ArticlePDF Available

Multi-strain Symbiotic Preparations as a Novel Adjuvant Approach to Allergic Rhinitis

Authors:
  • Azienda USL Toscana Centro

Abstract and Figures

Objective. To investigate the effects of Lactobacillus acidophilus NCFM / Bifidobacterium lactis BL-04 / fructo-oligosaccharide and Lactobacillus plantarum LP01/ Lactobacillus paracasei LPC00 / fructo-oligosaccharide preparations in the routine clinical management of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR), respectively. Materials and Methods. Seventy-six and fifty-one outpatients attending 36 Allergy Clinics in Italy with clinically documented allergic rhinitis consumed a symbiotic combination of Lactobacillus acidophilus NCFM / Bifidobacterium lactis BL-04/ fructo-oligosaccharide and Lactobacillus plantarum LP01/ Lactobacillus paracasei LPC00 / fructo-oligosaccharide over a period of 4 months. Data on Allergic Rhinitis and Impact on Asthma (ARIA) classification, nasal symptoms severity by Visual Analogical Scale (VAS), and concomitant use of corticosteroids and antihistamines drugs were collected after 2 and 4 months of treatment (T1 and T2 respectively). Results. After the treatment with two multi-strain symbiotic preparations a significant reduction between baseline evaluation (T0) and T1/T2 on total nasal symptoms and ARIA classification of rhinitis were observed. A significant decrease on VAS index at all time points of the treatment vs pre-treatment was detected for Lactobacillus plantarum / Lactobacillus paracasei symbiotic combination; significant decrease was observed for Lactobacillus acidophilus / Bifidobacterium lactis symbiotic combination between T0 and T1, while a further reduction at T2 did not reach statistical significance. In addition a decrease in consumption of orally-administered corticosteroids and antihistamines drugs was found. Conclusion. These data on the effect of Lactobacillus acidophilus NCFM/ Bifidobacterium lactis BL-04 / fructo-oligosaccharide and Lactobacillus plantarum LP01/ Lactobacillus paracasei LPC00 / fructo-oligosaccharide preparations support their potential positive effect in the routine clinical management of subjects with SAR and PAR, respectively. Future studies are warranted to confirm this potential beneficial effect.
Content may be subject to copyright.
Columbia International Publishing
Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
doi:10.7726/jci.2014.1008
Research Article
______________________________________________________________________________________________________________________________
*Corresponding e-mail: fassio.filippo@gmail.com
1 Allergy Outpatients Service, General Hospital, Treviglio, Italy
2 Ambulatorio di Allergologia - ASL TO3 Ospedale Civile "Edoardo Agnelli", Pinerolo, Turin, Italy
3* UO Medicina, ASL3 Ospedale San Jacopo, Pistoia, Italy
67
Multi-strain Symbiotic Preparations as a
Novel Adjuvant Approach to Allergic Rhinitis
Giuseppina Manzotti1, Enrico Heffler2, and Filippo Fassio3* on behalf of the SPANAAR Study Group
Received 28 September 2014; Published online 11 October 2014
© The author(s) 2014. Published with open access at www.uscip.us
Abstract
Objective. To investigate the effects of Lactobacillus acidophilus NCFM / Bifidobacterium lactis BL-04 / fructo-
oligosaccharide and Lactobacillus plantarum LP01/ Lactobacillus paracasei LPC00 / fructo-oligosaccharide
preparations in the routine clinical management of seasonal allergic rhinitis (SAR) and perennial allergic
rhinitis (PAR), respectively.
Materials and Methods. Seventy-six and fifty-one outpatients attending 36 Allergy Clinics in Italy with
clinically documented allergic rhinitis consumed a symbiotic combination of Lactobacillus acidophilus NCFM /
Bifidobacterium lactis BL-04/ fructo-oligosaccharide and Lactobacillus plantarum LP01/ Lactobacillus
paracasei LPC00 / fructo-oligosaccharide over a period of 4 months. Data on Allergic Rhinitis and Impact on
Asthma (ARIA) classification, nasal symptoms severity by Visual Analogical Scale (VAS), and concomitant use
of corticosteroids and antihistamines drugs were collected after 2 and 4 months of treatment (T1 and T2
respectively).
Results. After the treatment with two multi-strain symbiotic preparations a significant reduction between
baseline evaluation (T0) and T1/T2 on total nasal symptoms and ARIA classification of rhinitis were
observed. A significant decrease on VAS index at all time points of the treatment vs pre-treatment was
detected for Lactobacillus plantarum / Lactobacillus paracasei symbiotic combination; significant decrease
was observed for Lactobacillus acidophilus / Bifidobacterium lactis symbiotic combination between T0 and
T1, while a further reduction at T2 did not reach statistical significance. In addition a decrease in
consumption of orally-administered corticosteroids and antihistamines drugs was found.
Conclusion. These data on the effect of Lactobacillus acidophilus NCFM/ Bifidobacterium lactis BL-04 / fructo-
oligosaccharide and Lactobacillus plantarum LP01/ Lactobacillus paracasei LPC00 / fructo-oligosaccharide
preparations support their potential positive effect in the routine clinical management of subjects with SAR
and PAR, respectively. Future studies are warranted to confirm this potential beneficial effect.
