Nonylphenol induces depressive behavior in rats and affects gut microbiota: A dose-dependent effect.

Nonylphenol (NP), an endocrine disruptor absorbed through food intake, was investigated in this study for its potential dose-response relationship with the manifestation of depression-like behavior in rats. Based on this, the mechanisms of NP-induced depressive behavior, encompassing neurotransmitters, gut barrier function, inflammatory response, gut microbiota composition and metabolites were further explored. At medium and high NP doses, both mRNA and protein levels of zonula occludens protein-1 and claudin-1 were considerably downregulated, concomitant with an elevation in tumor necrosis factor-α and interleukin-1ß expression in a dose-dependent effect, resulting in damage to the gut mucosa. Despite a minimal impact on behavior and gut barriers at low NP doses, alterations in gut microbiota composition were observed. During NP exposure, dose-dependent changes in the gut microbiota revealed a decline in microbial diversity linked to the synthesis of short-chain fatty acids. NP not only adversely affected the gut microbiota structure but also exacerbated central nervous system damage through the gut-brain axis. The accumulation of NP may cause neurotransmitter disturbances and inflammatory responses in the hippocampus, which also exacerbate depressed behavior in rats. Therefore, NP could exacerbate the inflammatory response in the hippocampus and colon by compromising intestinal barrier integrity, facilitating the proliferation of pathogenic bacteria, impairing butyrate metabolism, and perturbing neurotransmitter homeostasis, thus aggravating the depressive behavior of rats. It is noteworthy that the changes in these indicators were related to the NP exposure dose.

Spontaneous and Microbiota-Driven Degradation of Anthocyanins in an In Vitro Human Colon Model.

SCOPE: The consumption of dietary anthocyanins is associated with various health benefits. However, anthocyanins are poorly bioavailable, and most ingested anthocyanins will enter the colon where they are degraded to small phenolic metabolites that are the main absorbed forms. Little is known about the processes of anthocyanin degradation in the gut and the role of the human gut microbiota. This study aims to determine the contribution of spontaneous and microbiota-dependent degradation of anthocyanins in the human colon. METHODS AND RESULTS: Purified anthocyanin extracts from black rice and bilberry were incubated in an in vitro human fecal-inoculated pH-controlled colon model over 24 h and anthocyanins were analyzed using HPLC-DAD. The study shows that the loss of anthocyanins occurs both spontaneously and as a consequence of metabolism by the gut microbiota. The study observes that there is high variability in spontaneous degradation but only modest variation in total degradation, which included the microbiota-dependent component. The degradation rate of anthocyanins is also shown to be dependent on the B-ring substitution pattern and the type of sugar moiety, both for spontaneous and microbiota-dependent degradation. CONCLUSION: Anthocyanins are completely degraded in a model of the human colon by a combination of spontaneous and microbiota-dependent processes.

Molecular Cloning, Expression and Characterisation of a Bacterial Myrosinase from Citrobacter Wye1.

Glucosinolates are plant natural products which on degradation by myrosinases give rise to the beneficial bioactive isothiocyanates. Recently, a myrosinase activity was detected in a Citrobacter strain isolated from soil. This enzyme was purified enabling its amino acid sequence and gene sequence (cmyr) to be determined. In order to study this myrosinase it was necessary to establish an expression system that would enable future work such as a structural determination of the protein to be carried out. The myrosinase gene was amplified, cloned and expressed in Escherichia coli with a 6XHis-tag. The heterologous expression of cmyr enabled relatively large amounts of myrosinase to be produced (3.4 mg cmyr/100 ml culture). Myrosinase activity was determined by mixing substrate and enzyme and determining glucose release. Optimum pH and temperature were determined to be pH 6.0 and 25 °C for the Ni-NTA purified protein. The kinetic parameters of the purified myrosinase were determined using sinigrin as a substrate. Km and Vmax were estimated as 0.18 mM and 0.033 mmol/min/mg respectively for sinigrin under optimum conditions and compared to other kinetic data for myrosinases. The substrate specificity of myrosinase was determined having the highest affinity for sinigrin followed by glucoiberin, progoitrin, glucoerucin, glucoraphanin and glucotropaeolin.

Effects of in vitro metabolism of a broccoli leachate, glucosinolates and S-methylcysteine sulphoxide on the human faecal microbiome.

