aims to control the symptoms. Due to
the multifactorial causes of these disorders, unimpressive results from conventional IBS medications, the
economic burden for patients and pharmacologic
effects, the treatment of IBS and constipation is challenging and the use of complementary and alternative
medicines, especially herbal therapies is increasing.
Complementary and alternative medicines (CAM) for
IBS and related disorders include hypnosis, acupuncture, cognitive behaviour therapy, yoga, faecal microbiota transplantation, and nutritional supplementation
with probiotics, prebiotics, and herbal medicine. The
practice of prescribing herbal medications for a variety
of gastrointestinal disorders has a long history in various parts of the world. Herbal medications have the
potential to target multiple organs and have exhibited
efcacy for UC and CD in experimental models and
clinical trials by maintaining the epithelial integrity
barrier, regulating macrophage activation, and modulating the immune response. In this chapter, the author
investigates the efcacy of herbal medicines in the management of irritable bowel syndrome, constipation, and
related disorders.
Keywords
Lifestyle diseases · Constipation · Herbal medicines
Eswara Rao Puppala and Neethu Prasad contributed equally with all
other contributors.
E. R. Puppala · P. Adhikari
University of Maryland, School of Medicine, Marlene and Stewart
Greenebaum Comprehensive Cancer Center,
Baltimore, Maryland, USA
N. Prasad · A. N. Prakash · V. G. M. Naidu (*)
Department of Pharmacology and Toxicology, National Institute of
Pharmaceutical and Research (NIPER)-Guwahati,
Guwahati, Assam, India
e-mail: vgmnaidu@niperguwahati.ac.in
M. Singh
Centre for GMP Extraction Facility, Sponsored by Department of
Biotechnology, National Institute of Pharmaceutical Education and
Research (NIPER)-Guwahati, Guwahati, Assam, India
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
A. K. Dhara, S. C. Mandal (eds.), Role of Herbal Medicines, https://doi.org/10.1007/978-981-99-7703-1_16
M. Abubakar
Department of Pharmacology and Toxicology, National Institute of
Pharmaceutical and Research (NIPER)-Guwahati,
Guwahati, Assam, India
Department of Pharmacology and Toxicology, National Institute of
Pharmaceutical Education and Research (NIPER)-Hajipur,
Hajipur, Bihar, India
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Abbreviations
ATF4 Activating transcription factor 4
ATG5 Autophagy related 5
Bcl-2 B-cell lymphoma 2
CAM Complementary and alternative medicine
CAT Catalase
CCR2 C-C chemokine receptor type 2
CD Crohn’s disease
CD4 Clusters of differentiation 4
CDX-2 Caudal Type Homeobox 2
CHOP C/EBP homologous protein
CINC-3 Cytokine-induced neutrophil chemoattrac-
tant 3
COX2 Cyclooxygenase-2
DAI Disease activity index
DAPI 4′,6-Diamidino-2-phenylindole
DCFDA 2′,7′-Dichlorouorescein diacetate
DIM Diindolylmethane
DSS Dextran sodium sulphate
DSS Dextran sulfate sodium
FFAs Free fatty acids
FOXP3 Forkhead box P3
GBF Germinated barley foodstuff
GLUT1 Glucose transporter 1
GOS Glucooligosaccharide
GSH Glutathione
GSH/GSH-Px Glutathione peroxidase
GSH-Rd Glutathione reductase
GSK-3 Glycogen synthase kinase 3
H&E Haematoxylin–eosin
H3K9me3 Histone 3 lysine 9 trimethylation
HO-1 Haeme oxygenase-1
HP Haptoglobin
IBD Inammatory bowel disease
ICAM-1 Colonic intercellular adhesion molecule-1
IFN-γ Interferon gamma
IgA Immunoglobulin A
IL-1β Interleukin 1 beta
IL-6 Interleukin 6
ISAPP International Scientic Association for
Probiotics and Prebiotics
JNK c-Jun NH2-terminal kinase