Keywords: Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum, Lactobacillus paracasei,
Allergic rhinitis, Clinical practice, Symbiotic preparations
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
68
1. Introduction
Allergic rhinitis is a chronic disorder which significantly impacts quality of life. Its prevalence
ranges from 10% to 25% in the general population, with a substantial increase over the last
decades (Bousquet et al., 2001; Janson et al., 2001; Asher et al., 2006). Several treatment strategies
for allergic rhinitis are available, and their use is well established (Bousquet et al., 2001; Bousquet,
et al., 2008; Brozek et al., 2010; Demoly et al., 2003). Recently, novel approaches aimed at reducing
and preventing allergic symptoms have been proposed. Data from pre-clinical and clinical research
have highlighted new trends based on the use of probiotics in the management of allergic rhinitis
(Kalliomaki et al., 2010; Laitinen et al., 2005; O'Flaherty 1982) as well as in other allergic diseases.
Probiotics are defined as live microorganisms capable to provide a health benefit to the host and
are frequently co-administered (symbiotic preparation) with non-digestible dietary compounds
(prebiotics) in order to enhance the growth/activity of specific probiotics (Guarner et al., 1998;
Gibson and Roberfroid, 1995; Van Zanten et al., 2012). Probiotics such as Lactobacillus and
Bifidobacterium species are commonly used for prevention/treatment of immune-mediated
diseases due to their immunomodulatory effect on immune response (Madsen et al., 1999; Madsen
et al., 2001; Pessi et al., 2000).
The effects of specific probiotic strains in the management (Isolauri et al., 2000) and in the
prevention of atopic eczema (Kalliomäki et al., 2007; Kalliomäki et al., 2003; Kalliomäki et al., 2001;
Manzotti et al., 2014) have been formally addressed in studies demonstrating their positive effects
on inflammation. To date, data on the effect of probiotics on allergic rhinitis are scarce (Isolauri et
al., 2000).
The aim of the present study is to evaluate the effect of specific multi-strain symbiotic preparations
in subjects with clinically confirmed seasonal (SAR) and perennial allergic rhinitis (PAR).
2. Materials and Methods
2.1 Participants, Study Protocol, Characteristics and Outcomes
Two different observational studies were performed to assess the effect of the administration of
multistrain symbiotics. In the first one, Lactobacillus acidophilus NCFM / Bifidobacterium lactis BL-
04 / fructo-oligosaccharide were used in the management of SAR, while in the second one
Lactobacillus plantarum LP01 / Lactobacillus paracasei LPC00 / fructo-oligosaccharide were used
in the routine management of PAR.
The populations involved in the two studies comprised of 76 and 51 outpatients affected by SAR
and PAR, respectively, attending 36 participating outpatient Allergy Clinics from April 2013 to May
2014 with clinically documented allergic rhinitis. Patients using prebiotics and/or probiotics at
enrollment were excluded from the study.
Industrial combinations of 2 different products were used in each individual study: i) Lactobacillus
acidophilus NCFM (1.25109 UFC/sachet) / Bifidobacterium lactis BL-04 (3.75 109 UFC/sachet) /
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
69
fructo-oligosaccharide (1 g) preparation (Pollagen® , Allergy Therapeutics Italia, Milan, Italy) in the
study involving patients with SAR ii) Lactobacillus plantarum LP01 (≥ 109 UFC/sachet) /
Lactobacillus paracasei LPC00 (≥ 109 UFC/sachet) / fructo-oligosaccharide (2.5 g) preparation
(AtiProb® , Allergy Therapeutics Italia, Milan, Italy) in the study performed to assess their effect on
PAR.
Each outpatient used 1 oral powder sachet per day (≥ 109 of bacteria for each strain). This dosage
is in agreement with the guidelines of the Italian Ministry of Health on probiotics (Italian Ministry
of Health, 2013). In addition, the AtiProb combination was microencapsulated in order to offer
significant protection against gastric juices, while the Pollagen combination is composed of acid-
resistant bacteria strains.
The study consisted of three consecutive time points: baseline visit (T0), evaluation after 2 months
(T1) and evaluation after 4 months (T2) of symbiotic consumption. The primary outcome of the
study was the change of total nasal symptoms evaluated by VAS, the shift in ARIA classification of
rhinitis (Bousquet et al., 2001; Bousquet, et al., 2008; Brozek et al., 2010; Demoly et al., 2003), and
the change of corticosteroids and antihistamines assumption before and after the treatment.
2.2 Data Recording and Questionnaire
All included subjects were evaluated using a questionnaire based on the following categories:
Demographic characteristics
VAS for total nasal symptoms
ARIA classification of allergic rhinitis
Concomitant treatment with corticosteroids and antihistamines medications
2.3 Statistical Analysis
Descriptive statistics were performed using Excel Microsoft Office. Comparisons at different time
points (T1/T2) vs baseline (T0) were analyzed using the Student’s unpaired t-test. The McNemar
test was used to compare the effect on ARIA severity score. A two-tailed P value ≤0.05 was
considered statistically significant. Statistical analyses were conducted using PSPP (psppire.exe
0.8.3-g5f5de6; A program for the analysis of sampled data; Free Software Foundation;
http://www.gnu.org/software/pspp/; GNU GENERAL PUBLIC LICENSE Version 3, 29 June 2007).
3. Results
3.1 Lactobacillus acidophilus NCFM / Bifidobacterium lactis BL-04 / fructo-oligosaccharide
preparation effect in SAR
Seventy-six participants (54% males and 46% females) were evaluated at T0/T1. The dropout rate
at T2 was 30% (23 patients withdrew from the study). At baseline the mean age of subjects was 32
years and the distribution of allergic sensitization was heterogeneous among different patients
with no clear prevalence of a specific airborne allergen (data not shown). Forty-five percent of the
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
70
evaluated patients were not concomitantly treated with allergen-specific immunotherapy, 17%
were treated with subcutaneous immunotherapy (SCIT) and 21% with sublingual immunotherapy
(SLIT) (Figure 1).
