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May 29, 2023 339 likes •528 views

Early prebiotic supplementation induces long-lasting consequences on microbiota composition and metabolic health of adult pigs consuming an unbalanced diet. C. Le Bourgot 1 *, B. Taminiau 2 , S. Ferret-Bernard 3 , A. Cahu 3 , L. Le Normand 3 , F.

SLIDE 1

C. Le Bourgot1*, B. Taminiau2, S. Ferret-Bernard3, A. Cahu3, L. Le Normand3, F. Respondek1,
E. Apper1, I. Le Huërou-Luron3, S. Blat3

1Tereos, France 2University of Liège, Belgium; 3 Numecan, INRA, INSERM, Univ Rennes 1, France

*Cindy.lebourgot@tereos.com

Early prebiotic supplementation induces long-lasting consequences on microbiota composition and metabolic health of adult pigs consuming an unbalanced diet.

SLIDE 2

Food transition and evolution of non-communicable chronic diseases

Family environment Lack of exercise Quantity, quality and structure of food

Overweight and obesity Diabetes

Increased prevalence of obesity and associated metabolic disorders

(% world population ; INSEE & OMS)

Perinatal nutrition

Combris (FAO Stat)

Carbohydrates Lipids Proteins

International Diabetes Federation

SLIDE 3

Developmental origins of health and disease (DOHaD): Barker’s hypothesis

Conception – Gestation – Birth – 2 years

= 1000 days

Critical developmental window

Importance of the early nutritional environnent Adult health

5 10 15 20 25 30 35 40 45 < 2,5

2,94
3,40
3,85
4,30

> 4,31

% adult population with intolerance to glucose or diabete

Hales et al., 1991

Birth weight

SLIDE 4

Non digestible food Microbiota SCFA

Gut

SCFA Mucus

Glucose metabolism Pancreas

Entero-insular axis GLP-1 Insulin

Muscle Adipose tissue Liver

GPR

The gut microbiota: an actor of metabolic programming

Complex interactions with host

SLIDE 5

The gut microbiota: an actor of metabolic programming

Establishment during early life and consequences later in life

Diet rich in lipids

Cox et al., 2014

Control Antibiotic

Gestation Lactation

D0 Weaning (D21-28) Conception Adult

Post-weaning

Control High-protein Prebiotic

Hallam et al., 2013 & 2014

22%

Prebiotics : A beneficial nutritional strategy for adult health ?

SLIDE 6

Beet Sucrose

Prebiotics – scFOS

Direct effects of scFOS :

↑ Beneficial bacteria Bifidobacteria & Lactobacilli, and SCFA production

(Saulnier et al., 2008; Le Blay et al., 2003)

↓ Adiposity and inflammatory markers (Shinoki et al., 2011)
↑ GLP-1 secretion (Kaji et al., 2011) and insulin sensitivity (Respondek et al., 2008 and 2010)

« The selective stimulation of growth and/or activity of one or a limited number of bacteria in the gut microbiota that confers health benefits to the host » (Roberfroid et al. 2010) Short-chain fructo-oligosaccharides (scFOS)

scFOS: Long-term effects when consuming during early life ?

SLIDE 7

scFOS

Objective

Glucose metabolism

?

Microbiota

SLIDE 8

Experimental design

Gestation Lactation Post-weaning

+28 +56/77 Age (days)

scFOS-supplemented diet = scFOS Control diet = CTRL HF HF

Diets Control High-Fat (HF) Digestible energy, MJ 13,43 14,99 % digestible energy :

Proteins

23,5 17,9

Lipids

7 22,6

Carbohydrates

69,5 59,5

CTRL scFOS +274 +190 0,33% = 10g/j 0,15% = 1,2g/j

* Microbiota analysis * Blood, intestinal contents, tissues and organs * Microbiota analysis

SLIDE 9

10 20 30 40 50 60 70 80 90 100

CTRL scFOS

Abondance relative (%)

↑ ↑ ↑ ↑ ↑

↑ ↑ ↓ ↓ ↓

scFOS

Firmicutes

Bacteroidetes

Bacteria_unclassified Spirochaetae Tenericutes Cyanobacteria Proteobacteria Lentisphaerae SHA-109 Verrucomicrobia Actinobacteria

↑

Microbiota – Bacterial composition

↑

Phylum

CTRL n=6 scFOS n=6

D+190: Standard diet

Genus

D+253

scFOS

Firmicutes Bacteroidetes Bacteria_unclassified Spirochaetae Tenericutes Cyanobacteria Proteobacteria Lentisphaerae SHA-109 Verrucomicrobia Actinobacteria Fibrobacteres Planctomycetes Candidate_division_TM7 Elusimicrobia Synergistetes Fusobacteria Deferribacteres

