Effect of diet and lifestyle on risk of
gastrointestinal infection and allergy in
early life; consumer knowledge attitudes
and needs
INFABIO QLK1 2002 02606
www.gla.ac.uk/infabio
Partners
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C A Edwards, Glasgow University, UK
A Gil, University of Granada, Spain
J Schmitt, Numico Research, Germany
H Schroten, University Children’s Hospital, Dusseldorf, Germany
E Norin, Karolinska Institute Stockholm, Sweden
S Amarri, University of Modena & Reggio Emilia Modena, Italy
J Dore, INRA Jouy en Josas, France
M Kiely, University College Cork, Ireland
F Romero, Hero, Spain
E Hamelmann, Pediatric Pneumology & Immunology, Charite
Humboldt University Berlin, Germany
M Fons, INRA Avignon, France
M Fons, Faculty Sciences et Techniques Marseille St Jerome
Marseilles, France
Gut flora and allergy in early life
• Food allergy thought to be increasing in incidence
• Gut microflora needed for correct maturation of
the immune system
• Diet and environment likely to influence both
colonisation and immune system sensitisation in
early life
Diet, environment and gut colonisation
Infant born with sterile gut
Many factors thought to affect colonisation of gut
–
–
–
–
–
Delivery mode
Genetics
Breast milk or formula
Environment
Weaning age and diet
The hygiene hypothesis
• Very hygienic lifestyles have been associated with
increased incidence of eczema and asthma (Strachan
1989)
• Children who live on farms or in large families or
have more infections have less allergy symptoms
(Strachan 2000, Matricardi et al 2000)
• The microflora of children with eczema and asthma
may have different colonic microflora than non
allergic peers (Bottcher et al 2000, Kalliomaki et al 2001)
INFABIO AIMS
•To evaluate the influence of diet and lifestyle on
the incidence of allergy, infection and illness in
infants, as well as analyse consumer needs and
attitudes to foods and food products across
Europe
•To have a better understanding of the
relationships between diet, lifestyle and infant
feeding practices in Europe.
Project organisation and workpackages
WORK PACKAGE 1
(Responsible partner 08)
Development of new tools
WP1a (RP 08) : needs of consumers
(parents & carers)& attitudes to
infant food products, processing
and labelling
WORK PACKAGE 3 (Responsible partner 08)
Consumer Survey
• Apply WP1a tool
• Sensory attributes leading to
liking, sustained consumption and
preference for food products
Sample transfer
Information transfer
WORK PACKAGE 6
(Responsible partner 03)
Collation, analysis and
dissemination of new information
WP1b (RP 01) : diet, feeding patterns
and lifestyles of infants, including
incidence of illness
WORK PACKAGE 4 (Responsible partner 01)
Diet & Lifestyle Survey
• Infant diet, feeding patterns
& lifestyle
• Potential allergen exposure
• Record of allergy, diarrhoea, G.I
and other illness
WORK PACKAGE 2
(Responsible partner 01)
WP6b (RP 01) :
Role of food and lifestyle in
promoting and sustaining
health of infants
Collection of Infant faecal material
WP2a (RP 10) : Allergy study
WP6a (RP 05) :
Database of food consumption
in European infants
WORK PACKAGE 5 (Responsible partner 07)
Identification of bio-markers/risk factors
WP2b (RP 02) : Intervention study
WP2c (RP 01) : Cross-cultural study
• Bacterial analysis
• Intestinal barrier function. sIgA,
sialic acid
• Bioactive molecules
• Bioactive enzymes
• Helicobacter antigen assay
WP6c (RP 08) :
Needs of consumers (parents
& carers) & attitudes to infant
food products, processing
and labelling
INFABIO cohort study
• 781 infants (606 with faecal samples for FISH) in
5 countries
• UK, Germany, Italy, Spain, Sweden
• Faecal samples collected at five times in first year
• Diet, Environmental and Health questionnaires at
same timepoints
Prevalence of any breastfeeding by INFABIO
centre
Breast feeding rates varied between centres with
Stockholm having the highest initial rates and
Glasgow the lowest.
The prevalence of breast feeding declined fastest in
Granada and slowest in Stockholm
Age of introduction of complementary foods by INFABIO
centre
1.0
Glasgow
Granada
Reggio-Emilia
Dusseldorf
Stockholm
Proportion of infants
0.8
0.6
0.4
0.2
0.0
0
4
8
12
16
20
24
Age (weeks)
28
32
36
40
Parental reported family history of allergy by
centre (n-=781)
• Dusseldorf had the highest self reported rate of
allergy for pollen/dust/animal fur, food
drugs/insect bites, cosmetics / detergents/metals.
