Most of us are in daily contact with antimicrobial substances, very often without knowing it. We are aware that we regularly use products such as hydroalcoholic gels, so often used since the Covid-19 pandemic, or many cleaning products containing alcohol or other disinfectants to clean surfaces in our homes or workplaces. These products can harm us, mainly by altering the microbiota of our skin, which is a very important protective mechanism. However, they are by far not our main source of exposure to antimicrobial products. Without being aware of it, every day our body comes into contact with and assimilates numerous substances with antibiotic effects that have a negative impact on our microbiota and our health. In the following articles I will review some of the substances with an antimicrobial effect that can unknowingly harm our health.
However, before we get into this topic, I would like to talk a little bit about hygiene. Hygiene is very important, because it is one of the things that has allowed us to progress as a society, preventing many communicable diseases. The problem is that we are currently living in a period of microbe phobia, where many people believe that we have to wage war against any micro-organism in our environment. This viewpoint is dangerous, as there is a lot of overwhelming scientific evidence confirming the importance of having a good microbiota throughout our bodies, and its relationship to health.
Since the advent of the Coronavirus several years ago, we have become accustomed to "over-disinfecting" our homes or workplaces and to "over-disinfecting" ourselves. If we add to this the effect of the antimicrobial toxins that surround us and the indiscriminate use of antibiotics by many health professionals, for example, to treat the asymptomatic bacteriuria I have already mentioned, the breeding ground for us to develop increasingly virulent infections is served.
In the case of urinary tract infections, the prevalence of multi-resistant germs is increasing. That is why, although I recommend a normal, daily hygiene routine, I do not recommend "over-hygiene", especially in the genital area, as this can alter the local microbiota. I do not usually recommend the use of intimate soaps or vaginal douches to my patients, even if they are from a pharmacy. The external genitalia can be washed with a little natural soap without additives (Aleppo soap, for example). The microbiota, if it is the right one, will do the rest.
Antimicrobial substances in agriculture and animal husbandry
Many pesticides act as antimicrobial pesticides, directly killing micro-organisms on plants. These pesticides may be applied directly to crops, or may be present in soils and irrigation water. Thus, it is possible that, despite eating organic vegetables, we are in contact with these substances due to this contamination.
On the other hand, antibiotics and antifungals are administered to livestock and farm animals, either to treat infectious diseases or to prevent them. In Western Europe, the use of antibiotics in livestock is more regulated than in other countries, but it is still not unheard of. In addition, some of these animals also ingest antimicrobials with their feed, as the cereals, soya or other feed they are given may have been pre-treated with antimicrobial agents to ensure their preservation. These substances, as well as accumulating in the animals' bodies and passing into ours when we feed on them, also pass into soils and waters when they are excreted in the urine of these animals or in their faeces, if these are subsequently used as fertiliser. So, again, our soils become contaminated with these products and subsequently contaminate us, regardless of whether we have an omnivorous or vegan diet.
Numerous studies have analysed the prevalence of microbial strains resistant to multiple antibiotics. It is postulated that one of the main sources of this type of multi-resistant bacteria is precisely the microbiota in our soils. Therefore, although we cannot protect ourselves from 100%, we can reduce our exposure to these substances by consuming organic products that have not been treated with pesticides and by avoiding the consumption of farmed fish and intensive livestock. Free-range animals, such as organic chickens or pasture-raised cattle, are less exposed to these products because the use of antibiotics as a preventive measure is prohibited. In addition, they do not receive as much antibiotic treatment as animals in intensive farming. Although antibiotic treatment is permitted in some cases if there is an infectious disease, we should be aware that these animals get sick less often, as they are in much better health thanks to their better living conditions. And within this type of meat, I recommend that you consume that which is of European production. It is not enough for it to be of European "origin", as it may have been packaged or manufactured in Europe. You must make sure that it is meat produced in Europe.
Food additives
There are many food additives, especially preservatives, that have harmful effects on our bodies and our microbiota. It is not the purpose of this article to talk about all of them, as there are too many and I am no expert. Be that as it may, we should be aware that we are surrounded by most of these toxins on a daily basis and, although it is not possible to avoid them completely, we can try to minimise our exposure (making home-cooked meals from unprocessed and organic foods if possible, buying few industrial foods, using paraben-free cosmetics or personal hygiene products, or even homemade ones, making them ourselves, etc.). It is obviously a financial and personal effort, but our health will thank us for it.
For more information, the tables 3 y 4 show you a list of the most common "E" preservatives in food and a list of all "E" additives and their safety levels. In addition, here are two links to the European Union's website where you will find up-to-date information on additives and their regulation:
Triclosan
Triclosan is a preservative with antimicrobial power. It is not approved for use in food, but is widely used in personal care products and cosmetics, as well as a preservative in some pharmaceuticals. It is widely present in the environment and, in addition to its antimicrobial power, it has also been found to have an endocrine disrupting effect on thyroid hormones. The European Union allows its use at a maximum concentration of 0.2% in mouthwashes and at a maximum concentration of 0.3% in soaps and gels, toothpastes, liquid or stick deodorants and make-up.
