Moderate Continuous Versus High Interval Intensity Training on Gut Dysbiosis and Glucagon Like Peptide Hormone in Irritable Bowel Syndrome
Phase: NA
Conditions: Irritable Bowel Syndrome, Obesity, Dysbiosis
Sponsor: Cairo University

MODERATE CONTINOUS VERSUS HIGH INTERVAL 
INTENSITY TRAINING ON GUT DYSBIOSIS AND 
GLUCAGON LIKE PEPTIDE HORMONE IN 
IRRITABLE BOWEL SYNDROME 
 
 
 
 
BY 
MARWA SAEED MOHAMED 
  
 
 
 
 
 
 
 
 
 
 
Submitted in Partial Fulfillment for the Requirements of Doctoral Degree in 
Physical Therapy, Department of Physical Therapy for  
Cardiovascular/Respiratory Disorder and Geriatrics 
Faculty of Physical Therapy 
Cairo University 
30th November 2022 
 
NCT06408610 

 
 
 
SUPERVISORS 
 
 
Prof. Dr. NESREEN GHAREEB EL NAHAS 
Professor and Head of Department of Physical therapy for 
Cardiovascular/ Respiratory Disorder and Geriatrics  
Faculty of Physical Therapy  
Cairo University 
Prof. Dr. GHADA ZAGHLOUL ABBASS 
Professor of Biochemistry and  Head  
of Food science Department  
National Nutrition  
Institute  
  
Prof. Dr. REHAM ASSEM ZEYADA 
Associate Professor of Clinical and Chemical Pathology  
Faculty of Medicine  
Cairo University 
 
Dr. DONIA MOHAMED EL-MASRY 
Lecturer of Physical Therapy for Cardiovascular/  
Respiratory Disorder and Geriatrics  
Faculty of Physical Therapy  
Cairo University 

 
1 
 
CHAPTER 1 
INTRODUCTION 
Trillions of microorganisms live inside every human being; The 
gastrointestinal tract is home to vast microbial communities known as gut 
microbiota which includes bacteria, fungi, archaea, and viruses. The homeostatic 
balance of gut microbiota is beneficial to the host as it acts as a gatekeeper to 
protect epithelial cell integrity from penetration and disease caused by pathogens. 
Other beneficial effects of gut microbiota include micronutrient production, such 
as vitamin K and folate (Singh et al.,2021). 
Colonic bacteria ferment unabsorbed carbohydrates to short-chain fatty acids 
(SCFAs), which can be subsequently absorbed through the colonic mucosa and 
used as an additional energy source (Koh et al., 2016). 
The main products of the bacterial fermentation of carbohydrates and 
proteins, under anaerobic conditions of the large intestine, are short chain fatty 
acids (SCFAs). SCFAs such as acetate, propionate, butyrate, are secreted in the gut 
lumen and their signaling to the multiple gut receptors which are implicated in the 
control of anorectic gut satiety hormones such as glucagon like peptide GLP-1 
(Koh et al., 2016). 
The imbalance in the microbial equilibrium is termed “dysbiosis”, which has 
been further defined as a disturbance to gut microbiota homeostasis due to an 
imbalance in the bacteria itself, changes in their functional composition and 
metabolic activities. Dysbiosis has been implicated in a wide range of diseases 
including irritable bowel syndrome (IBS) (DeGruttola et al.,2016). 
Gut dysbiosis, plays a fundamental role in the pathogenesis of IBS. It was 
found in IBS patients that gastrointestinal dysbiosis associated with visceral 

