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Effect of Probiotics, Bifidobacterium breve and Lactobacillus casei , on Bisphenol A Exposure in Rats
Abstract
Bisphenol A (BPA), a putative endocrine disruptor, may be taken up by humans via the diet and have adverse effects on human health. In this study, we evaluated whether the probiotics, Bifidobacterium breve strain Yakult (BbY) and Lactobacillus casei strain Shirota (LcS), could exert a protective effect against dietary exposure to BPA. A group of rats fed on a diet containing 5% BbY or 5% LcS showed three advantageous effects compared to the control group; (i) the area under the blood concentration-time curve of BPA after its oral administration was significantly decreased, (ii) the amount of BPA excreted in the feces was significantly greater (2.4 times), and (iii) the percentage of BPA bound to the sediment fraction of the feces was significantly higher. These results suggest that BbY and LcS reduced the intestinal absorption by facilitating the excretion of BPA, and that these probiotics may suppress the adverse effects of BPA on human health.
... Examples include drugs like diclofenac and irinotecan, where bacterial microbiota can generate toxic forms, leading to side effects such as diarrhea [123]. In turn, in vivo trials showed that LAB stimulated intestinal peristalsis, facilitating the elimination of chemicals from the body with feces [146]. Oishi et al. [146] showed that Bifidobacterium breve and Lactobacillus casei can reduce the intestinal absorption of BPA in rats. ...
... The capacity of probiotics to efficiently detoxify BPA and other chemical pollutants could lead to the development of BPA removal systems, which could be safely incorporated as additives in food or feed for both animals and humans [148]. In turn, in vivo trials showed that LAB stimulated intestinal peristalsis, facilitating the elimination of chemicals from the body with feces [146]. Oishi et al. [146] showed that Bifidobacterium breve and Lactobacillus casei can reduce the intestinal absorption of BPA in rats. ...
... In turn, in vivo trials showed that LAB stimulated intestinal peristalsis, facilitating the elimination of chemicals from the body with feces [146]. Oishi et al. [146] showed that Bifidobacterium breve and Lactobacillus casei can reduce the intestinal absorption of BPA in rats. After the oral administration of probiotics, the concentration of BPA in the blood was significantly reduced and the amount of BPA eliminated with feces was significantly increased. ...
Bisphenols, such as bisphenol A and its analogs, which include bisphenol S, bisphenol F, bisphenol AF, and tetramethyl bisphenol F, are chemical contaminants commonly found in food that raise serious health concerns. These xenobiotics can potentially have harmful effects on human health. The gut microbiota plays a crucial role in metabolizing and neutralizing these substances, which is essential for their detoxification and elimination. Probiotic supplementation has been studied for its ability to modulate the gut microbiota’s composition and function, enhancing detoxification processes. Next-Generation Probiotics (NGPs) may exhibit better properties than traditional strains and are designed for targeted action on specific conditions, such as obesity. By modulating inflammatory responses and reducing the secretion of pro-inflammatory cytokines, they can significantly improve host health. Research on NGPs’ ability to neutralize obesogenic bisphenols remains limited, but their potential makes this a promising area for future exploration. This review aims to understand the mechanisms of the chemical transformation of bisphenol through its interactions with the gut microbiota and the role of probiotics, particularly NGPs, in these processes. Understanding the interplay between bisphenols, gut microbiota, and NGPs may pave the way for strategies to counteract the negative health effects associated with daily and chronic exposure to bisphenols, which is crucial for food safety and consumer health protection.
... Some probiotic cultures, particularly lactic acid bacteria (LAB), including Lactobacillus plantarum and Lactobacillus rhamnosus, as well as probiotic yeasts, such as Saccharomysces cerevisiae (including S. cerevisiae var. boulardii) have been discovered to bind to and accelerate the removal of (Ibrahim et al., 2006;Jama et al., 2012;Zhai et al., 2013Zhai et al., , 2015, lead (Halttunen et al., 2007) and manganese (Tong et al., 2020) from the GIT, but also other toxic substances, like mycotoxines (Hernandez-Mendoza et al., 2009;Huang et al., 2018;Karazhiyan et al., 2016;Wacoo et al., 2019), benzo(a) pyrene (Shoukat et al., 2019;Zhao et al., 2013), phthalates (Lili et al., 2017b;Zhu et al., 2018) and BPA (Oishi et al., 2008;Zhu et al., 2017). Thus, probiotic cultures are expected to become significant among the other protective agents, such as vitamins and antioxidants, that have been proposed to reduce phthalate and BPA toxicity (Lili et al., 2017b;Oishi et al., 2008). ...
... boulardii) have been discovered to bind to and accelerate the removal of (Ibrahim et al., 2006;Jama et al., 2012;Zhai et al., 2013Zhai et al., , 2015, lead (Halttunen et al., 2007) and manganese (Tong et al., 2020) from the GIT, but also other toxic substances, like mycotoxines (Hernandez-Mendoza et al., 2009;Huang et al., 2018;Karazhiyan et al., 2016;Wacoo et al., 2019), benzo(a) pyrene (Shoukat et al., 2019;Zhao et al., 2013), phthalates (Lili et al., 2017b;Zhu et al., 2018) and BPA (Oishi et al., 2008;Zhu et al., 2017). Thus, probiotic cultures are expected to become significant among the other protective agents, such as vitamins and antioxidants, that have been proposed to reduce phthalate and BPA toxicity (Lili et al., 2017b;Oishi et al., 2008). In line with this, the findings of our previous research have demonstrated probiotic ability to protect various organs and tissues, including liver, kidneys, spleen and pancreas, as well as lipid status, and serum glucose level after subacute exposure of rats to a DEHP, DBP, and BPA mixture (Baralić et al., 2020b(Baralić et al., , 2021(Baralić et al., , 2020b. ...
... The addition of 5% Bifidobacterium breve or 5% Lactobacillus casei to rats' diet five days before oral administration of BPA (10 mg/kg) resulted in a timedependent decrease in unconjugated BPA concentration in blood and an increase in BPA faecal excretion. These findings showed that the used probiotic strains had the potential to absorb BPA and facilitate its excretion (Oishi et al., 2008). Probiotic protective effects were further proven in the present in vivo investigation, both in terms of redox status parameters and level of essential metals. ...
The aim of this study was to explore the mechanisms of bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and BPA mixture-induced asthma development and test probiotic as a potential positive intervention. Comparative Toxicogenomics Database (CTD) and ToppGene Suite were used as the main tools for in silico analysis. In vivo 28-day experiment was conducted on rats - seven groups (n = 6): (1) Control: corn oil, (2) P: probiotic (8.78 * 10⁸ CFU/kg/day); (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day; (6) MIX: DEHP + DBP + BPA; (7) MIX + P. Lungs, thymus and kidneys were extracted and prepared for redox status and essential metals analysis. By conducting additional in vitro experiment, probiotic phthalate and BPA binding ability was explored. There were 24 DEHP, DBP and BPA asthma-related genes, indicating the three most probable mechanisms - apoptosis, inflammation and oxidative stress. In vivo experiment confirmed that significant changes in redox status/essential metal parameters were either prominent, or only present in the MIX group, indicating possible additive effects. In vitro experiment confirmed the ability of the multy-strain probiotic to bind DEHP/DBP/BPA mixture, while probiotic administration ameliorated mixture-induced changes in rat tissue.
... Furthermore, the binding efficiency to the bacterial cell wall is strain-specific (Hernandez-Mendoza et al., 2009;Niderkorn et al., 2006;Oishi et al., 2008). Hernandez-Mendoza et al. (2009) reported that LABs exhibited different degrees of aflatoxin binding; Lactobacillus casei L30 had a high ability of the carcinogen AFB 1 binding which was 49.2% compared to the binding rate of L. casei ATCC which was 14% under the same test conditions. ...
... Kim et al., 2019), diabetes Hwang et al., 2018), fertility disorders Matuszczak et al., 2019;X.L. Zhang et al., 2015), and various types of cancer (Ma et al., 2015;Song et al., 2015). Oishi et al. (2008) described the potential of the probiotic Bifidobacterium breve and L. casei to increase the excretion of orally administered BPA in rats. Both bacterial strains caused a decrease in the concentration of unconjugated BPA in the blood over time and increased excretion of BPA in the feces of tested rats compared to the control group. ...
... Besides, analysis of the efficacy of heat-killed non-viable probiotic strains on BPA excretion showed that the nonviable cells promoted the secretion of BPA at similar levels as viable cells. These results suggest that hydrophobic BPA binding by LABs can be the primary pathway of the BPA detoxification rather than enzymatic mechanisms (Oishi et al., 2008). Furthermore, Endo et al. (2007) reported that the BPA-adsorbing ability of Lactococcus strains is due to the hydrophobic binding effect. ...
Nowadays, people are exposed to diverse environmental and chemical pollutants produced by industry and agriculture. Food contaminations such as persistent organic pollutants (POPs), heavy metals, and mycotoxins are a serious concern for global food safety with economic and public health implications especially in the newly industrialized countries (NIC). Mounting evidence indicates that chronic exposure to food contaminants referred to as xenobiotics exert a negative effect on human health such as inflammation, oxidative stress, and intestinal disorders linked with perturbation of the composition and metabolic profile of the gut microflora. Although the physicochemical technologies for food decontamination are utilized in many cases but require adequate conditions which are often not feasible to be met in many industrial sectors. At present, one promising approach to reduce the risk related to the presence of xenobiotics in foodstuffs is a biological detoxification done by probiotic strains and their enzymes. Many studies confirmed that probiotics are an effective, feasible, and inexpensive tool for preventing xenobiotic-induced dysbiosis and alleviating their toxicity.
This review aims to summarize the current knowledge of the direct mechanisms by which probiotics can influence the detoxification of xenobiotics. Moreover, probiotic-xenobiotic interactions with the gut microbiota and the host response were also discussed.
... Therefore, scientists have speculated that finding the agent that would bind to phthalates and bisphenol A in the gastrointestinal tract and prevent their intestinal absorption might be the key in protecting humans from the adverse effects of these compounds (Lili et al., 2017;Zhuting et al., 2018Zhuting et al., , 2017. As a result of this, probiotic cultures tend to find their rightful place among the other substances, such as vitamins and antioxidants, proposed to act beneficially against phthalates and bisphenol A toxicity (Lili et al., 2017;Oishi et al., 2008;Zhuting et al., 2018Zhuting et al., , 2017. Probiotic cultures are live microbial feed supplements that beneficially affect the host by improving its intestinal microbial balance (Wang et al., 2012). ...
... Several studies have shown the ability of LAB, including Lactobacillus plantarum and Lactobacillus rhamnosus, to facilitate the excretion of various toxic substances, and thus mitigate their adverse effects on the human health. Some LAB could efficiently bind to and remove toxic metals such as cadmium (Jama et al., 2012;Zhai et al., 2015Zhai et al., , 2013, lead (Halttunen et al., 2007) and manganese (Tong et al., 2020), as well as other toxic substances, such as benzo(a)pyrene ), phthalates (Zhuting et al., 2018 and bisphenol A (Oishi et al., 2008;Zhuting et al., 2017), lowering their absorption and increasing the elimination from the gastrointestinal tract. The ability of probiotic yeasts, such as Saccharomyces boulardii and Saccharomysces cerevisiae, to surface bind toxic substances, especially mycotoxines, has also been demonstrated (Barathi et al., 2014;Karazhiyan et al., 2016;Silva et al., 2015). ...
