Prebióticos, probióticos y

simbióticos en alergia y sus

aplicaciones clínicas

Bruno Paes Barreto Doutor em Ciências pela Universidade Federal de São Paulo/Brasil

Professor Adjunto de Pediatria da Universidade do Estado do Pará/Brasil Membro do Comitê de Alergias na Infância da Associação Brasileira de Alergia

I certify that all my affiliations with or without financial involvement in any organization or entity with respect to the subject matter or materials discussed, are fully expressed below:

DISCLOSURES/2012

Advisory Board – Probiotics • Danone • Sanofi-Aventis

Speaker • Mantecorp-Farmasa • Takeda

LESSON PLAN

• Concepts

• Theoretical basis

• Clinical applicability

– Immune regulation

–Allergic Diseases

• Prevention

• Treatment

LESSON PLAN

• Concepts

• Theoretical basis

• Clinical applicability

– Immune regulation

–Allergic Diseases

• Prevention

• Treatment

HYGIENE HYPOTHESIS: PROPOSED CHANGES

ISOLAURI, 2010 PAST PRESENT TIME

“WE ARE MORE HUMAN OR MORE BACTERIA?”

100 trillion

Genome 10x greater than the human

Metabolic capacity equal to the liver

Different strains

Inter-species communication with the host

Consume, store and distribute energy

Mediate physiologically important chemical transformations

Self-maintenance and self-repair by means of self-replication

WHAT ARE THE FUNCTIONS OF INTESTINAL MICROBIOTA?

FUNCTIONS OF INTESTINAL MICROBIOTA

• Due to the altered microbiota, the child becomes atopic?

• Being atopic, has changed its

microbiota?

Does the use of pre, pro or

symbiotics in childhood or even

early in pregnancy could favor a

process of immune regulation

and less development of

chronic inflammatory (allergic

or autoimmune) diseases?

LESSON PLAN

• Concepts

• Theoretical basis

• Clinical applicability

– Immune regulation

–Allergic Diseases

• Prevention

• Treatment

FACTORS GOVERNING THE COLONIZATION AND STABILITY OF INTESTINAL MICROBIOTA

Pediatria (São Paulo) 28 (2):117, 2006

INTESTINAL IMMUNE SYSTEM

IMMUNE REGULATION

IMMUNOLOGY OF PREGNANCY

Th2 RESPONSE

PLACENTAL CELLS Treg PROFILE

Th1 RESPONSE DECREASED

IMMUNOLOGY OF PREGNANCY

Th2 RESPONSE AMPLIFIED

Th1 RESPONSE GREATLY DECREASED

Early T cell development is different in allergic children?

“We don’t yet know what

is causing these differences,

but these works confirmed that

abnormal immune development

begins much earlier than previously

suspected, and even before birth”

Susan Prescott

Microbiota/Probiotics

TLrs

Transcription factors

• STp peptide from Lactobacillus

• Stimulates IL-10 production by dendritic cells

• Absent in patients with IBD biomarker for homeostasis

• Future: “Nutraceuticals products”

Stress X Immune Response

CORTISOL

ANXIETY

STRESS ↑RISK OF INFECTION IMMUNE RESPONSE

L. casei defensis

↓RISK OF INFECTION

Marcos, A. Eur J Nutr. 2004. 43: 381-9

LESSON PLAN

• Concepts

• Theoretical basis

• Clinical applicability

– Immune regulation

–Allergic Diseases

• Prevention

• Treatment

•Pregnancy: •Placebo or Lactobacillus GG (1 x 1010 UFC) •2 to 4 weeks before delivery

•After delivery: • Exclusively breast feeding Mother (Pb or LGG) or children (Pb or LGG) for 6 months

• Coorte Isolauri and cols.

(Lancet 2001)

• After 7 years: risk for eczema

was significantly lower in the

LGG group

• 42,6% x 66,1%;

• RR, 0,64; 95% CI, 0,45-0,92

• SPT 7 years: (ns)

• LGG: 32%

• Pb: 33%

• Rhinitis group: number of episodes/year • Intervenction: 3.2 (2.4-4.1) • Control: 4.8 (3.5-6.1) • Difference: 1.6 episode/year (p=0,04)

• Time for immune modulation? • End point (ns)

• loss of adherence? • 80%59,9% • 80%68%

N=187 (92 i/95 c) Age: 2-5 years

The gut microbiota shapes intestinal immune responses during health and disease June L. Round1 & Sarkis K. Mazmanian1

9, 313-323 (May 2009)

FACTORS THAT INFLUENCE THE DEVELOPMENT OF ALLERGIC DISEASES

MUCOSAL/EPITHELIAL

INTESTINAL MICROBIOTA /

PROBIOTICS

NERVOUS SYSTEM

IMMUNE SYSTEM

GENETICS ENVIRONMENT

MATERNAL-FETAL INTERACTION

CLINICAL EXPRESSION

OF THE DISEASE

Kalliomaki et al. J Nutr. 2010; 140: 713s-721s

epigenetics

Twentieth century was of Antibiotics 506,706 publications (8% Reviews)

Rijkers GT et al. J. Nutr (2010), 140: 671S- 676S

Bacillus Lactobacillus

Bifidobacterias Saccharomyces (Fungus)

XXI Century is of Probiotics 15,466 (28% Reviews)

DID YOU EAT YOUR BACTERIA TODAY?

brunopaesbarreto@terra.com.br