–
66.4% of families total allergies (p<0.001)
• Granada had the lowest self reported allergy for all
items.
– 30.6% of families total allergies
Foods parents in consumer study associated with food allergy
Foods Associated with Allergy
105
90
75
60
45
30
15
%
0
dairy-milk
seafood-shell fish
tree nuts
peanuts
Food Types
Foods Associated with Allergy
germany
italy
scotland
spain
sweden
105
90
75
60
45
30
15
Synnott et al
0
soy
wheat
gluten
eggs
spices
spain
sweden
Food Types
germany
italy
scotland
Parental attitudes and knowledge with regard to allergy
(Synnott et al)
Environment Factors and Infant Allergy
allergies are genetically inherited only
agree
pollution contributes to allergies in infants
the weather contributes to allergies in infants
neutral
too early exposure to the sun contributes to allergies in
infants
disagre
e
a little dirt prevents allergies in infants
having an overly clean house prevents allergies in infants
0
100
200
300
Participant
s
400
500
600
Infant Feeding and Allergy
breastfeeding prevents allergies in infants
agree
cow's milk consumption before the age of 1yr contibutes to
allergies in infants
cow's milk consumption after the age of 1yr contributes to
allergies in infants
neutral
introducing solids at an early age encourages allergies to
develop
disagre
e
food additives contribute to allergies in infants
food preservatives contribute to allergies in infants
0
100
200
300
Participant
s
400
500
Comparison of allergenic practices by level of allergy
risk
The only significant association of parental behaviour
with calculated infant allergy risk was use plastic cover on infant’s
mattress (P<0.001)
Infants with high risk of allergy were less likely to have a plastic
cover on their mattress than infants with possible or unlikely risk.
There was no association with feeding, smoking, or household
pets.
Infants with a probable or highly probable risk of allergy were no more
likely to be breastfed for longer than infants with a lower risk of allergy.
No relationship was seen between the level of allergy risk and the
age at which solids were introduced
History of infant illnesses in first 12 months of life by centre (n=642)
Total
Glasgow
Granada
Reggio-
Düsseldorf
Stockhol
P
(n=642)
(n=110)
(n=144)
Emilia
(n=176)
m
value a
(n==119)
%
%
%
%
(n=93)
%
%
Diarrhoea (any)
60.7
60.0
50.7
74.8
58.5
63.4
.002
Diarrhoea no fever
37.9
48.2
8.3
56.3
41.5
40.9
<.001
Diarrhoea with fever
31.0
20.9
46.5
30.3
25.0
31.2
<.001
Constipation
56.2
42.7
89.6
81.5
30.7
36.6
<.001
Colic
49.7
37.3
54.2
83.2
45.5
22.6
<.001
Itchy rash
43.3
33.6
34.7
75.6
36.9
38.7
<.001
Eczema
39.6
34.5
27.8
24.4
64.2
36.6
<.001
Vomiting (repeated)
35.8
27.2
26.4
56.3
30.1
45.2
<.001
Respiratory infection
26.9
23.6
22.2
31.1
38.1
11.8
<.001
Rhinitis
14.2
17.3
9.0
15.1
15.9
14.0
.339
Antibiotics prescribed
44.7
52.7
42.4
67.2
36.9
24.7
<.001
Those who had a family history of allergy
More likely to have eczema
(Odds Ratio 2.052; 95% CI 1.475-2.856).
Those who had cows milk introduced before 12 months
Less likely to report eczema by 12 months
(Odds Ratio 0.687; 95% CI 0.5 – 0.956).
As age of introduction of solids increased
Odds of reporting eczema increased
(OR 1.041; 95% CI 1.005-1.079).
Cohort faecal bacteria
• Expected differences seen in breast vs
formula fed infants
• Breast feeding favoured Bifidobacteria
• Formula fed infants more diverse flora –
more Lactobacilli, Bacteroides and C.
coccoides
Cohort faecal bacteria
• The microflora different between countries even
allowing for feeding method, caesarean,
antibiotics etc.
• Spain was the most different
• At 6 weeks
–
–
–
–
More predominant Bacteroides
less Bifidobacteria,
Greater diversity
different SCFA profile – less acetic and lactic acid
Factors affecting bacterial colonisation
• Impact of caesarean confirmed in terms of
bacteria and metabolic products –
Infants born by caesarean had
– higher propionate
– less Bacteroides and more C. coccoides
– some effect maintained after weaning.
