Benefits of Probiotics—Biodetoxification

Abstract

The rapid growth of the world’s population is generating escalating demands for food production. Global food demand is expected to increase by 35% to 56% between 2010 and 2050. Therefore, food mass production is becoming more challenging. The chemicalization of food production, processing, transport, packaging, and storage is almost impossible to avoid. These factors, along with environmental pollution, contribute to the increase in food product contamination. Xenobiotics appearing in food, including a variety of toxic substances (heavy metals, acrylamide, polycyclic aromatic hydrocarbons), and pathogens (pathogenic bacteria, fungi, molds, and yeast-producing mycotoxins) can threaten consumers’ safety and have negative economic implications. In this regard, the introduction of effective detoxification methods appears to be very important. It can be accomplished by physical, chemical, and biological means. Many reports have proved that probiotics are useful in food biodetoxification. Probiotics effectively reduce food contamination (at various stages of food production) and, moreover, annihilate toxins present in the human body. Many in vitro studies have confirmed the biodetoxification properties of probiotics, demonstrating that they diminish the toxic effects of the main types of food contaminants (heavy metals, polycyclic aromatic hydrocarbons, pesticides, mycotoxins, nitrates and nitrites, acrylamide, alkylphenols, biogenic amines, and dioxins). Probiotics produce various bioactive compounds, including antimutagenic, antioxidant, and anti-carcinogenic compounds. Their protective and beneficial influence on human microbiota can modulate host inflammatory processes, inhibit carcinogenesis, and modify immune resistance. Detoxification with probiotics is environment-friendly and, unlike physical and chemical methods, does not adversely affect the nutritional value and quality of food. In addition, probiotics in food are associated with well-known human health benefits; therefore, as a functional food, they have gained common consumer acceptance. The large-scale application of biodetoxification methods in both agriculture and the food industry is a challenge for the future. Based on contemporary research, this review provides the mechanism of probiotic biodetoxification, possible applications of various probiotics, and future trends.

1. Introduction

According to the United Nations World Population Prospects (2024), the world’s population will grow for the next 50 or 60 years. The peak of 10.3 billion people is expected in the mid-2080s [1]. This will require the production of more food, estimated at 35% to 56% between 2010 and 2050 [2]. This in turn necessitates the use of efficient production methods and, consequently, the use of various chemicals for fertilization, preservation, or prevention of food losses throughout the food production chain. Residues of these agents can contaminate food and pose a threat to consumers. Also, environmental pollution (air, water) contributes to the contamination of raw materials and food products on the one hand, and has a toxic effect on living organisms and disturbs the ecological balance on the other. In addition, these hazards become part of the human food chain.

Conventional strategies used for the detoxification or purification of residues are usually very expensive and have various side effects on health. One of the emerging, low-cost techniques is the potential use of probiotics for their biochemical removal [3].

Mycotoxins produced by molds at all stages of food production are also a huge problem. Currently, over 400 compounds have been identified that have been defined as mycotoxins. They can be stored as endotoxins in mycelium and conidia or released into the environment as exotoxins. Mold toxins are contaminants of feed, raw materials, and food products of plant and animal origin. The most favourable conditions for the growth of mold-producing toxins (e.g., aflatoxin B1) occur in tropical and subtropical climate zones. Soybean, rice, wheat, corn, and peanut crops located there are often contaminated with mycotoxins. Therefore, probiotic microorganisms are being tested for binding mycotoxins in food. For example, it was found that all tested strains of Saccharomyces cerevisiae were able to remove Ochratoxin A (OTA) and Zearalenone (ZEA). Live strains with mycotoxin-binding capacity and beneficial properties are potential probiotics that could be included in animal feed [4].

The human body has the ability to defend itself against external factors. This is expressed through physical barriers (e.g., skin, intestinal mucosa), biochemical barriers (antimicrobial peptides in mucous secretions), microbiota, and the immune system. Therefore, it is a holistic system, but external barriers are not always effective. When external barriers fail, the immune system is at risk. The immune response is expressed as the body’s ability to fight infections and diseases while maintaining appropriate tolerance to avoid allergies and autoimmune diseases. Lactic acid bacteria (LAB), including probiotics, can play a helpful role here, for example, by inhibiting the absorption of contaminants by the intestines and strengthening the intestinal barrier function, thereby reducing the accumulation and toxicity of selected heavy metals and pesticides in tissues. Probiotic microorganisms are defined by the International Scientific Association for Probiotics and Prebiotics as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [4]. The most functional food products contain microorganisms with probiotic properties, from the genera Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus, and from the family Lactobacillaceae [3,5,6].

Moreover, probiotics, by strengthening the anti-inflammatory effect of intestinal microbiota, can improve the body’s immune function. It should be emphasized that probiotics also reduce the risk of diarrhea associated with antibiotics, probably by competing with pathogenic bacteria and producing antagonistic compounds against them. Many studies indicate that probiotic bacteria may play a protective role in the body against toxicity caused by foodborne contaminants [7].

The protective and beneficial effects of probiotics on the human microbiota can modulate host inflammatory processes, inhibit carcinogenesis, and modify immune resistance. Probiotic detoxification is environmentally friendly and, unlike physical and chemical methods, does not negatively affect the nutritional value and quality of food. Moreover, probiotics in food are associated with well-known benefits for human health, which is why they have gained widespread consumer acceptance as functional foods. This review, based on contemporary research, presents the mechanism of probiotic biodetoxification, their protective activity, possible applications, and future trends.

