Macrolide: Sirolimus – a gut altering antifungal

A reader wrote:

I just started experimenting with Sirolimus.  Besides being an immune suppressor and life extender it also a very potent antifungal, more so than  Diflucan.  Just used 1mg, got the worst Herx ever , very high inflammation.   Did not expect that, was hoping more for a lessening of autoimmunity, which is more common.   Did not know I had such a high Candida load.  I was looking at the readout, found one Candida notation, but did not seem high enough to cause this, when you look around see what you can find that is fungal related.

Sirolimus (INN/USAN), also known as rapamycin, is a macrolide compound” [wikipedia]

We know the general characteristic of macrolides.. favorable shifts in the microbiome [post] and this family is also used by MDs Jadin and Botelo in their protocols for  CFS and other related conditions. As with strains with probiotics, each member of a antibiotic family has it’s own characteristics.

Sirolimus is well studies (18K articles on pubmed)

  • “a large number of small molecules such as farnesol, fatty acids, rapamycin, geldanamycin, histone deacetylase inhibitors, and cell cycle inhibitors have been reported to modulate the yeast-to-hypha transition in C. albicans.” [2011, Full Text]
    • “Rapamycin, a hydrophobic macrolide produced as a secondary metabolite by the soil bacterium Streptomyces hygroscopicus, was initially discovered as an antifungal agent against C. albicans (139).”
  • “Rapamycin markedly prolonged lifespan and health span in cancer- and infection-prone mice supporting disease mitigation as a mechanism for mTOR suppression-mediated longevity extension. It modestly altered gut metagenomes,” [2015]
  • Chronic Repression of mTOR Complex 2 Induces Changes in the Gut Microbiota of Diet-induced Obese Mice[2016]. [Full Text]
    • ” the abundance of unclassified Marinilabiliaceae and Turicibacter decreased in response to .. rapamycin (mTOR).”
    • “Mechanistic target of rapamycin (mTOR) is a central regulator of energy storage and consumption, and is implicated in deleterious states such as cancer, metabolic diseases and ageing17. Because over-activation of mTOR complex 1 (mTORC1) signaling by excessive energy intake plays a crucial role in metabolic disorders17,”
    • “rapamycin changed the relative abundances of Turicibacter, unclassified Marinilabiliaceae, Alloprevotella, unclassified Porphyromonadaceae, Ruminococcus, Bifidobacterium, Marvinbryantia, Ruminococcus (Lachnospiraceae), Helicobacter, and Coprobacillus to those observed in HFD-fed mice”


    • In charts above Res is resveratrol (grape seed extract)

Bottom Line

The reader’s observations appear to be spot on. There is evidence that it increases Lacobacillus and reduces unclassified bacteria (with a non-high fat diet). It is an antifungal. The drug is extracted from a bacteria that one day may be available as a probiotic. The last study above indicate that resveratrol (non prescription) has additional functions above those usually associated with it and will be revisited on a future post.

There are no studies for CFS/IBS/FM for this drug.