Flavia Indrio

Impact of ELN on Microbiota Development, Gut

Health and Long Term Health

PREBIOTIC AND GUT HEALTH

EVOLUCTIONARY MISMATCH

25.000 genes

Superorganism

Human - 10 trillion cells

deprived from sperm and egg

- 23000 genes

Microbiome- 100 trillion

microbial cells- 3000000 genes

November 2011

Offspring phenotype is influenced by genetic programming and by epigenetic

regulation of gene expression, elicited by prenatal/neonatal nutrition and

intestinal microflora composition in early life.

NUTRIENTS INVOLVED IN EPIGENETIC MECHANISM

Berni Canani et al 2011

Human Milk Formula

Increased

Bifidobacteria

Increased Folate

Increased DNA

Methylation

Increased Firmicutes

Increased Histone

Deacetylation

Decreased Gene

TranscriptionIncreased Gene

Transcription

Epigenetically Induced Metabolic Changes

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://wideshut.co.uk/the-power-of-dna-and-the-potential-for-misuse/&ei=YoUzVcnoB4rEsAW1_4DwCg&bvm=bv.91071109,d.b2w&psig=AFQjCNGkWsw4v1miVUsxOjMyW_lz-cnU8A&ust=1429526227570748http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://wideshut.co.uk/the-power-of-dna-and-the-potential-for-misuse/&ei=YoUzVcnoB4rEsAW1_4DwCg&bvm=bv.91071109,d.b2w&psig=AFQjCNGkWsw4v1miVUsxOjMyW_lz-cnU8A&ust=1429526227570748

What is the evoluctionary mismatch ?

A. A disease of the genes

B. The discrepancy between the ancient genes and the

modern environment

C. A model of epigenetics

D. A DNA sequency

A. B. C. D.

8%

0%

8%

85%

2 years

Establishedcommunity

Born with low diversity

Ob. AnaerobesBacteroidesClostridium

Fac. AnaerobesStreptococciColiformsEnterococciLAB

Development of the normal microbiota

Dominguez-Bello MG et. al., Gastroenterology. 2011,140(6):1713-9. Review

Establishment and stability of the microbiota

Delivery mode

Mothers gut, vaginal tract and skin

Antibiotics

Feeding patterns

Family structure

Geographc origin

Factors influencing the establishment of the intestinal

microbiota in infancy

Breast milk

PREBIOTIC

Critical Windows for Microbiome: Epigenome Interaction

Which factors influence the establishment of Microbiota ?

A. Delivery mode

B. Breast milk

C. Functional food

D. All of this

E. None of this

A. B. C. D. E.

5%

29%

0%

61%

5%

PREBIOTIC

“is a non-digestible food ingredient that beneficially

affects the host by selectively stimulating the

growth and/or activity of one or a limited number of

bacteria in the colon thereby improving the host’s

health”

Prebiotics

Non-Digestible Oligosaccharides(NDO)

INULIN FOS (fructo-oligosaccharides) GOS (galacto-oligosaccharides) LACTULOSE

Which of these is not a prebiotic ?

A. Inulin

B. Breast milk

C. Maltodestrine

D. Lactulose

A. B. C. D.

13%10%

72%

5%

PREBIOTICSInulin and fructooligosaccharides

TransgalactooligosaccharidesLactulose

Increase of bifidobacteria and lactobacilli

Non-digestible food ingredients that stimulate the growth and/or activity of bacteria

Immuno-modulation

Anti-microbial effect

Optimize stool consistency

Microbial fermentation of oligosaccharides

SCFA(butirate) Energy source for enterocitesand immune sistem cells

↓pH and increased uptake of Ca

Relieve constipation

EFFECTS OF PREBIOTICS

• Improvement and / or stabilization of the intestinal

microbiota composition

• Improvement of intestinal function (mass, regularity

and fecal consistency)

• Increased absorption of minerals and improvement

of bone health

• Modulation of the production of gastrointestinal

peptides, energy ,metabolism ,satiety

EFFECTS OF PREBIOTICS

•Improvement of intestinal barrier function, decreased of

hematic toxins

•Risk reduction of intestinal infections

•Risk reduction of obesity, type 2 diabetes, metabolic

syndrome, etc.