2. Probiotics—Biodetoxification of Food

2.1. General Consideration of Food Toxin Deactivation

People are endangered by many diverse food, chemical, and biological pollutants. The harmful effects of these pollutants are related to the occurrence of health disturbances and toxic damage to internal organs, including the increased risk of cancer. The nature of toxic effects can be acute and chronic. Food toxicity related to xenobiotics depends on the dose, as well as on age and individual vulnerability. There are different sources and origins of food contaminants [8]. Some of the pollutants present in raw food are natural toxins (i.e., mycotoxins) or chemical pollutants which have entered food intentionally or accidentally (i.e., pesticides used in agriculture, antibiotics used in livestock breeding), and some are applied during food processing (i.e., preservation additives). Some contaminants are created or can appear at various stages of food processing, packaging (migration from packaging materials), transportation, and storage. Food additives, whether naturally derived or synthetically produced, are incorporated into food products and categorized as colorants, preservatives, flavor enhancers, emulsifiers, or stabilizers [9,10]. Many chemical substances are used in agriculture, in plant cultivation, as well as in animal breeding. Moreover, there are many environmental pollutants present in water, air, and soil [11]. This has implications for the global food industry and economy. The rise of environmental pollution is accompanied by growing concern for food safety and public health [12]. A wide range of foods, from raw to processed products and including all food categories—fruit, vegetables, bakery products, meat, fish, and dairy products—are a potential source of contaminants [13]. The Codex Alimentarius Commission was established in 1963 to protect consumer health and promote fair practices in food trade according to international food standard-setting and provides information on the maximum permitted levels of food contaminants (FAO/WHO Codex Alimentarius Commission) [14]. The main food contaminants are heavy metals, polycyclic aromatic hydrocarbons (PAHs), pesticides, mycotoxins, nitrates and nitrites, acrylamide, alkylphenols, biogenic amines, and dioxins (Figure 1) [15].

In general, according to EFSA, “detoxification is a removal of the undesirable substance or converting it to a compound [that is] non-harmful or with a lower toxicity than the parent compound”. Non-compliant contaminations are “(i) on purpose removed, via a physical detoxification process, (ii) broken down or destroyed by a chemical substance into harmless compounds, in a chemical detoxification process, and/or (iii) metabolised or destroyed or deactivated into harmless compounds, in a (micro)biological detoxification process. Biological detoxifications commonly use microorganisms or enzymes to modify the chemical structure of the undesirable substance (e.g., by metabolism) or to remove it (e.g., by binding to cell wall polysaccharides of bacteria)” [16]. According to the Janet L. Black, “detoxification, or biotransformation, is an ongoing, natural process of the body involving primarily the liver, kidneys, and skin to remove waste products and endogenously or exogenously acquired toxins” [17]. In general, detoxification is a complex system that adequately minimizes potential harms caused by xenobiotics.

Numerous strategies have been developed to detoxify food, including elimination and reduction of toxic contaminants or the transformation of them into non-toxic compounds. In general, three categories of food detoxification can be distinguished: physical, chemical, and biological. The physicochemical methods of food contaminant elimination or reduction are not universal. They provide the possibility of removing one contaminant or one group of suspicious pollutants. These methods are usually suitable only for individual classes of food products. Physical removal of toxins includes methods such as adsorption, microwaves, radiation, high-pressure pulse, and extrusion. Chemical methods include, for example, combating microorganisms that produce toxins, e.g., fumigation, ammonia control, ozonation, etc. [18]. The physicochemical methods can decrease the nutritional value of food. Usually, they are expensive, and their effectiveness is limited. Moreover, chemical methods are not eco-friendly, can lead to secondary pollution and therefore do not achieve consumer acceptance. Some physical procedures can be effective to protect food or eliminate food contamination. Examples include peeling, brushing, soaking in solutions (chlorine, chlorine dioxide, hydrogen peroxide, ozone, acetic acid), or washing with water [19]. These methods can be useful in reducing surface pollutant residues of disinfectants and cleaning agents that remain after the cleaning phase and preparation of food products. Heating treatment, including cooking, baking, roasting, grilling, and frying, can lead to the formation of harmful toxic compounds [20]. Optimization of temperature treatment (lower temperature, shortened time) can diminish toxic compound formation. Packaging materials have direct or indirect contact with food. If inappropriate materials are used, there is a risk of migration of various toxic compounds into the food. Moreover, inadequate storage conditions such as elevated temperature or sunlight can have an impact on the transfer of pollutants into the food. The avoidance of improper packaging materials and the optimization of storage conditions can diminish food toxicity [12].

2.2. The Role of Probiotics in Food Biodetoxification

The cell wall of lactic acid bacteria is composed of a thick layer of peptidoglycan and also consists of teichoic acids, lipoteichoic acids, polysaccharides, and exopolysaccharides [21]. The probiotic binding ability is related mainly to the cell wall peptidoglycan content and is strain-specific [22]. The non-viable cells (paraprobiotics) have been shown to have similar activities to viable cells. According to Taverniti and Guglielmetti, paraprobiotics are “non-viable microbial cells (intact or broken) or crude cell extracts (i.e., with a complex chemical composition), which, when administered (orally or topically) in adequate amounts, confer a benefit on the human or animal consumer” [23]. This toxin bioabsorption can be even increased by peptidoglycan breakdown due to the exposition of new binding sites [24]. Moreover, it has been reported that pH changes can modify probiotics’ binding capacity [25,26,27]. Probiotics can deactivate toxins via secreted enzymes (hydrolysis, decarboxylation, deamination) or by biotransformation, converting toxins into non-toxic or reduced-toxicity compounds.