PURPOSE: Brassica are an important food source worldwide and are characterised by the presence of compounds called glucosinolates. Studies indicate that the glucosinolate derived bioactive metabolite sulphoraphane can elicit chemoprotective benefits on human cells. Glucosinolates can be metabolised in vivo by members of the human gut microbiome, although the prevalence of this activity is unclear. Brassica and Allium plants also contain S-methylcysteine sulphoxide (SMCSO), that may provide additional health benefits but its metabolism by gut bacteria is not fully understood. METHODS: We examined the effects of a broccoli leachate (BL) on the composition and function of human faecal microbiomes of five different participants under in vitro conditions. Bacterial isolates from these communities were then tested for their ability to metabolise glucosinolates and SMCSO. RESULTS: Microbial communities cultured in vitro in BL media were observed to have enhanced growth of lactic acid bacteria, such as lactobacilli, with a corresponding increase in the levels of lactate and short-chain fatty acids. Members of Escherichia isolated from these faecal communities were found to bioconvert glucosinolates and SMCSO to their reduced analogues. CONCLUSION: This study uses a broccoli leachate to investigate the bacterial-mediated bioconversion of glucosinolates and SMCSO, which may lead to further products with additional health benefits to the host. We believe that this is the first study that shows the reduction of the dietary compound S-methylcysteine sulphoxide by bacteria isolated from human faeces.

Lactobacillus plantarum-Mediated Regulation of Dietary Aluminum Induces Changes in the Human Gut Microbiota: an In Vitro Colonic Fermentation Study.

The gut microbiota has been identified as a target of toxic metals and a potentially crucial mediator of the bioavailability and toxicity of these metals. In this study, we show that aluminum (Al) exposure, even at low dose, affected the growth of representative strains from the human intestine via pure culture experiments. In vitro, Lactobacillus plantarum CCFM639 could bind Al on its cell surface as shown by electron microscopy and energy dispersive X-ray analysis. The potential of L. plantarum CCFM639 to reverse changes in human intestine microbiota induced by low-dose dietary Al exposure was investigated using an in vitro colonic fermentation model. Batch fermenters were inoculated with fresh stool samples from healthy adult donors and supplemented with 86 mg/L Al and/or 109 CFU of L. plantarum CCFM639. Al exposure significantly increased the relative abundances of Bacteroidetes (Prevotella), Proteobacteria (Escherichia), Actinobacteria (Collinsella), Euryarchaeota (Methanobrevibacter), and Verrucomicrobiaceae and decreased Firmicutes (Streptococcus, Roseburia, Ruminococcus, Dialister, Coprobacillus). Some changes were reversed by the inclusion of L. plantarum CCFM639. Alterations in gut microbiota induced by Al and L. plantarum CCFM639 inevitably led to changes in metabolite levels. The short-chain fatty acid (SCFAs) contents were reduced after Al exposure, but L. plantarum CCFM639 could elevate their levels. SCFAs had positive correlations with beneficial bacteria, such as Dialister, Streptococcus, Roseburia, and negative correlations with Erwinia, Escherichia, and Serratia. Therefore, dietary Al exposure altered the composition and structure of the human gut microbiota, and this was partially mitigated by L. plantarum CCFM639. This probiotic supplementation is potentially a promising and safe approach to alleviate the harmful effects of dietary Al exposure.

Systemic iron reduction by venesection alters the gut microbiome in patients with haemochromatosis.

BACKGROUND & AIMS: Iron reduction by venesection has been the cornerstone of treatment for haemochromatosis for decades, and its reported health benefits are many. Repeated phlebotomy can lead to a compensatory increase in intestinal iron absorption, reducing intestinal iron availability. Given that most gut bacteria are highly dependent on iron for survival, we postulated that, by reducing gut iron levels, venesection could alter the gut microbiota. METHODS: Clinical parameters, faecal bacterial composition and metabolomes were assessed before and during treatment in a group of patients with haemochromatosis undergoing iron reduction therapy. RESULTS: Systemic iron reduction was associated with an alteration of the gut microbiome, with changes evident in those who experienced reduced faecal iron availability with venesection. For example, levels of Faecalibacterium prausnitzii, a bacterium associated with improved colonic health, were increased in response to faecal iron reduction. Similarly, metabolomic changes were seen in association with reduced faecal iron levels. CONCLUSION: These findings highlight a significant shift in the gut microbiome of patients who experience reduced colonic iron during venesection. Targeted depletion of faecal iron could represent a novel therapy for metabolic and inflammatory diseases, meriting further investigation. LAY SUMMARY: Iron depletion by repeated venesection is the mainstay of treatment for haemochromatosis, an iron-overload disorder. Venesection has been associated with several health benefits, including improvements in liver function tests, reversal of liver scarring, and reduced risk of liver cancer. During iron depletion, iron absorption from the gastrointestinal (GI) tract increases to compensate for iron lost with treatment. Iron availability is limited in the GI tract and is crucial to the growth and function of many gut bacteria. In this study we show that reduced iron availability in the colon following venesection treatment leads to a change in the composition of the gut bacteria, a finding that, to date, has not been studied in patients with haemochromatosis.