• Similar differences in flora seen in infants from
mothers who had antibiotics late in pregnancy or
during lactation.
Faecal bacteria and parent reported
symptoms
Significant relationship between
• C. difficile at week 6 and history of eczema by 12
months (p<0.032),
• C. coccoides (p<0.021) and C. leptum (p<0.023)
postweaning and history of eczema by 12 months
• C. difficile (p<0.003) and Enterobacteria
(p<0.01) postweaning to rhinitis by 12 months.
Faecal biomarkers
Infants with parental reported eczema
– More likely to have higher levels of iso-caproic
acid >5mmol/l vs <2mmol/l (p<0.05)
Faecal SCFA and illness
• Higher faecal acetate 6 weeks and post weaning–
higher risk diarrhoea by 12 months (p<0.01),
higher risk of rash (p=0.013)
• Higher butyrate 6 weeks – higher number of visits
to doctor by 12 months (P<0.05)
• Higher butyrate post weaning- higher rhinitis and
constipation (P<0.05)
Cows milk protein allergy
case – control study
Characteristics of sample in case control study
Cases
Controls
(n= 132)
(n=132)
N
%
N
%
Males
132
50.0
132
50.0
Centre
Glasgow
16
12.1
16
12.1
Granada
46
34.8
46
34.8
Stockholm
32
24.2
32
24.2
Reggio-Emilia
8
6.1
8
6.1
Berlin
30
22.7
30
22.7
Cases had diagnosed cow’s milk protein allergy.
+ve SPT, high IgE and/or food challenge
Comparison of factors associated with cows
milk protein allergy
The only significant differences found so between far
cases and controls with relation to environmental
factors are family history of allergy (p=0.017) and a
higher level of antibiotic use in children with allergy.
Comparisons of common illness in cases of CMPA and
controls
Cases
(n= 132)
N
%
Ever had an itchy rash
Yes
No
Ever had eczema
Yes
No
Ever had repeated
vomiting
Yes
No
Ever had constipation
Yes
No
Ever had colic
Yes
No
Ever had bronchiolitis
Yes
No
Ever had diarrhoea
Yes, with fever
Yes, without fever
No
Controls
(n=132)
N
%
p
92
36
71.9
28.1
21
109
16.2
83.8
<0.001
81
48
63.3
36.7
31
100
23.7
76.3
<0.001
46
84
35.4
64.6
23
106
17.8
82.2
0.002
39
89
30.5
69.5
27
103
20.8
79.2
0.087
55
71
43.7
56.3
39
91
30.0
70.0
0.028
28
100
21.9
78.1
18
113
13.7
86.3
0.104
35
41
53
27.1
31.8
41.1
13
29
89
9.9
22.1
67.9
<0.001
Faecal bacteria
FISH
(Matteo et al )
Cases had
• higher proportion C Coccoides group, Atopobium
and C perfringens+ C difficile (P<0.05)
• Lower Enterobacter, Lactobacilli and
Streptococci.
Simililitud
• DNA patterns associated with
– C Sphenoides, Collinselli aerofaciens, Eubacteria
Halii, Mesorhiz Loti, Bacteroides distasonis, and C
coccoides
– More likely in cases than controls
1 0
2 0
234Hha-verd
245Hha-verd
174Hha-verd
250Hha-verd
290Hha-verd
122Hha-verd
251Hha-verd
193Hha-verd
101Hha-verd
266Hha-verd
330Hha-verd
262Hha-verd
155Hha-verd
117Hha-verd
230Hha-verd
172Hha-verd
102Hha-verd
337Hha-verd
299Hha-verd
237Hha-verd
221Hha-verd
121Hha-verd
264Hha-verd
256Hha-verd
341Hha-verd
228Hha-verd
353Hha-verd
390Hha-verd
313Hha-verd
178Hha-verd
Faecal bacteria
RT FLP
(only Granada infants measured; Gil et al)
0
-10
-20
-30
-40
3 0
Faecal biomarkers
(Khanna et al)
• No statistical difference in isocaproic acid
between cases and controls
• Higher level of β glucuronidase (p<0.02)
and branched chain fatty acids (p=0.051) in
cows milk protein allergy cases.
Conclusions
• Many different effects on infant microflora.
• Geographic effects may confound studies
comparing countries at high and low risk of
allergy
• Many parameters associated with ‘allergy’
confirmed for parent reported eczema
• Cows milk protein allergy differed from eczema
associations but C difficile and other bacteria need
to be considered further.