Fig. 1. Immunotherapy (SIT) treatments of the study subjects at baseline.
Abbreviations: SIT = Specific immunotherapy; SCIT= subcutaneous immunotherapy;
SLIT = sublingual immunotherapy; ND = not determined.
The mean VAS score for total nasal symptoms was significantly reduced after 2 months of
Lactobacillus acidophilus NCFM / Bifidobacterium lactis BL-04/ fructo-oligosaccharide
supplementation (5.16±0.29, p=0.02); after 4 months a further reduction trend could be observed,
but this change was not significantly different from T0 (4.94±0.37, p=0.06) (Figure 2).
Fig. 2. Mean VAS score for total nasal symptoms at T1 and T2 vs T0 in subjects affected by SAR.
(* p<0.05). Abbreviations: NS = not statistically significant vs T0.
no SIT
45%
SLIT
21%
SCIT
17%
ND
17%
SIT
5.82 5.16 4.94
0
1
2
3
4
5
6
7
8
9
10
T0 T1 T2
VAS score
VAS score for Total Nasal Symptoms
*
NS
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
71
Concomitantly, a shift in ARIA classification of rhinitis was observed, with more patients being
affected by intermittent (rather than persistent) and mild (rather than moderate-severe) rhinitis at
T1 and T2 (p=0.0003 and p=0.0011, respectively, compared to T0) (Figure 3).
Fig. 3. Patient classification of rhinitis (number of subjects in each group) according to ARIA, in
subjects affected by SAR (T1 vs T0, p=0.0003; T2 vs T0, p=0.0011).
Use of antihistamine drugs (mean ± se) in the last 2 months significantly decreased from
23.39±2.96 at T0 to 15.22.31 at T1 and finally to 10.15±1.73 at T2 (p<0.0001) (Figure 4). The
concomitant use of orally administered corticosteroid drugs (prednisone mg/die or other drug of
equivalent potency, mean ± se) in the last 2 months significantly decreased from 5.82±2.36 at T0 to
3.53±1.45 at T1 and finally to 1.72±0.96 at T2 (p=0.03 at T1 and p=0.02 at T2 vs T0) (Figure 5). The
concomitant use of intranasal corticosteroids in the last 2 months (number of packages, mean ± se)
significantly decreased at T1 (0.53±0.09, p<0.0001) vs T0 (1.01±0.12) but significantly increased at
T2 (3.81±0.45 p<0.0001) (Figure 6).
0
5
10
15
20
25
30
ARIA Classification of Rhinitis
t0 t1 t2
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
72
Fig. 4. Use of antihistamine drugs at T1 and T2 compared to T0, in the last 2 months in subjects
affected by SAR (***p<0.0001).
Fig. 5. Use of corticosteroid drugs (oral formulation) at T1 and T2 compared to T0, in the last 2
months in subjects affected by SAR (**p=0.03 at T1 and p=0.02 at T2 vs T0).
23.39
15.28
10.15
0
5
10
15
20
25
30
T0 T1 T2
A ntihistamines pills (last 2 months)
Antihistamines Consumption
***
***
**
**
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
73
Fig. 6. Use of intranasal corticosteroid drugs (number of packages used) at T1 and T2 compared to
T0, in the last 2 months in subjects affected by SAR (***p<0.0001).
3.2 Lactobacillus plantarum LP01/ Lactobacillus paracasei LPC00/ fructo-oligosaccharide
preparation effect on PAR.
Fifty-one subjects (57% males and 43% females) were evaluated at T0/T1. The dropout rate at T2
was 37%. At baseline the mean age of subjects was 31 years and the distribution of allergic
sensitization was heterogeneous among the different patients with no clear prevalence of a specific
airborne allergen (data not shown). Twentyseven percent of the evaluated patients were
concomitantly treated with allergen-specific immunotherapy, 10% were treated with SCIT and 17%
with SLIT (Figure 7).
Fig. 7. Immunotherapy (SIT) treatments of the study subjects at baseline. Abbreviations: SIT =
Specific immunotherapy; SCIT = subcutaneous immunotherapy; SLIT = sublingual immunotherapy;
ND = not determined.
no SIT
59%
SLIT
17%
SCIT
10%
ND
14%
SIT
***
***
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
74
With regard to total nasal symptoms VAS, the mean value was significantly decreased after 2
months of treatment (4.90±0.31, p=0.04) and after 4 months (3.88±0.49, p=0.01) vs baseline
(5.84±0.31) (Figure 8).
Fig. 8. Mean VAS score for total nasal symptoms at T1 and T2 vs T0, in subjects affected by PAR (*
p<0.05 vs T0).
A statistically significant shift in ARIA classification of rhinitis was observed, with more patients
being affected by intermittent (rather than persistent) and mild (rather than moderate-severe)
rhinitis at T1 (p=0.02); a further trend toward reduction was observed at T2 vs T0, but this change
was not significantly different from T0 (p=0.17) (Figure 9).
5.84
4.9
3.88
0
1
2
3
4
5
6
7
8
9
10
T0 T1 T2
VAS Score
VAS Score for Total Nasal Symptoms
*
*
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
75
Fig. 9. Patients classification of rhinitis (number of subjects in each group) according to ARIA, in
subjects affected by PAR (T1 vs T0, p=0.02; T2 vs T0, p=0.17).