Due to its ubiquity, there is growing concern about it because, in addition to its direct effects on our health, it is suspected that it may be another of the agents causing the appearance of resistant microorganisms in our environment, as its mode of action is similar to that of antibiotics. In fact, it has been studied as a possible protective agent against urinary tract infections in people with an indwelling catheter, using it as a coating for urinary catheters. These studies have been inconclusive precisely because resistant uropathogenic micro-organisms were observed to emerge (Escherichia coli, Proteus) shortly after use, as well as cross-resistance with some antibiotics. In addition, triclosan has been found to be ineffective against some bacteria such as Pseudomona aeruginosa or certain strains of Proteusboth of which are very frequently implicated in colonisation and encrustation of urinary catheters. Knowing that, according to some studies, it is estimated that 75% of adults excrete triclosan in urine, we can imagine that this chemical agent, in the same way as parabens, could be implicated in repeated urinary tract infections by altering the bladder microbiota and favouring the appearance of multi-resistant microbial strains. Unfortunately, there is no scientific literature on this subject, but it is a hypothesis that would be worth confirming.
Parabens
One source of inadvertent exposure to antimicrobials are preservatives in food and cosmetic products, in particular two of them: parabens and triclosan. These substances are used by industry precisely because of their anti-infective power. Parabens are a group of chemicals used as food preservatives and also as preservatives in cosmetics and personal care products, as well as biocides in textiles and paper, as they inhibit the growth of bacteria, fungi and viruses. In addition to their antibiotic effect, they also show an endocrine disrupting effect of the oestrogenic type and have been linked to some tumours, in particular breast cancer.
The most commonly used in cosmetics are methylparaben, propylparaben, butylparaben and ethylparaben, while in food they are "hidden" behind an E-code: E-214 and E-215 (ethylparabens), E-218 and E-219 (methylparabens). The EU Scientific Committee on Consumer Safety (SCCS) banned in 2014 the use of long-chain parabens: isopropylparaben, isobutylparaben, phenylparaben, benzylparaben and pentylparaben. In addition, E-216 (propylparaben) and E-217 (natriumpropylparaben) are banned in food and E-216 is also banned in products for children under 3 years of age in the nappy area.
They can be found in most cosmetic products that do not carry a "paraben-free" label: nail polishes, moisturisers, deodorants, shampoos, facial hygiene products, aftershave lotions, sunscreens, eyelash mascaras, eye shadows, make-up or lipsticks, among others. In food, they are used to preserve beverages (beers, soft drinks), syrups, sauces, desserts or ice cream, bakery products, processed vegetables, oils or cold cuts, among many others. Some fruits such as blueberries may contain them naturally.
When ingested, they are metabolised by the liver and kidney, and eliminated in the bile (faeces) and especially in the urine, which is why scientific studies on exposure to endocrine disruptors often measure these compounds in urine. Thanks to this rapid metabolisation, it is believed that they are less dangerous when ingested than when applied to the skin and absorbed by the skin, as is the case with cosmetics and personal hygiene products, as in this case the paraben does not reach the liver directly to be detoxified. Either way, ingestion or cutaneous application, what is certain is that the main route of elimination will be the urinary tract, so we must ask ourselves whether these products may be a cause of alteration of the urinary microbiota as well as alteration of the bladder wall, taking into account their oestrogenic effect and the high density of oestrogen receptors in our bladder. Considering that women consume much more cosmetics than men in general, I hypothesise that these substances could have an influence on the pathophysiology of urinary tract infections. Unfortunately, there is no scientific literature on this subject, so I cannot validate my hypothesis at this stage.
Bibliography:
https://www.epa.gov/pesticide-registration/what-are-antimicrobial-pesticides.
Malagón-Rojas JN, Parra Barrera EL, Lagos L. From environment to clinic: the role of pesticides in antimicrobial resistance. Rev Panam Salud Publica. 2020 Sep 23;44:e44.
Mie A, Andersen HR, Gunnarsson S, Kahl J, Kesse-Guyot E, et al. Human health implications of organic food and organic agriculture: a comprehensive review. Environ Health. 2017 Oct 27;16(1):111.
De Briyne N, Atkinson J, Pokludová L, Borriello SP. Antibiotics used most commonly to treat animals in Europe. Vet Rec. 2014 Oct 4;175(13):325.
Marshall BM, Levy SB. Food animals and antimicrobials: impacts on human health. Clin Microbiol Rev. 2011 Oct;24(4):718-33.