 
2 
 
hypersensitivity, increased gut permeability, mucosal immune activation, chronic 
inflammation, chronic fatigue, anxiety, and depression (Wang et al.,2020). 
Irritable bowel syndrome (IBS) is a common functional gastrointestinal 
disorder, with signs and symptoms including cramping, abdominal pain, bloating, 
gas, and diarrhea or constipation, or both (Gupta and Maity, 2021). 
Patients with IBS have shown success with dietary interventions; 
specifically 
limiting 
short-chain 
carbohydrates 
known 
as 
fermentable 
oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP). These 
carbohydrates have shown to be slowly absorbed and highly fermentable, which 
contributes to the gastrointestinal symptoms. Restriction of FODMAPs has been 
shown to improve symptoms in 70% of patients with IBS. Diet modifications and 
exercise combined showed a significant positive improvement in irritable bowel 
syndrome. (Sharaf et al.,2021). 
Exercise is a well-established way to alleviate constipation, distension and 
also for maintaining proper bowel function and reducing stresses. Physical activity 
improves colonic transit time, gas transit, and bloating by stimulating 
gastrointestinal motility and most importantly it is becoming more accepted as a 
safer and effective treatment for irritable bowel syndrome (Song et al.,2018).  
Exercise can determine changes in the gut microbial composition playing a 
positive role in energy homeostasis and regulation. Low intensity exercise can 
influence the gastrointestinal tract reducing the transient stool time and thus the 
contact time between the pathogens and the gastrointestinal mucus layer . As a 
consequence, it seems that exercise has protective effects, reducing the risk of 
colon cancer and inflammatory bowel disease (Monda et al.,2017). 

 
3 
 
Moderate aerobic exercise affects the intestinal system mainly through gut 
immune function, gut barrier integrity, as well as gut motility, intestinal pH and gut 
hormones release; and bile acids metabolism within enterohepatic circulation 
(Resende et al., 2021). 
Also High-intensity interval training is a popular, time-efficient mode of 
exercise to improve metabolic health and aerobic fitness, both of which have been 
associated with healthier gut bacterial community structure (Rettedal et al., 2020). 
Statement of the Problem:  
Is there a significant difference between the effect of moderate continuous 
versus high interval intensity training on gut dysbiosis and glucagon like peptide 
hormone in irritable bowel syndrome? 
The Purpose of the Study:  
To compare the effect of moderate continuous versus high interval intensity 
training on gut dysbiosis and glucagon like peptide hormone in irritable bowel 
syndrome. 
Significance of the Study:  
Irritable bowel syndrome affects around 11% of the global population with 
variation by geographic region: the highest in South America (21.0%) and the 
lowest occurring in South Asia (7.0%). In Egypt, the prevalence was 34% in 
primary healthcare center attendees. IBS significantly reduces work productivity 
and health-related quality of life (Mohamed et al.,2021). 
The quality of life for patients suffering from IBS is greatly affected 
physically, psychologically, and economically. Several cases reported difficulties 
in concentration, decreased energy level, and lower self-esteem. In-addition IBS is 

 
4 
 
inducing occupational hazards as it affects the performance of patients at their jobs 
(Elsayed et al.,2021). 
Although half of the cases referred to gastroenterologists is due to IBS, no 
clear etiology was found; however, some researches revealed that certain factors 
such as psychological factors, dietary habits, and exercise level were related to IBS 
onset and course (Elhosseiny et al.,2019). 
Previous studies have been done separately on the effect of moderate 
intensity continuous training program and high intensity interval training on 
irritable bowel syndrome and gut dysbiosis, it is rational to compare between two 
training programs to know which is more effective to improve gut microbiota 
balance. 
Delimitations:  
This study will be delimited to the following aspects:  
Subjects will be delimited to patients with irritable bowel syndrome selected 
from the outpatient of national nutrition institute with the following criteria: 
 Sixty six patients with irritable bowel syndrome of both genders. 
 Their ages ranged from 20 to 45 years. 
 Their Body mass index ranged from 30 to 34.9. 
 Patients will be divided into 3 groups  
o Group A: Patients will receive moderate intensity continues training 
exercise 
program 
along 
with 
following 
Low 
fermentable, 
oligosaccharides, disaccharides, monosaccharides and polysaccharides 
diet plan (FODMAPs diet). 
o Group B: Patient will receive high intensity interval training exercise 
program along with following FODMAP diet plan.  

 
5 
 
o Group C: Patients will follow FODMAP diet plan only.  
 Patients will be excluded if: 
o - Uncontrolled hypertension  
o - Gastrointestinal bleeding 
o - Colorectal cancer or any terminal diseases  
o - Communication disorders  
Basic Assumptions:  
It will be assumed that:  
1) The primary medical assessment will be done to every participating patient 
who includes:  
2) Complete medical history (personal, present and past) 
3) All patients will stick to the program and will follow instructions. 
4) All other factors which may influence the outcome such as noise and 
distraction will be controlled.  
Hypothesis:  
It will be hypothesized that there will be no significant difference between 
the moderate continuous versus high interval intensity training on gut dysbiosis 
and glucagon like peptide hormone in irritable bowel syndrome. 
 