... Various studies have demonstrated the ability of orally ingested LAB strains to rapidly bind contaminants, leading to less intestinal absorption and increased fecal excretion of dietary contaminants from the body, thus decreasing the risk of exposure to contaminants (Ercan et al., 2013;Oishi et al., 2008;Tsuda et al., 2008;Zhai et al., 2013;Zhuting et al., 2018). It has been revealed that the adsorption of toxic substances is mainly influenced by the cell wall components of LAB strains (Haskard et al., 2000). ...
Phthalates and bisphenol A, to which people are mainly exposed through food, interfere with the body's endocrine system, along with various other toxic effects. Literature data suggest that probiotic cultures might be able to decrease the adverse effects of toxic substances by various mechanisms. The aim of this study was to investigate if treatment with multi-strained probiotic could reduce the toxicity of phthalates and bisphenol A mixture in Wistar rats. Animals were divided into four experimental groups (n=6): (1) Control (corn oil); (2) P (probiotic (8.78 * 10⁸ CFU/kg/day): Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus planarum LP 6595+ Lactobacillus planarum HEAL9); (3) MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA); (4) MIX + P. Animals were euthanized after 28 days of daily oral gavage treatment; blood and organs were collected for further analysis. Probiotic reduced systemic inflammation and had protective effects on liver, kidneys, spleen, lipid status and serum glucose level. It almost completely annulled the changes in biochemical, hematological and hormonal parameters and mitigated changes in relative liver size, food consumption and organ histology. These results suggest considering multi-strained probiotics as a dietary therapeutic strategy against toxicity of the investigated mixture.
... Bisphenol A (2, 2-bis (4-hydroxyphenyl) propane) is an alkylphenol that is commonly used as a plasticiser in the production of polycarbonate, polyvinyl chloride, polystyrene and epoxy resins. Bisphenol A is a well-known oestrogenic compound that can compete with oestradiol for binding to the oestrogen receptors (Oishi et al. 2008;Errico et al. 2014;Solouki and Fazeli 2017). In recent years, several studies have been conducted to investigate the effects of bisphenol A on human health. ...
... Intestinal microbiota especially probiotic bacteria can play a major role in binding and neutralising toxins and thus preventing them from their adsorption in the body (Kohl et al. 2016). In recent years, the potential role of lactic acid bacteria in the removal of bisphenol A has been investigated (Oishi et al. 2008;Zhu et al. 2017). However, there is virtually no similar research about the effect of bacteria on the removal of bisphenol A in fermented dairy products. ...
... The results of previous studies (Zhu et al. 2017;Ju et al. 2019) indicated that the viability of the bacterium is not necessary for its binding to bisphenol A, because the decrease in bisphenol A concentration is due to its binding to the bacterial cell wall. Thus, probiotic bacteria can prevent the intestinal absorption of bisphenol A and prevent its entry into the blood by its excretion through the faeces (Oishi et al. 2008). ...
The present study aimed to evaluate the effects of Lactobacillus acidophilus and L. plantarum on the concentration of bisphenol A in yoghurt as a food model. The bisphenol A was extracted from samples using a hollow fibre liquid‐phase microextraction method, followed by analysis using HPLC. The concentration of bisphenol A was also analysed during four weeks of yoghurt storage. L. plantarum and L. acidophilus decreased the level of bisphenol A in yoghurt by 82.8% and 43.44%, respectively. At the end of the storage period, the reduction level of bisphenol A by L. plantarum (95.30%) was higher than that of L. acidophilus (90.77%).
... The ability of four probiotic bacteria and yeast to remove and biodegrade BPA towards the formation of less hazardous products has been recently reported (Kyrila et al., 2021). The protective action of probiotics against the BPA induced damage has been confirmed in rat employing either Bifidobacterium breve and Lactobacillus casei (Oishi et al., 2008) or a commercial multi-stain probiotic mixture (Baralić et al., 2020). However, the interaction of probiotics with pollutants requires further research (Średnicka et al., 2021). ...
... In the marine environment its biotransformation is performed mainly by bacteria (Ike et al., 2000;Zhang et al., 2013a;b) due to their ability of BPA transformation to nontoxic compounds, such as hydroquinone (Solouki et al., 2018;Ju et al., 2019;Kyrila et al., 2021;Ś rednicka et al., 2021). The protective action of probiotic bacteria against BPA, in addition to the oxidative stress response amelioration, includes other major mechanisms, such as the adsorption of the pollutant on their surface through hydrophobic interactions, facilitating its excretion (Endo et al., 2007;Oishi et al., 2008). On the other hand, BPA affects gut microbiota in rats, favoring Proteobacteria against Firmicutes and inducing dysbiosis (Liu et al., 2022). ...
In the present study, the bidirectional interactions of Artemia franciscana with BPA, administered either alone or following treatment with the probiotics Bacillus subtilis, Lactococcus lactis or Lactobacillus plantarum, were evaluated. A 24h exposure to BPA below LC50 induced oxidative stress to Artemia, indicated by diminished activity of superoxide dismutase, glutathione reductase, glutathione transferase and phenoloxidase, increased lipid peroxidation and decreased survival. Probiotic treatment prior to BPA exposure, led to increased survival, reduced lipid peroxidation and increased enzyme activities. BPA quantification in Artemia and its culture medium, showed a time dependent reduction in its levels, more evident in probiotic series, indicating its biotransformation. ESI-MS analysis confirmed the presence of the tentative BPA metabolites hydroquinone and BPA-sulfate, while BPA-disulfate formation was confirmed in only in the probiotic series. Our results provide evidence that probiotics alleviate the oxidative stress response induced by BPA, by enhancing the BPA biotransformation ability of Artemia.
... Lactobacillus rhamnosus GG (LGG) is one the best characterized probiotic strains and has been widely used for the management of a variety of diseases [30]. Probiotics have been successfully used to prevent BPA activity in mice and to detoxify aqueous solutions [31,32]. Here we demonstrated that BPA induce inflammation and interfere with the intestinal permeability both a low doses and at very low doses, circa 1000 and 10000 times below the WHO accepted doses mainly in diffentiated Caco2 cells. ...
... Previous works have highlighted the role of probiotics in BPAinduced effects. Bifidobacterium breve strain Yakult and Lactobacillus casei strain Shirota could exert a protective effect against dietary exposure to BPA in rats [31], and interestingly, certain probiotics were found to have the capability to remove BPA from an aqueous solution [32]. We used post-biotic from LGG probiotic to demonstrate that most of the effects of BPA can be prevented in the absence of bacterial bodies. ...
... Probiotics bacteria have been increasingly used in obesity prevention and treatment [9]. Several clinical trials [8,9,[33][34][35][36][37][38][39] had suggested the anti-obesity or weight-losing potential of multiple probiotic bacterial taxa in the genera Bifidobacterium and Lactobacillus [7]. Hence, to estimate the relationship between bacterial taxa and obesity, we first investigated these two probiotic genera, i.e. ...
... Associations of pre-identified and potential probiotic bacteria taxa with obesity Multiple bacterial species belonging to the genera Bifidobacterium and Lactobacillus have been used as probiotics to decrease the risk of obesity in both animal studies and human clinical trials [8,9,[33][34][35][36][37][38][39]. In this study, four species of Bifidobacterium and 12 species of Lactobacillus were observed. ...
Few studies have evaluated the relationship of oral microbiome with obesity. We investigated the oral microbiome among 647 obese and 969 non-obese individuals from the Southern Community Cohort Study, through 16S rRNA gene sequencing in mouth rinse samples. We first investigated 16 taxa in two probiotic genera, Bifidobacterium and Lactobacillus. Among them, eight showed nominal associations with obesity (P < 0.05). Especially, Bifidobacterium (odds ratio [OR] = 0.67, 95% confidence interval [CI]:0.54, 0.83) and Bifidobacterium longum (OR = 0.57, 95% CI: 0.45, 0.73) were significantly associated with decreased obesity prevalence with false-discovery rate (FDR)-corrected P of 0.01 and 5.41 × 10⁻⁴, respectively. Multiple other bacterial taxa were also significantly associated with obesity prevalence at FDR-corrected P < 0.05. Among them, five in Firmicutes and two respectively in Actinobacteria and Proteobacteria were significantly associated with increased obesity prevalence. Significant associations with decreased obesity prevalence were observed for two taxa respectively in Actinobacteria and Firmicutes. Most of these taxa were associated with body mass index at study enrollment and weight gain during adulthood. Also, most of these associations were observed in both European- and African-Americans. Our findings indicate that multiple oral bacterial taxa, including several probiotic taxa, were significantly associated with obesity.
... To this end, biodegradation has been proposed as an advanced technique for BPA elimination [13][14][15], since a variety of microorganisms have been identified to decompose BPA [15,16]. Probiotics are bacteria beneficial to the host, which have been recognized as safe for human consumption and are used in the production of food products [17,18]. Recently they have been reported to be ideal against heavy metal toxicity since they bind and sequester metals [19]. ...
... Recently they have been reported to be ideal against heavy metal toxicity since they bind and sequester metals [19]. Moreover, the probiotic bacteria Bifidobacterium breve and Lactobacillus casei when administered to rats showed a prophylactic effect against the detrimental effects of BPA, by reducing its intestinal absorption and facilitating its excretion, [18]. Likewise, the ability of Bacillus strains [20][21][22], certain Lactococcus strains [23] and Shingomonas paucimobilis [24] to degrade bisphenol has been documented. ...
Bisphenol-A, a synthetic organic compound with estrogen mimicking properties, may enter bloodstream through either dermal contact or ingestion. Probiotic bacterial uptake of bisphenol can play a major protective role against its adverse health effects. In this paper, a method for the quantification of BPA in bacterial cells of L. lactis and of BPA and its potential metabolites 4-hydroxybenzoic Acid, 4-hydroxyacetophenone and hydroquinone in the culture medium is described. Extraction of BPA from the cells was performed using methanol–H2O/TFA (0.08%) (5:1 v/v) followed by SPE. Culture medium was centrifuged and filtered through a 0.45 μm syringe filter. Analysis was conducted in a Nucleosil column, using a gradient of A (95:5 v/v H2O: ACN) and B (5:95 v/v H2O: ACN, containing TFA, pH 2), with a flow rate of 0.5 mL/min. Calibration curves (0.5–600 μg/mL) were constructed using 4-n-Octylphenol as internal standard (1 > R2 > 0.994). Limit of Detection (LOD) and Limit of Quantification (LOQ) values ranged between 0.23 to 4.99 μg/mL and 0.69 to 15.1 μg/mL respectively. A 24 h administration experiment revealed a decline in BPA concentration in the culture media up to 90.27% while the BPA photodegradation levels were low. Our results demonstrate that uptake and possible metabolism of BPA in L. lactis cells facilitates its removal.
