UNIVERSIDAD NACIONAL “SAN LUIS GONZAGA” DE ICA

FACULTAD DE MEDICINA HUAMAN “DANIEL ALCIDES CARRION”

SECCIÓN DE SEGUNDA ESPECIALIZACIÓN
GASTROENTEROLOGIA

Small Intestinal Bacterial Overgrowth

MR1 PELLON KARLOS, ANTHONY JAVIER

 Caso clinico
• Una mujer de 29 años viene a por intolerancias alimentarias y
sensibilidad al gluten. Ella informa que tiene hinchazón abdominal y
malestar después de comer varios alimentos, cólicos abdominales y
heces sueltas que van de 2 a 3 al día sin sangre durante el año
pasado. Los síntomas se alivian por el paso de las heces. También se
queja de fatiga.
• Ella hizo una dieta sin gluten hace dos meses. Ella se siente mejor,
pero ahora encuentra que otros alimentos también están
conduciendo a hinchazón, dolor y heces blandas. Ella está
preocupada por las alergias alimentarias y si tiene enfermedad
celíaca. También pregunta si su dieta cada vez más restrictiva
causará problemas nutricionales.
• ¿Cómo aborda las preocupaciones del paciente?
¿Cuáles son las Causas de las Reacciones
Adversas a los Alimentos del Paciente?
• Celiac disease
• Non-celiac gluten sensitivity (NCGS)
• Other food sensitivities
• Food allergies
• IBS or another FGID
• Small intestinal bacterial overgrowth (SIBO)
 Small Intestinal Bacterial Overgrowth:
What is It?
• Definition of small intestinal bacterial overgrowth (SIBO):
– Disruption of the normal small bowel bacterial population; may result in gas,
bloating, flatulence, altered bowel function, or malabsorption
– Widely accepted definition is >105-3 CFU/ml from the proximal jejunum
– Lower cut off may be appropriate for colonic type bacteria

• Wide array of effects

– Direct injury, changes in function/sensation, gut immunology, permeability, and loss
of brush border enzymes

• Clinical manifestations from asymptomatic to bloating to

frank malabsorption

Sleisenger & Fordtran’s. Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management;

The Gut Microflora in Health and GI Disease
• Bacteria exceed the number of host somatic cells by >one
order of magnitude
– Gut bacterial population ~100 trillion
– 500-1000 different species of bacteria
– 60% of fecal biomass is from bacteria
• Microflora exerts important effects on:
– Structure, physiology, biochemistry, immunology, maturation of
vasculature, and gene expression
– Bidirectional effects on gut neuromotor function
– Role in IBD, SIBO, IBS, diverticular disease?
– Differences in microflora reported in IBS vs. healthy controls
 Normal Intestinal Microflora & pH

Duodenum
101–103 Stomach
101–103 cfu/ml Most Common Bacteria
cfu/ml
pH ~6.4
Anaerobic Genera Aerobic Genera

Bifidobacterium Escherichia

Colon Clostridium Enterococcus

10 –1012 cfu/ml
11

Proximal pH~6.2 Jejunum/Ileum Bacteroides Streptococcus

Distal pH~7.3 104–107 cfu/ml
Ileal pH~7.6 Eubacterium Klebsiella

O’Hara AM, Shanahan F. EMBO Rep. 2006;7:688-693

Kloetzer et al. Gastroenterol 2007;132 (suppl 2):A461
 Factors Which Protect Against SIBO
Pancreatic &
Biliary Secretions Gastric Acid

Mucosal Immune
System

Migrating Motor
Complex (MMC)
IC Valve

O’Hara AM, Shanahan F. EMBO Rep. 2006;7:688-693, Kloetzer et al. Gastroenterol 2007;132 (suppl 2):A461
 Disorders Commonly Associated with SIBO
Gastric acid Pancreatic Motility Disorder Immune GI Structural
secretion enzymes Deficiency Defect
Potent acid Chronic Aging Immuno- Fistula
suppressive drugs pancreatitis suppressive Rx
Celiac sprue IC valve resection
Atrophic gastritis Cirrhosis CVID
Cirrhosis Bariatric surgery
Vagotomy Cystic fibrosis IgA deficiency
Crohn’s disease JI bypass

DM with AN Small bowel tics

Pseudo- Surgical blind loop

obstruction

Renal failure

Radiation enteritis

Scleroderma

Maneeratanaporn, Chey. SIBO, 2009

Breath Testing for SIBO

Saad & Chey, Gastroenterol 2007;133:1763

Breath Testing for SIBO in IBS
Methods of Detection
Direct Aspiration and Culture
Glucose
Glucose Breath Test
Lactulose Lactulose Breath Test

Bacterial Concentration,
Organisms/mL
<102
>105

Adapted from Lin HC. JAMA. 2004;292:852-858

 Testing for SIBO
77 patients with suspected SIBO underwent:
jejunal aspiration culture, gas chromatography of fatty acids,
H2BT— lactulose and – glucose

Test Sensitivity Specificity

Chromatography of fatty
acids in aspirate
56% 100%

H2 breath test-lactulose 68% 44%

H2 breath test-glucose 62% 83%

Corazza GR, et al. Gastroenterology. 1990;98:302-309.