JNKs c-Jun N-terminal kinases
LPS Lipopolysaccharide
MCP-1 Monocyte chemoattractant protein-1
MD Molecular dynamics
MDA Malondialdehyde
MIP-2 Macrophage inammatory protein
MLNs Mesentric lymph nodes
MMPs Matrix metalloproteases
MPO Myeloperoxidase
mRNA Messenger RNA
Msi-1 Musashi RNA binding protein 1
mTOR Mammalian target of rapamycin
MyD88 Myeloid differentiation primary response
88
NCI National Cancer Institute
NF-κB Nuclear factor kappa-light-chain-enhancer
of activated B cells
NO Nitric oxide
Nrf2 Nuclear factor erythroid 2-related factor 2
PAR2 Protease activated receptor 2
PERK Protein kinase R-like endoplasmic reticu-
lum kinase
PGE2 Prostaglandin E2
PHF Poly herbal formulation
PI3k Phosphatidylinositol 3-kinase
PKB Protein kinase B
p-NF-κB Phosphorylated nuclear factor kappa-light-
chain-enhancer of activated B cells
QRZSLXF Qing Re Zao Shi Liang Xue receipt
RIPA Radio-immunoprecipitation assay
RORγ RAR-related orphan receptor gamma
ROS Reactive oxygen species
SCFA Short chain fatty acids
SHD Sanhuangshu’ai decoction
SIRT1 Sirtuin 1
smad Suppressor of mothers against
decapentaplegic
SOC-1 Suppressor of cytokine signalling 1
SOD Superoxide dismutase
STAT Signal transducer and activator of
transcription
TBARS Thiobarbituric acid reactive substances
TF Transcription factor
Th1 Type 1 T helper
Th17 Type 17 T helper
TNBS Trinitrobenzene sulphonic acid
TNF-α Tumor necrosis factor alpha
UC Ulcerative colitis
ULK Unc-51-like kinase 1
Wnt Wingless-related integration site
ZO-1 Zonula occludens
ZWBQD Zhen-Wu-Bu-Qi Decoction.
1 Introduction
Inammatory bowel syndrome (IBS) or inammatory bowel
disease (IBD) is a chronic relapsing inammation of the gastrointestinal tract (GIT) resulting from a dysregulated
immune response and was initially reported as a rare case in
the Western world. Since then, their numbers and geographic
distribution have progressively grown, and they are now recognised on a global scale. Wilks described ulcerative colitis
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(UC) as a distinct pathological condition along with Moxon
in 1875. Later, Dr. Crohn and two colleagues submitted an
essay on the disorder “Terminal Ileitis” to the American
Medical Association in May 1932, in which they detailed the
symptoms of Crohn’s disease (CD) [1]. These two main
types of IBD share similar pathogenesis and both are characterised by a protracted inammatory state. However, they
differ considerably in characteristics such as location, the
involvement of layers in the intestine, and clinical complications [2].
In UC, mucosal inammation with ulceration extends
continuously from the rectum to the proximal part of the
colon and the main symptoms include bloody diarrhoea,
abdominal pain, urgency, rectal bleeding, fever, and tenesmus [3]. The sub-acute stage of the disease is marked by
mural thickening and luminal narrowing. Chronic UC is
characterised by rectal constriction and broadening of the
presacral region. On the other hand, any part of the digestive
system can be damaged by Crohn’s disease, but the proximal
colon and terminal ileum are the most frequently affected [4]
(see Fig.1). Focused inammation, aphthoid ulceration, and
nearby cobble-stoning are the hallmarks of the acute Crohn’s
disease. The chronic phase of CD is accompanied by transmural brosis and cicatrisation along with perianal disease
in most of the patients. Like UC, patients might go through
periods of are-ups and remission with symptoms such as
abdominal pain, diarrhoea, fever, anal ssures, and rectal
bleeding [5].
