Preventing GAS pharyngitis with BLIS-producing oral … · The probiotic for all ages Group B strep...
Transcript of Preventing GAS pharyngitis with BLIS-producing oral … · The probiotic for all ages Group B strep...
Preventing GAS pharyngitis with BLIS-producing oral probiotics
John Tagg
Preventing GAS pharyngitis with BLIS-producing oral probiotics
John Tagg
Probiotics
• Living microbes taken to confer a health benefit
• Metchnikoff - lactobacilli in yoghurt
• Principally intestinal commensals
BUT - no persistence
- benefits largely due to
immune stimulation
Intestinal probiotics no benefit for oral health
New-age Oral Probiotics
Incorporate the capability for Microbial Interference
Features :
– modulation (upgrading) of existing microbiota
– persistence of the implant strain
– BLIS-producing oral probiotics can specifically repress growth of targeted oral pathogens
The Oral Microbiota
• > 700 characterized species
• Provide “front line” protection against
potentially pathogenic microbes
• Germ-free animals vulnerable
(e.g. newborn)
Simultaneous antagonism
Deferred antagonism
BLIS activities
Bacteriocin-Like
Inhibitory
Substances
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Rose Mushin
A Background to BLIS
“What the streptococcus needs is
understanding not extermination”
- 1974
DR LEWIS WANNAMAKER
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HUNTING FOR ANTI-PYOGENES BLIS
- IN DUNEDIN
1980
Streptococcus salivarius
• Numerically-predominant
commensal of the human tongue
• Low virulence – S. thermophilus
• Produce a wide variety of mega-
plasmid-encoded bacteriocins
BACTERIOCINS
• Anti-competitor molecules shown to be produced and
to be active in situ
• Achieve population control by killing rapidly-
multiplying competitor bacteria (closely-related)
• Most are non-immunogenic peptides
• Resistance development is low
S. salivarius Megaplasmids
• ~15% S. salivarius strains (all produce BLIS)
• A survey of BLIS-producing streptococci showed
megaplasmids only in S. salivarius
• BLIS activities? (Up to 4 bacteriocins encoded)
- aid megaplasmid retention
• Other functions? (polyketide synthases, NRPS)
• No antibiotic resistance determinants
• Adhesion determinants
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Children with BLIS-producing S. salivarius less likely to acquire
Streptococcus pyogenes
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Early Investigations of BLIS Protection
Clonal expansion of indigenous
BLIS-producing S. salivarius
189 children dosed with BLIS milk
containing SalA+ S. salivarius
20 (10.9%) displayed substantial increase in
proportion of SalA-producing native S.
salivarius
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‘natural bacterial support for better health’
In 2000
S. salivarius K12
• Children with K12-like S. salivarius
are less likely to acquire S. pyogenes
• Adults have less halitosis
• Strongly adhesive
• GRAS status
• Produces several
megaplasmid-encoded bacteriocins
- lantibiotics salivaricin A and salivaricin B
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PRACTICAL APPLICATIONS
OF BLIS
• BLIS K12 Throat
Guard March 2002
Use Format
K12 Chewing gum
Bad breath
Product
Product Applications
Oral & intestinal support K12 Powder
with other gut probiotics
Natural Anti-Viral
immune stimulation
K12 Lozenge
Life-long Benefits of Probiotic S. salivarius
Dental caries
Periodontal disease Tonsillitis
Otitis media Candidosis
Gingivitis Sinusitis
Xerostomia Halitosis
The probiotic for all ages
Group B strep infection
Life-long Benefits of Probiotic S. salivarius
Dental caries
Periodontal disease Tonsillitis
Otitis media Candidosis
Gingivitis Sinusitis
Xerostomia Halitosis
The probiotic for all ages
Group B strep infection
BLIS control of
major childhood
infections
• All tested S. pyogenes killed in vitro by BLIS K12 and
by BLIS M18
• BLIS M18 also produces dextranase and urease
-spectrum includes mutans strep
- targets dental caries
• Children aged 5-10 with caries history (3 restorations)
• >104 cfu/ ml salivary S. mutans and no natural BLIS-
producing S. salivarius
• Clinical examination and recorded soft tissue health,
gingival health and dental plaque scores
• Active treatment was 2 lozenges daily for 3 months
• Parameters measured monthly
Recent Studies - BLIS M18
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Treatment month
M18 colonised (N=4)
Treatment (N=15)
Placebo (N=24)
Percentage of children for each group who had high pretreatment plaque scores (>7) and who
demonstrated plaque score improvements of three or greater at treatment months 1 and 3.
• 65 children aged 3 -12 with oral strep infection history
• Treated daily for 90 days with K12 (45 children)
or control (20) followed by 6 months non-treatment
• K12-treated children experienced 90% reduction in strep
pharyngitis and 40% in otitis media during treatment and
ca. 65% persistence of reduction during 6-month follow-up
• Follow-up study using adult subjects reported similar
findings
Di Pierro et al Int. J. Gen. Med. 5: 991-7 (2012)
Recent Studies - BLIS K12
Advantages of Probiotics
Compared to immunization and chemotherapy
REDUCED
• Resistance development
• Immunity dysfunction
• Expense
• Disruption of indigenous microbiota
Benefits of BLIS-producing
Probiotics
• Can target prevention and treatment of
specific infections
• Minimal disruption of indigenous microbiota
• A cost-effective natural method
• Preventative approach to infection control
WHAT NOW? Evaluation of a BLIS K12 BLIS M18 combo
3 groups of children required
(28 classrooms /group)
1. K12
2. K12/M18
3. Placebo
Dosage – one lozenge per school day for one year
Primary outcome – influence on S. pyogenes
infection (and carriage)
Secondary outcomes? – otitis media/ dental health
MAY THE BLIS BE WITH YOU
“What the streptococcus
needs is understanding not
extermination”