International Journal of Environmental Research and Public Health Review Toxicology and Microbiota: How Do Pesticides Influence Gut Microbiota? A Review Federica Giambò 1,†, Michele Teodoro 1,† , Chiara Costa 2,* and Concettina Fenga 1 1 Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Occupational Medicine Section, University of Messina, 98125 Messina, Italy; [email protected] (F.G.); [email protected] (M.T.); [email protected] (C.F.) 2 Clinical and Experimental Medicine Department, University of Messina, 98125 Messina, Italy * Correspondence: [email protected]; Tel.: +39-090-2212052 † Equally contributed. Abstract: In recent years, new targets have been included between the health outcomes induced by pesticide exposure. The gastrointestinal tract is a key physical and biological barrier and it represents a primary site of exposure to toxic agents. Recently, the intestinal microbiota has emerged as a notable factor regulating pesticides’ toxicity. However, the specific mechanisms related to this interaction are not well known. In this review, we discuss the influence of pesticide exposure on the gut microbiota, discussing the factors influencing gut microbial diversity, and we summarize the updated literature. In conclusion, more studies are needed to clarify the host–microbial relationship concerning pesticide exposure and to define new prevention interventions, such as the identification of biomarkers of mucosal barrier function. Keywords: gut microbiota; microbial community; pesticides; occupational exposure; dysbiosis Citation: Giambò, F.; Teodoro, M.; Costa, C.; Fenga, C. Toxicology and Microbiota: How Do Pesticides Influence Gut Microbiota? A Review. 1. Introduction Int. J. Environ. Res. Public Health 2021, 18, 5510. https://doi.org/10.3390/ In recent years, the demand for food has risen significantly in relation to the world ijerph18115510 population’s increase. At present, different types of pesticides are widely used worldwide to obtain better quality agricultural products and increase crop yields, thus bringing Academic Editor: significant economic benefits. Pesticides reach the soil, water and air, and non-target Mark Gregory Robson organisms, including humans [1]. As a result, health concerns about pesticide risks to animals have increased in recent years [2–4]. A growing number of studies have reported Received: 31 March 2021 that pesticides are linked to various pathologies, including metabolic diseases (such as Accepted: 19 May 2021 obesity and type 2 diabetes) [5], dysregulation of the immune system [6–8], neurotoxicity [9], Published: 21 May 2021 endocrine alterations, reproductive disorders [10,11], and even tumours [12,13], whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and Publisher’s Note: MDPI stays neutral immune functions. with regard to jurisdictional claims in Many efforts, focusing on the mechanisms of oxidative stress and the role played published maps and institutional affil- by the genetic profile in terms of susceptibility, have been conducted [14–16]. Recently, iations. different studies have demonstrated that gut microbiota (GM) can be affected and altered by different types of environmental pollutants, including some pesticides [17], therefore the role of the gut microbiota in pesticide-induced toxicity in non-target organisms is gaining increasing attention [18]. Copyright: © 2021 by the authors. The GM refers to the complex set of gut-resident bacteria, fungi and viruses that Licensee MDPI, Basel, Switzerland. have mutualistic relationships with their host. About 10–100 trillion symbiotic microbial This article is an open access article cells live in the human intestine [19]; the intestinal microbiota’s main components are distributed under the terms and bacteria species taxonomically classified by genus, family, order, and phyla. [20]. The GM is conditions of the Creative Commons complex and challenging to characterize. The intestinal bacterial community can be mainly Attribution (CC BY) license (https:// divided into 2172 species isolated in human beings, classified into 12 different phyla, of creativecommons.org/licenses/by/ which 93.5% belong to Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes [21]. The 4.0/). Int. J. Environ. Res. Public Health 2021, 18, 5510. https://doi.org/10.3390/ijerph18115510 https://www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2021, 18, x 2 of 17 Int. J. Environ. Res. Public Health 2021, 18, 5510 2 of 17 which 93.5% belong to Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes [21]. The microbiota composition and diversity remain relatively stable throughout life, although somemicrobiota changes composition have beenand observed diversity in infancy remain and relatively old age