The intestinal epithelium functions as a barrier to prevent
the inversion of antigens. The defective regulation of tight
junctions increases permeability and thereby the uptake of
antigens causes inammation as an immuno-protective
mechanism [6]. The aetiology of IBD is still poorly known.
Many factors, including genetic, immunological, gut microbiome, and environmental including nutrition, stress, and
free radicals, may contribute to the onset of IBD [7]. An
irregular immune system increases the production of cyto-
kines and chemokines that activate cellular or humoral
responses and exacerbate IBD progression by disrupting
homeostasis and persistently stimulating the local immune
response in the intestine [8]. Generally, the gut immune system maintains a commensal relationship with the microbiome and shows tolerance to dietary antigens. However,
aberrant immunological reactions to commensal nonpathogenic microorganisms lead to dysbiosis in the GIT. In
IBD pathogenesis environmental factors play an important
inuence that is one of the least understood and most challenging to address. Based on the proportionally rising incidence of IBD in the industrialised nations and the emergence
of new feeding behaviours in these regions over the past few
decades, numerous studies have emphasised the probable
aetiological role played by the diet [9].
IBD was previously widely reported in Europe, North
America, and Australia. But now it has a much wider geographic distribution and is becoming more common even in
nations that were previously thought to be low-risk zones.
Two population-based studies in Haryana and Punjab of
India reported a prevalence rate of 42.8/100,000 and
44.3/100,000 [10]. Additionally, hospital-based studies indicated a higher incidence of IBD in the southern states of
India. Urbanisation, nutritional shifts such as the
Westernisation of the Indian cuisine, improvements in environmental and hygienic conditions, as well as underlying
genetic predispositions have all certainly contributed to a
rise in the incidence of IBD.One modelling study from Iran
predicted a 1.5-fold increase in prevalence for East Asia with
4.5 million cases of IBD and quadrupling of the occurrence
for India with 2.2 million cases of IBD in 2035, as compared
to 2020 [11].
Regrettably, there is little hope for a complete cure for CD
and UC either through medical nor surgical treatment.
Approximately 10–20% patients experience relapses and
recurring symptoms. Medical treatment mostly addresses
symptoms of IBD and aims to treat abdominal pain; infec-
Fig. 1 Schematic
representation showing the
differences between the two
main forms of inammatory
bowel disease (IBD), Crohn’s
disease, and ulcerative colitis,
in terms of their location and
the pattern of the affected
areas (red-coloured) in the
gastrointestinal tract (GIT)
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tion; diarrhoea; and deciencies in proteins, electrolytes, and
vitamins. Medical treatments in allopathic medicine include
intestinal antibiotics, anti-diarrhoea medications, steroids,
immunomodulatory medicines, and surgery [12]. However,
these treatments merely manage the disease’s episodes; they
do not provide long-term treatment. Additionally, a number
of adverse effects are there for these modern drugs. Steroids
can damage CNS and can produce diseases like cardiovascular disease, infertility, renal disease, and liver disease. Long
intake of antibiotics has detrimental consequences on the
digestive system. Surgery can be performed to treat complications rather than to treat the disease and relapse is still a
possibility even after surgery [13].
In the modern era, Ayurveda is a good IBD therapy option.
As per Ayurveda, Crohn’s disease is specically considered
as ‟Vatikagrahani” and ulcerative colitis as ‟PittajaGrahani”.
