MANIPULATING THE AXILLARY MICROBIOME FOR ODOUR CONTROL
Dr A. Gordon James, FRSB
Deodorants Science Leader, Microbiology & Antimicrobials, Unilever BPC
1 THE HUMAN MICROBIOME – GOOD, BAD & UGLY
2 THE AXILLARY MICROBIOME
Microbiomics
Cutibacterium
Gram-positive anaerobic cocci (GPAC)
Typically, about 1 million bacteria per cm2 skin
3 James et al., 2013; Scholz & Kilian, 2016 THE AXILLARY MICROBIOME & MALODOUR – THE WAY WE WERE
4 James et al., 2013 S. HOMINIS & MALODOUR
• Model of thiol-based malodour production in S. hominis 1. S-Cys-Gly-3M3SH 2. Dipeptidase 3. C-S b-lyase (BO lyase) PepTSh PatBSh 4. 3M3SH
5 Bawdon et al., 2015; Minhas et al., 2018 PEPT SH + S-CYS-GLY-3M3SH CRYSTAL STRUCTURE
• Thiol precursor dipeptide transporter cloned from S. hominis
• Member of POT family – PepTSh • Preferred substrates L-Ala di/tripeptides • Co-crystallised with S-Cys-Gly-3M3SH
Acyl chain of 3M3SH moiety within hydrophobic pocket • Key residue Tyr411
6 Minhas et al., eLIFE, 2018
S. HOMINIS & MALODOUR IN-VIVO S. S. hominis
• Positive association between S. hominis (qPCR) & malodour
• Negative association between S. epidermidis / S. hominis ratio
S. hominis S. / and malodour
• As malodour increases, ratio of S. epidermidis (non-odiferous) to S. epidermidis S. S. hominis (odiferous) decreases
7 THE AXILLARY MICROBIOME & MALODOUR – THE RULEBOOK REWRITTEN
Staph. hominis
Anaerococcus
8 James et al., 2013; Fujii et al., 2014; Bawdon et al., 2015 SKIN INNATE IMMUNITY, AMPS & VIT. B 3
In-vivo In-vitro In-vitro
• Antimicrobial peptides (AMPs) form part of skin’s innate immune system LL-37 • Protect from infection by potentially-pathogenic opportunists
• Also help regulate commensal numbers to keep microbiome in balance S. S. hominis • Cathelicidin LL-37 shows bactericidal activity against S. hominis in-vitro
• Niacinamide (B3) stimulates AMP synthesis & secretion on skin • Shown to protect against E.coli & S. aureus on forearm • S. hominis in axilla….??
9 Majumdar et al., 2013 (EP3120850); 2016 AMP LEVELS IN HIGH-ODOUR SUBJECTS
• High-odour subjects have lower axillary AMP levels • Psoriasin (ELISA) • RNase7, FLG2, Psoriasin, S100A8, S100A9 (LC-MS/MS) • High-odour subjects have significantly higher S. hominis levels • High-odour subjects have lower natural defences against odour-forming S. hominis…..?? 10 VIT. B 3 HUMAN DEODORANCY STUDY
• Human deodorancy study conducted on unfragranced B3-containing deodorant roll-on product • Compared to equivalent vehicle control • Malodour scores expert-assessed at 5 h & 24 h; microbial samples collected at 24 h
• B3-containing product provided odour-control benefit at both timepoints
• Small reductions (<0.5 log10) in each cultured bacterial taxon evident at 24 h • Statistically-significant for staphylococci only 11 VIT. B 3 HUMAN DEODORANCY STUDY
• 24 h microbiology samples processed for analysis in species-level Staphylococcus qPCR assays
• B3-containing roll-on provided significant reduction in both S. epidermidis and S. hominis • Magnitude of reduction in S. hominis much greater than that of S. epidermidis (4.5-fold)
• Supports hypothesis that B3 boosts AMP production on axillary skin • Disproportionately targeting thioalcohol-producing S. hominis • Resulting in malodour reduction
12 VIT. B 3 HUMAN DEODORANCY STUDY
• Test subjects subdivided into a-priori low- & high-odour groups and MMS data reanalysed • At both 5 h & 24 h, MMS difference accounted for by high-odour group • Within low-odour group, no difference between products at either timepoint • Supports hypothesis that high-odour subjects have lower natural defences against S. hominis 13 CONCLUDING COMMENTS
• Staphylococcus hominis identified as a key causal bacterium of axillary malodour • Metabolic pathway to thioalcohols elucidated • Shows strong association with malodour intensity in-vivo
• Niacinamide (B3) acts as microbiome-reprofiling deo-active, based on AMP-boosting
• B3 induces synthesis & secretion of AMPs by skin in-vitro & in-vivo • Some AMPs (LL-37) show bactericidal activity against S. hominis in-vitro • High-odour individuals have lower levels of some AMPs in axilla
• B3-containing deodorant roll-on provides odour-control benefit for up to 24 h • Odour-control benefit driven by high-odour subjects
• B3-containing deodorant causes small but significant reduction in staphylococci
• At species-level, B3 selectively targets odour-forming S. hominis
14 ACKNOWLEDGEMENTS
• UNILEVER • Diana Cox; Rob Cornmell; Ann-Marie Carvell; Amitabha Majumdar • UNIVERSITY OF YORK • Gavin Thomas; Dan Bawdon; Michelle Rudden; Reyme Herman • UNIVERSITY OF OXFORD • Simon Newstead; Gurdeep Minhas • ADDITIONAL SUPPORT • UK Biotechnology and Biological Sciences Research Council (BBSRC) • Pandey Lab, John Hopkins University
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