gut health, microbiomes

Aspergillus metabolites

We were concerned about GI Aspergillus grown in our GI tracts. Can a good species ocntrol a bad one? WHhat about anti-fungal essential oil terpenes? What about species that produce terpenes? Cotty’s article 2021 paper: Degradation of Aflatoxins B1 by Atoxigenic Aspergillus flavus, Biocontrol Agents | Plant Disease [1]has inspired two ideas:

  1. Maybe a healthy Aspergillus such as Aspergillus oryzae may be beneficial by either degrading the bad Aspergillus mycotoxins in one’s body or maybe competing with it (although less likely).
  2. Microbiota transfer donors may already have “healthier” molds that either are less toxigenic (to compete), degrade mycotoxins, or have mycotoxins (that reduce virulence). (Definitely best to have single donor to decrease chance of any “bad” microbes).

This post was also an exploration of three terpenes from essential oils used in a pleasant mouth rinse to kill off bad fungi before introducing good fungi. Fungi also produce terpenes that might be fungicidal to other fungi.

  1. Citronellol, geranial, and nerol have some anti-Aspergillis activity [2]
  2. Menthol, carvacrol, and eugenol have Aspergillis biocidal activity. [3]
  3. Limonene can be produced by Aspergillis fumigatus. In fact, many terpenes dected in these cultures have commonality with citronellol and menthol [4]

Terpenes against Aspergillis species

These are the terpenes that are being investigated for anti-aspergillis activity: citronellol, menthol, and limonene. PubMed was used as a searching reference.

Citronellol [2]

A Korean paper was retrieved examining individually terpenes of a common essential oil. Terprenes with no inhibition were removed from the table. A as being the best.
I think this would be so synergistically helpful with whatever approach is taken.

CompoundsConc., ×10−3 mg/mL airInhibition rate (Mean±S.E., %)
Aspergillus ochraceusAspergillus flavusAspergillus niger
Isopulegol5634.6 ± 3.2d0d33.4 ± 2.2cd
Citronellal560f0d16.2 ± 11.8de
Citronellol5683.7 ± 3.3b90 ± 0.7a81.1 ± 9.0b
2829.4 ± 3.0de37.7 ± 4.1b35.3 ± 7.0c
28100a26.9 ± 2.1bc0e
734.1 ± 4.2d
Geraniol5664.6 ± 7.5c36.7 ± 11.3b77.1 ± 9.8b
2838.4 ± 4.4d0e
1420.1 ± 3.8e22.3 ± 3.5c
From Kim et al 2012. Different superscripts indicate different means at p<0.05 Note, there are aspects of this table that seem to be repeated information.

Menthol and more [3]

This study established the minimal inhibitory concentrations of four terpenes against 11 common food pathogens. This table summarizes the abstract only. All four of these compouns had anti fungal activity. These were the ones considered notable enough to make it into the abstract.

carvacrol100 μg/mL
menthol125 μg/mL125 μg/mL
thymol100 μg/mL
eguenol350 μg/mL
Information from the abstract reference [3] was put in table form.

Aspergillus fumigatus fumes, go figure [4]

So far the search for peer reviewed evidence of fungicidal activity of terpenes in a kid friendly mouth rinse have been fruitful but not earth shattering. Somehow our focus had been on killing the fungi rather than simply controlling them. Fumes emitted by fungi have been used to detect invasive infections. A continued search for limonene yielded a PubMed report demonstrating that Aspergillus can produce limonene and other terpenes. This sorts of makes intuitive sense to anyone who has noted a fruity aroma to fungal growth even when the mold is on a piece of bread or something. Heddergott and coauthors used what seemed to be a minimal medium called Brian Medium which was supplemented with divalent cations and inhibitors of terpene synthesis. . -pinene,camphene, and limonene were consistently detected terpenes

VOC type and peak no.FormulaTrivial nameCAS no.Substance classProbability
    1CO2Carbon dioxide124-38-92.04
VOCs produced upon growth on Brian’s medium

Iron supplemented cultures

These are the volatiles produced in iron supplemented cultures. Unidentified peaks have been edited out of the table. What are the implications for fungal growth in the gingiva of humans? If the growth is bad and there is bleeding, there will also be iron.

3-Methyl-1-butanol, aka isoamyl alcohol, has potential anti fungal properties according to PubChem.“Isoamylol is an primary alcohol that is butan-1-ol in which a hydrogen at position 3 has been replaced by a methyl group. It has a role as a xenobiotic metabolite, a Saccharomyces cerevisiae metabolite and an antifungal agent. It is a primary alcohol, a volatile organic compound and an alkyl alcohol. It derives from a hydride of an isopentane.”

2,4-Diacetylphloroglucinol, according to PubChem, ” 2,4-diacetylphloroglucinol is a benzenetriol that is phloroglucinol in which two of the ring hydrogens are replaced by acetyl groups. It has a role as a bacterial metabolite and an antifungal agent. It is a diketone, an aromatic ketone, a methyl ketone and a benzenetriol. 2,4-Diacetylphloroglucinol is a natural product found in Pseudomonas, Pseudomonas fluorescens, and Pseudomonas protegens with data available.

VOC type and peak no.FormulaTrivial nameCAS no.Substance classProbability
    54C15H24OLedene oxide(II)Sesquiterpene20.3
    57C15H24OIsoaromadendrene epoxideSesquiterpene12.1
This post has been rather wimpy in defining exactly what is meant by the probability. Finding reliable standards is not always easy.

Manganese and iron seem to promote terpene production while copper and zinc seem to inhibit production.

CuCl2, Fe2(SO4)3, FeSO4, and MnCl2 were added at a final concentration of 100 μM, and 1 mM ZnSO4·7 H2O was used.
  • fumagillin in spite of being produced by a fungi has anti-bacterial and protozoa activities as well as sellect anti-fungal properties
  • aspergillic acid also has antibacterial and anti-fungal properties
  • gibbereilic acid is a plant hormone
From Heddergott 2014. The structures of menthol and citronellol have been added. Limonene, in the lower right hand corner, has been starred. The red circles with the X on the side are metabolic deficient strains used in their study.

What does this mean?

The scientific community seems to be transfixed with terpenes from local foliage containing the latest and greatest anti microbial. It would seem that fungi produce plenty of metabolites to control each other. We know that those that do not produce aflatoxin can degrade the AF produced by other strains. [1] Is this true of terpenes as well? The change in metabolites in response to divalent cations has implications to our own oral microbiomes. Should we even consider a mouthrinse with EDTA?


  1. Maxwell LA, Callicott KA, Bandyopadhyay R, Mehl HL, Orbach MJ, Cotty PJ. Degradation of Aflatoxins B1 by Atoxigenic Aspergillus flavus Biocontrol Agents. Plant Dis. 2021 Sep;105(9):2343-2350. Free article
  2. Kim E, Park IK. Fumigant antifungal activity of Myrtaceae essential oils and constituents from Leptospermum petersonii against three Aspergillus species. Molecules. 2012 Sep 3;17(9):10459-69. PMC free article
  3. Abbaszadeh S, Sharifzadeh A, Shokri H, Khosravi AR, Abbaszadeh A. Antifungal efficacy of thymol, carvacrol, eugenol and menthol as alternative agents to control the growth of food-relevant fungi. J Mycol Med. 2014 Jun;24(2):e51-6. PubMed
  4. Heddergott C, Calvo AM, Latgé JP. The volatome of Aspergillus fumigatus. Eukaryot Cell. 2014 Aug;13(8):1014-25 PMC free article

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