 

 
6 
 
CHAPTER II 
REVIEW OF LITERATURE 
The human gastrointestinal (GI) tract represents one of the largest organ 
between the host, environmental factors and antigens in the human body. In an 
average life time, around 60 tonnes of food pass through the human GI tract, along 
with an abundance of microorganisms from the environment which impose a huge 
threat on gut integrity. The collection of bacteria, archaea and eukarya colonising 
the GI tract is termed the ‘gut microbiota’ and has co-evolved with the host over 
thousands of years to form an intricate and mutually beneficial relationship 
(Thursby and Juge,2017). 
The gut microbiota enjoys a mutualistic relationship with the host, 
harvesting additional energy and nutrients from the diet and protecting the host 
from pathogens. The resident bacteria produce a wide range of metabolites and 
chemicals that influence host function and these include short-chain fatty acids 
such as butyrate, which is essential for the integrity of the colonic epithelium. 
However, there is potential for these mechanisms to be disrupted as a result of an 
altered microbial composition, known as dysbiosis (Lin and Zhang,2017). 
Human Gut dysbiosis is linked to many pathologic conditions disturbing the 
energy metabolism; such as obesity and atherosclerosis. The microbiota in the 
human gut is mostly composed of bacterial phyla: Firmicutes and Bacteroidetes 
(Thursby and Juge,2017). 
Firmicutes bacteria are Gram-positive one. It plays a key role in the nutrition 
and metabolism of the host through SCFA synthesis. Through their metabolic 
products, Firmicutes bacteria are indirectly connected with other tissues and organs 
and regulate hunger and satiety. In contrast, Bacteroidetes bacteria are Gram 
negative and associated with immunomodulation. Increased or decreased 

 
7 
 
Firmicutes / Bacteroidetes (F/B) ratio are associated with the development of 
obesity or irritable bowel disease (IBD) (Stojanov et al.,2020). 
Short-chain fatty acids (SCFAs), the primary metabolite for colonocytes, are 
produced in the intestinal lumen by commensal anaerobic bacteria via 
carbohydrate fermentation. they play a role in preserving gut barrier functions, and 
have immunomodulatory and anti-inflammatory properties also it regulates the 
synthesis of the hunger-suppressing hormones leptin, peptide YY, and glucagon-
like peptide 1. The gut microbiota can also affect appetite and satiety via vagus 
nerve activation or immune-neuroendocrine mechanisms (Protincasa et al.,2022). 
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder 
characterized by chronic abdominal pain and changes in bowel habits without any 
known organic causes (Aziz and Simern, 2021). 
Fecal SCFAs abnormalities have been reported in patients with IBS, 
implying that alterations in SCFAs might be related to IBS. The cause of IBS 
remains unknown, and no single treatment is found to be universally applicable to 
all patients with IBS (Sun et al., 2019). 
Among humans, positive correlations were reported between bacterial 
diversity, butyrate-producing bacteria and cardiorespiratory fitness (VO2max), and 
higher turnover of carbohydrates and proteins, and concentrations of short-chain 
fatty acids in athletes compared to sedentary controls. There is also growing 
evidence that physical activity status and exercise training may shape the gut 
microbiome (Cataldi et al.,2022). 
Physical activity stimulates bacterial community richness by altering 
SCFAs-producing species, as well as favoring the colonization of health and 
athletic performance-promoting strains. The ability to promote a bacterial 

 
8 
 
composition capable of protecting the intestinal mucosa also it was found that the 
effects on gut microbiome seem to gradually disappear when the physical activity 
is no longer practiced (Cataldi et al., 2022). 
Moderate aerobic exercise affects the intestinal system mainly through gut 
immune function gut barrier integrity through tight junction proteins expression 
and IgA production hypothalamic–pituitary–adrenal (HPA) axis stimulation which, 
in turn, affects enteric nervous system and intestinal transit time, as well as gut 
motility, intestinal pH and gut hormones release and bile acids metabolism within 
enterohepatic circulation (Cella et al.,2021). 
High intensity interval training (HIIT) encompasses exercise prescriptions 
that are tailored to individual needs and can be used in most any exercise setting. 
This ability to adapt makes HIIT a valuable tool in the exercise programming of 
patients with a chronic disease. HIIT has a positive effect on the 
Bacteroidetes/Firmicutes ratio and also increased the alpha diversity in  gut 
microbiota (Denou et al.,2016). 
 
