Mestrado de Nutrição Humana e Metabolismo

FCM /NMS

Síndrome do Intestino Irritável (SII)

e
Síndrome de Supercrescimento Bacteriano
do Intestino Delgado (SIBO)
Do diagnóstico à intervenção terapêutica
Teresa Freitas
Gastrenterologista- D. Funcionais e Motilidade Digestiva
S. Gastrenterologia - CHVNG/E
tfreitas@CHVNG.MIN-SAUDE.PT
Julho /2022
Functional bowel disorders

Functional bowel disorders (FBD) are a spectrum of

chronic gastrointestinal (GI) disorders characterized
by predominant symptoms or signs of :

 abdominal pain,
 bloating,
 distention
 and/or bowel habit abnormalities
(constipation, diarrhea, or mixed constipation and
diarrhea).

Gastroenterology
2016;150:1393–1407
 Distúrbios Funcionais Intestinais

 Irritable bowel syndrome

 Functional constipation
 Functional diarrhea
 Functional abdominal
bloating/distension
 Unspecified functional bowel
disorders
 Opioid-induced constipation

There is a continuum between these

Gastroenterology
disorders”
2016;150:1393–1407
Functional bowel disorders
Irritable bowel syndrome
 The Global Impact of IBS

•50% of IBS patients seek medical advice: 90 % GP- 1/3 are referred
to secondary care

•50% of Gastrenterologist consultation

• Repetitively consult the GP or GI – as many as 10 times a year –

•Incresed number of consultations , both in primary and secondary care

, per year compared with patitents without IBS ( 8,6 – 9, 0 versus 4, 6)

•85% of IBS patients undergo an investigation

•Average of 4 years until diagnosis

Ther Adv Gastroenterol 2017, vol. 10(9)727-735
The Global Impact of IBS

Ther Adv Gastroenterol 2017, vol. 10(9)727-735

 Figure 2
IBS Classification
IBS-C; IBS-D; IBM; IBS-U

Gastroenterology 2016 150, 1393-1407.e5DOI: (10.1053/j.gastro.2016.02.031)

IBS Pathophysiology
The brain-gut axis (GBA) is a bidirectional communication system between the gut
and the brain. Along this conduit, the brain interacts with the gut through neural
components (CNS and ANS), endocrine system (hypothalamic-pituitary-adrenal
axis), immune components (cytokines and metabolic) and gastrointestinal
components (microbiota, intestinal barrier , intestinal immune response and ENS).
The main effects of stress are mainly on intestinal motility and permeability, visceral
sensitivity, immune responses and gut microbiota composition. The underlying
mechanism is likely through secretion of pro-inflammatory cytokines such as
interleukin-6 (IL-6) and interleukin-8 (IL-8) which activate hypothalamic-pituitary
adrenal

Frontiers in Microbiology, June 219, vol 10

 Dysbiosis in IBS

A dysbiosis frequency of 73% was observed among IBS patients.

Low Grade Mucosal Inflammation and Immune Activation:

Specific immune signaling pathways (IL) are involved and the interaction between
gut microbiota, enteric nervous system and immune activation during IBS
pathogenesis

Frontiers in Microbiology, June 219, vol 10

A specific intestinal microbiota signature that could be linked to the severity of IBS was
positively correlated with low CH4 exhaled, low microbial richness, absence of
Methanobacteriales and enrichment with Bacteroides enterotypes.

On the other hand, growing evidence of the development of visceral hypersensitivity

indicates fungi dysbiosis may have indispensable role in IBS pathogenesis ( IBS- D)
Pathophysiological links between dysbiosis , increased intestinal
permeability and hypersensitivity
 Pathophysiology of PI-IBS
Pooled prevalence of IBS after infection 10%

Barbara G et al., Gastroenterology

2019;156:46-58
Triggers of IBS Symptoms

Depression Coffee
Fiber
Anxiety Fatty
meals

Travelling

Barbara G et al; 2019

IBS Diagnosis
IBS Diagnosis
 IBS Diagnosis
The diagnosis of IBS should be based on:
IBS Diagnosis
Colonoscopia normal
 Questionário Psico- Social

 Ansiedade
 depressão
 ideação suicida
 Abuso sexual
 Severidade da dor
 preocupação com os sintomas ( somatização)
 Interferência com as actividades habituais
 Consumo álcool / drogas
IBS – Sequencing the treatments