... Previous studies reported an increase in Collinsella aerofaciens and Bifidobacterium adolescentis when a model of the gut microbial community was exposed to BPA and other molecules from the plastic industry [57]. Some species of the genus Bifidobacterium could proliferate in a xenobiotic-rich environment, a phenomenon potentially linked to their ability to sequester BPA in vitro [58]. This capac-ity for bioaccumulation not only enables these bacteria to thrive but also reduces BPA concentrations in the surrounding medium. ...
Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on individual metabolic capacity. This pilot study examines the impact of direct ex vivo BPA exposure on the gut microbiota of obese and normal-weight children, using 16S rRNA amplicon sequencing and anaerobic culturing combined methods. Results showed that direct xenobiotic exposure induced modifications in microbial taxa relative abundance, community structure, and diversity. Specifically, BPA reduced the abundance of bacteria belonging to the phylum Bacteroidota, while taxa from the phylum Actinomycetota were promoted. Consistently, Bacteroides species were classified as sensitive to BPA, whereas bacteria belonging to the class Clostridia were identified as resistant to BPA in our culturomics analysis. Some of the altered bacterial abundance patterns were common for both the BPA-exposed groups and the obese non-exposed group in our pilot study. These findings were also corroborated in a larger cohort of children. Future research will be essential to evaluate these microbial taxa as potential biomarkers for biomonitoring the effect of BPA and its role as an obesogenic substance in children.
... Potential probiotics used to remove chemical contaminants and xenobiotics 5% BbY and 5% LcS reduced intestinal absorption and increased excretion of BPA, thus suppressing its adverse effects in humans(Oishi et al. 2008) ...
Industrial pollutants have unavoidably increased the incidences of human exposure to organic and inorganic pollutants. The contaminants enter into foods accidently during production, manufacturing, processing, and packaging. Organic pollutants, nonessential heavy metals, mycotoxins, and many allergens, collectively called as xenobiotics, pose serious health threats such as toxicity, oxidative stress, inflammation, allergy, cancer, and perturbation of human microbiota. Among physical and chemical methods of bioremediation or reducing toxicity, the detoxification by using probiotics is germane and cost-effective.
... However, OPZCL ultimately improved the intestinal homeostasis. It has been found that exposure of mice to DEHP or BPA (plasticizer) increased the abundance of Lactobacillus, which reduces intestinal absorption by promoting the excretion of DEHP and BPA [55][56][57]. ...
Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer, which can cause damage to male reproductive organs, especially the atrophy of the testis. Meanwhile, DEHP can also lead to a decrease in testicular zinc content, but the role of zinc remains unclear. This study aims to prepare oyster peptide-zinc complex (OPZC) to alleviate DEHP-induced reproductive damage in mice. OPZC was successfully obtained through electron microscopy, X-ray diffraction, and thermogravimetric analysis, with stable structure and high water-solubility. Low dose oyster peptide-zinc complex (OPZCL) significantly reduced the reproductive damage caused by DEHP in mice. Further research had shown that OPZCL restored the content of serum hormones and the activity of oxidative stress kinases to normal, while also normalizing testicular zinc and selenium levels. In addition, it also recovered the disorder of gut microbiota, reduced the proportion of Bacteroides, increased the abundance of Ligilactobacillus, and restored the proportion of Acidobacterota, Chloroflexi, and Proteobacteria. Therefore, OPZCL can relieve the reproductive damage caused by DEHP in mice by restoring testicular zinc homeostasis and the composition of intestinal microbiota, indicating that OPZCL has a potential protective effect on male reproductive health.
... Hitherto, several studies have already demonstrated the potential of probiotics to counteract the harmful effects of contaminants. In rats, Bifidobacterium breve and Lactobacillus casei reduced the intestinal absorption of orally administered BPA (Oishi et al., 2008), whereas in zebrafish, L. rhamnosus antagonized perfluorobutanesulfonate (PFBS) metabolic Hu et al., 2021;Liu et al., 2021) and neurological toxicity . In addition, L. plantarum ST-III reduced the proinflammatory actions of triclosan in zebrafish (Zang et al., 2019). ...
... Xing et al. [45] represented lead elimination in laying hen's gut content by B. longum through binding to the bacterial surface. Oishi et al. [46] reported the ability of B. breve to enhance the excretion of oral bisphenol A in rats. The bacteria reduced the amount of bisphenol in the blood and raised bisphenol excretion in the feces of rats. ...
Contaminants such as mycotoxins, heavy metals, and chemicals in food are one of the major concerns of our world nowadays. So, food decontamination with the help of microbial biomass is a cheap, easy, efficient, and green method known as bio removal. Bifidobacterial are able to reduce the availability of contaminants in food products. The purpose of this review is to summarize the Bifidobacterium species' interesting role in food bio-decontamination. After a brief glance at the definition of bifidobacterial strains, their effect on human health is described. After that, food contaminants, including mycotoxins, heavy metals, and chemicals are defined and the bio-decontamination activity of bifidobacterial genera is described. Additionally, the effect of some factors in bio removal efficiency and the bio removal mechanism are explained. It is worth mentioning that this review article can be exerted in different food and beverage industries to eliminate the contaminants in food products.
... Uncultured bacteria represented 5% of the total bacteria isolated from the microbiota of normal-weight group, and 3% in population with obesity. Similarly, xenobiotic-tolerant and specifically BPA-tolerant gut microorganisms were previously described for the traditional probiotics Bifidobacterium breve strain Yakult (BbY) and Lactobacillus casei strain Shirota (LcS), that showed protective effects against BPA dietary exposure in rats by reducing the intestinal absorption of BPA and facilitating its excretion [59]. Likewise, Lactococcus lactis strains adsorbed BPA but it was not able to degrade it [60]. ...
Integrated data from molecular and improved culturomics studies might offer holistic insights on gut microbiome dysbiosis triggered by xenobiotics, such as obesity and metabolic disorders. Bisphenol A (BPA), a dietary xenobiotic obesogen, was chosen for a directed culturing approach using microbiota specimens from 46 children with obesity and normal-weight profiles. In parallel, a complementary molecular analysis was carried out to estimate the BPA metabolising capacities. Firstly, catalogues of 237 BPA directed-cultured microorganisms were isolated using five selected media and several BPA treatments and conditions. Taxa from Firmicutes, Proteobacteria, and Actinobacteria were the most abundant in normal-weight and overweight/obese children, with species belonging to the genera Enterococcus, Escherichia, Staphylococcus, Bacillus, and Clostridium. Secondly, the representative isolated taxa from normal-weight vs. overweight/obese were grouped as BPA biodegrader, tolerant, or resistant bacteria, according to the presence of genes encoding BPA enzymes in their whole genome sequences. Remarkably, the presence of sporobiota and concretely Bacillus spp. showed the higher BPA biodegradation potential in overweight/obese group compared to normal-weight, which could drive a relevant role in obesity and metabolic dysbiosis triggered by these xenobiotics.
... Lactobacillus casei strain Shirota (LcS) that showed protective effects against BPA dietary exposure in rats by reducing the intestinal absorption of BPA and facilitating its excretion [54]. Similarly, Lactococcus lactis strains adsorbed BPA but not degrade it [55]. ...
Background Integrated data from culturomics and functional omics may depict holistic understanding on gut microbiome eubiosis or dysbiosis, and microbial isolates can become a source of differential enzymes and useful bioactive compounds. Culturing methods developed during last decade swift increases the importance of gut microbial isolates, focusing on media, modifications and conditions that propitiate cultured taxa that previously were considered fastidious or unculturable. In this context and focusing on gut microbiota dysbiosis triggered by obesogens and microbiota disrupting chemicals (MDC), we have conducted a directed-culturing and bioinformatics combined approach, adding bisphenol A (BPA) and specific treatments to find resistant spore-forming bacteria, to obtain isolated strains for further explore their molecular BPA metabolizing or neutralizing capacities. Results Overall microbiota culturing media and conditions have been retrieved and organized according to main gut taxa isolated during last decade. Furthermore, a catalogue of BPA directed-cultured microorganisms has been obtained from 46 fecal samples from two populations, children with obesity and normo-weight. A total of 235 BPA tolerating and potentially BPA biodegrading microorganisms were mainly grouped to strictly anaerobic sporuled/non-sporuled, anaerobic facultative sporuled/non-sporuled. Firmicutes, Enterobacteria and Actinobacteria species showed the major representation in both groups. However, differential BPA tolerant microbiota composition from the populations was detected. Bioinformatics analysis disclosed and predicted the variability of harboring genes encoding specific enzyme for BPA biodegradation pathways that corroborated from directed-culturing microbiota consortia obtained. Conclusions Strains from Staphylococcus , Bacillus and Enterococcus genera represented the majority of the successfully cultured bacteria in both population specimens. From them, the bioinformatics prediction assigned to Bacillus spp. the higher potential for BPA biodegradation. Therefore, extensive directed-culturomics approaches could be designed for different MDC with common biodegradation pathways, such as parabens, phthalates, and benzophenones.
... Therefore, biosorbtion of these substances in GIT and inhibition of their intestinal absorption have been investigated as a possible solution in sheltering humans from their adverse effects (Lili et al., 2017;Zhu et al., 2017Zhu et al., , 2018. Some probiotic cultures, especially lactic acid bacteria (LAB), including Lactobacillus plantarum and Lactobacillus rhamnosus, but also probiotic yeasts such as Saccharomyces cerevisiae, were found to surface bind not only metals, including cadmium (Huang et al., 2020;Jama et al., 2012;Zhai et al, 2013Zhai et al, , 2015, lead (Halttunen et al., 2007), mercury (Alcántara et al., 2020), and copper (do Nascimento et al., 2019), but also other toxic substances, such as benzo(a) Fig. 1 pyrene , mycotoxines (Karazhiyan et al., 2016), as well as phthalates (Zhu et al., 2018) and BPA (Oishi et al., 2008;Zhu et al., 2017). Moreover, some probiotic cultures (e.g. ...
Linkage between bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA) co-exposure and type 2 diabetes mellitus (T2DM), as well as ability of multi-strained probiotic to reduce DEHP, DBP and BPA mixture-induced oxidative damage in rat pancreas were investigated. The Comparative Toxicogenomics Database, Cytoscape software and ToppGene Suite were used for data-mining. Animals were sorted into seven groups (n = 6): (1) Control group: corn oil, (2) P: probiotic: Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus plantarum LP 6595 + Lactobacillus plantarum HEAL9; (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day, and (6) MIX: 50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA; (7) MIX + P. Rats were sacrificed after 28 days of oral exposure. In silico investigation highlighted 44 DEHP, DBP and BPA mutual genes linked to the T2DM, while apoptosis and oxidative stress were highlighted as the main mechanisms of DEHP, DBP and BPA mixture-linked T2DM. In vivo experiment confirmed the presence of significant changes in redox status parameters (TOS, SOD and SH groups) only in the MIX group, indicating possible additive effects, while probiotic ameliorated mixture-induced redox status changes in rat pancreatic tissue.