2.2.1. Mycotoxins

Various strains of probiotics have been proven in vitro to annihilate common food mycotoxins (aflatoxin, ochratoxin, zearalenone, fumonisins) [28]. Sadiq et al. mention that many species of bacteria can degrade mycotoxins, including lactic acid bacteria [29]. For example, Lactobacillus acidophilus is effective for OTA, aflatoxin B₁ (AFB₁), and aflatoxin M₁ (AFM₁) biocontrol; Bifidobacterium animalis is useful for patulin control [30]. The degradation process depends on chosen factors, such as the pH, the microorganism species, and the incubation time as well as the concentration of the bacterial cells. Topcu et al. reported that many bacteria can degrade more than one mycotoxin [31]. Moreover, Pseudomonas fluorescens strain 3JW1 is able not only to degrade AFB₁ but also to inhibit the AFB₁ production of Aspergillus flavus. It reduces the amount of AFB₁ produced by Aspergillus in peanut medium and peanut kernels [32]. The efficacy of probiotics in removing mycotoxins is high. Wang et al. reported that Bacillus licheniformis BL010 reduced the content of aflatoxin B₁ by 97.3% [33]. Probiotics can also inhibit mycotoxin production. In the study by Gomaa et., al. Lactobacillus brevis and Lactobacillus paracasei showed inhibition of AFB₁ production by up to 96% [34]. In biodetoxification, paraprobiotics were shown to be even more effective than viable cells. In the study by Ondiek et al. heat-treated lactic acid bacteria were more effective in removing AFB₁ and trichothecene-2 (up to 62 and 52%, respectively) [35]. This was explained by the increased toxin-binding ability of the membrane of non-viable cells.

2.2.2. Heavy Metals

In general, the toxicity of heavy metals is the result of the formation of harmful free radicals. They are widespread in food and in the environment. Their toxic effects lead to carcinogenesis and neurotoxicity [3]. The most common heavy metals occurring in food are lead (Pb), cadmium (Cd), cobalt (Co), aluminum (Al), chromium (Cr), copper (Cu), iron (Fe), arsenic (As), nickel (Ni), zinc (Zn), and mercury (Hg) [18]. The main detoxification mechanisms include (i) the binding capacity of a probiotic cell wall, including accumulation inside the cell; (ii) biotransformation to less toxic compounds; and (iii) probiotics’ antioxidant activities [3]. Probiotics have been applied successfully to reduce heavy metal contamination in food. According to the reports, the rate of degradation of heavy metal contamination by probiotics was up to 90–100%. Many probiotic bacterial strains and yeasts (L. acidophilus, L. rhamnosus GG, L. fermentum L19, L. reuteri HS12, Saccharomyces spp.) were effective in removing cadmium, lead, zinc, nickel, and arsenic [18,36,37,38,39].

2.2.3. Pesticides

Pesticides are widespread, harmful contaminants of food products that generally appear in the food chain via plants. Their toxic effect particularly jeopardizes human endocrine, reproductive, and neurological functions. There are approximately 500 pesticide compounds registered and used worldwide. According to the purpose of use, several groups can be distinguished: fungicides, insecticides, herbicides, and pesticides [40]. Probiotics, via binding or enzymatic degradation (carboxylesterases, phosphatases, phosphotriesterases, hydrolases), have been shown to be effective in elimination of pesticides and amelioration of their toxicity [41]. Probiotic strains (L. acidophilus LA-5, Bif. animalis subsp. lactis BB-12, L acidophilus, L. delbrueckii subsp. bulgaricus, L. plantarum, L. rhamnosus, L. casei, S. thermophilus, Bif. bifidum) displayed successful reduction of organochlorine pesticides in dairy products [42,43]. Probiotic strains also reduce pesticides in vegetable products (kimchi, sauerkraut, pickles), grains, flours, sourdough, meat, meat products, wines, and fruit juices [40].

2.2.4. Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons are well-documented food contaminates, especially benzo(a)pyrene (B(a)P), which is classified by the International Agency for Research on Cancer (IARC) in the first group, which means there is sufficient evidence of its carcinogenicity in humans [44]. PAHs occur in various types of food, such as meat, cereals, and vegetable oils, usually when grilling, roasting, smoking, heating, and cooking [41,45]. Probiotic microorganisms annihilate B(a)P due to cell wall peptidoglycan binding capacity [41]. In the study by Shoukat et al., Bifidobacterium lactis BI-04HN019 and Bifidobacterium infantis BY12 were demonstrated to bind over 70% of B(a)P [46]. In the study by Zhao et al., fifteen LAB strains were investigated for B(a)P binding ability. L. pentosus CICC 23163 and L. plantarum CICC 22135 showed a B(a)P binding rate of over 60%, which was comparable to the results for heat-deactivated, non-viable cells [47].

2.2.5. Acrylamide

In various foods (fries, cereals, bakery products, cookies, coffee, meat) submitted to heat processing (e.g., frying, roasting, and baking), harmful acrylamide can be formed in the Strecker or acrolein pathway [48]. Acrylamide content in food is also related to storage conditions and duration as well as to domestic food cooking procedures. The main precursor is free asparagine, especially in foods rich in reducing sugars (fried potatoes and bakery products) [49,50]. Toxicological consequences of acrylamide include carcinogenesis, mutagenic, neurotoxicity, and reproductive toxicity [51]. After ingestion, it is easily absorbed and distributed in many organs (thymus, liver, heart, brain, kidneys) [50]. Due to the presence of peptidoglycan in cell walls, LAB strains can bind acrylamide, as confirmed in the in vitro study by Zhang et al. (2017) [52]. One of the strategies that have been tested on a lab scale to reduce the acrylamide content of food is the addition of asparaginase. In relation to the high cost of this enzyme, the study results showing that the bacterial L-asparaginase can inhibit acrylamide generation are of great importance. In the study by Onsi et al., L-asparaginase produced by Bacillus subtilis reduced the acrylamide content in fried potato chips by 20% [53,54,55].