Törnblom H, et al. Gut. 2014

  Relação médico-doente

• Explicar a base dos sintomas

• Avaliar os factores precipitantes dos sintomas
• Identificar preocupações
• Envolver o doente
• Confirmação do diagnóstico
• Iniciar o tratamento
• Dar continuidade
Os cuidados gerais de vida :

- promover alimentação saudável

- horas de sono adequadas : 8h/dia, mantendo o mesmo horário

- exercício físico regular, preferencialmente ao ar livre e em

contacto com a natureza

- Redução stress : yoga, meditação

 Food‐symptom diaries can generate
personalized lifestyle advice for managing
gastrointestinal symptoms A pilot study

https://doi.org/10.1111/nmo.13820

In a 12 week randomized, controlled trial which included 102 IBS patients, 20-60
minutes of moderate to vigorous physical activity 3-5 times per week significantly
improved IBS symptoms more than a control condition (p<0.001).

DOI: 10.1111/nmo.13703
 Fiber
1 -Systematic review and meta-analysis identified 12 trials
comparing fiber with control and found only a marginal
difference in the proportion of IBS patients with symptoms after
any type of fiber vs the control intervention.

2 - Subgroup analysis suggested that benefits for IBS symptoms

were confined to soluble (psyllium/ispaghula husk) and not
insoluble (bran) fiber.

3 - Certain forms of fiber, and particularly bran, can exacerbate

problems of abdominal distention and flatulence.

Brian E. Lacy et all

Gastroenterology 2016;150:1393–1407
 O que são FODMAPs?

• Oligossacarídeos (fruto-ologossacarídeos e galacto-

oligossacarídeos

• Dissacarídeos (lactose)

• Monossacarídeos (frutose)

• E (And)

• Polióis (sorbitol, manitol, xilitol e maltitol)

 FODMAPs
FODMAPs PRESENTES NOS ALIMENTOS
ALIMENTOS A EVITAR
(RICOS EM FODMAPs)
FRUTAS Maçã, pera, pêssego, cereja, ameixa
melancia,manga, lichia, amora, frutos secos e
oleaginoas (nozes, amêndoas…)
LEGUMES Alcachofra, espargos, repolho e derivados,
(couve-flor, bróculos, alho-francês, alho,
cebola, chalota, leguminosas (ervilha, feijão,
lentilhas), cogumelos
PRODUTOS Leite líquido, em pó, concentrado e
LÁCTEOS derivados, , gelado e sobremesas lácteas,
queijo fresco, iogurtes entre outros
PRODUTOS Trigo em grande quantidade se for bem
CEREALÍFEROS tolerado, em pequenas quantidades e todos
os derivados de trigo , cevada e centeio
OUTROS Prep. Industriais que contenham frutose,
molhos, tomate concentrado, mel, xarope
de ácer, e de milho, . Edulcorantes, doces
sem açúcar
ALIMENTOS PREFERENCIAIS
(POBRES EM FODMAPs)
Banana, arando, ananás, toranja, melão, limão, laranja,
maracujá, papaia, framboesa, ruibarbo, morango, coco,
kiwi
Cenoura, aipo, endívia, palmito, feijão verde, alface,
pastinaca, abóbora, batata-doce, tomate, courgete,
inhame, nabo, pimentão vermelho, acelga, beringela,
pimentos, espinafres
Leite sem lactose, bebida vegetal (ex soja), iogurte
caseiro com leite sem lactose, , ou com bebida vegetal.
Queijos curados de pasta mole, azuis, não curados. ,
duros.
Trigo sarraceno, espelta, arroz, aveia, polenta, milho
painço, tapioca, quinoa, , batata, milho
Carne, peixe, ovo
 FODMAPs

 Curto período: 4 a 8 semanas?

 Personalizada melhor que restrição
 Condicionada pelas modificações da
microbiota que provoca
 Combinada com probióticos?

Modificações na dieta, em particular, dieta pobre

em FODMAPs, podem ajudar a melhorar os
sintomas, mas precisamos de mais dados
prospectivos para estudar o papel dos
Testes Respiratórios – Intolerância aos dissacarídeos

Dissacarídeos
CO2
H2

CH4

Lactose
Sacarose
Frutose
Peppermint Oil
Probiotic, Prebiotic, Synbiotics

WGO, 2017
 Modulação do
Microbioma

Probióticos Prebióticos
“live microorganisms “Nondigestible
that confer benefit when ingredients that
consumed in adequate beneficially affect the
amounts” host by stimulating the
growth and/or activity of
limited number of
bacteria”

Vallianou et al. Curr Obes Rep. 2020;9(3):179-192.