... Although some studies have suggested that antioxidants, probiotics, prebiotics, or other food supplements (e.g. vitamins and minerals) can ameliorate the toxic effects of EDCs, including BPA (Amjad et al., 2020;Baralić et al., 2020;Le Magueresse-Battistoni, 2021;Oishi et al., 2008), majority of these findings have not yet been verified in human clinical trials Garcia-Gonzalez et al., 2020). Thus, the prospects of ameliorating BPA toxicity remain distant, indicating that, for the time being, we must continue to coexist with these products. ...
Bisphenol A (BPA) is a ubiquitous environmental toxin worldwide. Despite the many studies documenting the toxicity of this substance, it remains a popular choice for consumer products. The internet, magazine articles, and newspaper reports are replete with tips on how to avoid BPA exposure, which mostly spread contradictory and often unscientific information. Therefore, based on a comprehensive search of the available biomedical literature, we summarized several confounding factors that may be directly or indirectly related to human BPA exposure. We found that the unique properties of BPA materials (i.e. low cost, light-weight, resistance to corrosion, and water/air-tightness), lack of personal health and hygiene education, fear of BPA-substitutes (with yet unknown risks), inappropriate production, processing, and marketing of materials containing BPA, as well as the state of regulatory guidance are influencing the increased exposure to BPA. Besides, we detailed the disparities between scientifically derived safe dosages of BPA and those designated as “safe” by government regulatory agencies. Therefore, in addition to providing a current assessment of the states of academic research, government policies, and consumer behaviors, we make several reasonable and actionable recommendations for limiting human exposure to BPA through improved labeling, science-based dosage limits, and public awareness campaigns.
... For example, consumption of probiotic foods containing Lactobacillus plantarum ST-III improved microbial diversity in the guts of animals which corresponded with a reduction in toxicity due to chronic triclosan exposure, as evidenced by reduced damage to intestinal, spleen, and kidney tissues (50). Similarly, Bifidobacterium breve BbY and Lactobacillus casei LcS strains have been shown to promote fecal sedimentation and excretion of BPA, thereby decreasing intestinal absorption and systemic exposure (51). ...
Background:
Given policy regulations restricting bisphenol A (BPA) in food-related products, and consumer concerns about adverse health effects, newer bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) have been developed. Exposure to BPA has been linked to dietary behaviors and poor health outcomes.
Objectives:
We sought to examine how the Healthy Eating Index (HEI) and its 13 subgroups, the healthy American diet, the Mediterranean diet, the vegetarian diet, and other dietary quality behaviors are related to BPA and the newer substitutes in a representative sample of US adults.
Methods:
Dietary intakes from the NHANES were used to determine dietary scores. Osmolality-adjusted urinary BPA (n = 6418) and BPF and BPS (n = 2520) concentrations were tested for their association with dietary intake in models that adjusted for sociodemographics.
Results:
Compared with low scores, high scores for total HEI and the American, Mediterranean, and vegetarian diets were associated with lower odds of high BPA concentration (OR: 0.65, 0.60, 0.59, and 0.60, respectively). Of the HEI subgroups, lower BPA concentration was associated with high total fruit (OR: 0.61; 99.95% CI: 0.42, 0.89), whole fruit (OR: 0.59; 99.95% CI: 0.41, 0.86), and whole grain (OR: 0.68; 99.95% CI: 0.40, 0.94) intake, when compared with low intakes. Compared with low intakes, high intakes of plain and tap water were associated with lower odds of high BPA concentration (OR: 0.65; 99.95% CI: 0.47, 0.91 and OR: 0.70; 99.95% CI: 0.50, 0.99, respectively). A perception of high, compared with low, dietary quality was also associated with lower odds of high BPA concentration (OR: 0.72; 99.95% CI: 0.53, 0.98).
Conclusions:
Healthier dietary quality and several HEI subgroups were related to lower urinary BPA concentrations; no significant (P ≤ 0.0005) findings were observed for BPF and BPS. The association between bisphenol substitutes and dietary quality should continue to be monitored as bisphenol substitutes continue to increase in the food system.
... salivarius REN) in rats exposed to 4-NQO could be related to the suppression of cell proliferation, induction of cell apoptosis and/or downregulation of cyclooxygenase-2 expression (Zhang et al. 2013). Rodent models have been also used to investigate the effects of BPA and ethinyl estradiol exposure on gut microbiota (Javurek et al. 2016), and the protective effects of L. casei and B. breve against BPA (Oishi et al. 2008). As previously stated, mice and rats have been used extensively to study antigenotoxicity properties of probiotics. ...
Nowadays, the interest in the role of dietary components able to influence the composition and the activity of the intestinal microbiota and, consequently, to modulate the risk of genotoxicity and colon cancer is increasing in the scientific community. Within this topic, the microbial ability to have a protective role at gastrointestinal level by counteracting the biological activity of genotoxic compounds, and thus preventing the DNA damage, is deemed important in reducing gut pathologies and is considered a new tool for probiotics and functional foods. A variety of genotoxic compounds can be found in the gut and, besides food-related mutagens and other DNA-reacting compounds, there is a group of pollutants commonly used in food packaging and/or in thousands of everyday products called endocrine disruptors (EDs). EDs are exogenous substances that alter the functions of the endocrine system through estrogenic and anti-estrogenic activity, which interfere with normal hormonal function in human and wildlife. Thus, this paper summarizes the main applications of probiotics, mainly lactobacilli, as a bio-protective tool to counteract genotoxic and mutagenic agents, by biologically inhibiting the related DNA damage in the gut, and highlights the emerging perspectives to enlarge and further investigate the microbial bio-protective role at intestinal level.
... Several in vivo studies showed that Bifidobacteria can act against BPA. This probiotic in fact, can suppress BPA entry into the blood and facilitate its excretion [106]. ...
Background
Bisphenol A (BPA) is worldwide diffused as a monomer of epoxy resins and polycarbonate plastics and has recognized activity as Endocrine Disruptor (ED). It is capable to interfere or compete with endogenous hormones in many physiological activities thus having adverse outcomes on health. Diet highly affects health status and in addition to macronutrients, provides a large number of substances with recognized pro-heath activity, and thus called nutraceuticals.
Objective
This mini-review aims at summarizing the possible opposite and simultaneous effects of BPA and nutraceuticals on endocrine functions. The possibility that diet may represent the first instrument to preserve health status against BPA damages has been discussed.
Methods
The screening of recent literature in the field has been carried out.
Results
The therapeutic and anti-oxidant properties of many nutraceuticals may reverse the adverse health effects of BPA.
Conclusion
In vitro and in vivo studies provided evidence that nutraceuticals can preserve the health. Thus, the use of nutraceuticals can be considered a support for clinical treatment. In conclusion, dietary remediation may represent a successful therapeutic approach to maintain and preserve health against BPA damage.
... In an interesting rat study, probiotics Bifidobacterium breve and Lactobacillus casei were shown to bind BPA in the gut and increase excretion in the stools. 32 Both α-tocopherol and α-lipoic acid have been shown in a rat model to decrease BPA toxicity as has N-acetylcysteine (NAC). 33,34 Dioxins (Other Than PCBs) ...
The incidence of diabetes has increased 7 to 10-fold in the past 50 y. Although increased sugar consumption, obesity, and lack of exercise certainly contribute, the effect of environmental toxins may be far greater. The data are so compelling that some researchers now label these toxins as diabetogens. This editorial summarizes the research showing which toxins are the worst offenders, how they disrupt blood sugar control, where they come from, how to assess body load, and strategies for detoxification and excretion.
... Probiotics are nowadays generally defined as live microorganisms, preferentially of human origin, that upon ingestion in specific and sufficient numbers confer non-specific health benefits to the host [81]. Probiotics are capable of stabilizing the mucosal barrier by increasing mucin expression, reducing bacterial over growth, stimulating mucosal immunity (secretory IgA), and synthesizing antioxidant substance [82,83]. The main probiotics used in current commercial preparations are lactic acid bacteria including Lactobacilli (casei, reuteri, fermentum, plantarum, paracasei, salivarius, rhamnosus) and Bifidobacteria (bifidum, infantis, longum) [84][85][86]. ...
The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
... In addition to the host-microbe interactions and the direct effects of the chemicals discussed above, we suggest that microbes may affect obesity and diabetes by altering the ADME of environmental chemicals. Microbially mediated effects on ADME could include the direct activation of chemicals (Van de Wiele et al. 2005Wallace et al. 2010), production of microbial metabolites that compete for limited host biotransformation capacity (Clayton et al. 2009;Wallace et al. 2010), alteration of host biotransformation enzyme activities (Claus et al. 2011;Meinl et al. 2009), changes in enterohepatic circulation (Meijer et al. 2006), or altered bioavailability of environmental chemicals and/ or antioxidants from food Lhoste et al. 2003;Oishi et al. 2008;van Duynhoven et al. 2010). Increased bioavailability may also result from changes in gut motility and barrier function. ...
Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.
... These results are considered to have clinical implications in that they suggest administration of corresponding probiotics may restore the profile of enteric microorganisms to match that of a non-UC status. Indeed, several studies to date have evaluated the therapeutic efficacy of probiotic administration using Lactobacilli [24,25] , Bifidobacteria [11,26,27] , E. coli Nissle 1917 [16,28] , or VSL#3 [15,[29][30][31] . The degrees to which these individual supplements successfully resolved the UC varied, which led to the hypothesis that administration of a combination of probiotics may provide more benefit to the patients. ...
To determine the efficacy profiles of different concentrations of Lactobacillus acidophilus (L. acidophilus) for treating colitis using an experimental murine model.
Colitis was established in 64 BALB/c mice by adding 5% dextran sodium sulfate (DSS) to the drinking water and allowing ad libitum access for 7 d. The mice were then randomly divided into the following control and experimental model groups (n = 8 each; day 0): untreated model control; negative-treatment model control (administered gavage of 1 mL/10 g normal saline); experimental-treatment models C4-C8 (administered gavage of 10(4), 10(5), 10(6), 10(7), or 10(8) CFU/10 g L. acidophilus, respectively); positive-treatment model control (administration of the anti-inflammatory agent prednisone acetate at 45 μg/10 g). Eight mice given regular water (no DSS) and no subsequent treatments served as the normal control group. Body weight, fecal traits, and presence of fecal occult blood were assessed daily. All animals were sacrificed on post-treatment day 7 to measure colonic length, perform histological scoring, and quantify the major bacteria in the proximal and distal colon. Intergroup differences were determined by one-way ANOVA and post-hoc Student-Newman-Keuls comparison.