Fig.10. Use of antihistamine drugs in the last 2 months, at T1 and T2 compared to T0, in subjects
affected by PAR (***p<0.0001).
37.53
16.82
5.73
0
5
10
15
20
25
30
35
40
45
50
T0 T1 T2
Antihistamines pills (last 2 months)
Antihistamines Consumption
***
***
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
76
The concomitant use of antihistamine drugs (mean ± se) in the last 2 months significantly
decreased from 37.53±5.47 at T0 to 16.82±3.51 at T1 and finally to 5.73±1.68 at T2 (p<0.0001)
(Figure 10).
The concomitant use of orally administered corticosteroids drugs (Prednisone mg/die or other
drug of equivalent potency) in the last 2 and 4 months showed a decreased trend that did not
reach statistical significance because of the reduced sample size of the study population due to
drop-outs (data not shown).
The concomitant use of intranasal corticosteroids in the last 2 months (number of packages, mean
± se) significantly decreased at T1(0.51±0.11, p<0.0001) vs T0 (1.27±0.21) and significantly
increased at T2 (2.59±0.50 p<0.0001) (Figure 11).
Fig. 11. Use of intranasal corticosteroid drugs (number of packages used) at T1 and T2 compared to
T0, in the last 2 months in subjects affected by PAR (***p<0.0001).
4. Discussion
Direct evidence of specific Lactobacillus plantarum LP01, Lactobacillus paracasei LPC00,
Lactobacillus acidophilus NCFM, Bifidobacterium lactis BL-04 strains activity in the control of
allergic rhinitis symptoms is well reported in literature with a number of studies using these stains
separately. Here we reported the effects of two different multi-strain symbiotic preparations on
patients affected by SAR and PAR after 2 and 4 months of treatment.
1.27
0.51
2.59
0
0.5
1
1.5
2
2.5
3
3.5
T0 T1 T2
of Packages (last 2 months)
Intranasal Corticosteroids
***
***
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
77
Of the total of 76 subjects affected by SAR who were evaluated at T0/T1, 53 were checked at T2; 23
patients didn’t show for the follow-up evaluation. No significant adverse events were reported by
any participant. The dropout rate of 30% is acceptable given that this is an observational study.
Of the total of 51 subjects affected by PAR who were evaluated at T0/T1, 32 were checked at T2;
nineteen patients didn’t show for the follow-up evaluation, with a dropout rate of 37%. No
significant adverse events were reported by any participant. The reasons for the higher rate of
dropout, compared to the subjects affected by SAR, are not known.
The results obtained from these two different observational studies showed a significant reduction
between T0 and T1/T2 on total nasal symptoms and a shift in ARIA classification of disease during
the four-month observation period.
A significant decrease on VAS index at all time points of treatment vs pre-treatment was detected
for the symbiotic multi-strain composed of Lactobacillus plantarum LP01/ Lactobacillus paracasei
LPC00 / fructo-oligosaccharide (ATIprob® ; Allergy Therapeutics, Milan, Italy); for the other
symbiotic multi-strain (Pollagen® ; Allergy Therapeutics, Milan, Italy), composed of Lactobacillus
acidophilus NCFM / Bifidobacterium lactis BL-04/ fructo-oligosaccharide , a significant decrease was
observed only between T1 and T0, with a further reduction trend at T2 which approached
statistical significance (without reaching it possibly because of the reduced size of the study
population due to dropouts).
These data support a potential positive effect of Lactobacillus acidophilus NCFM / Bifidobacterium
lactis BL-04 / fructo-oligosaccharide preparation and Lactobacillus plantarum LP01/ Lactobacillus
paracasei LPC00 / fructo-oligosaccharide preparation in subjects with SAR and PAR, respectively, in
the context of routine clinical practice, with a significant reduction in severity after 2 and 4 months
of treatment compared to baseline. This suggests the importance of the strain-specific effects of
Lactobacillus acidophilus NCFM, Bifidobacterium lactis BL-04, Lactobacillus plantarum LP01,
Lactobacillus paracasei LPC00 highlighting the concept of the strain-specific effects of probiotic
preparations.
The observed decrease in the utilization of co-administered oral antihistamine drugs and oral
corticosteroids, during the study period with this symbiotic multi-strain combination, may
represent additional evidence of the beneficial effect of the two studied multi-strain symbiotic
preparations in the management of SAR and PAR.
These studies also show an increase in the concomitant use of intranasal corticosteroids at T2,
probably due to an improvement in nasal symptoms which prompts the patient to consume less
oral drugs and use more intranasal drugs.
Importantly, the symbiotic multi-strain formulation used in the present study contained ≥109
bacteria for each strain (at the end of the 2 year shelf-life). Moreover, the utilization of
microencapsulated products capable of offering considerable protection against gastric juice and
the addition of prebiotic FOS could be important factors ensuring a better colonization of the
intestinal tract with an increased number of viable bacteria, and therefore positively influencing the
effect of these probiotic strains.
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
78
Our data support the hypothesis that an adequate symbiotic multi-strain supplementation can be
suggested as a novel adjuvant approach in the management of SAR and PAR, and that Lactobacillus
acidophilus NCFM, Bifidobacterium lactis BL-04, Lactobacillus plantarum LP01, Lactobacillus
paracasei LPC00 are relevant candidates for this puropose. Further studies and randomized trials
with larger patient populations are needed to confirm this positive effect with particular focus on
strain-specific outcomes, usefulness of concomitant prebiotic and probiotic supplementation, dose
optimization, microencapsulation, and other relevant manufacturing specifications.