stable [22]. throughout Several scientific life, although studies pointsome out changes that maintaining have been observed a healthy in GM infancy plays and a key old role age in [ 22human]. Several health. scientific The intestinal studies microbiotapoint out that acts maintaining as an interface a healthy between GM foods, plays allows a key role the inassimilation human health. of nutrients, The intestinal helps themicrobiota digestion acts of fibres, as an interface participates between in the foods,synthesis allows of some the assimilation vitamins and of amino nutrients, acids, helps and regulatesthe digestion the absorption of fibres, participates of fatty acids, in the calc synthesisium and of magnesium. some vitamins Furthermore, and amino the acids, gut andmi- crobiotaregulates is theindispensable absorption for of fattythe development acids, calcium and and maturation magnesium. of the Furthermore, gastrointestinal the tract gut [23,24],microbiota a protective is indispensable barrier against for the developmentpathogenic microorganisms and maturation and of thetoxins. gastrointestinal The loss of stabilitytract [23 ,of24 ],a healthy a protective microbiota barrier leads against to the pathogenic transition microorganisms from eubiosis to and dysbiosis toxins. and, The consequently,loss of stability pathological of a healthy conditions microbiota ranging leads to from the transitioninflammatory from damage eubiosis to to chronic dysbiosis de- generativeand, consequently, diseases, pathological including tumour conditionss and ranging neurological from inflammatorydisorders [25–27]. damage to chronic degenerativeIn vitro, in diseases, vivo and including epidemiological tumours andstudies neurological have linked disorders human [ 25exposure–27]. to pesti- cidesIn to vitroseveral, in chronic vivo and diseases. epidemiological In vivo, thes studiese effects have have linked been human investigated exposure primarily to pesti- in modelcides to organisms several chronic representing diseases. humansIn vivo (such, these as effects rats or have mice). been investigated primarily in modelThe organisms mechanisms representing of interaction humans between (such pesticides as rats or mice).and GM have been hypothesized in otherThe studies mechanisms [28,29] of and interaction will therefore between be described pesticides andshortly GM in have this beenmanuscript. hypothesized Regard- in ingother how studies pesticides [28,29 ]can and interact will therefore with GM, be describedthe main types shortly of in interactions this manuscript. are illustrated Regarding in Figurehow pesticides 1. The GM can interactmetabolizes with GM,multiple the main chemicals types ofafter interactions intake. Mutually, are illustrated pesticides in Figure can1 . impairThe GM the metabolizes GM activity multiple and composition chemicals with after adverse intake. Mutually,repercussions pesticides for the can host. impair Though the itGM is known activity that and GM composition perturbations with can adverse affect repercussions the homeostatic for theequilibrium host. Though between it is favour- known ablethat GMand perturbationshostile microorganisms, can affect the it homeostatic is not still clear equilibrium how the between GM and favourable pesticides and interact hostile andmicroorganisms, whether these it isinteractions not still clear are how relevant the GM for andhuman pesticides health. interactIn fact, andit is whetherreasonable these to affirminteractions that not are all relevant statistically for human significant health. perturbations In fact, it is are reasonable also biologically to affirm relevant that not and all vicestatistically versa [30]. significant perturbations are also biologically relevant and vice versa [30]. Figure 1. GM metabolizes multiple chemicals after intake. Mutually Mutually,, pesticides can impair GM activity and composition with adverse repercussion for the host. with adverse repercussion for the host. InIn this this review, review, we we mainly mainly discussed discussed the the mechanisms mechanisms by which by which different different types types of pes- of ticidespesticides induce induce changes changes in inmicrobiota microbiota composition composition and and function, function, leading leading to to the the alteration of the hosts homeostasis. We We believe that th thee gut microbiota, an underestimated target, might play a significant significant role in pesticide-induced toxicity. Int. J. Environ. Res. Public Health 2021, 18, 5510 3 of 17 2. Materials and Methods A literature search was performed on PubMed and Scopus databases up to January 2021. The following search terms were used: ‘microbiota’ AND ‘pesticides’ (all fields), and ‘gut microbiota’