Correction: Metabolite quantification of faecal extracts from colorectal cancer patients and healthy controls.

[This corrects the article DOI: 10.18632/oncotarget.26022.].

A decrease in iron availability to human gut microbiome reduces the growth of potentially pathogenic gut bacteria; an in vitro colonic fermentation study.

Iron supplements are widely consumed; however most of the iron is not absorbed and enters the colon where potentially pathogenic bacteria can utilise it for growth. This study investigated the effect of iron availability on human gut microbial composition and function using an in vitro colonic fermentation model inoculated with faecal microbiota from healthy adult donors, as well as examining the effect of iron on the growth of individual gut bacteria. Batch fermenters were seeded with fresh faecal material and supplemented with the iron chelator, bathophenanthroline disulphonic acid (BPDS). Samples were analysed at regular intervals to assess impact on the gut bacterial communities. The growth of Escherichia coli and Salmonella typhimurium was significantly impaired when cultured independently in iron-deficient media. In contrast, depletion of iron did not affect the growth of the beneficial species, Lactobacillus rhamnosus, when cultured independently. Analysis of the microbiome composition via 16S-based metataxonomics indicated that under conditions of iron chelation, the relative abundance decreased for several taxa, including a 10% decrease in Escherichia and a 15% decrease in Bifidobacterium. Metabolomics analysis using 1 H-NMR indicated that the production of SCFAs was reduced under iron-limited conditions. These results support previous studies demonstrating the essentiality of iron for microbial growth and metabolism, but, in addition, they indicate that iron chelation changes the gut microbiota profile and influences human gut microbial homeostasis through both compositional and functional changes.

Metabolite quantification of faecal extracts from colorectal cancer patients and healthy controls.

Colorectal cancer (CRC), a primary cause of morbidity and mortality worldwide is expected to rise in the coming years. A better understanding of the metabolic changes taking place during the disease progression is needed for effective improvements of screening strategies and treatments. In the present study, Nuclear Magnetic Resonance (NMR) metabolomics was used to quantify the absolute concentrations of metabolites in faecal extracts from two cohorts of CRC patients and healthy controls. The quantification of over 80 compounds revealed that patients with CRC had increased faecal concentrations of branched chain fatty acids (BCFA), isovalerate and isobutyrate plus valerate and phenylacetate but diminished concentrations of amino acids, sugars, methanol and bile acids (deoxycholate, lithodeoxycholate and cholate). These results suggest that alterations in microbial activity and composition could have triggered an increase in utilisation of host intestinal slough cells and mucins and led to an increase in BCFA, valerate and phenylacetate. Concurrently, a general reduction in the microbial metabolic function may have led to reduced levels of other components (amino acids, sugars and bile acids) normally produced under healthy conditions. This study provides a thorough listing of the most abundant compounds found in human faecal waters and presents a template for absolute quantification of metabolites. The production of BCFA and phenylacetate in colonic carcinogenesis warrants further investigations.

Processing and Structure of the Lantibiotic Peptide Nso From the Human Gut Bacterium Blautia obeum A2-162 analysed by Mass Spectrometry.

A previously reported gene cluster encoding four nisin-like peptides, three with the same sequence (NsoA1-3) and the unique NsoA4, produced antimicrobial activity in the presence of trypsin after heterologous expression in Lactococcus lactis. Protein extracts were separated by SDS gel electrophoresis or immunoprecipitation using an antibody to the NsoA2 leader. Tryptic peptides observed by LC-MS/MS covered the complete sequence of preNsoA1-3 and part of the leader sequence of preNsoA4 and confirmed the expression and the predicted sequences of the preNsoA peptides. Further, the data revealed that the preNsoA1-3 peptides were partly modified with dehydrations and formation of lanthionine rings. A certain amount of fully modified preNsoA1-3 was observed. Details of modifications of the core peptide and the C-terminal tryptic peptide TATCGCHITGK covering rings D and E indicated that 22% of these preNsoA1-3 peptides were completely modified. A lower amount of ring formation is estimated for rings A-C. Intact masses of immunoprecipitation-derived peptides determined by LC-MS accurately matched the expected preNsoA precursor peptides. The most abundant peptides detected were preNsoA2-3-8H2O followed by preNsoA1-8H2O and other states of dehydration. The results confirm incomplete processing of preNsoA peptides in the heterologous system, with the formation of a certain amount of fully modified peptides.