Acknowledgements
The authors acknowledge Antonio Pappacoda, for original study design, and the SPANAAR Study
Group: Gianpietro Aromolo, Calogero Belluzzo, Elena Bernardini, Cristina Besana, Paolo Borrelli,
Barbara Bra, Sebastiano Bucolo, Daniela Cagnetti, Anna Maria Carbonara, Maria Caruso, Luca
Catelli, Vincenzo Coco, Stefano Crescioli, Alessandra De Serio, Daniela Della Valle, Andrea Di Rienzo
Businco, Valentina Fanelli, Antonio Floriddia, Maria Fortunato, Stefano Fucile, Francesca
Giovannelli, Orazio Grimaldi, Giuseppe Iadarola, Antonino Ingrassia, Ignazio La Mantia, Antonio
Maiuolo, Paolo Marraccini, Carolina Miele, Saverio Nenna, Maria Patafi, Sara Pellegrini, Sipontina
Renzullo, Alberto Sirena, Carina Uasuf.
The authors would also like to acknowledge Valentina Franco for her writing and editorial
assistance and Guido Fedele for assisting in biostatistics.
Conflict of Interests
Filippo Fassio received consultancy fees from Allergy Therapeutics Italia.
References
Asher MI, Montefort S, Björkstén B, Lai CK, Strachan DP, Weiland SK, Williams H. Worldwide time trends in
the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC
Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006; 368: 733-743
http://dx.doi.org/10.1016/S0140-6736(06)69283-0
Bousquet J, Van Cauwenberge P, Khaltaev N, ARIA Workshop Group; World Health Organization. Allergic
Rhinitis and Its Impact on Asthma. J Allergy Clin Immunol. 2001;108 (5 suppl): S147-334
http://dx.doi.org/10.1067/mai.2001.118891
Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, Zuberbier T, Baena-Cagnani CE, Canonica
GW, van Weel C, Agache I, Aït-Khaled N, Bachert C, Blaiss MS, Bonini S, Boulet LP, Bousquet PJ, Camargos
P, Carlsen KH, Chen Y, Custovic A, Dahl R, Demoly P, Douagui H, Durham SR, van Wijk RG, Kalayci O,
Kaliner MA, Kim YY, Kowalski ML: Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 Update (in
collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy 2008, 63:S8-160.
http://dx.doi.org/10.1111/j.1398-9995.2007.01620.x
Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T,
Schünemann HJ, Global Allergy and Asthma European Network, Grading of Recommendations
Assessment, Development and Evaluation Working Group. Allergic Rhinitis and its Impact on Asthma
(ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010, 126:466-476.
http://dx.doi.org/10.1016/j.jaci.2010.06.047
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
79
Demoly P, Allaert FA, Lecasble M, Bousquet J. Validation of the classification of ARIA (allergic rhinitis and its
impact on asthma). Allergy 2003, 58:672-675.
http://dx.doi.org/10.1034/j.1398-9995.2003.t01-1-00202.x
Daniel C, Poiret S, Goudercourt D, Dennin V, Leyer G, Pot B. Selecting lactic acid bacteria for their safety and
functionality by use of a mouse colitis model. Appl Environ Microbiol 2006; 72: 5799-5805
http://dx.doi.org/10.1128/AEM.00109-06
Foligne B, Nutten S, Grangette C, Dennin V, Goudercourt D, Poiret S, Dewulf J, Brassart D, Mercenier A, Pot B.
Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria. World J
Gastroenterol 2007; 13: 236-243
http://dx.doi.org/10.3748/wjg.v13.i2.236
Gibson, G.R.; Roberfroid, M.B. Dietary modulation of the human colonic microbiota: Introducing the concept of
prebiotics. J. Nutr. 1995, 125, 14011412
Guarner F, Schaafsma GJ: Probiotics. Int J Food Microbiol 1998; 39: 237238.
http://dx.doi.org/10.1016/S0168-1605(97)00136-0
Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S. Probiotics in the management of atopic eczema. Clin Exp
Allergy 2000; 30: 1604-1610
http://dx.doi.org/10.1046/j.1365-2222.2000.00943.x
Italian Ministry of Health. Linee guida su probiotici e prebiotici (Revised May 2013). Accessed on
http://www.salute.gov.it/imgs/C_17_pubblicazioni_1016_allegato.pdf
Janson C, Anto J, Burney P, et al. The European Community Respiratory Health Survey: what are the main
results so far? European Community Respiratory Health Survey II. Eur Respir J 2001; 18: 598611
http://dx.doi.org/10.1183/09031936.01.00205801
Kalliomaki M, Antoine JM, Herz U, Rijkers GT, Wells JM, Mercenier A: Guidance for substantiating the evidence
for beneficial effects of probiotics: prevention and management of allergic diseases by probiotics. J Nutr
2010, 140:713721
http://dx.doi.org/10.3945/jn.109.113761
Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of
atopic disease: a randomised placebo-controlled trial. Lancet 2001; 357: 1076-1079
http://dx.doi.org/10.1016/S0140-6736(00)04259-8
Kalliomäki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-
year follow-up of a randomised placebo-controlled trial. Lancet 2003; 361: 1869-1871
http://dx.doi.org/10.1016/S0140-6736(03)13490-3
Kalliomäki M, Salminen S, Poussa T, Isolauri E. Probiotics during the first 7 years of life: a cumulative risk
reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol 2007; 119: 1019-
1021
http://dx.doi.org/10.1016/j.jaci.2006.12.608
Laitinen K, Isolauri E: Management of food allergy: vitamins, fatty acids or probiotics? Eur J Gastroenterol
Hepatol 2005, 17:13051311
http://dx.doi.org/10.1097/00042737-200512000-00007
Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, Yachimec C, Doyle J, Jewell L, De Simone C: Probiotic
bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 2001; 121:
580591.
