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Irritable
bowel
syndrome
(IBS)-SIBO
Dr.S.Vadivel Kumaran.,MD.,DM
Consultant Medical
Gastroenterologist/Interventional
Endoscopist/Hepatologist
Functional gastrointestinal (GI) disorder
abdominal pain and altered bowel habit
Absence of a specific and unique organic
pathology
Incidence-1%-2% per year
Prevalence-10%-20%
 Normal bowel movement- 3/day to 3/week.
 Problems arises when bowel movements
frequency decreases or increases.
 Control loss of bowel sphincters.
Normal bowel movements
Bowel movement Disorders
• Diarrhea
Passage of loose or watery stools, typically at least three times in a
24-hour period
• Constipation
Stool frequency of less than three per week
• Irritable Bowel Syndrome
Four bowel patterns
IBS-D (diarrhea predominant)
IBS-C (constipation predominant)
IBS-M (mixed diarrhea and constipation)
IBS-U (unclassified; the symptoms cannot
be categorized into one of the above three
subtypes)
Causes of diarrhea
• Infection: Diarrhoea caused by a host of bacterial, viral and
parasitic organisms- spread by faeces-contaminated water
.
• Malabsorption
• Inflammatory bowel disease
• Irritable bowel syndrome
Constipation
Constipation is a symptom, not a disease.
Different patients have different perceptions:
-Straining
-Hard, pellet-like stools
-Inability to defecate when desired
-Infrequent defecation.
Causes of Constipation
Mechanical causes:
Colorectal tumors
Strictures
Neurological causes:
Autonomic neuropathy
Multiple sclerosis
Gastrointestinal:
IBS
Diet:
Low fiber intake
Fluid depletion
Metabolic causes:
Diabetes mellitus
Electrolytes imbalance
Medications:
Antidepressants, calcium-
channel blockers.. etc.
The frequency of SIBO among IBS patients
ranges between 4 and 78%
Attributable to differences in the
geographical origins of the studied
populations, dietary or ethnicity differences
in the microbiomes
CURRENT SCENARIO
Several therapeutic trials targeting gut microbes
using antibiotics and probiotics have further
demonstrated that not all symptoms in patients
with IBS originate in the brain but rather in the
gut.
Gut Liver 2017;11:196-208
In contrast to the earlier belief, SIBO is known to
occur in absence of anatomical factors
predisposing to it
SIBO may be associated with symptoms of IBS,
led to a paradigm shift in understanding the
organic nature
GUT FLORA AND SIBO
Human gut harbor 10-14 bacterial cells- 10 times
higher than the number of cells in the human
body
70% of microbes reside in colon
500 (using culture approaches) to 1,000 (by 16S
rRNA gene sequencing)-bacterial species
SI-Gram positive and aerobic bacteria
LI-Gram negative and anaerobic bacteria
MICROORGANISMS IN GI TRACT
ACG Guidelines SIBO. Am J Gastroenterol 202;115:165-178
IBS and SIBO
Gut Liver. 2017 Mar; 11(2): 196–208
FACTORS PREVENTING OVERGROWTH OF SI
BACTERIA
INTRINSIC
Secretion Of Gastric
Juice And Bile
Peristaltic Movement
Humoral And Cellular
Mechanisms
Mucin Production
Gut Antibacterial
Peptides
Ileocecal Valve
EXTRINSIC
Diet And Drugs
Gastric Acid
Suppressants
Drugs Altering Motility
CULTUROMICS
New platform for identification of large number of
bacterial colonies as well as noncultivable
species
Matrix-assisted laser desorption ionization
time-of-flight (MALDI-TOF).
Feasible, rapid, cost-effective and reproducible
for the study of gut microbiota
BREATH TESTS
Glucose And Lactulose Hydrogen Breath Tests
80% Of The Gases Like Hydrogen And Methane
Are Eliminated With The Flatus And The
Remaining 20% Are Absorbed And Exhaled By
Lung, Which Can Be Measured In Breath
GHBT, Rise In Hydrogen By 12ppm
OTHER METHODS
CO2 breath tests
14C/13C D-xylose
13C glucose
13C cholyl-glycine hydrolase)
FACTORS ASSOCIATED WITH SIBO
AMONG PATIENTS
WITH IBS
Female Gender
Older Age(reduced GI motility, intestinal surgery,
small bowel diverticulosis and medications)
Predominant Symptom Of Bloating and
Flatulence
Diarrheal-subtype Of IBS
Bacterial Colonies In The Small Bowel Influenced
Bristol Stool Type (higher number-looser stools)
PATHOGENESIS OF IBS SYMPTOMS AMONG
PATIENTS
WITH SIBO
Dysbiosis- qualitative alteration of gut flora & also its
quantitative change (SIBO).