Modulação da
Microbiota
Microbioma & Patologia Intestino

Síndrome do Intestino Irritável

53 estudos, 5545 doentes

Pouca evidência sobre prebióticos ou simbióticos.
Combinação de estirpes: melhoria significativa
bem estar e sintomas Risco relativo de
persistência de sintomas com probiótico versus
placebo 0.79 (95% CI 0.68 - 0.91, I2 = 76%).
59 estudos, 6761 doentes
Risco relativo de melhoria ou resposta com
probiótico versus placebo 1.52 (95% CI 1.32–
1.76; I2 = 71%).
 Fecal microbiota Transplantation

Fecal microbiota transplantation (FMT) consists of the infusion of faeces

from a healthy donor to the gastrointestinal tract of a recipient patient,
in order to treat a specific disease associated with alteration of gut
microbiota.

1. Cammarota G, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017 Apr;66(4):569-580.

IBS – Sequencing the treatments

Törnblom H, et al. Gut. 2014

 SII-TRATAMENTO
Tratamento farmacológico
Diarreia
Tratamento Dose

Análogo opioide Loperamida; 2−4 mg( sos) até 16 mg/ dia

Sequestrante dos sais biliares Cholestyramine*(9 g ,2 a 3 x dia)

Colestipol *(2 g, 1 a 2 x dia)

Colesevelam *(625 mg, 1 a 2 x dia)

Prébióticos/Probióticos/ Simbióticos

Antibióticos Rifaximina, 550 mg po 3xdia - 14 d

Antagonistas 5-HT3  Alosetron * (0.5−1 mg 2xdia) *risco colite isquémica

Ondansetron (4−8 mg 3xdia)

Ramosetron* 5 μg 1 x dia

Agonista dos receptores μ e k-opióides e antagonista Eluxadolina* / ** 75- 100 mg 2 x dia** contraindicado pós-colecistectomia e
dos receptores d-opióides, consumo de álcool

AGA Institute: Guideline 2019 update *não disponível em Portugal

Use of Pharmacological Therapies in the IBS Treatment
Joel J. Heidelbaugh, Walter Smalley, G. Nicholas Verne, Lin Chang,Anthony Lembo,Shahnaz Sultan
Rifaximina
Desenho : Ensaio Clínico Aleatorizado

População : doentes com SII não obstipados com

sintomas leves a moderados
Estudo 1: N=623
Estudo 2: N=637

Intervenção : Rifaximina 550 mg/8 h/ duas

semanas ou placebo

Seguimento: 12 semanas

End point: alívio adequado dos sintomas durante

2 das 4 semanas posteriores à intervenção

Pimentel et al. N Engl J Med 2011;364:22-32.

 SII-TRATAMENTO

Tratamento farmacológico

Obstipação Psyllium Em doses fracionadas até to 30 g/d

Goma Guar Em doses fracionadas de 5 a 20 g/d

PEG-Polietilenoglicol 17−34 g/d

Activador dos canais de cloro Lubiprostona*, 8 μg 2xdia

Inibidor dos receptores NHE3 Tenapanor 50 mg 2 x dia ( em investigação )

Agonista do receptor da guanilato ciclase-C Linaclotida 290 μg 1 x d

Plecanitide * 3-6 mg/dia

Antagonistas Opioides

Antagonistas do transporte Íleal dos sais biliares Eloxibat**

*não disponível em Portugal

* * em investigação

AGA Institute: Guideline 2019 update Use of Pharmacological Therapies in the IBS Treatment
Joel J. Heidelbaugh, Walter Smalley, G. Nicholas Verne, Lin Chang,Anthony Lembo,Shahnaz Sultan
Linaclotida: mecanismo de acção

“Secretagogo”
Inibe a atividade
nociceptiva no
cólon

Agonista da Guanilato Ciclasa C

Aumenta a secreção e
acelera o trânsito intestinal

Jamuz A. Neurogastroenterology and Motility 2015.