http://dx.doi.org/10.1053/gast.2001.27224
Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN. Lactobacillus species prevents colitis in
interleukin 10 gene-deficient mice. Gastroenterology 1999; 116: 11071114.
http://dx.doi.org/10.1016/S0016-5085(99)70013-2
Manzotti G, Heffler E, Fassio F. Probiotics as a Novel Adjuvant Approach to Atopic Dermatitis Journal
Contemporary Immunology 2014;1(2):57-66)
Giuseppina Manzotti, Enrico Heffler, and Filippo Fassio / Journal of Contemporary Immunology
(2014) Vol. 1 No.2 pp. 67-80
80
O'Flaherty JT. Lipid mediators of inflammation and allergy. Lab Invest 1982, 47:314329
Pessi T, Sutas Y, Hurme M, Isolauri E. Interleukin-10 generation in atopic children following oral Lactobacillus
rhamnosus gg. Clin Exp Allergy 2000; 30: 18041808.
http://dx.doi.org/10.1046/j.1365-2222.2000.00948.x
Van Zanten, G.C., Knudsen, A., Röytiö, H., Forssten, S., Lawther, M., Blennow, A., Lahtinen, S.J., Jakobsen, M.,
Svensson, B., Jespersen, L. The effect of selected symbiotics on microbial composition and short-chain
fatty acid production in model system of the human colon. PLoS One 2012, 7, e47212
http://dx.doi.org/10.1371/journal.pone.0047212
... Lactobacillus acidophilus NCFM and Bifidobacterium lactis BL-04, are relevant candidates for this purpose. 32 This combination of probiotic strains also prevented the pollen-induced infiltration of eosinophils into the nasal mucosa. This is an objective marker of AR directly correlating with the intensity of the disease, and it indicated a trend for reduced nasal symptoms in this study. ...
... The patients took 1 sachet per day as suggested by the instructions for use, for 4 months. 24,32 Patient population Patients were eligible if they were aged 18-65 years, non-smokers or had quit smoking at least 1 year ago, with a documented history of clinically relevant birch pollen sensitization (skin prick test [SPT] wheal diameter to birch ! 3 mm), and rhinoconjunctivitis symptoms induced by birch pollen for at least 2 years according to the ARIA criteria. All patients had to have a positive nasal provocation test (NPT) to birch pollen and/or a reaction to birch pollen in an AEC of TNSS ! 3 before this study. ...
Article
Full-text available
Background Allergic rhinitis/rhinoconjunctivitis is the most common immune disease worldwide, but still largely underestimated, underdiagnosed, and undertreated. Dysbiosis and reduced microbial diversity is linked to the development of allergies, and the immunomodulatory effects of pro- and prebiotics might be used to counteract microbiome dysbiosis in allergy. Adequate symbiotic (multi-strain pro-, plus prebiotic) supplementation can be suggested as a complementary approach in the management of allergic rhinitis. Objective The effects of the daily intake of a symbiotic food supplement (combination of Lactobacillus acidophilus NCFM and Bifidobacterium lactis BL-04 with Fructo-Oligosaccharides) for 4 months in birch pollen allergic rhinoconjunctivitis patients were investigated for the first time in an allergen exposure chamber (AEC) allowing standardised, reproducible pollen exposure before and after intake. Methods Eligible patients were exposed to birch pollen (8000 pollen/m³ for 120 min) at the GA²LEN AEC, at baseline (V1) and final visit (V3) outside the season. The Total Symptom Score (TSS) and the scores for nose, eye, bronchial system, and others were evaluated every 10 min during exposure. Other secondary endpoints were the changes in well-being, Peak Nasal Inspiratory Flow (PNIF), lung function parameters, and safety. Co-primary endpoints were differences in Total Nasal Symptom Score (TNSS) and TSS after 120 min of exposure between both visits. Temporal evolution of symptom scores were analysed in an exploratory way using linear mixed effects models. Results 27 patients (mean age 45 years, 15% male) completed the study. Both co-primary endpoints showed significant improvement after intake of the symbiotic. Median TNSS and TSS were decreased 50% and 80% at 120 min (adjusted p-value = 0.025 and p < 0.01 respectively). All four symptom scores and the personal well-being, improved to a clinically relevant extent over time, visible by a weaker increase in symptoms during 120 min of the final birch pollen exposure. No relevant differences were observed for PNIF, PEF, and spirometry. There were no airway obstructions or lung restrictions before and after both exposures. Late phase reactions after exposure were reduced after V3, documenting a better birch pollen tolerability of the patients. The safety and tolerability profile of the symbiotic food supplement was excellent, no adverse events (AEs) were observed. Conclusions This first evaluation of a symbiotic food supplement in an AEC in rhinoconjunctivitis patients with or without asthma induced by birch pollen revealed a significant beneficial effect, harnessing significant improvements of symptoms and well-being while maintaining an excellent safety and tolerability profile.