 

 
9 
 
Chapter III 
PATIENTS, MATERIALS AND METHODS  
The current study is designed to compare between the effect of moderate 
continuous and high interval intensity training on gut dysbiosis and glucagon like 
peptide hormone in irritable bowel syndrome. 
I. 
Patients: 
This study will be carried out on sixty six irritable bowel syndrome patients 
of both sexes with an age range between twenty to forty five years. Patients will be 
recruited and practical work of the study will be carried out in national nutrition 
institute physiotherapy out clinic. Patient will be randomly assigned to three 
groups. 
To avoid type II error, sample size calculation is performed using 
G*POWER statistical software (version 3.1.9.2; Franz Faul, Universitat Kiel, 
Germany). To detect a large effect size of 0.4 with power of 80% and α=0.05, the 
required sample size required for this study was N=66.   
 
  

 
10 
 
Ethical consideration: 
 Approval of faculty ethical committee. 
 The study procedure will be explained for all participants. 
 Confidentiality will be assured. 
 An informed consent will be taken from each subject prior to participation. 
(Appendix ) 
Criteria for the patient selection: 
Inclusion criteria:   
1) Patients will be selected with age range of 20 to 45 years of both genders. 
2) Body mass index (BMI) will range from 30 to 34.9 kg\m2. 
3) Having more than one symptom for ROME IV for IBS diagnostic criteria 
(Appendix ).        
4) Prediabetic with glycated hemoglobin HbA1c of 5.7 – 6.4. 
5) Sedentary subjects with daily steps count less than five thousand steps 
measured by pedometer (Prince et al.,2020). 
Exclusion criteria: 
Patients with the following criteria will be excluded from the study: 
1) Communication disorders 
2) Gasterointestinal bleeding  
3) Antibiotics or probiotics in the last 2 months  
4) Recent surgeries in the last 6 months  
5) Colorectal cancer or any terminal diseases 
6) Fibromylgia or Multiple sclerosis  
7) Palpable abdominal mass 
8) Cardiovascular diseases  

 
11 
 
9) Active smokers 
10) Musculoskeletal injuries that interfere with exercise program  
11) Upper respiratory infections  
12) Uncontrolled hypertension 
Patients will be divided into 3 groups: 
 Group (A): This group will include 22 patients with IBS. These patients 
will receive 40 minutes of MICT on the treadmill: 5 minutes of warm-up 
followed by 30 minutes of 65-75% of target heart rate ending with a 5 min 
cool-down period for 12 weeks along with following low FODMAP diet 
plan.  
 Group (B): This group will include 22 patients with IBS. These patients 
will receive HIIT sessions consisting of a 30 minutes treadmill session a 5 
minutes warm-up followed by 10 bouts of 1 minute at 90% of target heart 
rate interspersed by 10 bouts of 1 min of active recovery at 50% of target 
heart rate (totaling 20 min), and a 5 minutes cool-down period for 12 
weeks along with following low FODMAP diet plan. 
 Group (C) This group will include 22 patients with IBS. These patients 
will follow low FODMAP diet plan for 12 weeks  
Materials and Methods 
 Evaluation 
Out comes to be measured: 
1) Primary outcomes 
a- Short chain fatty acids via gas chromatography 
b- Glucagon like peptide 1 via Elisa kit 
2) Secondary outcomes  
a- Irritable bowel syndrome scoring system  