Bacterial fermentation produces hydrogen, methane and
carbon dioxide gases
De-conjugation of bile salts, enterotoxic effect of
bacterial metabolites, increased small intestinal
permeability, Low B12 and low grade inflammation-
immune activation
Short chain fatty acids-inhibits nutrient absorption and
inhibits jejunal motility (ileal brake) through peptide
YY, neurotensin and GLP-1
IBS patients had higher levels of IL-1 α and β than those
without SIBO
Intraepithelial lymphocytes, mast cells and
enterochromaffin cells-triggers enteric nervous system
H2S and visceral hypersensitivity
Fibromyalgia had positive LHBT
THE BRAIN GUT AXIS
 Multilevel dysregulation of the nervous
and intestinal system interactions
 The brain-gut axis constitutes a
bidirectional signaling pathway between
the CNS and GIT
 This signaling pathway is regulated at
multiple neural, hormonal and
immunological levels
 Alterations presented in any of these
levels (eg. autonomic nervous system
dysregulation, altered serotonin
metabolism, mast cell activation) contribute
to the presentation of functional bowel
disorders
Immunogastroenterology 2012; 1:23-26
Treatment of IBS
• Dietary modification
Low FODMAP diet
Avoid gas producing food
Gluten free diet
Lactose-free diet
Increased fiber
Insoluble worsen pain & bloating
Soluble (e.g. psyllium) improve
constipation
Elimination diet (with high IgG)
• Lifestyle modification
Exercise
Proper sleep
• Psychological therapies
Cognitive behavior therapy
Gut-directed hypnotherapy
Relaxation therapy
Multi-component therapy
• Pharmacological treatment
Drugs for IBS-C
Drugs for IBS-D
Drugs for pain
Drugs for associated anxiety /
depression
Aliment Pharmacol Ther. 1996 Oct;10(5):787-93
High FODMAP versus Low
FODMAP Food
Aliment Pharmacol Ther. 1996 Oct;10(5):787-93.
Potential effect of Microbiota in IBS
• Diet can change the makeup of bacteria in
the GI tract, potentially contributing to
symptoms in patients with IBS;
• Antibiotic use, which can disrupt gut
microbiota is associated with IBS;
• Changes in the gut microbiota may
influence the ability of the GI tract to
contract to move waste through the
system; and
• Changes in the gut microbiota can impair
communication networks between the
immune, nervous and endocrine
systems, predisposing people to IBS
symptoms.
Yogesh Bhattarai et al. Irritable bowel syndrome: a gut microbiota-related disorder?, American Journal of Physiology - Gastrointestinal and Liver
Physiology (2017)
Dysbiosis as a hallmark of IBS
• Dysbiosis is often defined as
an “imbalance” in the gut
microbial community that is
associated with disease.
• This imbalance could be due
to the gain or loss of
community members or
changes in relative
abundance of microbes. 1
1. Jeannette S. Messer, Eugene B. Chang, in Physiology of the Gastrointestinal Tract (Sixth Edition), 2018
2. Rodiño-Janeiro, B.K., Vicario, M., Alonso-Cotoner, C. et al. A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies. Adv
Ther 35, 289–310 (2018). https://doi.org/10.1007/s12325-018-0673-5
Taxon Percentage in
IBS
Enterobacteriaceae Higher
Lactobacillus Lower
Bifidobacterium Lower
Firmicutes/Bacteroides Higher / Lower
Summary of dysbiosis findings in IBS 2
https://doi.org/10.1053/j.gastro.2019.03.049
Selection and safety of a
Probiotic composition
The high sensitivity of probiotics to antibiotics prevents stable
colonization of the gut, thus ensuring only non-significant and transient
effects.
Use of antibiotic-resistant bacteria could be beneficial
Do we have any antibiotic-resistant probiotic strains for use with specific
antibiotics?
