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Science and
nature in
balance
Irritable Bowel Syndrome (IBS) – A complex modern Syndrome?
Karen Harrison BSc (Hons) and
Dr. Ashton Harper
17th October 2017
Science
and nature
in balance
Contents
• Introduction
• The gut flora’s role in IBS
• How our modern lifestyle has influenced this syndrome
• The latest research behind the use of probiotics for IBS
Science
and nature
in balance
My background
• Karen Harrison BSc (Hons) studied at CNELM,
Bachelor’s Degree (Hons) in Nutritional Science
and has a Naturopathic nutrition diploma from the
College of Naturopathic Medicine (CNM).
• Nutrition Advisor for the South East (UK) visiting
health food stores and pharmacies training staff,
hosting In-store events and creating window
displays. I also spend time in the US supporting the
teams at trade shows.
• Karen has her own private clinic in Buckhurst Hill,
Essex specialising in gut health.
• Joined Probiotics International (Protexin),
manufacturers of Bio-Kult and Lepicol ranges 3
years ago.
Science
and nature
in balance
Introduction to the gut flora
• Probiotic: ‘Live microorganism that confer a health benefit to the
host when administered in adequate amounts’ WHO (2017)
• Microbiota: all the microorganisms present in a specific habitat
• Microbiome: a collection of different microbes and their functions
or genes found in an environmental habitat
• Dysbiosis: disturbance or imbalance in the types and numbers of
bacteria in the gut which may lead to disease
Science
and nature
in balance
Amounts of Bacteria
Feature Figure
Bacteria in gut 40 trillion (~30 trillion eukaryotes) (Sender 2016)
Diversity of gut >1000 species (Lozupone 2012)
Microbiota genes
(Microbiome)
>3 million (150-fold more than
human) (Qin 2010)
Science
and nature
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Commensal bacteria evolution
Eukaryotes 2.1 billion yrs Earliest ancestors 6 million yrs
88 yrs Antibiotics 68 yrs Fast Food
Science
and nature
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Commensal bacteria evolution
Clemente et al (2015)
Yanomami
Amerindian village
Science
and nature
in balance
IBS – Gastrointestinal disorder
IBS is one of the most common
gastrointestinal disorders, affecting
10-15% of adults.
Abdominal pain, alterations of bowel
habits, bloating and flatulence, straining
and urgency are all common symptoms.
Science
and nature
in balance
Functional Bowel Disorder - IBS Rome IV Criteria for Diagnosing IBS:
Recurrent abdominal pain, on average, at least 1 day/week
in the last 3 months, associated with two or more of the
following criteria:
Related to defecation
Associated with a change in frequency of stool
Associated with a change in form (appearance) of stool
Criteria fulfilled for the last 3 months with symptom onset at
least 6 months before diagnosis. IBS is the most common functional
GI disorder accounting for up to
50% of visits to general
practitioners for GI complaints (Lacy et al 2015)
Science
and nature
in balance
Western world - A change in microbiota creating the habitat for functional GI disorder to potentially develop?
Science
and nature
in balance
Western world – Stress
Modern lifestyle – Online activity
Working more unpaid overtime
Interactive games
App’s
Smart phones are becoming much easier to us with a high percentage
of people now checking their phones before bed and within 15 mins of
waking
The food eaten, the lifestyle our clients have is creating disorders of the gut-brain…
Science
and nature
in balance
Functional GI disorders are ‘disorders of gut–brain interaction’.
It is a group of disorders classified by GI symptoms related to any combination of the following:
Altered mucosal and immune
function
Visceral
hypersensitivity
Motility
Matr
icon e
t al (2
012)
Science
and nature
in balance
Gut-brain-microbiota stats
• Intestinal surface = 100m2 (100x greater than the surface area of the skin)
• 200-600 million neurones in the human ENS
• 100 trillion bacteria in the gut (>14,000 times the world population)
• 40,000 bacterial species in the gut and >100x more genes than human
• Gut-associated immune system = 2/3 body’s immune cells
• Thousands of enteroendocrine cells: >20 identified hormones
Science
and nature
in balance
Gut-brain-microbiota
Microbiome-gut-brain axis:
• Central nervous system (CNS)
• Neuroendocrine system
• Neuroimmune system
• Autonomic nervous system (ANS)
• Enteric nervous system (ENS)
• Gut microbiota
A triad of bi-directional
communication lines:
• Neural
• Hormonal
• Immunological
Science
and nature
in balance
Gut-brain-microbiota stats
Parameter IBS Healthy
Phylum
difference
Increased
Firmicute:Bacteroidetes (Kennedy et al 2014)
Diversity Low (Kennedy et al 2014) High
Mucosal
biifidobacteria
Low abundance in IBS-D
vs IBS-C (Parkes et al 2012)
Bifidobacteria
abundance
Low in children with IBS-
D (Rigsbee et al 2012)
5-fold less in
those reporting
pain (Jalanka-Tuovinen
et al 2011)
Luminal
bifidobacteria
and lactobacilli
Decreased (Straudacher et al
2014)
Science
and nature
in balance
IBS and Microbiota: indirect evidence
• Post-infectious IBS
• Antibiotic usage
• SIBO
Science
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Post-Infectious IBS
• D-IBS clients have alterations in their small bowel microbial flora:
• breath testing
• culture studies
• deep sequencing of small bowel flora
• 10% of individuals who develop acute gastroenteritis develop long-lasting D-IBS symptoms, referred to as post-infectious IBS (PI-IBS)
• Contamination of water supply (Marshall et al 2006)
• E. coli 0157:H7 and C. jejuni
• >2,000 residents followed up 2yrs after
• Rome I criteria met for 36.2% of clinically suspected gastroenteritis
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and nature
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IBS and antibiotics
Publication Findings
Mendall et
al 1998
• GP survey of 421 subjects 18-80yrs
• IBS was strongly related to antibiotic use OR
3.70 (1.80-7.60)
Maxwell et
al 2002
• Prospective case-control study – London - GPs
• General population – 16-49yrs, non-GI
complaint abx prescriptions
• Subjects given a course of antibiotics >3 times
as likely to report more bowel symptoms 4
months later than controls.