 
12 
 
b- Irritable bowel syndrome quality of life questionnaire (IBS QoL) 
c- Change in body weight via body mass index (BMI) 
Evaluation equipment and tools: 
a) Gas chromatography: SCFAs butyrate and acetate  
For SCFA analyses, fecal sample will be separated. Applying four analytes, 
including total SCFAs, acetate, propionate, and butyrate, will be targeted. Final 
concentrations will be calculated based on internal standards and are expressed 
as micromoles per gram of wet feces (μmol/g). Techniques and predictive 
approaches will be used across. gas chromatography will be used to quantify 
Short Chain Fatty Acids (SCFAs) from fecal samples (Chen et al.,2021). 
b) Elisa Kit for serum GLP 1 hormone 
This kit is an Enzyme-Linked Immunosorbent Assay (ELISA). The plate will 
be pre-coated with Human GLP-1 antibody (Kuhre et al.,2015).  
c) Weight and Height measurements  
Weight and height will be recorded to calculate body mass index (BMI) 
according to the following equation: (Shukohifar et al.,2022) 
BMI= weight/height2 (Kg/m2).  
d) IBS severity scoring system (Appendix ) 
This five-item questionnaire will measure IBS symptom severity by 
addressing abdominal pain (frequency and severity), bloating, dissatisfaction with 
bowel habits, and interference with daily activities. Each question score ranges 
from 0 to 100 and a higher score indicates more severe GI symptoms. A total score 
of 75–175 represents mild IBS, 176–300 moderate IBS and >300 severe IBS (Zeid 
et al.,2020). 
 

 
13 
 
e) Irritable bowel syndrome quality of life questionnaire (IBS QoL) 
(Appendix V) 
The IBS-QoL is a condition-specific instrument will be used to assess the 
impact of IBS and effects of treatment. It consists of 34 questions which cover 
eight domains including dysphoria, interference with activity, body image, health 
worry, food avoidance, social reaction, sexual, and relationships. Each item has a 
five-point response scale (not at all, slightly, moderately, quite a bit, extremely). 
The responses are summed and averaged for a total score and transformed to a 
scale between 0 and 100: higher scores indicating better IBS-specific QoL (Hou et 
al.,2015). 
3-Management procedure: 
After collecting the consent forms, will be examined by the researcher for 
the inclusion and exclusion criteria. Each eligible patient (according to the consent 
form and examination) will participate in the study. 
Group A 
Patients will receive moderate intensity continuous training (MICT). 
The program will be in form of: (Clark et al.,2020). 
 Frequency: Moderate continues training will be scheduled 3 times per 
week for 12 weeks 
 Intensity: 65-75% of target heart rate. 
 Duration: 40 minutes per session. Patients will be instructed to follow low 
fermentable short chain carbohydrates diet (low FODMAP) intervention 
for 12 weeks limiting daily fermented carbohydrate and dairy products 
intake and increase intake of protein, whole grains, fruits and vegetables 
(Appendix V)  

 
14 
 
 Group B  
Patients will receive high intensity interval training (HIIT) 
The program will be in form of: (Clark et al.,2020). 
 Frequency: High intensity interval training will be scheduled 3 times per 
week for 12 weeks 
 Intensity: 90% of target heart rate including 10 bouts of 1 minute 
interspersed with 10 bouts of 1 minute of active recovery 50% of target 
heart rate. 
 Duration: the session will last 30 minutes includes warming up and 
cooling down periods  
Patients will be instructed to follow low fermentable short chain 
carbohydrates diet (low FODMAP) intervention for 12 weeks limiting daily 
fermented carbohydrate and dairy products and increase intake of protein, whole 
grains, fruits and vegetables  
Group C 
Patients will be instructed to follow low fermentable short chain 
carbohydrates diet (low FODMAP) intervention for 12 weeks limiting daily 
fermented carbohydrate and dairy products and increase intake of protein, whole 
grains, fruits and vegetables (Vareny et al.,2017). 
Only the patients who will attend > 80% of the exercise training sessions 
will be included in this study. 
 