All treatments (L. acidophilus and prednisone acetate) protected against colitis-induced weight loss (P < 0.05 vs model and normal control groups). The extent of colitis-induced colonic shortening was significantly reduced by all treatments (prednisone acetate > C4 > C5 > C7 > C8 > C6; P < 0.05 vs untreated model group), and the C6 group showed colonic length similar to that of the normal control group (P > 0.05). The C6 group also had the lowest disease activity index scores among the model groups. The bacterial profiles in the proximal colon were similar between all of the experimental-treatment model groups (all P > 0.05). In contrast, the bacterial profile in the distal colon of the C6 group showed the distinctive features (P < 0.05 vs all other experimental-treatment model groups) of Lactobacillus sp. and Bifidobacterium sp. being the most abundant bacteria and Staphylococcus aureus being the least abundant bacteria.
The most therapeutically efficacious concentration of L. acidophilus (10(6) CFU/10 g) may exert its effects by modulating the bacterial profile in the distal colon.
... Consistent with this notion is the prediction that a sizable proportion of the average bifidobacterial genome is dedicated to carbohydrate metabolism (2,86). More than 50 bifidobacterial carbohydrases have been studied to date (for reviews, see references 42 and 7), and various carbohydrate utilization pathways, such as those dedicated to the metabolism of fructose, galactan, starch, ribose, isomaltulose, cellodextrin, and fructo-oligosaccharides, have been characterized in B. breve UCC2003 (8,14,38,41,52,59,87). ...
Members of the genus Bifidobacterium are common inhabitants of the gastrointestinal tracts of humans and other mammals, where they ferment many diet-derived carbohydrates
that cannot be digested by their hosts. To extend our understanding of bifidobacterial carbohydrate utilization, we investigated
the molecular mechanisms by which 11 strains of Bifidobacterium breve metabolize four distinct α-glucose- and/or α-galactose-containing oligosaccharides, namely, raffinose, stachyose, melibiose,
and melezitose. Here we demonstrate that all B. breve strains examined possess the ability to utilize raffinose, stachyose, and melibiose. However, the ability to metabolize melezitose
was not common to all B. breve strains tested. Transcriptomic and functional genomic approaches identified a gene cluster dedicated to the metabolism of
α-galactose-containing carbohydrates, while an adjacent gene cluster, dedicated to the metabolism of α-glucose-containing
melezitose, was identified in strains that are able to use this carbohydrate.
... Polychlorinated biphenyls can further compromise the integrity of the intestinal lining and cause deficits to the normal BBB permeability [60,61]. Meanwhile, probiotics have been shown to influence removal of environmental toxins from the gastrointestinal tract [62]. ...
In recent years there has been a renewed interest concerning the ways in which the gastrointestinal tract -- its functional integrity and microbial residents -- might influence human mood (e.g. depression) and behavioral disorders. Once a hotbed of scientific interest in the early 20th century, this area lay dormant for decades, in part due to its association with the controversial term 'autointoxication'. Here we review contemporary findings related to intestinal permeability, small intestinal bacterial overgrowth, lipopolysaccharide endotoxin (LPS) exposure, D-lactic acid, propionic acid, and discuss their relevance to microbiota and mental health. In addition, we include the context of modern dietary habits as they relate to depression, anxiety and their potential interaction with intestinal microbiota.
... For example, it was shown that when fed a diet containing a Bifidobacterium or Lactobacillus strains, BPA-exposed rats had a reduced BPA blood concentration over time and 2.4-fold increase in BPA fecal www.frontiersin.org excretion (Oishi et al., 2008). Therefore, dietary alterations can be powerful tools for counteracting modern environmental exposures by restoring inflammation to a proper range in which chronic states are suppressed but vital acute responses still efficiently occur. ...
The advent of modern medicine has allowed for significant advances within the fields of emergency care, surgery, and infectious disease control. Health threats that were historically responsible for immeasurable tolls on human life are now all but eradicated within certain populations, specifically those that enjoy higher degrees of socio-economic status and access to healthcare. However, modernization and its resulting lifestyle trends have ushered in a new era of chronic illness; one in which an unprecedented number of people are estimated to contract cancer and other inflammatory diseases. Here, we explore the idea that homeostasis has been redefined within just a few generations, and that diseases such as colorectal cancer are the result of fluctuating physiological and molecular imbalances. Phytochemical-deprived, pro-inflammatory diets combined with low-dose exposures to environmental toxins, including bisphenol-A (BPA) and other endocrine disruptors, are now linked to increasing incidences of cancer in westernized societies and developing countries. There is recent evidence that disease determinants are likely set in utero and further perpetuated into adulthood dependent upon the innate and environmentally acquired phenotype unique to each individual. In order to address a disease as multi-factorial, case-specific, and remarkably adaptive as cancer, research must focus on its root causes in order to elucidate the molecular mechanisms by which they can be prevented or counteracted via plant-derived compounds such as epigallocatechin-3-gallate (EGCG) and resveratrol. The significant role of epigenetics in the regulation of these complex processes is emphasized here to form a comprehensive view of the dynamic interactions that influence modern-day carcinogenesis, and how sensibly restoring homeostatic balance may be the key to the cancer riddle.
... In addition to the host-microbe interactions and the direct effects of the chemicals discussed above, we suggest that microbes may affect obesity and diabetes by altering the ADME of environmental chemicals. Microbially mediated effects on ADME could include the direct activation of chemicals (Van de Wiele et al. 2005Wallace et al. 2010), production of microbial metabolites that compete for limited host biotransformation capacity (Clayton et al. 2009;Wallace et al. 2010), alteration of host biotransformation enzyme activities (Claus et al. 2011;Meinl et al. 2009), changes in enterohepatic circulation (Meijer et al. 2006), or altered bioavailability of environmental chemicals and/ or antioxidants from food Lhoste et al. 2003;Oishi et al. 2008;van Duynhoven et al. 2010). Increased bioavailability may also result from changes in gut motility and barrier function. ...
Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic.
We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs.
We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified.
Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function.
Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans.
Environmentally relevant toxic substances may affect human health, provoking numerous harmful effects on central nervous, respiratory, cardiovascular, endocrine and reproductive system, and even cause various types of carcinoma. These substances, to which general population is constantly and simultaneously exposed, enter human body via food and water, but also by inhalation and dermal contact, while accumulating evidence suggests that probiotic cultures are able to efficiently adsorb and/or degrade them. Cell wall of probiotic bacteria/fungi, which contains structures such as exopolysaccharide, teichoic acid, protein and peptidoglycan components, is considered the main place of toxic substances adsorption. Moreover, probiotics are able to induce metabolism and degradation of various toxic substances, making them less toxic and more suitable for elimination. Other probable in vivo protective effects have also been suggested, including decreased intestinal absorption and increased excretion of toxic substances, prevented gut microbial dysbiosis, increase in the intestinal mucus secretion, decreased production of reactive oxygen species, reduction of inflammation, etc. Having all of this in mind, this review aims to summarize the state-of-the-art knowledge regarding the potential protective effects of different probiotic strains against environmentally relevant toxic substances (mycotoxins, polycyclic aromatic hydrocarbons, pesticides, perfluoroalkyl and polyfluoroalkyl substances, phthalates, bisphenol A and toxic metals).
Exposure to heavy metals (HMs) is a threat to human health. Although probiotics can detoxify HMs in animals, their effectiveness and mechanism of action in humans have not been studied well. Therefore, we conducted this randomized, double-blind, controlled trial on 152 occupational workers from the metal industry, an at-risk human population, to explore the effectiveness of probiotic yogurt in reducing HM levels. Participants were randomly assigned to two groups: one consumed probiotic yogurt containing the HM-resistant strain Pediococcus acidilactici GR-1 and the other consumed conventional yogurt for 12 weeks. Analysis of metal contents in the blood revealed that the consumption of probiotic yogurt resulted in a higher and faster decrease in copper (34.45%) and nickel (38.34%) levels in the blood than the consumption of conventional yogurt (16.41% and 27.57%, respectively). Metagenomic and metabolomic studies identified a close correlation between gut microbiota (GM) and host metabolism. Significantly enriched members of Blautia and Bifidobacterium correlated positively with the antioxidant capacities of GM and host. Further murine experiments confirmed the essential role of GM and protective effect of GR-1 on the antioxidative role of the intestine against copper. Thus, the use of probiotic yogurt may be an effective and affordable approach for combating toxic metal exposure through the protection of indigenous GM in humans.
ClinicalTrials.gov identifier: ChiCTR2100053222
Bisphenol-A (BPA) is a constituent of polycarbonate plastics and epoxy resins, widely applied on food packaging materials. As BPA exposure results in health hazards, its efficient removal is of crucial importance. In our study five potentially probiotic microorganisms, namely Lactococcus lactis, Bacillus subtilis, Lactobacillus plantarum, Enterococcus faecalis, and Saccharomyces cerevisiae, were tested for their toxicity tolerance to BPA and their BPA removal ability. Although BPA toxicity, evident on all microorganisms, presented a correlation to both BPA addition time and its concentration, all strains exhibited BPA-removal ability with increased removal rate between 0-24 h of incubation. BPA degradation resulted in the formation of two dimer products in cells while the compounds Hydroquinone (HQ), 4-Hydroxyacetophenone (HAP), 4-Hydroxybenzoic acid (HBA) and 4-Isopropenylphenol (PP) were identified in the culture medium. In the proposed BPA degradation pathways BPA adducts formation appears as a common pattern, while BPA decomposition as well as the formation, and the levels of its end products present differences among microorganisms. The BPA degradation ability of the tested beneficial microorganisms demonstrates their potential application in the bioremediation of BPA contaminated foods and feeds and provides a means to suppress the adverse effects of BPA on human and animal health.
The human gut microbiota encompasses a complex and dynamic ecosystem that provides crucial signals for host development and physiology. The altering composition of the human microbiota is associated with modifications in human behavior and the rising prevalence of pathogenesis of late onset diseases such as life style non-communicable diseases, metabolic and neurological disorders etc. The factors that trigger modifications in the composition and function of the gut microbiota will aid in understanding and designing of therapies that target it, which may be quite formidable. Though several studies have been reported on altered gut microbial composition and its association with diseases, but information on mucin layer degradation, production and immune cell interactions is scanty. The alignment of the gut microbiota can be an emerging indicator or marker of health, as it could be a sensitive tool for identifying various risks. This review unzips the role and type of gut microbiota associated with different non-communicable diseases and their impact on intestinal mucosal immunity which could be the signatures required to promote the human health by the clinicians.
Recently, with rapid progress in scientific research, increasing health-care costs, changing food habits, aging population, and elevated risk of toxicity or side effects of drugs consumers are interested to intake food supplements to improve or maintain good health. Nutraceuticals are natural active compounds that can be defined as a food/or part of a food that offer medical or health benefits, including the prevention and/or treatment of a disease. Fermented foods, notably soy products, barley, and rice bran are enriched with nutraceuticals like phytochemicals, dietary fibers, and antioxidant compounds (polyphenols). Lactic acid bacteria and yeast are the major microorganisms that are used for the fermentation process which may confer the bioavailability of nutrients and enrich the food with bioactive compounds. Nutraceutical products have chemoprotective, antioxidative, anti-inflammatory, and immune-modulatory properties. Thus, nutraceuticals are of special interest in research, since many studies in vitro as well as in vivo show evidence on the prevention of lifestyle-related diseases like cardiovascular disease, type 2 diabetes, metabolic syndrome, obesity, cancer, and neurodegeneration disease. Finally, this review summarizes the recent studies regarding nutraceuticals consumption from several fermented foods and their health benefits.