 SIBO: Which test?
• Aspiration and Culture
– Gold standard?
– Difficult to perform, sampling error, costly
• Deconjugation of bile salts (SeHCAT, 23-seleno-25-homotaurocholic acid)
• C14 - xylose breath test
• Breath tests
– Lactulose
• Sensitive but not specific - Likely leads to overtreatment
– Glucose
• Specific but likely not as sensitive - May lead to under treatment
– Bottom line: Best choice of breath test remains to be determined

Saad & Chey, Gastroenterol 2007;133:1763

What is the Evidence to Support
the Use of Antibiotics in IBS?
 Efficacy of Antibiotics for SIBO
Antibiotic Efficacy in SIBO

Metronidazole (250 mg TID) <20%

Neomycin (500 mg BID) 25%

Augmentin (250-875 mg TID/BID) or
30%-40%
doxycycline (100 mg BID)
Rifaximin (400 mg TID) 70%*

*Di Stefano M, et al. Aliment Pharm Ther. 2000;14(8):551-556.

 Placebo Control Antibiotic
Studies in IBS
Study Treatment % Improved*
Placebo, n = 44 11%
Pimentel, 2003 Neomycin, n = 43 35%
(500 mg, BID) (p<0.05)
Placebo, n=61 12%
Sharara, 2006 Rifaximin, n = 63 29%
(400 mg, BID) (p=0.03)
Placebo, n = 56 21%
Pimentel, 2006 Rifaximin, n = 55 36%
(400 mg, TID) (p=0.026)
Placebo, n = 197 44 %
Lembo, 2008 Rifaximin, n = 191 52 %
(550 mg, BID) (p=0.03)
Placebo, n ~600 32 %
Pimentel, 2010 Rifaximin, n ~600 41 %
Vanner S. Gut.. 2008, 57:1315 (550 mg, TID) (p=0.0008)
Lembo A, et al. DDW 2008. Abs T1390
Pimentel M, et al. DDW 2010
 Dose-Finding Study of Rifaximin
in SIBO Patients With IBS
100
n=90 *
600 mg/d

80 800 mg/d
†
1200 mg/d
Patients (%)

60 Dosing duration, 7 days

40 ns • No significant
differences in
adverse events
20 among 3 groups

0
Glucose Breath Test Normalization
*p<0.001.
†p<0.01.

Lauritano EC, et al. Aliment Pharmacol Ther. 2005;22(1):31-35.

 Rifaximin for Non-Constipated IBS:
Results from 2 phase III RCTs
50

40
* *
Placebo
% Responders

30 Rifaximin
* P < 0.0008
20 NC-IBS with mild to moderate symptoms
N = 1,260, Target 1 = 623, Target 2 = 637
Rifaximin 550 mg tid x 14 days
10 Patients followed for an additional 10 wks

0
AR - IBS symptoms AR - Bloating

Pimentel, et al. DDW 2010

Antibiotics & IBS: The Way Forward?
• Reasons for symptom improvement unclear
– SIBO vs. alteration of colonic flora/fermentation?

• Optimal diagnostic test for SIBO unclear

– Breath test results may not predict response to antibiotics

• Optimal antibiotic therapy unclear

• Benefits appear transient
– How can we increase the durability of response?
– How best to treat recurrent symptoms?

• Potential consequences of repeated, widespread

antibiotic use?
Chey. AGA Perspectives 2009;4:5-8
 Breath Test Recurrence
After Treatment with Rifaximin
50 46

40

% 28
30
Positive
LBT
20
13

10

0
3 6 9
61 consecutive IBS pts Months of Follow-up
Rifaximin 1.2 grams/day x 7 d
Positive LBT associated with pain,bloating,
Lauritano, et al. Am J Gastroenterol 2008; 103:2031
flatus, diarrhea
 What are the Options to Reduce IBS
Symptom Relapse?

• Prokinetics
• Probiotics
• Rotating antibiotics
• Dietary manipulation
– Low FODMAP
– Gluten-free
– Low fat
– Others?
– statins
 Biological Variables that Influence
the Developing Immunophenotype of an Infant

Brandtzaeg, Nat Rev Gastroenterol Hepatol, 7: 380-400, 2010