Comparative metabolomic analysis reveals global cadmium stress response of Lactobacillus plantarum strains.

Our previous work demonstrated the protective effects of Lactobacillus plantarum (L. plantarum) strains against cadmium (Cd) toxicity in vivo, and also indicated that the Cd tolerance of the strains played an important role in this protection. The goal of this study was to investigate the Cd resistance mechanism of L. plantarum by liquid chromatography-mass spectrometry (LC-MS) based metabolomic analysis, with a focus on the global Cd stress response. L. plantarum CCFM8610 (strongly resistant to Cd) and L. plantarum CCFM191 (sensitive to Cd) were selected as target strains, and their metabolomic profiles with and without Cd exposure were compared. The underlying mechanisms of the intra-species distinction between CCFM8610 and CCFM191 in terms of Cd tolerance can be attributed to the following aspects: (a) CCFM8610 possesses a higher intracellular content of osmolytes; (b) CCFM8610 can induce more effective biosynthesis of extracellular polymeric substance (EPS) to sequestrate Cd;

Morphological and Functional Characterization of IL-12Rß2 Chain on Intestinal Epithelial Cells: Implications for Local and Systemic Immunoregulation.

Interaction between intestinal epithelial cells (IECs) and the underlying immune systems is critical for maintaining intestinal immune homeostasis and mounting appropriate immune responses. We have previously showed that the T helper type 1 (TH1) cytokine IL-12 plays a key role in the delicate immunological balance in the gut and the lack of appropriate levels of IL-12 had important consequences for health and disease, particularly with regard to food allergy. Here, we sought to understand the role of IL-12 in the regulation of lymphoepithelial cross talk and how this interaction affects immune responses locally and systemically. Using a combination of microscopy and flow cytometry techniques we observed that freshly isolated IECs expressed an incomplete, yet functional IL-12 receptor (IL-12R) formed solely by the IL-12Rß2 chain that albeit the lack of the complementary IL-12ß1 chain responded to ex vivo challenge with IL-12. Furthermore, the expression of IL-12Rß2 on IECs is strategically located at the interface between epithelial and immune cells of the lamina propria and using in vitro coculture models and primary intestinal organoids we showed that immune-derived signals were required for the expression of IL-12Rß2 on IECs. The biological relevance of the IEC-associated IL-12Rß2 was assessed in vivo in a mouse model of food allergy characterized by allergy-associated diminished intestinal levels of IL-12 and in chimeric mice that lack the IL-12Rß2 chain on IECs. These experimental models enabled us to show that the antiallergic properties of orally delivered recombinant Lactococcus lactis secreting bioactive IL-12 (rLc-IL12) were reduced in mice lacking the IL-12ß2 chain on IECs. Finally, we observed that the oral delivery of IL-12 was accompanied by the downregulation of the production of the IEC-derived proallergic cytokine thymic stromal lymphopoietin (TSLP). However, further analysis of intestinal levels of TSLP in IL-12Rß2-/- mice suggested that this event was not directly linked to the IEC-associated IL-12Rß2 chain. We interpreted these data as showing that IEC-associated IL12Rß2 is a component of the cytokine network operating at the interface between the intestinal epithelium and immune system that plays a role in immune regulation.

Gut Glucosinolate Metabolism and Isothiocyanate Production.

The glucosinolate-myrosinase system in plants has been well studied over the years while relatively little research has been undertaken on the bacterial metabolism of glucosinolates. The products of myrosinase-based glucosinolate hydrolysis in the human gut are important to health, particularly the isothiocyanates, as they are shown to have anticancer properties as well as other beneficial roles in human health. This review is concerned with the bacterial metabolism of glucosinolates but is not restricted to the human gut. Isothiocyanate production and nitrile formation are discussed together with the mechanisms of the formation of these compounds. Side chain modification of the methylsulfinylalkyl glucosinolates is reviewed and the implications for bioactivity of the resultant products are also discussed.

Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review.

Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). There have been many well-conducted randomized controlled trials and thousands of patients reported in case series that describe success rates of approximately 90% following one or more FMT. Although the exact mechanisms of FMT have yet to be fully elucidated, replacement or restoration of a 'normal' microbiota (or at least a microbiota resembling those who have never had CDI) appears to have a positive effect on the gut dysbiosis that is thought to exist in these patients. Furthermore, despite being aesthetically unappealing, this 'ultimate probiotic' is a particularly attractive solution to a difficult problem that avoids repeated courses of antibiotics. The lack of clarity about the exact mechanism of action and the 'active ingredient' of FMT (e.g., individual or communities of bacteria, bacteriophage, or bioactive molecules such as bile acids) has hindered the ability to produce a standardized and well-characterized FMT product. There is no standard method to produce material for FMT, and there are a multitude of factors that can vary between institutions that offer this therapy. Only a few studies have directly compared clinical efficacy in groups of patients who have been treated with FMT prepared differently (e.g., fresh vs. frozen) or administered by different route (e.g., by nasojejunal tube, colonoscopy or by oral administration of encapsulated product). More of these studies should be undertaken to clarify the superiority or otherwise of these variables. This review describes the methods and protocols that two English NHS hospitals independently adopted over the same time period to provide FMT for patients with recurrent CDI. There are several fundamental differences in the methods used, including selection and testing of donors, procedures for preparation and storage of material, and route of administration. These methods are described in detail in this review highlighting differing practice. Despite these significant methodological variations, clinical outcomes in terms of cure rate appear to be remarkably similar for both FMT providers. Although both hospitals have treated only modest numbers of patients, these findings suggest that many of the described differences may not be critical factors in influencing the success of the procedure. As FMT is increasingly being proposed for a number of conditions other than CDI, harmonization of methods and techniques may be more critical to the success of FMT, and thus it will be important to standardize these as far as practically possible.

Bacteria Facilitate Enteric Virus Co-infection of Mammalian Cells and Promote Genetic Recombination.

RNA viruses exist in genetically diverse populations due to high levels of mutations, many of which reduce viral fitness. Interestingly, intestinal bacteria can promote infection of several mammalian enteric RNA viruses, but the mechanisms and consequences are unclear. We screened a panel of 41 bacterial strains as a platform to determine how different bacteria impact infection of poliovirus, a model enteric virus. Most bacterial strains, including those extracted from cecal contents of mice, bound poliovirus, with each bacterium binding multiple virions. Certain bacterial strains increased viral co-infection of mammalian cells even at a low virus-to-host cell ratio. Bacteria-mediated viral co-infection correlated with bacterial adherence to cells. Importantly, bacterial strains that induced viral co-infection facilitated genetic recombination between two different viruses, thereby removing deleterious mutations and restoring viral fitness. Thus, bacteria-virus interactions may increase viral fitness through viral recombination at initial sites of infection, potentially limiting abortive infections.

Identification of key proteins and pathways in cadmium tolerance of Lactobacillus plantarum strains by proteomic analysis.

Our previous study confirmed the protective potential of Lactobacillus plantarum (L. plantarum) strains in alleviation of cadmium (Cd) toxicity in vivo and demonstrated that the observed protection largely depended on the tolerance of the strains to Cd-induced stress. It was also observed that there were significant intra-species differences in Cd tolerance of L. plantarum strains. In this study, we investigated the mechanism of Cd induced stress response of L. plantarum strains using the isobaric tags for relative and absolute quantitation (iTRAQ) based comparative proteomics. L. plantarum CCFM8610 (strongly resistant to Cd) and L. plantarum CCFM191 (sensitive to Cd) were selected as target strains, and their proteomic profiles in the presence and absence of Cd exposure were compared. We propose that the underlying mechanism of the exceptional Cd tolerance of CCFM8610 may be attributed to the following: (a) a specific energy-conservation survival mode; (b) mild induction of its cellular defense and repair system;

Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress.

Aluminum (Al) is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy) were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury.

Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction.

Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes.

Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier.

UNLABELLED: The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. IMPORTANCE: The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd contamination. Moreover, Cd exposure causes the disruption of the intestinal barrier and further induces the amplification of Cd absorption. The present study confirms that, along with initial intestinal Cd sequestration, oral administration of probiotics can inhibit Cd absorption by protecting the intestinal barrier. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure.

Dietary strategies for the treatment of cadmium and lead toxicity.

Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy.