The early pathogenic microbiota theory of breast inflammation

By the 1980s a disease-centric view of human milk had taken hold. Because human milk was believed to be sterile, any bacteria cultured from milk was considered to be either infective or contaminant washed back from the infant oral cavity and maternal skin.1, 2 Applying this pathogenic model of breast inflammation, antibiotics were commenced if

1. Signs and symptoms of mastitis, however defined, persist for more than 12-24 hours;

2. The woman has concurrent nipple damage; or

3. The woman feels acutely unwell, for example, with fever.3-5

'Blocked' ducts were believed to be caused by plugs of bacteria and other materials, requiring deep lump massage. This resulted in worsened breast inflammation, due to the effects of micro-haemorrhage in the breast stroma, and is likely to have increased the risk of abscess formation. There is no place for lump massage or vibration in treatment of breast inflammation.

Although ultrasound studies show that milk may have rich fat droplet content as it passes through the ducts, there is no evidence to suggest that fat droplets coalesce to block milk flow, causing clinical inflammation.15

As knowledge of the human milk microbiome has grown, proponents of a pathogenic microbiota model of breast inflammation have hypothesised that the irregular, branching, and densely interlaced human lactiferous ductal system favours the growth of biofilm-forming bacteria, perhaps in association with Candida albicans (Appendix 2). Biofilm is theorised to result in narrowed or blocked lactiferous ducts, causing cascades of epithelial inflammation and stromal oedema.6-9

The Academy of Breastfeeding Medicine's Clinical Protocol #36 promotes the pathogenic microbiota theory of breast inflammation by erroneously claiming that dysbiosis is one of two fundamental causes

These early pathogenic microbiota theories have been superceded by an updated pathogenic microbiota theory of breast inflammation, claimed as factual 9rather than hypothetical) in the Academy of Breastfeeding Medicine Clinical Protocol #36 'The mastitis spectrum'. But there is no physiological rationale or evidence to support the hypothesis that biofilms form inside the lactiferous ducts to cause clinical inflammation.

Clinical Protocol #36 asserts that “under physiological conditions, coagulase-negative Staphylococci and viridans Streptococci (i.e. S mitis and S salivarius) form thin biofilms that line the epithelium of the mammary ducts, allowing a normal milk flow”. This pathogenic microbiota hypothesis of lactation-related breast inflammation is illustrated in Figure 2 page 361 of the publication.

The illustration is adapted from a 2014 Fernandez et al article, which was peer-reviewed and published prior to the explosion in human microbiome and human milk microbiome science.[10] The same illustration was also published in 2017 in a book chapter (not subject to scientific peer review mechanisms).[11]

The physiological, cellular, or biochemical reasons why coagulase-negative Staphylococcus and Streptococcus bacteria – and why these genera and not other micro-organisms – might form a physiologic ductal biofilm (instead of remaining planktonic) in healthy lactating women are not discussed.

Clinical Protocol #36 then asserts that “in the setting of dysbiosis these species proliferate and function under opportunistic circumstances whereby they are able to form thick biofilms inside the ducts, inflaming the mammary epithelium”. The pathophysiological mechanisms by which dysbiosis makes physiological ductal biofilm develop into pathological biofilm are also not discussed. The hypothetical causative role of dysbiosis is given as fact in Figure 1 page 361.

You can read here why the latest research in human milk microbiomes renders the pathogenic microbiota hypothesis of lactation-related breast inflammation outdated.[4] Eubiosis must be defined before dysbiosis can be described.

For example, Kvist et al 2007 found no correlation between scores for erythema, breast tension, pain or total severity of symptoms and the type of bacteria in breast milk.21 The high counts of Staphylococcus aureus and decreased microbial diversity associated with breast inflammation are more plausibly explained as secondary responses of the mammary immune system, which aims to downregulate inflammation, rather than as causes of breast inflammation.[20]

You can find out about Staphylcoccus aureus and the human milk microbiome here.

Selected references

Comprehensive citations are found in the two research publications upon which this breast inflammation module is built (Douglas 2022 mechanobiological mode; Douglas 2022 classification, prevention, management; Douglas 2023)

1. Douglas P. Re-thinking benign inflammation of the lactating breast: a mechanobiological model. Women's Health. 2022;18:17455065221075907.

2. Douglas PS. Re-thinking benign inflammation of the lactating breast: classification, prevention, and management. Women's Health. 2022;18:17455057221091349.

3. Douglas PS. Does the Academy of Breastfeeding Medicine Clinical Protocol #36 'The Mastitis Spectrum' promote overtreatment and risk worsened outcomes for breastfeeding families? Commentary. International Breastfeeding Journal. 2023;18:Article no. 51 https://doi.org/10.1186/s13006-13023-00588-13008.

4. Fernandez L, Pannaraj PS, Rautava S, Rodriguez JM. The microbiota of the human mammary ecosystem. Frontiers in cellular and infection microbiology. 2020;10:Article 5866667.

5. Rodriguez JM, Fernandez L, Verhasselt V. The gut-breast axis: programming health for life. Nutrients. 2021;13(606):https://doi.org/10.3390/nu13020606.

6. Amir LH, The Academy of Breastfeeding Medicine Protocol Committee. ABM Clinical Protocol #4: Mastitis, Revised March 2014. Breastfeeding Medicine. 2014;9(5):239-43.

7. Amir LH. Managing common breastfeeding problems in the community. BMJ. 2014;348:g2954.

8. Amir LH, Trupin S, Kvist LJ. Diagnosis and treatment of mastitis in breastfeeding women. Journal of Human Lactation. 2014;30(1):10-3.

9. Rodriguez JM, Fernandez L. Infectious mastitis during lactation: a mammary dysbiosis model. In: McGuire M, Bode L, editors. Prebiotics and probiotics in human milk: Academic Press; 2017. p. 401-28.

10. Mitchell K, Eglash A, Bamberger E. Mammary dysbiosis and nipple blebs treated with intravenous daptomycin and dalbavancin. Journal of Human Lactation. 2020;36(2):365-8.

11. Mitchell K, Johnson HM. Breast pathology that contributes to dysfunction of human lactation: a spotlight on nipple blebs. Journal of Mammary Gland Biology. 2020:http://doi.org/10.1007/s10911-020-09450-7.

12. Angelopoulou A, Field D, Ryan CA, Stanton C, Hill C, Ross RP. The microbiology and treatment of human mastitis. Medical Microbiology and Immunology. 2018;207:83-94.

13. Berens P, Eglash A, Malloy M, Steube AM. Persistent pain with breastfeeding: ABM clinical protocol #26. Breastfeeding Medicine. 2016;11:46-56.

14. Kvist L. Diagnostic methods for mastitis in cows are not appropriate for use in humans: commentary. International Breastfeeding Journal. 2016;11(2):doi 10.1186/s13006-016-0061-1.

15. Ingman WV, Glynn DJ, Hutchinson MR. Inflammatory mediators in mastitis and lactation insufficiency. Journal of Mammary Gland Biology and Neoplasia. 2014;19:161-7.

16. Sakwinska O, Bosco N. Host microbe interactions in the lactating mammary gland. Frontiers in Microbiology. 2019;10:doi:10.3389/fmicb.2019.01863.

17. Kvist LJ. Toward a clarfication of the concept of mastitis as used in empirical studies of breast inflammation during lactation. Journal of Human Lactation. 2010;26(1):doi:10.1177/0890334409349806.

18. Ramsay DT, Kent JC, Owens RA, Hartmann PE. Ultrasound imaging of milk ejection in the breast of lactating women. Pediatics. 2004;113:361-7.