According to Ayurveda, perfect health exists when the three
basic energies (doshas: Vata, Pitta, and Kapha) are in harmony [14]. The underlying cause of IBD lies within the process of digestion, supported by a healthy lifestyle and right
quantity of food [15]. Ayurveda treatment is essential and
has been shown to be successful in alleviating the symptoms
of IBD.Ayurveda uses both allopathic and ayurvedic criteria
to assess the severity of the IBD condition. Internal medications (ShamanaChikitsa), Panchakarma therapy
(ShodanaChikitsa), dietary restrictions, and lifestyle changes
are all part of the treatment. Panchakarma therapy is crucial
in more severe cases as it swiftly detoxies and regenerates
the digestive system, reduces inammation, ceases rectal
bleeding, and cures ulcerations [16]. Overall health and
digestion of the patients are improved by several herbal treatments, which also help to keep these conditions under control. There are several plants, including Bilva (Aegle
marmelos), Vacha (Acorus calamus), Giloy (Tinospora cor-
difolia), Vaividang (Emblicaribes), Mulethi (Liquorice root),
Daruharidra (Berberis aristata), Kutaj (Holarrhena antidysenterica), and Mustak (Cyperus rotundus) that have anti-
inammatory, anti-microbial, and anti-oxidant properties
[14]. Thus, lifestyle management through the use of mindfulness techniques promotes overall health once the disease has
been put into remission by taking these herbal medicines
[17].
Constipation is another very common medical condition
worldwide, negatively affecting patient’s quality of life and
health-care system. It is accompanied by nausea, anorexia,
and discomfort. Moreover, it may result in extra-intestinal
symptoms such as headaches, bad breath, restlessness, and
confusion. Collectively, these symptoms signicantly lower
the patients’ quality of life. It is reported that 12–19% of
Americans and 14% of Asians suffer from constipation, with
symptoms varying by geographic location. Pharmacologic
agents for constipation include mainly laxatives, but many
patients are dissatised with these due to ineffectiveness,
inconsistent results, and safety-related or adverse-effect concerns and are interested in other treatment options and complementary/alternative therapies. Three often used herbal
remedies for achieving regular bowel movements are rhubarb, senna leaf, and aloe. In addition, rhubarb is a signicant component of MaZiRenWan, a Chinese medicine
formulation occasionally used in eastern nations to treat
constipation.
2 Unravelling theAetiopathogenesis
Even though the exact pathogenesis of IBS remains obscure,
it is generally believed that the disease is caused by crosstalk between the host immune system and the gut microbiota,
along with genetic predisposition, environmental factors,
and socio-economic development. The causes of constipation are mainly three: lifestyle related, disease related, and
drug induced. A diet low in both soluble and insoluble bre,
inadequate daily intake of uids, lack of physical activity,
routine changes, age, and certain drugs are all common
causes of constipation. Research on the pathogenesis of IBS
and constipation has increasingly relied on the gut microbiota in the past few decades [18]. It should be noted that several IBS drugs, especially antibiotics have been suspected of
affecting either the metabolic stability of intestinal cells or
the metabolism of gut microbiota. Numerous investigations
have revealed alterations in the gut ora in patients having
CD, UC, and constipation demonstrating the momentous
role of gut microbiota in intestinal homeostasis [7].
2.1 A Healthy Gut Microbiota andIts Role
The “gut microbiota”, a population of more than 100 trillion
microorganisms comprising bacteria, virus, archaea, and
eukaryote that inhabit the GI tract has a signicant impact on
the shaping and maturation of the immune system [19]. The
majority of the GI tract is composed of bacteria, both useful
bacteria “commensals” and opportunistic harmful bacteria
“pathobionts” [20]. The prevailing consensus is that the
development of the microbiota is a lifetime process that
begins at birth and changes erratically with age and in
response to environmental changes. Additionally, each person’s pace of change in the composition of the microbial
population differs and there is no one-size-ts-all recipe for
a healthy microbiome [21].
majority of the healthy gut microbiota, followed by the phyla
Actinobacteria, Proteobacteria, Fusobacteria, and
Verrucomicrobia [22]. While virome primarily resides in the
ofIBS andConstipation
inHuman Health
Altogether, Firmicutes and Bacteroidetes make up the
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form of bacteriophages, the most frequent fungal genera that
cohabit with bacteria in the gut are Aspergillus, Bullera,
Candida, Galactomyces, Penicillium, Pleospora,
Rhodotorula, Sclerotinia, Saccharomyces, and Trametes.
Nearly 96% of healthy people possess archaea mainly,
Methanobrevibacter smithii in their GI microbiota, which
generates methane from the hydrogen produced by bacterial
catabolism [23].