2.2.6. Nitrite and Nitrate

Nitrite and nitrate are commonly used in meat preservation. They are responsible for carcinogenic N-nitrosamine formation in food matrices, as well as endogenously, after ingestion [56]. Nitrites (most commonly sodium nitrite—E250) are preservatives widely used in the food industry, particularly in processed meat products. Nitrates and nitrites can occur naturally in food products [57,58,59], as well as be added as preservatives or in the form of plant extracts. They extend the shelf life of food items, inhibit microbial growth, delay rancidity, and improve the flavor and color of meat products. Long-term exposure to N-nitrosoamines may increase the risk of developing cancer [60]. LAB is naturally present in meat as well as strains added as starter cultures or additive cultures. Many reports have confirmed the ability of LAB (i.e., L. pentosus, L. curvatus, and L. sakei, L. plantarum) to break down and reduce nitrate and nitrosamine content [18]. LAB produces organic acids, especially lactic acid, leading to acidification of the meat, which has an impact on reduced N-nitrosamine generation [61]. Moreover, LAB strains can be used as meat preservatives, avoiding the use of nitrates in meat preservation [62]. The new EU regulations aim to reduce the permissible levels of nitrates and nitrites by approximately 20 percent. This decision follows an in-depth scientific assessment conducted by the European authorities. The updated limits take into account the diverse range of products and production conditions across the European Union. By sending a clear signal to both the food industry and smaller producers, the Commission intends to address the challenges posed by the presence of nitrites and nitrates throughout the EU food supply chain [63].

2.2.7. Biogenic Amines

A further category of hazardous food contaminants is biogenic amines (BAs). They are generated by bacterial decarboxylation from amino acids in various foods (dairy products, meat, fish, wine, fruit juices). They can be found in high concentration in various fermented foods [64]. Three groups of BAs with a potential risk of various intoxications are distinguished: heterocyclic (histamine and tryptamine), aliphatic BAs (putrescine and cadaverine), and aromatic (tyramine and phenylethylamine). Biogenic amines in excess may be toxic. Histamine and tyramine may influence the cardiovascular, gastrointestinal, and nervous systems, while cadaverine and putrescine may create carcinogenic nitrosamines [65]. LAB can degrade biogenic amines and decrease their generation by pathogenic bacteria [66]. Probiotics produce numerous antimicrobial compounds (bacteriocines, organic acids, diacetyl, hydrogen peroxide exopolysaccharides) that effectively counteract the growth of pathogenic and spoilage microorganisms [67].

2.2.8. Bisphenol A

Polycarbonate plastics epoxy resins are commonly used as utility products and packaging materials. They contain an added hardening component—harmful bisphenol A (BPA)—which can migrate to the food matrix. Prolonged contact time, increased temperatures, and food composition can accelerate the migration of xenobiotics from packaging materials. Fatty and acidic foods promote migration of BPA [68]. The presence of this xenobiotic is related to toxic effects, including increased risk of cancer, and endocrine and fertility disorders [69]. The EU Commission Regulation (EU) 2024/3190 of 19 December 2024 on the use of bisphenol A and other bisphenols and bisphenol derivatives prohibits the use of BPA in polycarbonate drinking cups and bottles for infants and young children [70]. There are many reports confirming the usefulness of probiotics in BPA biodetoxifications. Ju et al. investigated six probiotic strains (L. reuteri, L. helveticus, L. brevis, L. delbrueckii, L. casei, and Bacillus subtills), confirming the potential of probiotics in the biodegradation of BPA. The highest degradation rate of BPA in this in vitro study was reached (69.83%) with Lactobacillus reuteri [71].

3. Probiotics—Detoxification in the Human Body

Probiotics play an important role in the detoxification process in the body. This process takes place thanks to their ability to modify metabolic and genetic pathways, which ultimately leads to the neutralization of toxins and the improvement of the functioning of the immune system and the digestive tract. The participation of probiotics in the process of biodetoxification in the human organism is shown in Figure 2.

3.1. Biotransformation of Xenobiotics

Humans are exposed to a wide range of dangerous chemicals from food and the environment. Xenobiotics are alien compounds that enter a live creature via food, water, or inhaled air yet are not part of it. These include endobiotics when they are present in higher concentrations than their typical levels, as well as naturally occurring poisons and manmade environmental contaminants that serve as other organisms’ defensive mechanisms [72,73].

Long-term consumption of contaminated food with xenobiotics may be tied to a widespread range of human health problems like the disruption of the gut microbiome, also known as dysbiosis; reproductive tract disorders; mental health disorders; and immune system disorders. Some authors have suggested that probiotics are a promising strategy for the alleviation of their toxicity and accumulation in the human body [74,75]. In

Table 1. Probiotic actions in the process of xenobiotic detoxification—examples.

