Science and

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balance

Irritable Bowel Syndrome (IBS) – A complex modern Syndrome?

Karen Harrison BSc (Hons) and

Dr. Ashton Harper

17th October 2017

Science

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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

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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.

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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

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Diversity of our microbiome?

Morgan et al 2013

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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)

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Bacteria

Digestion Vitamin synthesis

Intestinal barrier function

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Commensal bacteria evolution

Eukaryotes 2.1 billion yrs Earliest ancestors 6 million yrs

88 yrs Antibiotics 68 yrs Fast Food

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Commensal bacteria evolution

Clemente et al (2015)

Yanomami

Amerindian village

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Introduction to IBS

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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.

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Types of IBS

Lacy et al (2016)

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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)

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How our modern lifestyle has influenced this syndrome

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Western world - A change in microbiota creating the habitat for functional GI disorder to potentially develop?

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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…

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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)

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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

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The microbiota – Gut brain axis

Rea et al (2015)

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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

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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)

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IBS and Microbiota: indirect evidence

• Post-infectious IBS

• Antibiotic usage

• SIBO

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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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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’

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The gut flora’s role in IBS

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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)

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Diet and IBS

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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

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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

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IBS and the FODMAP diet

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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)

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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?

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Probiotic mechanisms

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Probiotic Mechanisms

Bermudez-Brito (2012)

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Thank you very much for listening – We will hand over to Dr Ashton Harper for the next part of this presentation