Villarreal et
al 2012
• Retrospective study – 26,107 adults
• 115 on broad-spectrum abx diagnosed with
IBS within 12 months
• Macrolides and tetracyclines particularly
associated
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IBS and SIBO
• Conflicting results in studies
• Conclusion: ‘SIBO-IBS hypothesis lacks convincing evidence but remains under scrutiny’
Science
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Visceral hypersensitivity
IBS patient
Visceral hypersensitivity – link to bacteria
Association Details
Antibiotics Antibiotic treatment perturbed gut flora, increased
myeloperoxidase activity and substance P
immunoreactivity in the colon, and produced visceral
hypersensitivity (Verdu et al 2005)
Infection Citrobacter rodentium colitis evokes post-infectious
hyperexcitability of mouse nociceptive colonic dorsal
root ganglion neurons (Ibeakanma et al 2009)
Endotoxin
administration
Maternal
separation
Probiotics
Mast cells
Association Details
Antibiotics Antibiotic treatment perturbed gut flora, increased
myeloperoxidase activity and substance P immunoreactivity in
the colon, and produced visceral hypersensitivity (Verdu et al 2005)
Infection Citrobacter rodentium colitis evokes post-infectious
hyperexcitability of mouse nociceptive colonic dorsal root
ganglion neurons (Ibeakanma et al 2009)
Endotoxin Administration of LPS to rats increased visceral sensitivity (O’Mahony 2013)
Maternal
separation
Raised corticosterone, increased systemic immune response to
LPS challenge and altered faecal microbiota (O’Mahony et al 2009)
Mast cells Evidence that mast cells exposed to bacteria down-regulate
degranulation in response to IgE/Allergen stimulation (Wesolowski
2011)
Probiotics • B. infantis – visceral antinociceptive effects (McKernan et al 2010)
• L. acidophilus induces opioid and cannabinoid receptors (Rousseaux et al 2007)
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The microbiota and neurotransmitters
• Tryptophan – essential AA and
precursor for serotonin (5-HT)
• Availability is coordinated by the gut
microbiota (Clarke et al 2013)
• Plasma concentrations can be
normalised following colonisation of GF
animals and augmented with probiotic
bacteria (Desbonnet et al 2008)
• What is the mechanism?
Currently unclear
May involve alternative pathways
GF animals have decreased ratio of
Kyn:Tryp (index of IDO/TDO
activity)
Increased IDO activity found in IBS populations – potentially
leads to serotonin deficiency and production of neurotoxic
metabolites (Kennedy et al 2014)
Science
and nature
in balance
IBS - Food regime
Mechanisms by which short-chain fermentable carbohydrates might induce symptoms in IBS
• Unabsorbed fructose, polyols and lactose lead to osmotic shifts in the ileum.
• Unabsorbed fermentable carbohydrates are fermented in the colon leading to luminal gas production.
• Visceral hypersensitivity and altered colonic functioning and luminal distension =
symptom exacerbation
From Staudacher et al 2014
Science
and nature
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IBS and the FODMAP diet
• 9 of 10 IBS clients report that food generates symptoms
• 2/3 of IBS individuals initiate dietary restrictions
• Up to 70% of patients report symptom improvement with FODMAP restriction
First approach: ‘healthy eating’
Second approach: ‘low FODMAP’ food regime
Science
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Possible consequences of dietary restriction
• FODMAP can be complex to understand and implement, not every client is willing to make this change
• Nutritional insufficiencies is a potential risk
• Risk of calcium insufficiency with lower calcium intake – possible need for supplementation
• Marked reduction in luminal bifidobacteria concentration following 4-weeks FODMAP diet (Staudacher et al 2012) – unknown long-term consequences!
• Multiple beneficial effects of bifids documented (Russel
et al 2011)
• Negative correlation to pain and bowel frequency (Parkes et al 2012)
Science
and nature
in balance
Not just FODMAP’s – Prebiotics?
• IBS clients have an altered microbiota and probiotics have been shown in studies to help to rebalance the gut flora and to improve symptoms.
• Prebiotics?