Probiotic	Mechanism Removal	Xenobiotics	Effect on the Host	References
Lactobacillus rhamnosus	Binding/degradation of bacterial toxins and heavy metals	Aflatoxins, Cadmium (Cd)	Reduces bioavailability and absorption of toxins, protects the liver function	[78,79]
Lactobacillus plantarum	Antioxidant activity, ROS neutralization	Pesticides, reactive oxygen species	Protects intestinal barrier integrity, minimizes oxidative stress	[80,81]
Bifidobacterium breve	Modulates microbial metabolism, enzyme activity	Bisphenol A (BPA)	Mitigates endocrine-disrupting effects, supports microbiota stability	[82,83]
Lactobacillus acidophilus	Enzymatic degradation of carcinogenic amines	Nitroamines, aromatic hydrocarbons	Reduces the mutagenic and carcinogenic potential of foodborne toxins	[18]
Saccharomyces boulardii	Adsorption of heavy metals	Arsenic (As), Cuprum (Cu), Cadmium (Cd), Mercury (Hg)	Decreases metal bioavailability, supports intestinal homeostasis	[3,84]
Lactobacillus casei	Suppression of microbial beta-glucuronidase	Drug metabolites	Aids in detoxifying drugs and hormones, reducing toxicity in the gut	[85,86]

, we present examples of probiotics’ mechanisms of action in the process of xenobiotic detoxification [76,77].

Lactic acid bacteria, the yeast Saccharomyces (S. cerevisiae var. boulardii), and Bifidobacterium spp. are the most often utilized probiotics [7,87,88,89,90,91,92]. Numerous advantageous characteristics of these strains can be crucial for xenobiotic detoxification, including their potent ability to bind, tolerate, or detoxify; their high tolerance to bile and acid; their strong adherence to the gut mucosa; and their potent antioxidant or immunoregulatory capabilities, which allow them to adjust to changes in the gut environment brought on by xenobiotics [8,93,94,95]. Recent research has demonstrated that probiotic multiple-strain mixes are more successful, and new strains with specialized functions need to be isolated, even though the mechanisms of action of probiotics are not entirely understood [96,97].

Detoxification processes occurring in a living organism are located mainly in the liver—the most important detoxification organ. It is the liver that is primarily responsible for the inactivation and effective elimination of both endogenous metabolites and xenobiotics. The metabolism of xenobiotics makes them more soluble in water, which facilitates their removal from the body [93]. The first pass effect is the term used to describe the process by which xenobiotics that are consumed orally travel to the upper gastrointestinal system and, if absorbed, are transferred to the liver via the hepatic portal vein. The cytochrome P450 (CYP 450) family of enzymes in the human liver chemically changes both endogenous and foreign substances [94]. Phase I (activation by oxidation, reduction, or hydrolysis), Phase II (conjugation to polar moieties), and Phase III (transport without chemical alteration) are the three stages of liver metabolism. Unmetabolized and expelled xenobiotics build up in the body and can cause inflammation and chronic illnesses [98,99].

The harmful effects of xenobiotics are becoming an increasingly serious problem both for the environment and for human health, which requires an interdisciplinary scientific solution. It should be noted that inter-individual genetic differences among people modulate the extent of damage that they can cause to our body. This is mainly due to individual effects on xenobiotic metabolism and detoxification processes. The microbiota of the gut may be essential for in vivo biodetoxification. Probiotics have garnered attention in recent decades because of their many benefits, including in vivo biodetoxification and digestive system health [100,101].

The bacterial microbiota present in the gastrointestinal tract synthesizes various types of chemicals that have the ability to affect the metabolism and absorption of many xenobiotics. Enterocytes, or intestinal epithelial cells, as in the liver, also contain monooxygenases, enzymes involved in the processes occurring during the first phase of detoxification, responsible for the biotransformation stage of xenobiotics. In addition, in the regions of the peak intestinal villi, high activity of transmembrane pumps has also been recorded, through which transport is directed from the inside of the cell towards the intestinal lumen (antiport). These enterocytic transport systems are considered phase III of detoxification. Their action to reduce the concentration of toxins in the interior of intestinal epithelial cells reduces the amount of toxins transported to the liver via the portal circulation. Toxins returned to the lumen of the gastrointestinal tract can be safely removed from the body together with fecal masses without the need to burden the liver. Currently, the three most important genes (MDR1, MDR2, MDR3) have been identified, encoding proteins from the P-glycoprotein (Pgp) family, which participate in the active transmembrane transport of toxins from the inside of the cell to the outside [102,103,104,105].

In order to assess the innate activity of enzymes associated with the first phase of detoxification, analysis of the two best-studied genes CYP1A1 and CYP1B1 is most often carried out. These genes encode enzymes belonging to the cytochrome P450 family. They are responsible, among other things, for the detoxification of polycyclic aromatic hydrocarbons, which are frequent atmospheric pollutants. They can enter the body through the lungs via inhalation of fumes and fumes floating in the air, with food and water, and even directly through the skin [106,107].

In contrast, the enzymatic activity of phase II detoxification is regulated by the expression of the GSTM1, GSTT1, and GSTP1 genes. These genes encode S-glutathione transferases, enzymes found in the liver and lymphocytes. The level of activity of these enzymes determines the effectiveness of detoxification and removal of substances such as pesticides, chemicals, fungicides, plant protection products, insecticides, and heavy metals from the body. If they work efficiently, these enzymes ensure that these harmful substances are effectively filtered out of the body. However, there are polymorphisms (varieties) of these genes that encode S-glutathione transferases with reduced activity. This does not allow for proper detoxification, which leads to the accumulation of toxins in the body and increases the risk of developing many different diseases, including cancer.