D+253: HF diet

CTRL n=6 scFOS n=6

10 20 30 40 50 60 70 80 90 100

CTRL-HF FOS-HF

Abondance relative (%)

↑ ↑ ↑ ↑ ↑

↑ ↑ ↓ ↓ ↓

CTRL scFOS

Perinatal scFOS: ↑ Prevotella

16S rRNA sequencing

SLIDE 10

Microbiota – Metabolic activity

Faecal SCFA Faecal metabolome

scFOS vs CTRL Isobutyric acid

↑

Fermentative metabolites Hydroxy-methyl butyric acid

↑

Taurocholic acid

↑

Bile acid L-Threonine

↑

Amino acid Glycerol

↑↓

Energy metabolism

*

CTRL n=7 scFOS n=7

D+253

70 80 90 100 110 120 130 J190 J211 J253 mmol/kg CTRL-HF FOS-HF CTRL n=7 scFOS n=7

↑ Acetate : + 28,6% ↑ Propionate : + 21,7%

* P < 0,05

Gaz chromatography Liquid chromatography coupled to mass spectrometry (LC/MS)

Perinatal scFOS: ↑ Fermentative metabolites and bile acids

SLIDE 11

Microbiota

D+253

↑ Taurocholic

acid

R = 0,64

↑ SCFA and other

fermentative metabolites

↑ Bacteroidetes

(Prevotella)

Perinatal scFOS

Pancreas Muscle Adipose tissue Gut

What are the consequences for adult metabolic health?

SLIDE 12

L cell GLP-1

Entero-insular axis and glucose homeostasis

1 2 3 4 5 HF HF-FOS Nb/mm2 mucosa

Nb GLP-1 secreting L cells

(caecum)

*

CTRL scFOS 10 20 30 40 HF HF-FOS Pmol/L

Plasma GLP-1

CTRL scFOS

D+274

0.47

+

* P < 0,05 + P < 0,10 n=11 CTRL n=13 scFOS

SLIDE 13

L cell GLP-1

Entero-insular axis and glucose homeostasis

1 2 3 4 5 HF HF-FOS Nb/mm2 mucosa

Nb GLP-1 secreting L cells

(caecum)

*

CTRL scFOS 10 20 30 40 HF HF-FOS Pmol/L

Plasma GLP-1

CTRL scFOS

D+274

+

* P < 0,05 + P < 0,10 n=11 CTRL n=13 scFOS Pancreas Insulin content Endocrine tissue 0.65

SLIDE 14

L cell GLP-1

Entero-insular axis and glucose homeostasis

1 2 3 4 5 HF HF-FOS Nb/mm2 mucosa

Nb GLP-1 secreting L cells

(caecum)

*

CTRL scFOS 10 20 30 40 HF HF-FOS Pmol/L

Plasma GLP-1

CTRL scFOS

D+274

+

* P < 0,05 + P < 0,10 n=11 CTRL n=13 scFOS Pancreas Insulin content Endocrine tissue

50 100 150 200 250

10 20 30 40 50 60 70

µUI/ml

Insulin (IVGTT)

+ +

* * * *

Diet p=0,09 Time p<0,001 Diet*t p=0,01 Glucose injection

Chan et al., 2011

Muscle Adipose tissue Genes : GLUT4, INSR, SREBP1-C

Perinatal scFOS: Stimulation of capacity to secrete GLP-1 and improvement of

pancreas sensitivity to glucose (Le Bourgot et al., in preparation)

SLIDE 15

PLS-DA discriminating both groups (LC/MS)
LysoPC : identified as a potential plasma

marker of obesity and metabolic disorders (↓)

(Zhao et al., 2010; Barber et al., 2012; Yea et al., 2009)

Plasmatic metabolome

L y s o P C p la s m a

X 1 0 8

C T R L s c F O S 2 4 6 8 1 0

Lysophosphatidylcholine (18:0) (LysoPC)

CTRL scFOS

D+253

Glucose intolerant Glucose tolerant Glucose tolerant and glycemia <6,4 mmol/l

Perinatal scFOS: ↑ LysoPC (18:0) = improvement of glucose control

SLIDE 16

Microbiota scFOS : 0.15 to 0.33% of the diet = physiological dose

Conclusion

Metabolic adaptation

Sustained effect on microbiota Stimulation of entero-insular axis (GLP-1)

SLIDE 17