While forecasts predict an increase in the prevalence of mental health disorders in the worldwide general population, the response rate to classical psychiatric treatment remains unsatisfactory. Resistance to psychotropic drugs can be due to clinical, pharmacological, pharmacokinetic, and pharmacodynamic factors. Among these factors, recent animal findings suggest that microbiota may have an underestimated influence on its host's behavior and on drug metabolism that may explain ineffectiveness or increased side effects of psychiatric medications such as weight gain. The following issues were identified in the present review: (i) microbiota dysbiosis and putative consequences on central nervous system functioning; (ii) chronic microbiota dysbiosis-associated illnesses in humans; (iii) microbiota-oriented treatments and their potential therapeutic applications in psychiatry.
Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Oral administration of Lactobacillus reuteri CP3012 or Lactobacillus acidophilus L-92 for 60 days in rats that were previously administered 3,3',4,4',5-pentachlorobiphenyl (PCB126) orally at a dose of 100 mu g/kg of body weight resulted in a significant decrease in hepatic bioaccumulation of PCB126 ( p < 0.05), with levels of 30.7 +/- 3.7 ng/g and 92.6 +/- 25.0 ng/g of liver tissue, respectively, compared with 133.1 +/- 12.7 ng/g of liver tissue in the controls. The electron paramagnetic resonance signal level of the liver PCB126-specific g = 2.49 species in rats administered L. reuteri CP3012 decreased significantly (p < 0.05). Both the bile acid concentration in the feces and total stool output increased significantly following administration of lactobacilli ( p < 0.05); however, adsorption of PCB126 onto the bacterial cells was not observed. These results suggest that these bacteria inhibit reabsorption of PCB126 with bile acid by blocking enterohepatic circulation through absorbing and/or deconjugating the bile acids in the intestinal tract and by promoting excretion of bile acids from the body, thus reducing PCB126 accumulation in the liver.
We evaluated the effects of chitosan intake on fecal excretion of bisphenol A (BPA) and di(2-ethyl)phthalate (DEHP) in rats. The rats were fed a chitosan diet (CHI group) or a control diet (control group) for 10 d and orally administrated BPA or DEHP (100, 500 mg/kg body weight, respectively) on day 4. Feces were collected and the rates of fecal excretion of BPA and DEHP were calculated. Fecal excretion rates of BPA and DEHP were significantly higher in the CHI group than in the control group. A significant negative correlation was observed between the fecal excretion rates of BPA and DEHP and apparent fat digestibility. Furthermore, the CHI group showed not only increased but also accelerated BPA excretion into the feces. In conclusion, we found that that chitosan intake significantly increased the fecal excretion of BPA, DEHP, and fat, suggesting that it might be useful for reducing adverse effects caused by lipophilic xenobiotics.
In silico analysis of the Bifidobacterium breve UCC2003 genome predicted two distinct loci, which encode three different restriction/modification systems, each comprising a modification methylase and a restriction endonuclease. Based on sequence homology and observed protection against restriction we conclude that the first restriction endonuclease, designated BbrI, is an isoschizomer of BbeI, the second, BbrII, is a neoschizomer of SalI, while the third, BbrIII, is an isoschizomer of PstI. Expression of each of the B. breve UCC2003 methylase-encoding genes in B. breve JCM 7017 established that BbrII and BbrIII are active and restrict incoming DNA. By exploiting knowledge on restriction/modification in B. breve UCC2003 we successfully increased the transformation efficiency to a level that allows the reliable generation of mutants by homologous recombination using a non-replicative plasmid.
We present data showing that some foods preserved in lacquer-coated cans and the liquid in them may acquire estrogenic activity. Hormonal activity was measured using the E-screen bioassay. The biological activity of vegetables packed in cans was a result of plastic monomers used in manufacturing the containers. The plastic monomer bisphenol-A, identified by mass spectrometry, was found as a contaminant not only in the liquid of the preserved vegetables but also in water autoclaved in the cans. The amount of bisphenol-A in the extracts accounted for all the hormonal activity measured. Although the presence of other xenoestrogens cannot be ruled out, it is apparent that all estrogenic activity in these cans was due to bisphenol-A leached from the lacquer coating. The use of plastic in food-packaging materials may require closer scrutiny to determine whether epoxy resins and polycarbonates contribute to human exposure to xenoestrogens.
Bisphenol A (BPA) is used to produce polymers for food contact applications, thus there is potential for oral exposure of humans to trace amounts via the diet. BPA was weakly estrogenic in screening assays measuring uterine weight/response, although much higher oral doses of BPA were required to elicit a uterotropic response as compared to other routes of administration. The objective of this study was to determine if a route dependency exists in the pharmacokinetics and metabolism of 14C-labeled BPA following single oral (po), intraperitoneal (ip), or subcutaneous (sc) doses of either 10 or 100 mg/kg to Fischer 344 rats. Results indicated a marked route dependency in the pharmacokinetics of BPA. The relative bioavailability of BPA and plasma radioactivity was markedly lower following oral administration as compared to sc or ip administration. The major fraction of plasma radioactivity following oral dosing was the monoglucuronide conjugate of BPA (68-100% of plasma radioactivity). BPA was the major component in plasma at Cmax following sc or ip administration exceeded only by BPA-monoglucuronide in females dosed ip. Up to four additional unidentified metabolites were present only in the plasma of animals dosed ip or sc. One of these, found only following ip administration, was tentatively identified as the monosulfate conjugate of BPA. The monoglucuronide conjugate was the major urinary metabolite; unchanged BPA was the principal component excreted in feces. These results demonstrated a route dependency of BPA bioavailability in rats, with oral administration resulting in the lowest bioavailability, and offer an explanation for the apparent route differences in estrogenic potency observed for BPA.
The antimicrobial activity of the intraurethrally administered probiotic Lactobacillus casei strain Shirota against Escherichia coli in a murine urinary tract infection (UTI) model was examined. UTI was induced by intraurethral administration of Escherichia coli strain HU-1 (a clinical isolate from a UTI patient, positive for type 1 and P fimbriae), at a dose of 1 x 10(6) to 2 x 10(6) CFU in 20 microl of saline, into a C3H/HeN mouse bladder which had been traumatized with 0.1 N HCl followed immediately by neutralization with 0.1 N NaOH 24 h before the challenge infection. Chronic infection with the pathogen at 10(6) CFU in the urinary tract (bladder and kidneys) was maintained for more than 3 weeks after the challenge, and the number of polymorphonuclear leukocytes and myeloperoxidase activity in the urine were markedly elevated during the infection period. A single administration of L. casei Shirota at a dose of 10(8) CFU 24 h before the challenge infection dramatically inhibited E. coli growth and inflammatory responses in the urinary tract. Multiple daily treatments with L. casei Shirota during the postinfection period also showed antimicrobial activity in this UTI model. A heat-killed preparation of L. casei Shirota exerted significant antimicrobial effects not only with a single pretreatment (100 microg/mouse) but also with multiple daily treatments during the postinfection period. The other Lactobacillus strains tested, i.e., L. fermentum ATCC 14931(T), L. jensenii ATCC 25258(T), L. plantarum ATCC 14917(T), and L. reuteri JCM 1112(T), had no significant antimicrobial activity. Taken together, these results suggest that the probiotic L. casei strain Shirota is a potent therapeutic agent for UTI.
There is broad human exposure to bisphenol A (BPA), an estrogenic endocrine-disrupting chemical widely used for the production of plastic products. BPA is reported to affect preimplantation embryos or fetuses and alter their postnatal development at doses typically found in the environment. We measured contamination of BPA in various kinds of human biological fluids by a novel enzyme-linked immunosorbent assay.
Blood samples were obtained from healthy premenopausal women, women with early and full-term pregnancy, and umbilical cord at full-term delivery. Ovarian follicular fluids obtained during IVF procedures and amniotic fluids obtained at mid-term and full-term pregnancy were also subject to BPA measurements.
BPA was present in serum and follicular fluid at approximately 1-2 ng/ml, as well as in fetal serum and full-term amniotic fluid, confirming passage through the placenta. Surprisingly, an approximately 5-fold higher concentration, 8.3 +/- 8.7 ng/ml, was revealed in amniotic fluid at 15-18 weeks gestation, compared with other fluids.
These results suggest accumulation of BPA in early fetuses and significant exposure during the prenatal period, which must be considered in evaluating the potential for human exposure to endocrine-disrupting chemicals.
The anti-infectious activity of probiotic Bifidobacteria against Shiga toxin-producing Escherichia coli (STEC) O157:H7 was examined in a fatal mouse STEC infection model. Stable colonization of the murine intestines was achieved
by the oral administration of Bifidobacterium breve strain Yakult (naturally resistant to streptomycin sulfate) as long as the mice were treated with streptomycin in their drinking
water (5 mg/ml). The pathogenicity of STEC infection, characterized by marked body weight loss and subsequent death, observed
in the infected controls was dramatically inhibited in the B. breve-colonized group. Moreover, Stx production by STEC cells in the intestine was almost completely inhibited in the B. breve-colonized group. A comparison of anti-STEC activity among several Bifidobacterium strains with natural resistance to streptomycin revealed that strains such as Bifidobacterium bifidum ATCC 15696 and Bifidobacterium catenulatum ATCC 27539T did not confer an anti-infectious activity, despite achieving high population levels similar to those of effective strains,
such as B. breve strain Yakult and Bifidobacterium pseudocatenulatum DSM 20439. The effective strains produced a high concentration of acetic acid (56 mM) and lowered the pH of the intestine
(to pH 6.75) compared to the infected control group (acetic acid concentration, 28 mM; pH, 7.15); these effects were thought
to be related to the anti-infectious activity of these strains because the combination of a high concentration of acetic acid
and a low pH was found to inhibit Stx production during STEC growth in vitro.
Polycarbonate engineering resins have been applied to a wide range of industrial, consumer, automotive, medical, business equipment, electrical/electronic, lighting, optical, packaging, building/construction, and appliance products. This is due largely to its superior dimensional stability, good electrical properties, good thermal stability, and outstanding impact strength. They also offer excellent moldability and extrudability, low-temperature toughness, and the availability of flame-retardant and other special grades.
Bisphenol A (BPA) is used to produce polymers for food contact applications, thus there is potential for oral exposure of humans to trace amounts via the diet. BPA was weakly estrogenic in screening assays measuring uterine weight/response, although much higher oral doses of BPA were required to elicit a uterotropic response as compared to other routes of administration. The objective of this study was to determine if a route dependency exists in the pharmacokinetics and metabolism of 14 C-labeled BPA following single oral (po), intraperitoneal (ip), or subcutaneous (sc) doses of either 10 or 100 mg/kg to Fischer 344 rats. Results indicated a marked route dependency in the pharmacokinetics of BPA. The relative bioavailability of BPA and plasma radioactivity was markedly lower following oral administration as compared to sc or ip administration. The major fraction of plasma radioactivity following oral dosing was the monoglucuronide conjugate of BPA (68-100% of plasma radioactivity). BPA was the major component in plasma at Cmax following sc or ip administration exceeded only by BPA-monoglucuronide in females dosed ip. Up to four additional unidentified metabolites were present only in the plasma of animals dosed ip or sc. One of these, found only following ip administration, was tentatively identified as the monosulfate conjugate of BPA. The monoglucuronide conjugate was the major urinary metabolite; unchanged BPA was the principal component excreted in feces. These results demonstrated a route dependency of BPA bioavailability in rats, with oral administration resulting in the lowest bioavailability, and offer an explanation for the apparent route differences in estrogenic potency observed for BPA.