The course and effectiveness of detoxification processes occurring in the liver are largely genetically determined. There are many genes that control these processes. These genes control the action of enzymes that bind and neutralize toxic substances in the body. Some of our individual genetic traits may limit the body’s ability to synthesize these enzymes, which increases exposure to the toxic effects of xenobiotics. Modern genetic diagnostics gives the opportunity to study the individual capabilities of the body to neutralize toxins [102,108,109]. Genetics as a branch of science plays a key role in the processes of biodetoxification involving microorganisms with probiotic properties. Future directions of development in this aspect include the following: (1) medical personalization (genotyping of detoxification enzymes allows adjustment of pharmacological therapy, minimizing the risk of side effects of drugs related to their metabolism); (2) gene editing (CRISPR-Cas9) (precise genetic modifications of microorganisms to increase their ability to detoxify pollutants); and (3) creation of genetic biomarkers (possibility to assess the risk of diseases associated with chemical poisoning, and monitoring of toxin exposure).

In addition to directly influencing xenobiotic metabolism, the human microbiome can also influence host enzyme activity and the expression of metabolizing genes. Conversely, xenobiotics have the ability to change the microbiome’s makeup, resulting in dysbiosis, which is associated with a number of illnesses and negative health outcomes, including heightened toxicity of some xenobiotics. The human microbiome has a strong metabolizing capacity that even surpasses the host’s metabolic capabilities because of its immense diversity. Specifically, xenobiotics, which can include anything from dietary substances to prescription chemicals, can be biotransformed by the human gut microbiota. Whether the xenobiotic is poorly absorbed and moves from the small intestine into the large intestine, binds to one of the efflux proteins, or is absorbed into the circulation, the microbiome can change the half-lives of xenobiotics, their possible effects on the human body, and the rate and extent to which they reach the bloodstream or their receptors. Eventually, the xenobiotic will come into contact with the microbiota and its enzymes [73]. The host’s capacity to metabolize medications or xenobiotics may also be indirectly impacted by the gut microbiota [105]. The intestine microbiota is engaged in energy absorption. The excessive abundance of Firmicutes is considered to cause obesity [110]. The ratio of Firmicutes/Bacteroidetes (F/B) in obese individuals is increased [111]. Probiotics can influence gut microbiota and have potential to reduce the F/B ratio [112]. Bacteroidetes produce butyric and propionic acid, which improve epithelial intestine cell functions and therefore reduce endotoxins as well as lipopolysaccharide absorption. As a result, they are less effective in calorie absorption, with subsequent possible weight reduction [113].

The gut microbiota’s metabolic enzymatic capacity is so distinct from the host’s metabolic capacities that the microbial metabolism of xenobiotics can occasionally be the opposite of the host biotransformation. While microbial enzymatic processes primarily involve reduction and hydrolysis, host enzymes primarily carry out oxidation and conjugation [7]. One example of the differences between host and microbiome xenobiotic metabolism is demethylation, which produces carbon sources for microorganisms to continue growing and dividing while making a xenobiotic more polar for excretion outside the body in the host [114,115,116].

3.2. Modulation of Intestinal Microbiota and Immunomodulation

Probiotics help maintain the balance of intestinal microbiota, which supports digestive processes and improves the intestinal barrier. Good intestinal health promotes the effective removal of toxins by preventing harmful substances from entering the bloodstream. Probiotics are effective in treating a wide range of illnesses, including intestinal-related conditions, in many ways, including lowering intestinal pH, metabolite production, pathogen colonization and multiplication, increasing the host immune response, and binding toxins [117,118,119]. The primary way that probiotics affect human health is through their capacity to protect and maintain the gut epithelium’s healthy function by (i) directly influencing the epithelium—goblet cells express and secrete mucin, and epithelial cells secrete more β-defensin; (ii) boosting mucosal immunity—increasing cells that produce IgA; and (iii) lowering the number of pathogens and/or their gene expression [97,120,121,122].

Probiotics can stimulate the immune system, which improves the body’s overall ability to defend against toxins and pathogens. Good functioning of the immune system accelerates regeneration processes and helps in the elimination of unwanted substances. Lymphoid tissue associated with the intestines (gut-associated lymphoid tissue, GALT) is an element of the immune system. It forms part of the larger immune system of lymphoid tissue associated with the mucous membranes of the gastrointestinal tract (mucosa-associated lymphoid tissue, MALT). Mucous membranes of the digestive system are a barrier that protects the body against infections and the development of systemic inflammation. Within GALT, there are 70–75% of the entire immune system’s lymphatic cells. Thanks to this, the intestines are called the main pillar of the immune system. In addition, GALT is responsible for the recognition, capture, and control of harmful pathogens taken with food. Its activation takes place at the time of birth. The gut microbiota is closely related to the activation and modulation of the immune response throughout human life [123,124,125].

The primary colonization of the newborn during childbirth and the simultaneous contact of the first intestinal bacteria with GALT are the main factors affecting the development of immune tolerance. The intestinal microbiota affects both the cytokine balance (the balance of Th1/Th2/Th17) and the modulation of nonspecific immunity. Intestinal bacteria modulate cytokine balance by affecting regulatory T cells (Tregs). Inactivated Tregs do not secrete cytokines. It is only after activation that they begin to produce the transforming growth factor beta-TGF and Il-10, and thus inhibit the proliferation of effector cells (basophils, eosinophils, and mast cells) and their secretion of proinflammatory cytokines [126]. The microbiota, by inducing TGF and IL-10 secretion, affects the differentiation of T helper lymphocytes (Th): Th1, Th2, Th17. Th1 lymphocytes are involved in the cellular immune response. In the case of increased stimulation of Th1 lymphocytes, we are dealing with inflammatory diseases. Th2 lymphocytes are involved in the humoral type of response. In the case of an excessive response of Th2 lymphocytes, an increased number of allergic reactions is observed. Th17 lymphocytes, in turn, play a role in antibacterial and antifungal defense, and may also be important in the pathogenesis of autoimmune diseases. The role of the pro-health microbiota, including probiotics, is to ensure that the cytokine balance of Th1/Th2/Th17, and thus the immune tolerance, is maintained. A lack of bacterial stimulation has been shown to reduce the production capacity of IL-10 and TGF by Treg lymphocytes [127].

It should be emphasized that the intestinal microbiota also increases innate immunity, including the synthesis of secretory IgA (sIgA) or defensins (natural antibacterial proteins). The production of sIgA is one of the main functions of GALT and significantly correlates with the presence and activity of the pro-health intestinal microbiota. Secretory IgA is an immunoglobulin secreted on most mucous membranes of our body and is one of the most important elements of mucosal defense. sIgA can flatten and agglutinate microorganisms, exerts a bacteriostatic effect, and prevents the adhesion of antigens to the epithelium, and thus their penetration into the mucous membranes, as well as neutralizing bacterial toxins [94,128,129].

It is also important that the intestinal microbiota is involved in building immunity by creating a natural barrier on the surface of the intestinal epithelium. Beneficial bacteria take up space on the receptors, thus preventing them from being occupied by pathogenic bacteria. In addition, they compete for nutrients with pathogens. Intestinal bacteria, through the production of bacteriocins, including hydrogen peroxide, are capable of direct bacteriostatic and bactericidal action. In addition, by synthesizing lactic acid, they lower the pH within the intestines, which changes the environment to one that is less hospitable for pathogenic bacteria [130,131,132].

Regular consumption of products with probiotics or supplementation with probiotic preparations may contribute to a more effective biodetoxification process, supporting the natural functions of the body that are responsible for the removal of toxins [121,128,129].

Antimutagenic and Anticarcinogenic Probiotic Activity

The gut microbiota plays a major role in the human body’s capacity to maintain homeostasis. Probiotics are becoming more and more significant in the medical profession because of their beneficial effects on the human body and their ability to prevent and treat a number of chronic illnesses, including cancer, without having any harmful side effects [106]. Probiotics’ anticarcinogenic activity stems from the following: (1) altering the composition of the intestinal microbiota; (2) altering the intestinal microbiota’s metabolic activity; (3) producing anticarcinogenic compounds like conjugated linoleic acid and short-chain fatty acids; (4) inhibiting cell proliferation and inducing apoptosis in cancer cells; (5) influencing other mutagenic and carcinogenic factors (they can alter the activity of certain enzymes involved in the cellular detoxification process, preventing the activity of free radicals and carcinogenic substances); (6) binding and degradation of carcinogenic compounds present in the intestinal lumen; (7) immunomodulation promoting the production of antibodies, NK cells (natural killer cells), and macrophages; (8) improvement of the intestinal barrier; and (9) support for the production of anti-inflammatory cytokines, such as IL-10, which can prevent inflammation that leads to the development of cancer [133,134,135,136]. In

Table 2. Antimutagenic and anticarcinogenic probiotic activity—examples.

Probiotic	Mechanism	References
L. casei and L. paracasei	Observed anti-cancer activity in K562 cells (blood cancer)	[137]
Bifidobacterium pseudolongum	Inhibited IL-6/JAK1/STAT3 signaling pathway via GPR43 activation (liver cancer)	[138]
Lactobacillus brevis MK05	Induction of apoptosis via Lb-PPSPs in MCF-7 cells, positive modulation in the expression of apoptosis pathway mediators, BAX, BCL-2, and BCL2L11	[139]
BLactobacillus rhamnosus, S. cerevisiae	A significant effect on AFB1 reduction in the simulated gastrointestinal tract condition	[140]
Bifidobacterium lactis Bb-12, Lactobacillus acidophilus T20	A tool for protecting DNA against genotoxic agents	[141]

, examples of antimutagenic and anticarcinogenic probiotic activity are shown.

The innate immune response is extremely important in the context of cancer. The first line of defense of the body against the development of cancer is NK cells, dendritic cells (DC), T-lymphocytes, cytokines (IFN, TNF, IL-12, and IL-18), chemokines (RANTES, MIP-1a, MIP-1b), chemokines, oxygen radicals, and nitrogen oxides and granulocytes (mainly neutrophils). NK cells are the first to destroy cancer cells that do not express molecules of the main MHC (Major Histocompatibility Complex) tissue compatibility system. NK cells destroy cancer cells by releasing cytotoxic proteins such as perforins and granzymes that lead to cell lysis. Lysis of cancer cells releases their antigens, then they activate DC cells, which then present antigens to CD8+ T cells. In addition, NK cells, in response to cellular stress, increase the expression of ligands for NK cells on cancer cells, which activate other NK cells. Cytokines, such as interferons IL-12, IL-18, and IL-15, affect the faster maturation of NK cells. Most of the T cell subpopulation of TCR receptors is able to recognize phosphoantigens, antigens expressed on cancer cells. Activated T lymphocytes produce cytotoxic perforins and granzymes, as well as cytokines such as IFN and TNF. Additionally, expression of the CD16 molecule on T lymphocytes facilitates the mechanism of antibody-dependent cell cytotoxicity directed against cancer cells [142]. IFN, produced by NK cells, enhances HLA antigen presentation. Also, on cancer cells, it affects the polarization of macrophages in the direction of anti-cancer type M1, and has an anti-angiogenic effect on the CXCR3-dependent pathway. In addition, by inducing the expression of the CXCL9, 10, and 11 IFN chemokines, it stimulates the chemotaxis of NK, Th1, and CD8+ T cells in place of cancer. TNF produced by active macrophages and monocytes is associated with the development of inflammation through strong activation of NF-κB factor and the MAPK signaling pathway (kinases activated by mitogens, Mitogen—Activated Protein Kinases). In addition, cytokine increases the antitumor activity of other cytokines, such as IFN-gamma or IL-2 [143]. IL-12 is a cytokine necessary for the differentiation of cells towards Th1 and the acquisition of cytolytic functions by CD8+ T cells. Indirect antitumor activity of IL-12 consists in stimulating NK cells and T cells to produce IFN and TNF [109]. Moreover, IL-12 exhibits antiangiogenic activity on the path dependent on vascular endothelial growth factor (VEGFR3) [144,145,146,147].