•Risk reduction and / or improvement in the management

of inflammatory bowel disease

• Risk reduction of colon cancer

PP activation

MLN activation

vascular permeability

Changes in tight junctions and

epithelial function

Water secretion

inflammatory cells

infiltration

Luminal Antigens (food, toxins, etc)

Systemic Immune Activation

DEVELOPEMENT AND PRODUCTION OF SPECIFIC SUBSTANCES (SCFA

Cytokine ect )FOR APPROPRIATE FUNCTION (immunity Intestinal motility )

One of these is NOT a function exert by prebiotic

A. Improvement and / or stabilization of the intestinal microbiota composition

B. Improvement of intestinal function (mass, regularity and fecal consistency)

C. Increased absorption of minerals and improvement of bone health

D. Decrease production of SCFA

A. B. C. D.

0%

74%

26%

0%

Many studies in animal and in human…..

ACTION ON

INTESTINAL FUNCTION

Prebiotic Effects on Gut Barrier

epithelial cell tight junctions

mucus production

Reduction of bacterial adhesion

Induction of defensins/sIgA

enhanced cell survival

• Prebiotics enhance gut barrier function bothdirectly through effects on tight junctions andindirectly through immune modulation

• Prebiotics can protect against tight junctiondisruption induced by pathogens and pro-inflammatory cytokines

-,03

0

,03

,05

,08

,1

,13

,15

,17

,2

,23

La/M

a r

atio

g0 g10 g20 g40

p

ELETRIC WAVES PROPAGATION

0

5

10

15

20

25

p= 0.036 Placebo group

Prebiotic group

Pro

pag

ati

on

(%

)

JPGN 2009

HALF EMTYING TIME

Tim

e 0

Tim

e 15

day

s

Tim

e 0

Tim

e 15

day

s

0

20

40

60

80

100*

**

Prebiotic group

Placebo group

Half

em

pty

ing

tim

e (

min

)

*p=0.006

**p=0.002JPGN 2009

.....BEYOND THE GUT…

Gastroenterology 2013

Four weeks intake of a FMPP by healthy women affected

activity of brain regions that control central processing of emotion

and sensation.

……BEYON THE GUT….AND THE BRAIN

POSSIBLE RELATIONSHIP BETWEEN OBESITY AND MICROFLORA

The fermentation of fructani in the colon contributes to the control of food intake (obesity, insulin resistance metabolic syndrome) involving intestinal peptide and controlling the inflammatory status of the intestinal mucosa

EFFECTS OF PREBIOTIC SUPPLEMENTATION IN NEWBORNS ON WEIGHT GAIN DURING THE FIRST THREE

YEAR OF LIFE

Indrio et al submitted

Demographical and clinical characteristic at baseline

Tot n = 106 Breastfed n = 30 Gos:Fos n = 39 Placebo n = 37

Gestational age 38w (1,2) 38w (1,2) 39w (0,7)

Gender (M/F) 16/14 18/21 15/17

Birth weight (g) 3143 (285) 2920 (491) 2870 (371)

Apgar score 10’ 9,4 (0,3) 8,7 (0,7) 9,1 (0,7)

Way of delivery (SD/CS) 18/12 25/14 25/12

Table 1. Demographical and clinical characteristic of the study population at baseline

1.3

-0.1 -0.1-0.2

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

Placebo 2.6 (2.2 – 3.5) yrs

Prebiotic 3.1 (2.3 – 3.5) yrs

Breast feeding3.2 (2.6 - 3.5) yrs

BM

I SD

SMean BMI according to feeding group

Placebo vs Prebiotic: p = 0.005Placebo vs Breast feeding: p = 0.004Prebiotic vs Breas feeding: n.s.

The potential beneficial effect of prebiotic are targeting on:

A. Intestine

B. Liver

C. Brain

D. Bone

E. All of this

A. B. C. D. E.

2% 0%

90%

4%4%

CONCLUSION

Most studies indicate that, when taken in sufficient amounts, prebiotics :

•soften stools,

• increase stool frequency (without episodes of diarrhea),

•increase the ratio of bifidobacteria to total fecal bacteria.

In infants receiving prebiotic-supplemented formula, water balance remains

normal and, in most studies, the infants continue to grow appropriately.

CONCLUSION

EFSA observed that the addition of the prebiotic

mixture of inulin-type fructans and GOS in a 9:1 ratio

at a concentration of 8 g/L to infant formula is

considered safe, although additional data on growth,

body composition, nutrient availability, and water

balance still must be obtained.

A number of questions remain about the mechanisms

underlying the potential benefits of prebiotics.