The estrogenic activities of bisphenol A (BPA) and its major metabolite BPA glucuronide (BPA-G) were assessed in a number of in vitro and in vivo assays. BPA competed with [H-3]-17 beta -estradiol (E2) for binding to mouse uterine cytosol ER, a glutathione S-transferase (GST)-human ER D, E, and F domain fusion protein (GST-hER alpha def) and full-length recombinant hER beta. The IC50 values for E2 were similar for all three receptor preparations, whereas BPA competed more effectively for binding to hER beta (0.96 muM) than to either mouse uterine cytosol ER (26 muM) or GST-hERadef (36 CIM) In contrast, BPA-G did not competitively displace [H-3]E2 from any of the ER preparations. In MCF-7 cells transiently transfected with Gal4-hER alpha def or Gal4-hER beta def, BPA induced reporter gene activity with comparable EC50 values (71 and 39 muM, respectively). No significant induction of reporter gene activity was seen for BPA-G. Cotreatment studies showed that concentrations of (10 muM) BPA and BPA-G did not antagonize EB-induced luciferase mediated through either Gal4-hER alpha def or Gal4-hER beta def. In vivo, the uterotropic effect of gavage or subcutaneous (sc) administration of 0.002-800 mg of BPA/kg of body weight/day for three consecutive days was examined in immature rats. Dose-related estrogenic effects on the rat uterus were observed at oral doses of 200 and 800 mg/kg and at sc doses of 10, 100, and 800 mg/kg. These results demonstrate that BPA competes more effectively for binding to ER beta, but induces ER alpha- and ER beta -mediated gene expression with comparable efficacy. In contrast, BPA-G did not exhibit any in vitro estrogenic activity. In addition, there was a clear route dependency on the ability of BPA to induce estrogenic responses in vivo.
Plastics and pesticides are examples of products that contain oestrogenic endocrine-disrupting chemicals, or EEDCs, which can interfere with mammalian development by mimicking the action of the sex hormone oestradiol¹. For instance, the exposure of developing rodents to high doses of EEDCs advances puberty and alters their reproductive function². Low environmental doses of EEDCs may also affect development in humans³. Effects have become apparent in humans over the past half century that are consistent with those seen in animals after exposure to high doses of EEDCs, such as an increase in genital abnormality in boys⁴ and earlier sexual maturation in girls⁵. Here we show that exposing female mouse fetuses to an EEDC at a dose that is within the range typical of the environmental exposure of humans alters the postnatal growth rate and brings on early puberty in these mice.
The present study was designed to determine whether tumor induction by 3-methylcholanthrene (MC), a carcinogenic hydrocarbon,
can be inhibited by oral administration of Lactobacillus casei strain Shirota (LC). C3H/HeN mice were divided into four groups and assigned to the following treatments: treated with MC
and given control or LC-containing diet; treated with vehicle only and given control or LC-containing diet. MC (1 mg) was
injected intradermally at 7 weeks of age and the tumor incidence was monitored; LC was mixed into a diet at a concentration
of 0.05% (w/w) and the diet was fed from the day of MC injection throughout the study. Spleen cells were analyzed for the
immune parameters at 12 and 16 weeks after the MC injection. Oral feeding of mice with LC reduced tumor incidence (P < 0.05). MC treatment lowered the in vitro response to concanavalin A (Con A) of spleen cells, the secretion of interleukin-2
in spleen cell culture after stimulation of the cells with Con A and the proportions of CD3+, CD4+ and CD8+ splenic cells. However, the analysis of the spleen cells obtained from the mice treated with MC and given the LC-containing
diet revealed that these disrupted host immune parameters were maintained at the level of normal controls. These results suggest
that oral feeding of mice with LC inhibits MC-induced tumorigenesis by modulating the disrupted host immune responses during
MC carcinogenesis.
The ability of 22 strains of intestinal bacteria to bind the mutagenic pyrolyzates--3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole [(Trp-P-1) CAS: 62450-06-0], 3-amino-1-methyl-5H-pyrido [4,3-b]indole [(Trp-P-2) CAS: 62450-07-1], 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole [(Glu-P-1) CAS: 67730-11-4], 2-aminodipyrido[1,2-a:3',2'-d]imidazole [(Glu-P-2) CAS: 67730-10-3], 2-amino-3-methylimidazo[4,5-f]quinoline [(IQ) CAS: 76180-96-6], 2-amino-3,4-dimethylimidazo[4,5-f]quinoline [(MeIQ) CAS: 77094-11-2], and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline [(MeIQx) CAS: 77500-04-0]--was investigated and compared to their ability to bind to some dietary fibers (corn bran, apple pulp, soy bean fiber, cellulose, chitin, and chitosan). The pyrolyzates are potent mutagenic and carcinogenic heterocyclic amines formed during cooking. Solution of these amines was mixed with aqueous suspension of bacterial cells or dietary fibers, and removal of these amines from the reaction mixture by centrifugation was defined as the binding. Trp-P-1 and Trp-P-2 were effectively bound to all gram-positive and some gram-negative bacterial cells, corn bran, apple pulp, and soy bean fiber. Binding of Trp-P-1 and Trp-P-2 to Escherichia coli, Klebsiella pneumoniae, and cellulose was moderate, and to chitin and chitosan it was little. None but corn bran bound Glu-P-1 and Glu-P-2 effectively. Corn bran effectively bound all mutagens tested. The quantity of the binding of IQ, MeIQ, and MeIQx was dependent on the strain of bacteria and the kind of fiber. The mechanism of binding of Trp-P-2 to freeze-dried feces, Lactobacillus casei YIT 9018 (LC9018), and corn bran was investigated. The binding was pH dependent, occurred instantaneously, and was inhibited by the addition of metal salts. These results indicate that the binding was mostly due to a cation-exchange mechanism, but some irreversible binding of Trp-P-2 was observed, most notably to freeze-dried feces. The mutagenicity of Trp-P-2 for Salmonella typhimurium TA98 in the presence of S9 mix was inhibited by the addition of LC9018 or corn bran to the reaction mixture. The results indicate that bound Trp-P-2 did not cause mutation under the assay conditions.
It is known that the ingestion of cooked meat which contains carcinogenic heterocyclic amines causes increase in urinary mutagenicity in humans. Using 6 healthy non-smokers, we examined the effect of 3-week oral administration of Lactobacillus casei (bacilli commonly present in yoghurt), on the urinary mutagenicity derived from ingestion of fried ground beef. Comparison of the urinary mutagenicity found before and after the L. casei treatment showed that the treatment resulted in a decrease (6-67%, average 47.5%) of the mutagenicity. This suppressing effect is possibly related to the changes in the intestinal microflora population.
The inhibitory effect of lyophilized cultures of Bifidobacterium longum on 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced carcinogenesis was investigated in male and female F344 rats. Beginning at 5 weeks of age, male and female rats were divided into various experimental groups and fed one of the high-fat, semipurified diets containing 0 and 0.5% lyophilized cultures of B. longum with or without 125 ppm IQ in the diet. All animals were continued on this regimen until the termination of the study. All animals were necropsied during the 58th week. The results indicated that dietary B. longum significantly inhibited the IQ-induced incidence (percentage of animals with tumors) of colon (100% inhibition) and liver (80% inhibition) tumors and multiplicity (tumors/animal) of colon, liver, and small intestinal tumors in male rats. In female rats, dietary supplementation of Bifidobacterium cultures also suppressed the IQ-induced mammary carcinogenesis to 50% and liver carcinogenesis to 27% of those observed in animals fed the control diet, but the differences did not reach a statistical significance at P < 0.05; however, the mammary tumor multiplicity (tumors/animal) was significantly (P < 0.05) inhibited in female rats fed the diet containing Bifidobacterium cultures. These findings suggest that Bifidobacterium supplements in the diet inhibit IQ-induced colon and liver tumors and to a lesser extent mammary tumors in F344 rats.
The aims of this investigation were to determine whether viable cultures of lactic acid-producing organisms (LAB) can bind dietary carcinogens and to assess the consequences of binding for the absorption from the gut, distribution in the body and in vivo genotoxicity of ingested carcinogens. The carcinogens used in this study were ones known to be present in the human diet, namely benzo[a]pyrene (B(a)P, aflatoxin B1 (AFB1) and the cooked food carcinogens 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 5-phenyl-2-amino-1-methylimidazo [4,5-f]pyridine (PhIP) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). They represent a range of structural types so that the specificity of any binding effects could be addressed. Of the carcinogens tested, B(a)P and Trp-P-2 were bound most effectively by the two LAB strains Bifidobacterium longum and Lactobacillus acidophilus. AFB1 was poorly bound, while MeIQx, MeIQ, PhIP and IQ were bound to an intermediate degree. The extent of the binding of the heterocyclic amine carcinogens was dependent on the pH conditions during incubation and this effect was more apparent with B. longum than with L. acidophilus. Using the host-mediated assay (HMA), an in vivo bacterial mutation assay, it was demonstrated that the administration of bacterial cell suspensions of B. longum and L. acidophilus did not lead to a reduction in induced mutagenicity by MeIQ, MeIQx or Trp-P-2, detectable in the liver of treated mice compared with controls. The lack of a protective effect could not be attributed to a short period of contact between bacterial cells and mutagens, since similar results were obtained after preincubating bacteria and mutagens together at pH 5 for 50-60 min, to maximize the binding, before gavaging the mice. Lack of activity of B(a)P in the HMA prevented the determination of the effect of LAB on genotoxicity of the polycyclic aromatic hydrocarbon. However, it is clear from the radiolabel distribution study that the amount of the carcinogen entering the blood was not significantly reduced by B. longum administration. In addition, the amount of radiolabelled B(a)P that reached the target organs (liver, lungs and heart) was also not affected by the LAB administration. A similar lack of inhibitory effect of B. longum on blood concentration and accumulation in the liver of Trp-P-2 was apparent. The results of the present study suggest that although LAB may bind carcinogens in vitro, this does not lead to major changes in absorption and distribution of carcinogens in the body, or in their genotoxic activity in the liver.