The gut microbiota delivers a number of promising benets to the host, among which the most signicant roles in
maintaining the integrity of the mucosal barrier, supplying
nutrients like vitamins, and mitigation of infections [24]. Gut
bacteria involves in the breakdown and absorption of bile
acids, urea, sterols, essential vitamins, xenobiotics, plantbased polysaccharides, and some amino acids [25]. The subsequent metabolites are SCFAs like propionate, butyrate, and
acetate which regulate functions including altering interstitial epithelial cell signalling, gene expression, chemotaxis,
differentiation, proliferation, and apoptosis. Firmicutes are
involved in butyrate production and Bacteroidetes phylum
can produce propionate [26]. Butyrate, a primary energy
source for colon epithelial cells and a regulator of mucin
secretion, helps to maintain intestinal homeostasis, by keeping the integrity of the intestinal epithelial barrier and controlling the immunological response. Acetate and propionate,
on the other hand, serve as substrates for the processes of
lipogenesis and gluconeogenesis [27]. The GI microbiota is
also vital for the de novo synthesis of essential vitamins
which the host is unable to generate, such as riboavin, vitamin K, biotin, nicotinic acid, pyridoxine, pantothenic acid,
and thiamine [28]. Vitamin B12 is mostly produced by lactic
acid bacteria, and folate, a vitamin essential for the creation
and repair of host DNA, is primarily produced by bidobacteria [19]. Gut microbiota interacts with innate immunity and
adaptive immunity in an extensive bidirectional manner and
the interaction site is the intestinal barrier which requires the
interplay of multiple components: interstitial epithelial cells
(IECs), the gut microbiota, and mucosal and submucosal
immune cells [29]. IECs serve as innate immunity mediators
under normal physiological circumstances. IECs express
cell-surface and intracellular pattern recognition receptors
such as toll-like receptors (TLRs) and NOD-like receptors,
respectively, just like other cell types. Intestinal homeostasis
depends on the immune response, which is activated as a
result of gut microorganisms stimulating PRRs [30].
2.2 Gut Microbiota Dysbiosis inIBS
andRelated Disorders
Numerous studies have revealed the fact that many risk variables for IBS contribute to the host–microbe interactions that
lead to the severe imbalance of gut microbiota which is a key
feature of IBS (i.e. dysbiosis) [31]. Dysbiosis occurs when
the microbiota is unable to provide the host with all of its
advantageous traits. Usually, various factors can contribute
to inammation in IBS. The imbalance of commensal to
pathogenic microbiota may cause an excessive amount of
pro-inammatory chemicals to be produced, which exacerbates intestinal inammation [7, 32] (Fig.2).
The gut microbiota of IBS patients exhibits decreased
microbial diversity, less prevalence of the Firmicutes phylum, particularly F. prausnitzii, one of the most prominent
bacterial species in the GI tract, and decreased abundance of
Bacteroidetes phylum [7]. A decreased population of mucolytic bacteria such as Akkermansiamuciniphila increaseingthe abundance of mucin-degrading bacteria such as
Ruminococcusgnavus and decreasing the presence of butyrate producers (e.g. Blautia, Lachnospiraceae, Roseburia,
and Eubacterium rectale) were also observed in CD and UC
patients [33]. Distortions in the epithelial barrier’s integrity
can enhance the uptake of luminal antigens, which in turn
can cause inammation. Additionally, IBS may be brought
on by a decrease in mucin production driven by the destruction of goblet cells and malfunctioning of epithelial cell tight
junctions [6]. This supports the key role of dysbiosis in IBS
development. Recent studies have found that germ-free mice
(decient in the gut microbiota) which received intestinal
microbiota transplantation from IBS individuals exhibit an
exacerbation in the severity of colitis induction compared
with the healthy population [34]. Even though it is proven
that faecal microbiota transplantation effectively treats IBS,
its safety is yet unknown. Variations in nutrient sources, oxygen levels, luminal pH, and the proliferation of different bacterial species can all be altered by inammation and have an
impact on the bacterial population’s equilibrium [35]. The
representative gut microbiota alterations and interactions
with host cells seen in IBS patients are listed in Table1.
