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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50

60

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90

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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”