Lactobacillus casei strain Shirota (LcS) has been shown to have potent anti-tumour and anti-metastatic effects on transplantable tumour cells and to suppress chemically-induced carcinogenesis in rodents. In particular, intrapleural (i.pl.) administration of LcS into tumour-bearing mice has been shown to effectively inhibit the growth of tumour cells in the thoracic cavity and to significantly prolong survival time. Also, i.pl. administration of LcS has been shown to induce the production of several cytokines, such as IFN-gamma, IL-1beta and TNF-alpha, in the thoracic cavity of mice, resulting in the inhibition of tumour growth and increased survival. On the other hand, oral administration of LcS has been shown to inhibit the growth of implantable tumour cells in rodents, and to restore the decreased mitogenic response of tumour-bearing mice. Administration of LcS has also been shown to inhibit chemically-induced bladder cancer in rodents. These findings suggest that treatment with LcS has the potential to ameliorate or prevent a variety of diseases through modulation of the host's immune system, specifically cellular immune responses.
Using mice, we found that oral administration of Bifidobacterium breve YIT4064 (B. breve) activated the humoral immune system, augmented anti-rotavirus IgA production or anti-influenza virus (IFV) IgG production and protected against rotavirus infection or influenza infection, respectively. Furthermore, when the B. breve was given to infants from an infant home, there was a significant reduction of the frequency of rotavirus shedding in stool samples during the administration of the bacteria. It was also found, again using mice, that oral administration of Lactobacillus casei strain Shirota (LcS) stimulated type 1 helper T (Th1) cells, activated the cellular immune system and inhibited incidence of tumors and IgE production. These results demonstrated that these two strains of lactic acid bacteria modulated the different immune systems each in its own way and prevented against various diseases.
For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria.
The interaction of a potent carcinogen, aflatoxin B(1) (AFB(1)), with a probiotic strain of lactic acid bacteria, Lactobacillus rhamnosus strain GG (GG), has been investigated. The binding of AFB(1) to GG in the late exponential-early stationary phase was studied for viable, heat-killed and acid-killed bacteria. In general, viable, heat-killed and acid-killed GG responded in a similar manner. The effects of pronase E, lipase and m-periodate on AFB(1) binding and release were consistent with AFB(1) binding predominantly to carbohydrate components of the bacteria. The effect of urea suggested hydrophobic interactions play a major role in binding. Increasing concentration (0.01-1 M) of NaCl or CaCl(2) had minor effects on AFB(1) binding suggesting some involvement of electrostatic interactions. An increase in pH from 2.5 to 8.5 had no effect on AFB(1) binding but decreased binding of AFB(2a), possibly due to hydrogen bonding interactions.
The estrogenic activities of bisphenol A (BPA) and its major metabolite BPA glucuronide (BPA-G) were assessed in a number of in vitro and in vivo assays. BPA competed with [3H]-17beta-estradiol (E2) for binding to mouse uterine cytosol ER, a glutathione S-transferase (GST)-human ER D, E, and F domain fusion protein (GST-hERalphadef) and full-length recombinant hERbeta. The IC(50) values for E2 were similar for all three receptor preparations, whereas BPA competed more effectively for binding to hERbeta (0.96 microM) than to either mouse uterine cytosol ER (26 microM) or GST-hERalphadef (36 microM). In contrast, BPA-G did not competitively displace [3H]E2 from any of the ER preparations. In MCF-7 cells transiently transfected with Gal4-hERalphadef or Gal4-hERbetadef, BPA induced reporter gene activity with comparable EC(50) values (71 and 39 microM, respectively). No significant induction of reporter gene activity was seen for BPA-G. Cotreatment studies showed that concentrations of (10 microM) BPA and BPA-G did not antagonize E2-induced luciferase mediated through either Gal4-hERalphadef or Gal4-hERbetadef. In vivo, the uterotropic effect of gavage or subcutaneous (sc) administration of 0.002-800 mg of BPA/kg of body weight/day for three consecutive days was examined in immature rats. Dose-related estrogenic effects on the rat uterus were observed at oral doses of 200 and 800 mg/kg and at sc doses of 10, 100, and 800 mg/kg. These results demonstrate that BPA competes more effectively for binding to ERbeta, but induces ERalpha- and ERbeta-mediated gene expression with comparable efficacy. In contrast, BPA-G did not exhibit any in vitro estrogenic activity. In addition, there was a clear route dependency on the ability of BPA to induce estrogenic responses in vivo.
The environmental estrogen bisphenol A, orally introduced into the body, passes through the liver and modulates the endocrine system to elicit irreversible changes in the functioning of reproduction. To elucidate the actual and dynamic metabolism of bisphenol A in the liver before its arrival at target organs, this study evaluated the metabolism and disposition of the compound within the passage through the liver in Sprague-Dawley rats. On perfusion of 7.5 micromol of bisphenol A into the liver via the portal vein, approximately 91% of the infused bisphenol A was absorbed by the liver tissue, and about 65% of the absorbed bisphenol A was glucuronidated within 60 min. Roughly 65% of the bisphenol A glucuronide that formed in the liver was excreted into the bile and about 35% into the hepatic vein. On perfusion of 0.01, 0.05, and 0.1 mM bisphenol A solution into the liver, free bisphenol A was excreted only into the vein at 5.6, 9.3, and 14.6%, respectively, of the total bisphenol A. These results suggest that most bisphenol A absorbed by the intestine is probably glucuronidated exclusively in the liver and the conjugate is excreted mainly into the bile.
The antioxidative effects of live bifidobacteria on lipid peroxidation in the colonic mucosa were investigated. Bifidobacterium bifidum strain Yakult, which has been used for production of fermented milk, most effectively inhibited lipid peroxidation catalyzed by ferrous iron in liposomes among 10 species of bifidobacteria from human intestinal flora. Oral administration of B. bifidum strain Yakult for 2 wk significantly decreased the level of lipid peroxide (thiobarbituric acid reactive substance) in the colonic mucosa of iron-overload mice (Fe 0.07% in diet). The iron concentrations in plasma and cecum contents were not affected by administration of B. bifidum strain Yakult. Bifidobacterium bifidum strain Yakult had no chelating or incorporating activity for ferrous iron in vitro. Therefore, the antioxidative effect of B. bifidum strain Yakult in the colonic mucosa was not thought to be based on the removal of ferrous iron from the reaction system of lipid peroxidation. These results suggested that B. bifidum strain Yakult protected the colonic mucosa from oxidative injury without inhibiting iron absorption.
The environmental estrogen bisphenol A (BPA) is regarded as a modulator of endocrine systems and has been reported to have adverse effects on the reproductive organs of animals. In rats, BPA is metabolized to glucuronide by UDP-glucuronosyltransferase UGT2B1 in the liver and excreted into the bile. In the present study, we found that most of the bisphenol A-glucuronide (BPA-GA) excreted into the small intestine was deconjugated in the contents of the cecum. After BPA administration, BPA-GA was (immediately should be 15 min) found in the contents of the upper part of the small intestine, and then it moved to the lower part of the small intestine. However, only free BPA was found in the content of the cecum, and there was smaller amount of free BPA in the colon contents, indicating that BPA had been reabsorbed in the colon. BPA-GA was deconjugated by extract prepared from the cecum content which included highest beta-glucuronidase (beta-Gase) observed in Western blot analysis using antibodies against bacterial beta-Gase. These results indicate enterohepatic circulation of BPA and suggest that the adverse effects of BPA are enhanced by repeated exposure.
The antioxidative effects of lactic acid bacteria on lipid peroxidation in the colonic mucosa were investigated. Among 49 strains of lactic acid bacteria, Streptococcus thermophilus YIT 2001 showed the highest inhibitory activity against lipid peroxidation in liposomes induced by ferrous iron. Feeding a diet containing 0.4% St. thermophilus YIT 2001 (2 x 10(8) colony-forming units per mouse per day) for 2 weeks caused a significant decrease of lipid peroxide (thiobarbituric acid reactive substance) in the colonic mucosa of iron-overloaded mice (0.07% Fe in the diet). The mucosal lipid peroxide level did not correlate with the soluble iron concentration of the cecal contents. Therefore, it is suggested that the antioxidative effect of St. thermophilus YIT 2001 in the colonic mucosa was not due to the removal of ferrous iron from the reaction system of lipid peroxidation.
Modifications in gastrointestinal parameters, intestinal colonization and tolerance are some of the main goals claimed for probiotics. However, although healthy people are the common target for these new functional food products, the number of clinical trials analysing the effects of probiotics in gastrointestinal parameters of healthy subjects is very scarce. A randomized, double blind, placebo-controlled human clinical trial involving 30 healthy adults was performed to investigate the effect of a fermented product containing two probiotic strains, Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711, on several blood and fecal parameters, most of them related to the host intestinal function. The volunteers were randomly distributed into two groups, one receiving a standard yogurt and the other a similar dairy fermented product in which the Lactobacillus delbreuckii subsp. bulgaricus yogurt strain had been replaced by a combination of the probiotic strains L. gasseri CECT5714 and L. coryniformis CECT5711. The volunteers that received the probiotic strains reported no adverse effects and the strains could be isolated from their feces at a relatively high level. In fact, the concentration of fecal lactic acid bacteria significantly increased in the probiotic group. Additionally, the oral administration of the probiotic strains led to an improvement of parameters such as the production of short chain fatty acids, the fecal moisture and the frequency and volume of the stools. As a result, the volunteers assigned to the probiotic group perceived a clear improvement in their intestinal habits. The study revealed that probiotics may exert a positive effect on healthy adults.
Ten strains of the genus Lactococcus were examined for their ability to remove bisphenol A [2, 2-bis(4-hydroxyphenyl)propane; BPA], which is known as an endocrine disrupter. Nine strains of the lactococci tested could remove BPA from media during growth, although the removal ratio was below 9%. When BPA was incubated with lyophilized cells of lactococci for 1 h, the concentration of BPA in the media was decreased by 9-62%. Especially, the highest removal ratio of BPA was observed for Lactococcus lactis subsp. lactis 712. The lactococci could adsorb BPA but not degrade it, because the lactococci maintained the ability to remove BPA from the medium after autoclaving. When the lyophilized cells of L. lactis subsp. lactis 712 were also incubated with six analogues of BPA, they effectively adsorbed hydrophobic compounds such as 2, 2'-diphenylpropane and bisphenol A dimethylether. The BPA-adsorbing ability of lactococci could be due to the hydrophobic binding effect. The removal ratio of BPA by L. lactis subsp. lactis 712 was increased after treatment with sodium dodecyl sulfate and decreased after digestion with trypsin. These results suggest that the hydrophobic proteins on cell surface may be involved in the BPA-adsorbing ability of lactococci.
Xenoestrogens are chemicals with diverse structure that mimic estrogen. Bisphenol A (BPA), a monomer of polycarbonate and epoxy resins, has been detected in canned food and human saliva. BPA stimulates cell proliferation and induces expression of estrogen-responsive genes in vitro, albeit with a relatively low potency. In vivo, BPA increases prolactin release and stimulates uterine, vaginal and mammary growth and differentiation. BPA shares similarities in structure, metabolism and action with diethylstilbestrol (DES), a known human teratogen and carcinogen. This review considers the hypothesis that BPA is converted in vivo to hydroxylated metabolite(s) with enhanced estrogenicity and genotoxicity.