Kasimanickam V, Kasimanickam M, Kasimanickam R. Antibiotics Use in Food Animal Production: Escalation of Antimicrobial Resistance: Where Are We Now in Combating AMR? Med Sci (Basel). 2021 Feb 21;9(1):14.
Feng Y, Zhang WJ, Liu YW, Xue JM, Zhang SQ, et al. A Simple, Sensitive, and Reliable Method for the Simultaneous Determination of Multiple Antibiotics in Vegetables through SPE-HPLC-MS/MS. Molecules. 2018 Aug 6;23(8):1953.
https://food.ec.europa.eu/safety/food-improvement-agents/additives_en
https://ec.europa.eu/food/food-feed-portal/screen/food-additives/search
Bibliography:
Jackson-Browne MS, Henderson N, Patti M, Spanier A, Braun JM. The Impact of Early-Life Exposure to Antimicrobials on Asthma and Eczema Risk in Children. Curr Environ Health Rep. 2019 Dec;6(4):214-224.
Vindenes HK, Lin H, Shigdel R, Ringel-Kulka T, Real FG, et al. Exposure to Antibacterial Chemicals Is Associated With Altered Composition of Oral Microbiome. Front Microbiol. 2022 Apr 28;13:790496.
Capper-Parkin KL, Nichol T, Smith TJ, Lacey MM, Forbes S. Antimicrobial and cytotoxic synergism of biocides and quorum-sensing inhibitors against uropathogenic Escherichiacoli. J Hosp Infect. 2023 Apr;134:138-146.
Fisher LE, Hook AL, Ashraf W, Yousef A, Barrett DA, et al. Biomaterial modification of urinary catheters with antimicrobials to give long-term broadspectrum antibiofilm activity. J Control Release. 2015 Mar 28;202:57-64.
Loose M, Naber KG, Purcell L, Wirth MP, Wagenlehner FME. Anti-Biofilm Effect of Octenidine and Polyhexanide on Uropathogenic Biofilm-Producing Bacteria. Urol Int. 2021;105(3-4):278-284.
Stickler DJ, Jones GL. Reduced Susceptibility of Proteus mirabilis to triclosan. Antimicrob Agents Chemother. 2008 Mar;52(3):991-4.
Mahalak KK, Firrman J, Lee JJ, Bittinger K, Nuñez A, et al. Triclosan has a robust, yet reversible impact on human gut microbial composition in vitro. PLoS One. 2020 Jun 25;15(6):e0234046.
Liu J, Tao Y, Haikun W, Lanfang Y, Jingyi L, Ping Y. Triclosan exposure induced disturbance of gut microbiota and exaggerated experimental colitis in mice. BMC Gastroenterol. 2022 Nov 18;22(1):469.
Gao B, Tu P, Bian X, Chi L, Ru H, et al. Profound perturbation induced by triclosan exposure in mouse gut microbiome: a less resilient microbial community with elevated antibiotic and metal resistomes. BMC Pharmacol Toxicol. 2017 Jun 12;18(1):46.
Westfall C, Flores-Mireles AL, Robinson JI, Lynch AJL, Hultgren S, et al. The Widely Used Antimicrobial Triclosan Induces High Levels of Antibiotic Tolerance In Vitro and Reduces Antibiotic Efficacy up to 100-Fold In Vivo. Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02312-18
Henly EL, Dowling JAR, Maingay JB, Lacey MM, Smith TJ, et al. Biocide Exposure Induces Changes in Susceptibility, Pathogenicity, and Biofilm Formation in Uropathogenic Escherichia coli. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e01892-18
SCCS (Scientific Committee on Consumer Safety), Opinion on triclosan (antimicrobial resistance), 22 June 2010 ISSN 1831-4767 ISBN 978-92-79-12484-6 doi:10.2772/11162 ND-AQ-09-001-EN-N
Bibliography:
Olea N (2019). Free yourself from toxins. RBA libros.
Hager E, Chen J, Zhao L. Minireview: Parabens Exposure and Breast Cancer. Int J Environ Res Public Health. 2022 Feb 8;19(3):1873
Apel P, Angerer J, Wilhelm M, Kolossa-Gehring M. New HBM values for emerging substances, inventory of reference and HBM values in force, and working principles of the German Human Biomonitoring Commission. Int J Hyg Environ Health. 2017 Mar;220(2 Pt A):152-166.
Zhang D, Xiao J, Xiao Q, Chen Y, Li X, et al. Infant exposure to parabens, triclosan, and triclocarban via breastfeeding and formula supplementing in southern China. Sci Total Environ. 2023 Feb 1;858(Pt 1):159820.
Hu J, Raikhel V, Gopalakrishnan K, Fernandez-Hernandez H, Lambertini L, et al. Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model. Microbiome. 2016 Jun 14;4(1):26.