Probiotics exhibit multifaceted anti-cancer effects, both through microbiota modulation and direct effects on cells and molecular pathways. However, there is a need to conduct more clinical trials to clearly determine their effectiveness and optimal application in the prevention and treatment of cancer.

4. Probiotics—Advantages of Biodetoxification

According to the literature, detoxifying can improve the human body’s ability to absorb nutrients [32]. Removing toxins from the body helps prevent inflammation and supports immune system function. When combined, probiotics and biodetoxification work synergistically to enhance overall wellness. Probiotics promote a healthy gut, which is essential for effective detoxification. A well-balanced microbiome helps the body break down and eliminate toxins more efficiently. Food contamination by mycotoxins is a great threat to food safety [148]. With mycotoxin detoxification by microorganisms, the biological process is reliable, efficient, less costly, and easier to use than physical and chemical ones. However, it is important to discover the metabolite’s toxicity resulting from mycotoxin biodegradation. Microorganisms exhibiting activity against mycotoxins have important properties that can be used in the future to develop biological preservation methods based on enzymes produced by these microorganisms.

In vitro studies show promising results for the use of probiotics to detoxify xenobiotics and pollutants. These studies evaluate the effectiveness of different probiotic strains in breaking down harmful substances and converting them into less toxic forms. This approach can lead to safer food products that do not have a negative impact on the health of the consumer. Although probiotic supplementation may reduce the toxicity of xenobiotics, it should be recognized that food is a complex matrix containing many different xenobiotics that may exhibit synergistic or additive properties [149]. This should be taken into account when evaluating the effectiveness of biodetoxification methods. A common source of probiotics is fermented foods. As fermentation is a natural, traditional, and effective method of food preservation, the use of chemical preservatives is significantly reduced or they are not used at all. The presence of xenobiotics in such products is rather the result of contamination of the raw product, the source of which is, among other things, environmental pollution. Średnicka et al. highlighted that the consumption of fermented dairy products supplemented with xenobiotic-binding probiotic strains could provide a simple and effective method of mitigating the adverse effects of food contaminants. In this regard, the use of probiotic biodetoxification appears to be particularly relevant in regions with high levels of pollution [150]. Maher et al. tested the ability of 37 LAB and 13 yeast strains in binding acrylamide. The most effective acrylamide binding ability was found in Pediococcus acidilactici, achieving reduction of acrylamide levels by 87.6%. It should be noticed that the acrylamide binding ability remained comparably high when non-viable cells (thermally inactivated) were used. In addition to detoxification, the tested strains decreased acrylamide-induced DNA damage, therefore reducing its genotoxicity. The reported findings indicate that LAB and yeast possess great potential for the detoxification of food contaminated with acrylamide and reducing its harmful genotoxic effects [151].

The large-scale application of biodetoxification methods in both agriculture and the food industry is a challenge for the future. The widespread and successful implementation of probiotic microorganisms in this field may be of great importance for food safety. It can contribute to the limited use or even replacement of the traditional chemical and physical methods by an eco-friendly biological approach [62,152]. In addition, it should be mentioned that the use of probiotics can support the detoxification of xenobiotics already present in the body and has many other health-promoting benefits for the host [32].

5. Conclusions, Challenges, and Future Trends

Nowadays, the use of probiotics is due to their food preservation properties and human health benefits. In general, probiotics are not intended to be used as a biodetoxification means. Most biodetoxification studies are small in vitro studies, showing the potential of probiotics in food pollutant annihilation, including the main food toxins. In this regard, there is a need for further studies to confirm the efficacy and safety of particular probiotic strains in various food categories. Moreover, the mechanisms involved in the detoxification of food by probiotics should be elucidated in detail. Despite encouraging study results, insufficient data limit the use of probiotics as biodetoxificants in the food sector. Additionally, the use of probiotics in this field is also limited by the lack of adequate legislation by relevant authorities. The indication and strategy of probiotic use in the removal of xenobiotics from food, including when and how they should be applied, need to be formulated. In conclusion, it should be stated that probiotics effectively reduce food contamination (at various stages of food production) and, moreover, annihilate toxins present in the human body. Detoxification with probiotics is environment-friendly and, unlike physical and chemical methods, does not adversely affect the nutritional value or quality of food. They may participate in the biodetoxification process by regulating the expression of host genes responsible for neutralizing toxins; the genetically conditioned activity of the host’s own bacterial enzymes that break down toxins; modulation of the intestinal microbiota, which affects the epigenetic mechanisms of detoxification; and strengthening the immune system through immunomodulation mechanisms. The success of food detoxification relies on complex activities, including a wide range of actions from reducing environmental pollution through industrial food processing, food storage, and transportation to detoxification in the digestive tract. In the scope of a holistic attitude of detoxification, probiotics have emerged as more effective and eco-friendly food detoxicates that can have multiple applications for various food categories with unlimited prospects for the future.