... The therapeutic potential of probiotic strains against allergic conditions was also explored by an observational study published in 2014. This study focused on the efficacy of two different symbiotic formulations (Lactobacillus acidophilus NCFM, Bifidobacterium lactis BL-04 and fructo-oligosaccharide (FOS); Lactobacillus plantarum LP01, Lactobacillus paracasei LPC00 and FOS) in the management of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) [28]. Aspects such as total nasal symptoms score, ARIA classification [29] for AR severity and data on the concomitant treatments were collected at the beginning of the study and evaluated at two different time points, 1 and 2 months after the beginning of the supplementation period. ...
... The observed decrease in the utilization of co-administered oral antihistamine drugs and oral corticosteroid drugs during the study period with this symbiotic multistrain combination may represent additional evidence of the beneficial effect of probiotics in the management of allergic rhinitis [28]. ...
Article
Full-text available
The socio-economic burden of allergic respiratory conditions on continental Europe is even higher than that of mainstream diseases, such as diabetes and cardiovascular disease, as allergic rhinitis alone accounts for billions of Euros in healthcare expenses across Europe. House dust mites (HDM) are one of the most common triggers behind allergic rhinitis and asthma. The role of probiotics in the treatment and prevention of some allergic conditions, such as atopic dermatitis, is already well recognized, whereas evidence about their efficacy in patients with respiratory allergies—while increasing—is still limited. Here the current evidence for the use of probiotics in patients with allergic rhinitis and/or asthma is discussed.
... Symbiotic is a combination of probiotic and prebiotic. This formulation allows an increase in the survival of the probiotic organisms, because it immediately makes its substrate available for fermentation (Manzotti, Heffler, Fassio, et al. 2014;Manzotti, Heffler, and Fassio 2014). ...
... Symbiotic is a combination of probiotic and prebiotic. This formulation allows an increase in the survival of the probiotic organisms, because it immediately makes its substrate available for fermentation (Manzotti, Heffler, Fassio, et al. 2014;Manzotti, Heffler, and Fassio 2014). ...
Article
Full-text available
Irritable bowel syndrome (IBS) is a very common chronic functional disorder of the lower gastrointestinal tract. It tipically includes chronic and/or recurrent abdominal pain/discomfort, which can be relieved by defecation, and alteration of stool form or frequency. Probiotics have been proposed as a therapeutic approach in several pathologic conditions of the gastrointestinal tract associated with dysbiosis, including IBS. In this observational study we investigated the efficacy of a symbiotic formulation (SynGut TM ), composed of four probiotic strains and the prebiotic inulin, in the treatment of adult subjects affected by IBS. Seventy-one out of 96 patients reported an improvement of IBS symptoms, 19 of them reporting a substantial improvement. Two patients discontinued the treatment after a few days because of worsening of symptoms, but no serious adverse effects were reported. In the subgroup of patients (n = 18) who underwent faecal calprotectin dosage, this marker of gut inflammation was significantly decreased (127,3 vs 78,6, p < 0,0001) after two months of treatment respect to baseline. Our data confirm that this multi-strain symbiotic is well tolerated, and support the hypothesis that this symbiotic could improve IBS symptoms.
... In this study, the administration of probiotics resulted efficacious in preventing the pollen-induced infiltration of eosinophils into the nasal mucosa, and found a trend toward a reduction of nasal symptoms. Also Manzotti et al. [23] showed the effect of Lactobacillus acidophilus NCFM/Bifidobacterium lactis BL-04 / fructooligosaccharide preparations in the routine clinical management of subjects with seasonal allergic rhinitis over a period of 4 months. After the treatment with two multi-strain symbiotic preparations a significant reduction of total nasal symptoms and a shift toward a lower level of the ARIA classification of rhinitis were observed. ...
Article
Full-text available
Probiotics are increasingly recognized as capable of modulating immune responses. Some probiotic strains show the potential of inducing a different lymphocyte polarization, promoting the Th1 phenotype and inhibiting, at the same time, the allergy-prone Th2 phenotype. On this basis, we could expect that probiotics may act synergistically to improve the clinical efficacy of sublingual allergen immunotherapy (SLIT). In this study, 30 patients affected by allergic rhinitis undergoing SLIT, were concomitantly administered a probiotic supplement (n = 14) or not (n = 16), according to their preference. Nasal symptom score, rescue medication score and ‘well-days’ were evaluated after 2 and 4 months of treatment. Patients who were administered SLIT plus probiotics showed a trend toward reduction of the nasal symptoms (-7.1%, p = ns) with a significant reduction of medication score (-32.6, p = 0.02) and an increase of ‘well-days’ (35.1, p = 0.02). These preliminary data, from a small study population, suggest that this combined approach with SLIT and probiotics could result in an increased efficacy of the SLIT treatment.
Article
Sublingual immunotherapy (SLIT) is considered a safe and beneficial treatment for allergic rhinitis (AR). Probiotics are unusual treatment options for AR and have lately created great concern in the scientific community. The aim of this study was to investigate the efficacy of combined probiotics plus SLIT on nasal symptoms in AR children. In this study, the SLIT only group (n = 15) received SLIT for 6 months, combined treatment group (n =15) received probiotics plus SLIT for 2 months and then SLIT for another 4 months. After 6 months of therapy, all symptoms of AR were significantly improved in both groups. The nasal obstruction was significantly resolved in both groups, p < 0.001. Total nasal symptom score (TNSS) was significantly decreased after treatment in both groups (p< 0.001). However, a significant difference was observed between the percent change in TNSS between both groups (P= 0.031). Also statistically significant difference was found between the studied groups regarding decrease use of anti-allergic medications (P= 0.034). In Conclusion: combined probiotics plus SLIT showed efficacy in improving symptoms of AR in children.