2.3 Association ofPathobionts andPRRs
inIBS
Pathobionts are bacteria that are typically present in the
intestines but can become pathogenic when certain endogenous and exogenous triggers alter the gut microbiota’s function in the emergence of pathological diseases. Virulent E.
coli strains, Helicobacter species, Klebsiella species,
Campylobacter concisus, and Vancomycin-resistant
Enterococcus faecalis are some of the pathobionts. By dis-
rupting the intestinal barrier and regulating inammatory
reactions, these bacteria promote inammation [32].
Intestinal epithelial cells are involved in pathobiont interactions, which can be direct (via adhesion and translocation)
or indirect (by the modication of epithelial cell activities).
Pathobionts can also interfere with the proper growth and
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Fig. 2 Dysbiotic interaction in IBS and related disorders. In healthy
state, commensal bacteria performs functions which are benecial to
the host. To maintain the homeostasis of the intestinal tract, certain bacteria produce SCFAs like butyrate. The intact mucus layer and antimicrobial peptides produced by paneth cells stop bacteria from penetrating
the epithelial layer. SCFAs help in maintaining the epithelial barrier,
and also promote the production of anti-inammatory cytokines
through facilitating the regulatory T cells (Treg) and effector T cells
(Teff). Contrarily, in IBS patients, the decrease in commensal bacteria,
including those that produce SCFAs, leads to imbalance of Treg and
Teff cells which further increases the production of pro-inammatory
function of intestinal epithelial cells. For instance, pathobionts like Enterobacteriaceae faecalis can adhere to and
move through monolayers of epithelial cells, while C. conci-
sus can cause apoptosis in the same monolayers of epithelial
cells. In addition, pathobionts may continue to trigger inammation long after infection by increasing pro-inammatory
signalling in intestinal epithelial cells which might result in
dysbiosis and colitis. C. difcile is one of the notable pathobionts which is associated with nosocomial infections that
induce mild to severe pseudomembranous colitis. Usually, a
healthy microbiome offers resistance against C. difcile
pathogenicity [51]. However, a dysbiotic microbiota is what
fuels the growth of this bacteria and ensuing disease pathology. The pathogenesis of C. difcile pathobionts begins with
the germination of its spores into vegetative cells, which
multiply in the GI tract and release toxins that break the
intestinal epithelial barrier to cause severe pseudomembranous colitis [52]. IBS-associated E. coli is also a signicant
factor in the aetiology of IBS and may contribute to disease
relapses in IBS patients [53]. Pathobiont bacteria suppress
cytokines. As a result, the mucosal layer is disrupted resulting in the
invasion of bacteria. The mucosal layer is then damaged, allowing bacteria to invade and prompting an inammatory cascade to combat the
invasive bacteria. Moreover, pathobionts and commensal bacteria that
could exhibit pathogenic traits under the appropriate circumstances,
arise and proliferate in inammatory conditions. As a result, the modied pathobionts survive, further limiting the growth of commensal
organisms. The reduction of commensals, the growth of pathobionts,
and an imbalance in immune regulation lead to a chronic inammatory
condition
the expression of tight junction proteins and enhance
mislocalisation, cause dysregulation of apoptosis and proliferation, and enhance ER stress and pro-inammatory signalling. These effects result in the development of dysbiosis and
facilitate inammatory signalling following infection. In
contrast, commensal bacteria provide mucosal health by
enhancing mucin and IgA secretion, bolstering barrier integrity, pro-inammatory responses and apoptosis, and facilitating commensal colonisation. These actions prolong
inammatory signalling after infection and aid in the development of symbiosis [54].