This resistance must not be transferable and must not be located in
plasmid DNA as probiotics could otherwise be responsible for dangerous
horizontal gene transfer to pathogens
ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth, The American Journal of Gastroenterology: February 2020 - Volume
115 - Issue 2 - p 165-178 doi: 10.14309/ajg.0000000000000501.
Introduction
• Bifidobacterium longum includes 3 subspecies- longum,
infantis, and suis;
• Several strains from the sub species infantis and longum
isolated from the infant and adult intestine of man and
developed as probiotics for use in children and adults
• Commercially available strains studied: B. longum bb536;
B.longum es 1; B. longum w11; B. longum NCC 3001; B.
longum 1714 and many more
Bifidobacterium longum W11
• Tolerates Low Ph And Is Resistant To
Bile Salts
• Efficient Colonizer
• Stabilizes The Intestinal Mucosal
Barrier
• Exclude Pathogenic Bacteria
• Immune-modulatory Activity
• Resistant To Rifaximin
• Safe Probiotic
SIBO – Treatment in IBS
Antibiotics Rifaximin is the most
extensively studied antibiotic with effective
dose 1200-1600mg/day for 7-10 days
Probiotics Lactobacillus,Saccharomyces
boulardii,Bacillus clausii,Bifidobacterium
Dietery modification
Prokinetics
Fecal microbiota transplantation
Treatment of SIBO in IBS leads to significant
improvement of symptoms
ACG Guidelines SIBO. Am J Gastroenterol 202;115:165-178
Clinical study (Rifaximin & Probiotic Study)
Aim. To evaluate the efficacy of rifaximin alone or in association with the probiotic
strain of Bifidobacterium longum W11 in reducing symptoms in patients
with IBS.
• Study Design: A monocentric, prospective open trial.
• Total Study subjects: 70
• Group A (n=41): 400 mg rifaximin for 1st 10 days of every month followed by 6 days of
Probiotic B longum w11 on alternate weeks .
• Group B (n=29): Only 400 mg rifaximin for 1st 10 days.
Resistance to Rifaximin
SIBO associates
Restless Leg Syndrome
Interstitial Cystitis
Rosacea
Fibromyalgia
Rheumatoid Arthritis
Psoriasis
Psychological intervention
Cognitive-behavioral therapy
Dynamic psychotherapy,
Hypnotherapy
Relaxation therapy- usual care
Patient education remains the cornerstone of successful
treatment of irritable bowel syndrome. Teach the patient to
acknowledge stressors and to develop avoidance
techniques. Many patients successfully manage their
symptoms with attention to dietary triggers.
Thank You
For Your Attention

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IBS-SIBO

  • 2. Functional gastrointestinal (GI) disorder abdominal pain and altered bowel habit Absence of a specific and unique organic pathology Incidence-1%-2% per year Prevalence-10%-20%
  • 3.
  • 4.  Normal bowel movement- 3/day to 3/week.  Problems arises when bowel movements frequency decreases or increases.  Control loss of bowel sphincters. Normal bowel movements
  • 5. Bowel movement Disorders • Diarrhea Passage of loose or watery stools, typically at least three times in a 24-hour period • Constipation Stool frequency of less than three per week • Irritable Bowel Syndrome
  • 6. Four bowel patterns IBS-D (diarrhea predominant) IBS-C (constipation predominant) IBS-M (mixed diarrhea and constipation) IBS-U (unclassified; the symptoms cannot be categorized into one of the above three subtypes)
  • 7. Causes of diarrhea • Infection: Diarrhoea caused by a host of bacterial, viral and parasitic organisms- spread by faeces-contaminated water . • Malabsorption • Inflammatory bowel disease • Irritable bowel syndrome
  • 8. Constipation Constipation is a symptom, not a disease. Different patients have different perceptions: -Straining -Hard, pellet-like stools -Inability to defecate when desired -Infrequent defecation.
  • 9. Causes of Constipation Mechanical causes: Colorectal tumors Strictures Neurological causes: Autonomic neuropathy Multiple sclerosis Gastrointestinal: IBS Diet: Low fiber intake Fluid depletion Metabolic causes: Diabetes mellitus Electrolytes imbalance Medications: Antidepressants, calcium- channel blockers.. etc.
