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:
- 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).
- 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.
- Citronellol, geranial, and nerol have some anti-Aspergillis activity [2]
- Menthol, carvacrol, and eugenol have Aspergillis biocidal activity. [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.
Compounds | Conc., ×10−3 mg/mL air | Inhibition rate (Mean±S.E., %) | ||
Aspergillus ochraceus | Aspergillus flavus | Aspergillus niger | ||
Isopulegol | 56 | 34.6 ± 3.2d | 0d | 33.4 ± 2.2cd |
Citronellal | 56 | 0f | 0d | 16.2 ± 11.8de |
Citronellol | 56 | 83.7 ± 3.3b | 90 ± 0.7a | 81.1 ± 9.0b |
28 | 29.4 ± 3.0de | 37.7 ± 4.1b | 35.3 ± 7.0c | |
Neral | 56 | 100a | 100a | 100a |
28 | 100a | 26.9 ± 2.1bc | 0e | |
14 | 100a | – | – | |
7 | 34.1 ± 4.2d | – | – | |
Geraniol | 56 | 64.6 ± 7.5c | 36.7 ± 11.3b | 77.1 ± 9.8b |
28 | 38.4 ± 4.4d | – | 0e | |
Geranial | 56 | 100a | 100a | 100a |
28 | 100a | 29.8±3.3bc | 0e | |
14 | 20.1 ± 3.8e | 22.3 ± 3.5c | – |
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.
terpene | Aspergillis | Cladosporum |
carvacrol | 100 μg/mL | |
menthol | 125 μg/mL | 125 μg/mL |
thymol | 100 μg/mL | |
eguenol | 350 μg/mL |
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. | Formula | Trivial name | CAS no. | Substance class | Probability |
1 | CO2 | Carbon dioxide | 124-38-9 | 2.04 | |
2 | C5H8 | Isoprene | 78-79-5 | Diene | 3.74 |
3 | C6H10 | (Z,Z)-2,4-Hexadiene | 6108-61-8 | Diene | 15.3 |
4 | C10H16 | α-Pinene | 80-56-8 | Monoterpene | 15.7 |
5 | C10H16 | Camphene | 79-92-5 | Monoterpene | 45.9 |
6 | C10H16 | Terpinolene | 586-62-9 | Monoterpene | 28.1 |
7 | C10H16 | o-Cymene | 527-84-4 | Monoterpene | 28.8 |
8 | C10H16 | d-(+)-Limonene | 5989-27-5 | Monoterpene | 9.46 |
10a | C10H16 | γ-Terpinen | 99-85-4 | Monoterpene | 13.1 |
10b | C9H14N2 | 2,3-Diethyl-5-methyl-pyrazine | 18138-04-0 | Pyrazine | 24 |
11 | C15H22 | 8,9-Dehydro-cycloisolongifolene | Sesquiterpene | 24.9 | |
12 | C15H24 | α-Santalene | 512-61-8 | Sesquiterpene | 58.5 |
13 | C15H24 | α-Bergamotene | 17699-05-7 | Sesquiterpene | 54.9 |
14 | C15H24 | (−)-β-Santalene | 511-59-1 | Sesquiterpene | 67.2 |
16 | C15H24 | β-trans-Bergamotene | 28973-97-9 | Sesquiterpene | 10.9 |
17 | C15H24 | β-Bisabolene | 495-61-4 | Sesquiterpene | 41.2 |
18a | C15H23 | 4,5,9,10-Dehydro-isolongifolene | 156747-45-4 | Sesquiterpene | 71.7 |
18b | C15H24 | β-Vatirenene | Sesquiterpene | 34.6 |
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. | Formula | Trivial name | CAS no. | Substance class | Probability |
19 | C2H6O | Ethanol | 64-17-5 | Alcohol | 90.5 |
20 | C5H12O | 3-Methyl-1-butanol | 123-51-3 | Alcohol | 76.9 |
21 | C9H14 | 3-Ethylidenecycloheptene | 17.9 | ||
22 | C10H16 | α-Phellandrene | 99-83-2 | Monoterpene | 61.5 |
23 | C8H12N2 | 2-Methyl-5-isopropylpyrazine | 13925-05-8 | Pyrazine | 64.4 |
24 | C10H16 | α-Phellandrene | 99-83-2 | Monoterpene | 33 |
25a | C9H18O | (E)-6-Nonen-1-ol | 31502-19-9 | 28.5 | |
25b | C10H16 | Terpinolene | 586-62-9 | Monoterpene | 23.6 |
28 | C11H18N2 | 2-(2-Methylpropyl)-3-(1-methylethyl)pyrazine | Pyrazine | 81.2 | |
30 | C15H24 | (Z,E)-α-Farnesene | 26560-14-5 | Sesquiterpene | 20.2 |
33 | C15H24 | Cedr-8(15)-ene | 11028-42-5 | Sesquiterpene | 11.6 |
34 | C15H24 | α-Curcumene | 644-30-4 | Sesquiterpene | 53.2 |
36a | C15H24 | Dihydrocurcumene | 1461-02-5 | Sesquiterpene | 46.6 |
36b | C15H24 | (+)-Epi-β-santalene | 25532-78-9 | Sesquiterpene | 43.6 |
40 | C15H24 | α-Curcumene | 644-30-4 | Sesquiterpene | 42.1 |
41 | C10H10O5 | 2,4-Diacetylphloroglucinol | 2161-86-6 | Polyketide | 70.9 |
45 | C15H24 | α-Patchoulene | 560-32-7 | Sesquiterpene | 20.9 |
46 | C15H24 | cis-α-Bisabolene | 29837-07-8 | Sesquiterpene | 26.1 |
49 | C15H24 | β-Vatirenene | Sesquiterpene | 19.1 | |
51 | C15H20 | 4,5,9,10-Dehydro-isolongifolene | 156747-45-4 | Sesquiterpene | 74.8 |
54 | C15H24O | Ledene oxide(II) | Sesquiterpene | 20.3 | |
56 | C15H20 | 4,5,9,10-Dehydro-isolongifolene | 156747-45-4 | Sesquiterpene | 79.9 |
57 | C15H24O | Isoaromadendrene epoxide | Sesquiterpene | 12.1 | |
58 | C15H24O | Santalol | 11031-45-1 | Sesquiterpene | 17.6 |
59 | C20H32 | Biformene | 5957-33-5 | Diterpene | 37.1 |
60 | C20H31 | Rimuene | 1686-67-5 | Diterpene | 22.1 |
61 | C20H32 | (5α,9α,10β)-Kaur-15-ene | 511-85-3 | Diterpene | 77.2 |
62 | C20H32 | 13-Isopimaradiene | 1686-56-2 | Diterpene | 55.3 |
63 | C20H32 | (8β,13β)-Kaur-16-ene | 20070-61-5 | Diterpene | 42.8 |
Manganese and iron seem to promote terpene production while copper and zinc seem to inhibit production.

- 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

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?
References
- 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
- 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
- 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
- Heddergott C, Calvo AM, Latgé JP. The volatome of Aspergillus fumigatus. Eukaryot Cell. 2014 Aug;13(8):1014-25 PMC free article