Why does strain matter when testing ingredients?

Most bacterial species do not fall exclusively under the umbrella of mutualists or pathogens, with many possessing strains that lie across a continuum between the two extreme states. It is important to consider the effect of this when devising formulations to treat common skin disorders as the same ingredients used against pathogenic strains can wipe out beneficial populations helping to maintain skin health.

What we know:

• The phylotype I strain of Cutibacterium acnes is more commonly associated with diseases such as acne vulgaris. It forms biofilms and secretes adhesion proteins that allow them to attach and invade neighbouring skin cells, causing disruption of the epithelial barrier and increasing risk of inflammation and infection (Spittaels et al., 2020).

• Other more beneficial strains of Cutibacterium acnes like type II instead secrete anti-inflammatory molecules, modulate the immune system, prevent colonisation by pathogens, and provide antioxidant activity to keep the skin healthy (Yu et al., 2016; Ahle et al., 2023).

• Staphylococcus epidermidis strains of Staphylococcus protect the skin by synthesising lantibiotics that target and kill more virulent strains like S. aureus, secreting enzymes that degrade pathogen biofilms, and releasing pheromones that restrict their ability to colonise and invade the skin (Cogen & Gallo 2008; Byrd et al., 2018).

• S. aureus releases virulence factors interfering with the cutaneous immune system (e.g., inflammation, white blood cell activation), secretes enzymes that damage skin tissue, and brings about dysbiotic changes to the skin’s normal microflora to trigger skin conditions like atopic dermatitis (Cogen & Gallo 2008; Geoghegan et al., 2018; Kobayashi et al., 2015).

• Cross-species strain interactions also control virulent populations. Corynebacterium accolens prevents Streptococcus pneumoniae from growing on the skin by generating fatty acids that make the external environment uninhabitable for it (Bomar et al., 2016).

Industry Impact & potential:

Prebiotics and phage therapies are now being considered as alternatives to traditional antibiotics for treating skin disorders owing to their greater level of strain specificity during treatment. Some brands are using ingredients containing C. acnes phages to target pathogenic strains while allowing healthy strains to persist. Other brands are also using prebiotic products to selectively promote the growth of good bacteria while restricting growth of harmful ones. 

Our solution:

Sequential is able to offer invivo strain-specific testing of your product on the skin to help distinguish between the effects of your product on good and bad bacteria. Our experienced panel of experts can also help brands develop personalised formulations that act against bad bacteria while maintaining the good to maximise the effects of your ingredients and prevent any unwanted dysbiotic effects.

References:

Ahle CM, Feidenhansl C, Brüggemann H. Cutibacterium acnes. Trends Microbiol. 2023 Apr;31(4):419-420. doi: 10.1016/j.tim.2022.10.006. Epub 2022 Oct 31. PMID: 36328874.

Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP. Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols. mBio. 2016 Jan 5;7(1):e01725-15. doi: 10.1128/mBio.01725-15. PMID: 26733066; PMCID: PMC4725001.

Byrd, A., Belkaid, Y. & Segre, J. The human skin microbiome. Nat Rev Microbiol 16, 143–155 (2018). https://doi.org/10.1038/nrmicro.2017.157

Cogen AL, Nizet V, Gallo RL. Skin microbiota: a source of disease or defence? Br J Dermatol. 2008 Mar;158(3):442-55. doi: 10.1111/j.1365-2133.2008.08437.x. PMID: 18275522; PMCID: PMC2746716.

Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and Atopic Dermatitis: A Complex and Evolving Relationship. Trends Microbiol. 2018 Jun;26(6):484-497. doi: 10.1016/j.tim.2017.11.008. Epub 2017 Dec 9. PMID: 29233606.

Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, Kong HH, Amagai M, Nagao K. Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis. Immunity. 2015 Apr 21;42(4):756-66. doi: 10.1016/j.immuni.2015.03.014. PMID: 25902485; PMCID: PMC4407815.

Spittaels KJ, Ongena R, Zouboulis CC, Crabbé A, Coenye T. Cutibacterium acnes Phylotype I and II Strains Interact Differently With Human Skin Cells. Front Cell Infect Microbiol. 2020 Nov 16;10:575164. doi: 10.3389/fcimb.2020.575164. PMID: 33330124; PMCID: PMC7717938.

Yu Y, Lu L, Sun J, Petrof EO, Claud EC. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model. Am J Physiol Gastrointest Liver Physiol. 2016 Sep 1;311(3):G521-32. doi: 10.1152/ajpgi.00022.2016. Epub 2016 Aug 4. PMID: 27492329; PMCID: PMC5076002.