Article
Full-text available
Candida species are frequently found in the human microflora of the oral, intestinal and vaginal mucosa, where they usually live as commensals and interact with microbial communities and immune cells for the development and homeostasis of the immune response. However, many Candida spp. also act as opportunistic pathogens and are capable of causing a wide range of fungal diseases, among which vulvovaginal candidosis is very frequent. In recent years, probiotics have been investigated in several pathologic conditions as an approach to modulate the microbiota, and in this regard, they have also been proposed as an adjuvant therapy in prevention and treatment of vulvovaginal candidosis. In this review we focus on mechanisms of Candida tissue invasion and of host defense and discuss the role of probiotics in prevention and management of vulvovaginal candidosis. Anti-Candida potential of Lactobacillus acidophilus W22 and Lactococcus lactis W19, which are contained in a recently introduced multi-strain symbiotic, is discussed.
Article
Full-text available
Objective. The aim of this observational study is to investigate the effect of Lactobacillus rhamnosus and Bifidobacterium lactis in atopic dermatitis (AD) in the context of routine clinical practice. Materials and Methods. 107 adult subjects with documented AD receiving a symbiotic combination of Lactobacillus rhamnosus LR05, Bifidobacterium lactis BS01 and fructo-oligosaccharide (FOS) were assessed for severity of AD using the SCOring Atopic Dermatitis index (SCORAD) and Visual Analogue Scale (VAS) for AD-related global burden of the disease at baseline and after 2 and 4 months of symbiotic supplementation. Secondary evaluations involved the changes in concomitant use of corticosteroids, antihistamines drugs and calcineurin inhibitors. Results. Treatment with Lactobacillus rhamnosus and Bifidobacterium lactis significantly decreased atopic dermatitis severity (determined by SCORAD index) after 2 and 4 months of administration, while no effect was registered on the VAS score. In addition a decrease in consumption of corticosteroids, antihistamines drugs and calcineurin inhibitors was found.
Article
Full-text available
Prebiotics, probiotics and synbiotics can be used to modulate both the composition and activity of the gut microbiota and thereby potentially affecting host health beneficially. The aim of this study was to investigate the effects of eight synbiotic combinations on the composition and activity of human fecal microbiota using a four-stage semicontinuous model system of the human colon. Carbohydrates were selected by their ability to enhance growth of the probiotic bacteria Lactobacillus acidophilus NCFM (NCFM) and Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) under laboratory conditions. The most effective carbohydrates for each probiotic were further investigated, using the colonic model, for the ability to support growth of the probiotic bacteria, influence the composition of the microbiota and stimulate formation of short-chain fatty acids (SCFA).The following combinations were studied: NCFM with isomaltulose, cellobiose, raffinose and an oat β-glucan hydrolysate (OBGH) and Bl-04 with melibiose, xylobiose, raffinose and maltotriose. All carbohydrates showed capable of increasing levels of NCFM and Bl-04 during fermentations in the colonic model by 10(3)-10(4) fold and 10-10(2) fold, respectively. Also the synbiotic combinations decreased the modified ratio of Bacteroidetes/Firmicutes (calculated using qPCR results for Bacteroides-Prevotella-Porphyromonas group, Clostridium perfringens cluster I, Clostridium coccoides - Eubacterium rectale group and Clostridial cluster XIV) as well as significantly increasing SCFA levels, especially acetic and butyric acid, by three to eight fold, as compared to the controls. The decreases in the modified ratio of Bacteroidetes/Firmicutes were found to be correlated to increases in acetic and butyric acid (p = 0.04 and p = 0.03, respectively). The results of this study show that all synbiotic combinations investigated are able to shift the predominant bacteria and the production of SCFA of fecal microbiota in a model system of the human colon, thereby potentially being able to manipulate the microbiota in a way connected to human health.
Article
Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.
Article
Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.
Article
BackgroundReversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in Western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy).MethodsIn a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint.FindingsAtopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0·51 [95% Cl 0·32–0·84]). The number needed to treat was 4·5 (95% Cl 2·6–15·6).InterpretationsLactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.
Article
Background & aims: Intestinal luminal microflora, or their products, are likely an important initiating factor in the pathogenesis of inflammatory bowel disease. The aim of this study was to determine the role of colonic aerobic luminal bacteria and Lactobacillus species in the development of colitis in interleukin (IL)-10 gene-deficient mice. Methods: Intestine from 2-16-week-old mice was scored histologically and cultured for bacteria. Lactobacillus sp. repopulation of the colonic lumen was achieved via daily rectal delivery of Lactobacillus reuteri or oral lactulose therapy. Results: At 2 weeks of age, IL-10 gene-deficient mice showed no colonic injury but did display abnormal colonic bacterial colonization with increased colonic mucosal aerobic adherent and translocated bacteria in conjunction with reduced Lactobacillus sp. levels. In association with the abnormal colonic bacterial colonization, colitis developed by 4 weeks of age. Restoring Lactobacillus sp. to normal levels reduced levels of colonic mucosal adherent and translocated bacteria and attenuated the development of the colitis. Conclusions: In the neonatal period, IL-10 gene-deficient mice have decreased levels of colonic Lactobacillus sp. and an increase in colonic mucosal adherent and translocated bacteria. Normalizing Lactobacillus sp. levels reduced colonic mucosal adherent and translocated bacteria and prevented colitis.