  • 10. The frequency of SIBO among IBS patients ranges between 4 and 78% Attributable to differences in the geographical origins of the studied populations, dietary or ethnicity differences in the microbiomes
  • 11. CURRENT SCENARIO Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut. Gut Liver 2017;11:196-208
  • 12. In contrast to the earlier belief, SIBO is known to occur in absence of anatomical factors predisposing to it SIBO may be associated with symptoms of IBS, led to a paradigm shift in understanding the organic nature
  • 13. GUT FLORA AND SIBO Human gut harbor 10-14 bacterial cells- 10 times higher than the number of cells in the human body 70% of microbes reside in colon 500 (using culture approaches) to 1,000 (by 16S rRNA gene sequencing)-bacterial species SI-Gram positive and aerobic bacteria LI-Gram negative and anaerobic bacteria
  • 14. MICROORGANISMS IN GI TRACT ACG Guidelines SIBO. Am J Gastroenterol 202;115:165-178
  • 15. IBS and SIBO Gut Liver. 2017 Mar; 11(2): 196–208
  • 16. FACTORS PREVENTING OVERGROWTH OF SI BACTERIA INTRINSIC Secretion Of Gastric Juice And Bile Peristaltic Movement Humoral And Cellular Mechanisms Mucin Production Gut Antibacterial Peptides Ileocecal Valve EXTRINSIC Diet And Drugs Gastric Acid Suppressants Drugs Altering Motility
  • 17. CULTUROMICS New platform for identification of large number of bacterial colonies as well as noncultivable species Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF). Feasible, rapid, cost-effective and reproducible for the study of gut microbiota
  • 18. BREATH TESTS Glucose And Lactulose Hydrogen Breath Tests 80% Of The Gases Like Hydrogen And Methane Are Eliminated With The Flatus And The Remaining 20% Are Absorbed And Exhaled By Lung, Which Can Be Measured In Breath GHBT, Rise In Hydrogen By 12ppm
  • 19. OTHER METHODS CO2 breath tests 14C/13C D-xylose 13C glucose 13C cholyl-glycine hydrolase)
  • 20. FACTORS ASSOCIATED WITH SIBO AMONG PATIENTS WITH IBS Female Gender Older Age(reduced GI motility, intestinal surgery, small bowel diverticulosis and medications) Predominant Symptom Of Bloating and Flatulence Diarrheal-subtype Of IBS Bacterial Colonies In The Small Bowel Influenced Bristol Stool Type (higher number-looser stools)
  • 21. PATHOGENESIS OF IBS SYMPTOMS AMONG PATIENTS WITH SIBO Dysbiosis- qualitative alteration of gut flora & also its quantitative change (SIBO). Bacterial fermentation produces hydrogen, methane and carbon dioxide gases De-conjugation of bile salts, enterotoxic effect of bacterial metabolites, increased small intestinal permeability, Low B12 and low grade inflammation- immune activation
  • 22. Short chain fatty acids-inhibits nutrient absorption and inhibits jejunal motility (ileal brake) through peptide YY, neurotensin and GLP-1 IBS patients had higher levels of IL-1 α and β than those without SIBO Intraepithelial lymphocytes, mast cells and enterochromaffin cells-triggers enteric nervous system H2S and visceral hypersensitivity Fibromyalgia had positive LHBT
  • 23. THE BRAIN GUT AXIS  Multilevel dysregulation of the nervous and intestinal system interactions  The brain-gut axis constitutes a bidirectional signaling pathway between the CNS and GIT  This signaling pathway is regulated at multiple neural, hormonal and immunological levels  Alterations presented in any of these levels (eg. autonomic nervous system dysregulation, altered serotonin metabolism, mast cell activation) contribute to the presentation of functional bowel disorders Immunogastroenterology 2012; 1:23-26
  • 24. Treatment of IBS • Dietary modification Low FODMAP diet Avoid gas producing food Gluten free diet Lactose-free diet Increased fiber Insoluble worsen pain & bloating Soluble (e.g. psyllium) improve constipation Elimination diet (with high IgG) • Lifestyle modification Exercise Proper sleep • Psychological therapies Cognitive behavior therapy Gut-directed hypnotherapy Relaxation therapy Multi-component therapy • Pharmacological treatment Drugs for IBS-C Drugs for IBS-D Drugs for pain Drugs for associated anxiety / depression Aliment Pharmacol Ther. 1996 Oct;10(5):787-93
  • 25. High FODMAP versus Low FODMAP Food Aliment Pharmacol Ther. 1996 Oct;10(5):787-93.