Linaclotida: eficácia
Dor Abdominal Placebo (n = 403)
LIN 290 µg (n = 401)
70
Pacientes com
resposta(%) 60
50

40

30 Estudo 31 Estudo 302

20
**** **** Muy severo
10 -1.9 -1.9
Distensão -1.1 -1.0
0 abdominal O
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Semana

Número de dejeções Placebo (n = 403)

LIN 290 µg (n =
DE/semana 7 401)

6
5
4 Nada

3
2
1
0
BL 2 4 6 8 10 12 14 16 18 20 22 24 26 Rao S et al 2012. Chey WD et al 2012
Semana

Chey WD et al 2012
 SII-TRATAMENTO

Dor abdominal Antiespasmódicos músculo liso Dicycylomine* (10−20 mg qd−qid)

Brometo de otilónio (40mg 2 a 3 x dia)

Cloridrato de mebeverina (135 mg 3 x dia )

Hortelã-pimenta 250-730mg, 2 a 3 x dia

Prometo de pinavério ( 50mg 3 x dia/100mg 2x dia)

Tiropramida( 200mg 2 x dia)

Associações floroglucinol 62,23 mg (+ simeticone 133 mg) – 2 cáps. até 3 x dia

 
Antidepressivos tricíclicos Desipramina (25−100 mg 1 x dia),

amitriptyline (10−50 mg 1 x dia ); outros

SNRIs Venlafexina- (37,5 – 375 mg / dia)

Duloxetina – 60 – 120 mg /dia

Activador dos canais de cloro Lubiprostona* 8 μg 2xdia

Agonista do receptor da guanilato ciclase-C Linaclotida 290 μg 1 x d

Antagonistas 5-HT3  Alosetron* 0.5−1.0 mg bid

AGA Institute: Guideline 2019 update Use of Pharmacological Therapies in the IBS Treatment
*não disponível em Portugal.
Joel J. Heidelbaugh, Walter Smalley, G. Nicholas Verne, Lin Chang,Anthony Lembo,Shahnaz Sultan
Espasmolíticos
Fármacos serotoninérgicos
Antagonistas 5-HT3

1mg /id
The growing field of neurogastrenterology now requires that we
consider changing these names to neuromodulators.
Neuromodeladores

Augmentation
Therapy
IBS – Sequencing the treatments

Törnblom H, et al. Gut. 2014

 Psychological Treatments in IBS

 Approximately 15% of IBS patients are resistant to medical therapy.

 Psychological treatments are usually reserved for these refractory

patients and those who relapse despite an initial response to
medical treatment.
 Between 42%-64% of IBS patients meet criteria for a psychiatric
diagnosis compared to a median incidence of 19% in patients with
organic gastrointestinal disease, and 16% in healthy controls.

 The most common diagnoses are a generalised anxiety disorder and

depression.

 There is no unique psychological profile which characterises IBS.

Jin S, et al. BMJ Open 2019;9:e027778.
doi:10.1136/bmjopen-2018-027778
Ther Adv Gastroenterol
2019, Vol. 12: 1–19
DOI: 10.1177/
COGNITIVE BEHAVIORAL THERAPY (CBT)

 CBT is the most widely-studied psychotherapy treatment for IBS and

there is a strong evidence base to support the use of CBT as a first-
line treatment

 There is no singular standardized protocol of CBT for IBS, and different

research studies have applied this treatment in slightly different ways,
typically within 6–12 therapy sessions.

 CBT affects IBS symptom expression, independent of its effects on

psychological distress.

Jin S, et al. BMJ Open 2019;9:e027778.

doi:10.1136/bmjopen-2018-027778
HYPNOTHERAPY IN IBS

 Gut-directed hypnotherapy is a variation of

medical hypnosis that focuses post-
hypnotic suggestions on the health of the
gastrointestinal tract.

 This treatment typically involves 7–12

weekly sessions in which patients first learn
to achieve and deepen a hypnotic state and
are then led through a series of scripted,
gut-focused imageries with hypnotic
suggestions in each session
 visualisation is also employed, using the
analogy of a gently flowing river and a gently
flowing bowel to reinforce a positive bowel
image
Jin S, et al. BMJ Open 2019;9:e027778.
doi:10.1136/bmjopen-2018-027778
SII-Colaboração
multidisciplinar

Medicina
Geral e

Ga
Familiar

st
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t
ia

en
u

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siq

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P

lo
Doente

gi
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com

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Ps a
ic SII i st
ól
og i on
o tri c
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Farmacêutico
Small Intestinal Bacterial Overgrowth
(SIBO)
Small Intestinal Bacterial Overgrowth – (SIBO)
Small Intestinal Bacterial Overgrowth – (SIBO)
Joshua Ledberg, 2001 Microbiota #
Microbioma #
100 triliões de microrganismos Metaboloma
Bactérias, vírus, archaea, fungos

95% no sistema gastrointestinal

1,3:1 células microbianas : humanas

> 10.000 espécies diferentes 3 milhões / 23 mil
genes
5:1 vírus : bactérias

90% das patologias humanas parecem ter relação com

microbioma

MANIPULAÇÃO muito mais fácil que o genoma

humano
Small Intestinal Bacterial Overgrowth – (SIBO)
Overgrowth of intestinal bacteria proximal to the colon
 Small Intestinal Bacterial Overgrowth – (SIBO)

 The population-based prevalence of SIBO is unclear.