Pattern recognition receptors such as toll-like receptors
(TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors are capable of detecting a wide variety of microbes and
their metabolites and can exert both pro- and antiinammatory actions. During infections, cells express these
PRRs more intensely and produce more pro-inammatory
mediators. PRRs can activate specic T-cell phenotypes; for
example, few Clostridia strains can activate Tregs in colonic
mucosa and thereby protect from colitis examples include
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Table 1 Dysbiosis and its interaction in IBS and related disorders
Changes
Gut microbiota
Firmicutes
Clostridioides
difcile
Eubacterium spp.
Faecalibacterium
prausnitzii
Listeria
monocytogenes
Roseburia
intestinalis
Ruminococcus
albus
Ruminococcus
gnavus
Bacteroidetes
Bacteroidetes spp.
Verrucomicrobia
Akkermansia
muciniphila
Actinobacteria
Bidobacterium
bidum
Eggerthella lenta
Mycobacterium
avium
Atopobium
parvulum
Proteobacteria
Campylobacter
spp.
Eikenella
corrodens
Escherichia coli
Haemophilus
parainuenzae
Fusobacteria
Fusobacterium
nucleatum
in IBS Mechanisms Evidence References
↑
↓
↓
↑
↓
↓
↓
↑
↓
↓
↑
↑
↑
↑
↑
↑
↑
↑
Toxins released by this bacteria can activate
pro-inammatory cytokines and can cause
epithelial barrier damage
Produce butyrate and is essential in maintaining the
epithelial barrier integrity
Highly active metabolic commensal bacteria that
contributes to the production of butyrate which is
essential for the anti-inammatory activity,
maintenance of homeostasis of barrier function,
and immune responses
Cause epithelial cell infection High infection rates in IBS patients [39]
Protect colonic mucosa
Produce butyrate
Produce SCFAs and have anti-inammatory
actions
Involved in bile and amino-acid biosynthesis
pathways
Production of propionate and damages the mucin
layer
Production of SCFAs and activate the number of T
cells in colon
Strengthen epithelial barrier function by enhancing
the mucin production
Lack of possible mechanism More prevalence in IBS patients [46]
Increased production of pro-inammatory
cytokines
Induction of colitis and mitochondrial dysfunction
in IBS
Can survive even in anaerobic conditions in IBS Increased in IBS patients [49]
Involved in pro-inammatory response Increased in IBS patients [42]
Damage intestinal epithelial cells monolayers High abundance in colonic and ileal
Promote inammation in IBS Increased in stool of IBS patients [42]
Involved in damaging mucus layer Increased in CD samples [49]
High levels of C. difcile in IBS patients [36]
Low prevalence in CD and UC patients [37]
Low F. prausnitzii levels may be indicative
of CD and IBS.Surgery patients with IBS
who have low F. prausnitzii levels are more
likely to experience post-operative
recurrence
Decreased in CD/UC patients [40]
Decreased in IBS patients’ samples [41]
Decreased in CD patient stool samples [42]
Increased in CD patients’ samples [43]
Less prevalence in stool of both CD and
UC patients
Decreased levels in IBS patients. Also, few
studies reveal that treatment with
probiotics which contain this bacterium
can show positive response in IBS
High abundance in IBS patients [47]
Increased in CD patients [48]
mucosa of IBS patients
319
[38]
[44]
[45]
[50]
MAMPs, PAMPs, and DAMPs. While NOD-like receptors
(NLRs) and RIG-I-like receptors are found in the cytoplasm,
TLRs and CLRs are found on the surface of immune cells,
epithelial cells, and other cell types. PRRs are generally
expressed at greater levels in colonic epithelia and regulating
PRR responses is essential to achieving improved clinical
outcomes in IBS [32].
2.4 Diet–Microbiota Interaction inIBS
andRelated Disorders
Diet, gut microbiota, colonocytes, and immune cells are intimately associated during both the intestinal healthy conditions and inammatory state. The composition of microbiota
is dynamic, uctuating with age and environmental factors
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