  • 26. Potential effect of Microbiota in IBS • Diet can change the makeup of bacteria in the GI tract, potentially contributing to symptoms in patients with IBS; • Antibiotic use, which can disrupt gut microbiota is associated with IBS; • Changes in the gut microbiota may influence the ability of the GI tract to contract to move waste through the system; and • Changes in the gut microbiota can impair communication networks between the immune, nervous and endocrine systems, predisposing people to IBS symptoms. Yogesh Bhattarai et al. Irritable bowel syndrome: a gut microbiota-related disorder?, American Journal of Physiology - Gastrointestinal and Liver Physiology (2017)
  • 27. Dysbiosis as a hallmark of IBS • Dysbiosis is often defined as an “imbalance” in the gut microbial community that is associated with disease. • This imbalance could be due to the gain or loss of community members or changes in relative abundance of microbes. 1 1. Jeannette S. Messer, Eugene B. Chang, in Physiology of the Gastrointestinal Tract (Sixth Edition), 2018 2. Rodiño-Janeiro, B.K., Vicario, M., Alonso-Cotoner, C. et al. A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies. Adv Ther 35, 289–310 (2018). https://doi.org/10.1007/s12325-018-0673-5 Taxon Percentage in IBS Enterobacteriaceae Higher Lactobacillus Lower Bifidobacterium Lower Firmicutes/Bacteroides Higher / Lower Summary of dysbiosis findings in IBS 2 https://doi.org/10.1053/j.gastro.2019.03.049
  • 28. Selection and safety of a Probiotic composition The high sensitivity of probiotics to antibiotics prevents stable colonization of the gut, thus ensuring only non-significant and transient effects. Use of antibiotic-resistant bacteria could be beneficial Do we have any antibiotic-resistant probiotic strains for use with specific antibiotics? This resistance must not be transferable and must not be located in plasmid DNA as probiotics could otherwise be responsible for dangerous horizontal gene transfer to pathogens ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth, The American Journal of Gastroenterology: February 2020 - Volume 115 - Issue 2 - p 165-178 doi: 10.14309/ajg.0000000000000501.
  • 29. Introduction • Bifidobacterium longum includes 3 subspecies- longum, infantis, and suis; • Several strains from the sub species infantis and longum isolated from the infant and adult intestine of man and developed as probiotics for use in children and adults • Commercially available strains studied: B. longum bb536; B.longum es 1; B. longum w11; B. longum NCC 3001; B. longum 1714 and many more
  • 30. Bifidobacterium longum W11 • Tolerates Low Ph And Is Resistant To Bile Salts • Efficient Colonizer • Stabilizes The Intestinal Mucosal Barrier • Exclude Pathogenic Bacteria • Immune-modulatory Activity • Resistant To Rifaximin • Safe Probiotic
  • 31. SIBO – Treatment in IBS Antibiotics Rifaximin is the most extensively studied antibiotic with effective dose 1200-1600mg/day for 7-10 days Probiotics Lactobacillus,Saccharomyces boulardii,Bacillus clausii,Bifidobacterium Dietery modification Prokinetics Fecal microbiota transplantation Treatment of SIBO in IBS leads to significant improvement of symptoms ACG Guidelines SIBO. Am J Gastroenterol 202;115:165-178
  • 32. Clinical study (Rifaximin & Probiotic Study) Aim. To evaluate the efficacy of rifaximin alone or in association with the probiotic strain of Bifidobacterium longum W11 in reducing symptoms in patients with IBS. • Study Design: A monocentric, prospective open trial. • Total Study subjects: 70 • Group A (n=41): 400 mg rifaximin for 1st 10 days of every month followed by 6 days of Probiotic B longum w11 on alternate weeks . • Group B (n=29): Only 400 mg rifaximin for 1st 10 days.
  • 34. SIBO associates Restless Leg Syndrome Interstitial Cystitis Rosacea Fibromyalgia Rheumatoid Arthritis Psoriasis
  • 35. Psychological intervention Cognitive-behavioral therapy Dynamic psychotherapy, Hypnotherapy Relaxation therapy- usual care
  • 36. Patient education remains the cornerstone of successful treatment of irritable bowel syndrome. Teach the patient to acknowledge stressors and to develop avoidance techniques. Many patients successfully manage their symptoms with attention to dietary triggers.
  • 37. Thank You For Your Attention