 The incidence of SIBO increases with age.

 Microbiota Aerobic
do sistema digestivo gram +

<102/g Anaerobic
Acid gastric gram -
secretion
(<<<PH)
<104/g
Pancreatobiliar
y secretion 102 - 104/g
( proteases ;
lípases; bile)

Fast and feed 107 - 109/g

Motility -
MMC( migratation
motor complex)
1011 - 1012/g

Structural
barriers
(ICV)
Schmidt et al. Cell. 2018;172(6):1198-1215. 
Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome:
A Systematic Review and Meta-Analysis of Case-Control Studies

The American Journal of GASTROENTEROLOGY

VOLUME 115 | FEBRUARY 2020
 Small Intestinal Bacterial Overgrowth (SIBO)

Overgrowth of intestinal bacteria proximal to the colon

Clinical manifestations:
 Asymptomatic

 Nonspecific abdominal symptoms : abdominal pain, bloating and

flatulence, diarrhea and constipation

 Steatorrhea, malabsortption and weight loss

Diagnosis

Small Intestinal
Fluid Aspiration
for Quantitative
Culture
Diagnosis
Small Intestinal Fluid Aspiration for Quantitative Culture

SIBO = > 105 CFU / ml (Colony -Forming Units / ml) in jejunum

SIBO = > 10 3 CFU/ml in duodenum

Qualitative culture :

- gram + aerobic organisms – SIBO Upper GI tract

- Gram negative anaerobic organisms – SIBO Lower GI tract

(colon)
 Diagnosis

Non invasive
Simple
Less expensive
More widely avaible
Diagnosis
Glucose Hydrogen Breath Test ( GHBT)

Glucose, 75 mg/vo

SIBO  Hydrogen (H2) > 20ppm

Sensitivity =77%
Metane (CH4) > 10 ppm ( + 31%) Specificity = 66% - 84 %

Lactulose Hydrogen Breath Test ( LHBT)

Lactulose, 10g/vo

SIBO  Hydrogen (H2) > 20ppm

Metane (CH4) > 10 ppm ( + 17%)

Small Intestinal Bacterial Overgrowth (SIBO)

Treatment

 Decontamination

 Prevention of recurrance

 Treatment of the underlying cause

Small Intestinal Bacterial Overgrowth (SIBO)
Treatment
SIBO recurrence following a course of antibiotic therapy

3 M = 12, 6%;
6M = 27,5%
9M = 47,3 %

There are no universally accepted treatment approaches:

Frequency of retreatment should be basead on timing and characteristics of

symptoms reccurance .

Short reccurance < 3M

Treat with an alternative antibiotic regime

Continuous course of antibiotic therapy: 5-10 days every month

SIBO recurrence following a course of antibiotic therapy

Risk of continuous courses of antibiotic therapy :

 Diarrhea (Cl difficile infection )

Intolerance

Costs

Management should be individualized

Small Intestinal Bacterial Overgrowth (SIBO)

Diet

Low FODMAP diet

There are no clinical trials in SIBO

May provide adjunctive management strategy in patients with

repetitive episodes of SIBO
Small Intestinal Bacterial Overgrowth (SIBO)
Herbal Therapy
Antimicrobial properties

-Garlic
-Ciannamon
-Mustard
-All spices
-Black cumin
Small Intestinal Bacterial Overgrowth (SIBO)

Probiotics

14 trials and 8 abstracts

There was no significant difference in SIBO incidence between the probiotic

and non probiotic arms.

There are currently data inconclusive data to support probiotics in SIBO

treatment
Small Intestinal Bacterial Overgrowth (SIBO)

ProKinetics

Restauration of normal GI motility

5 patients with sclerodermia : Octreotide , 50 ug / sc/ id , 3 Weeks

12 patients with cirrhosis : cisapride/id / 6 M

 SIBO-Colaboração
multidisciplinar

Medicina
Geral e

Ga
Familiar

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Doente

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Outras SIBO a
i st
especialidades i on
tri c
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Internista
Obrigada pela vossa atenção !!!