 
 

 
15 
 
Data Analysis and statistical design 
 The collected data was analyzed using the statistical program SPSS ver. 
20.0.  
 The mean and standard deviation were calculated for all measured 
variables. 
 Pearson correlation coefficient was used to determine the relationship 
between the measured variables. 
 Statistical significance was set at p < 0.05. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
16 
 
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Appendix I 
Sample consent form 
I am …………………….. freely and voluntarily consent to participate in 
this research study under the direction of the researcher Marwa Saeed Mohamed 
Salama  
A thorough description of the procedures has been explained and I 
understand that I may withdraw my consent and discontinue participation in this 
research at any time without prejudice to me. 
Date:   /    / 20 
Participant:  
 
 
 
 
 
 
 
 
 
 
 
 

 
21 
 
 
Appendix II 
ROME IV IBS diagnostic criteria  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
22 
 
 
Appendix III 
 
IBS Severity Scoring System  
 
 
 
 
 
 
 
 
 
 
 
 

 
23 
 
Appendix IV 
 
IBS Quality of Life Questionnaire  
 
Please think about your life over the past month (last 30 days), and look at the statements 
below. Each statement has five different responses. For each statement, please circle the 
response that best describes your feelings.  
 
 
Not 
At All 
Slightly 
 
Moderately 
  Quite 
A Bit 
Extremely 
Q1 
I feel helpless because of my bowel 
problems.  
 
 
 
 
 
Q2 
I am embarrassed by the smell 
caused by my bowel problems 
 
 
 
 
 
Q3 
I am bothered by how much time I 
spend on the toilet 
 
 
 
 
 
Q4 
I feel vulnerable to other illnesses 
because of my bowel problems 
 
 
 
 
 
Q5 
I feel fat/bloated because of my 
bowel problems 
 
 
 
 
 
Q6 
I feel like I'm losing control of my life 
because of my bowel problems 
 
 
 
 
 
Q7 
I feel my life is less enjoyable 
because of my bowel problems 
 
 
 
 
 
Q8 
I feel uncomfortable when I talk 
about my bowel problems 
 
 
 
 
 
Q9 
I feel depressed about my bowel 
problems 
 
 
 
 
 
Q10 I feel isolated from others because 
of my bowel problems 
 
 
 
 
 
Q11 I have to watch the amount of food I 
eat because of my bowel problems 
 
 
 
 
 
Q12 Because of my bowel problems, 
sexual activity is difficult for me 
 
 
 
 
 
Q13 I feel angry that I have bowel 
problems 
 
 
 
 
 
Q14 I feel like I irritate others because of 
my bowel problems 
 
 
 
 
 
Q15 I worry that my bowel problems will 
get worse 
 
 
 
 
 
Q16 I feel irritable because of my bowel 
problems 
 
 
 
 
 
Q17 I 
worry 
that 
people 
think 
I 
exaggerate my bowel problems 
 
 
 
 
 
Q18 I feel I get less done because of my 
bowel problems 
 
 
 
 
 
Q19 I have to avoid stressful situations  
 
 
 
 

 
24 
 
 
 
Not 
At All 
Slightly 
 
Moderately 
  Quite 
A Bit 
Extremely 
because of my bowel problems 
Q20 My bowel problems reduce my 
sexual desire 
 
 
 
 
 
Q21 My bowel problems limit what I can 
wear 
 
 
 
 
 
Q22 I have to avoid strenuous activity 
because of my bowel problems 
 
 
 
 
 
Q23 I have to watch the kind of food I 
eat because of my bowel problems 
 
 
 
 
 
Q24 Because of my bowel problems, I 
have difficulty being around people I 
do not know well 
 
 
 
 
 
Q25 I feel sluggish because of my bowel 
problems 
 
 
 
 
 
Q26 I feel unclean because of my bowel 
problems 
 
 
 
 
 
Q27 Long trips are difficult for me 
because of my bowel problems 
 
 
 
 
 
Q28 I feel frustrated that I cannot eat 
when I want because of my bowel 
problems 
 
 
 
 
 
Q29 It is important to be near a toilet 
because of my bowel problems 
 
 
 
 
 
Q30 My life revolves around my bowel 
problems 
 
 
 
 
 
Q31 I worry about losing control of my 
bowels 
 
 
 
 
 
Q32 I fear that I won't be able to have a 
bowel movement 
 
 
 
 
 
Q33 My bowel problems are affecting my 
closest relationships 
 
 
 
 
 
Q34 I feel that no one understands my 
bowel problems 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
25 
 
Appendix V 
 
Low FODMAP food List 
 
 

 
26