- Title
- Gut microbes: heavy metal(loid) interactions
- Creator
- Bolan, Shiv Shankar
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2019
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Abstract: Specific microorganisms in the human gut (i.e., gut microbes) provide positive benefits to the host such as fermenting unused energy substrates, training the immune system, preventing growth of pathogenic microbes, and producing vitamins for the host. The intake of contaminants including heavy metal(loid)s can occur through food, air, water and some medicines. The gut microbes not only can be affected by environmental contaminants but they themselves can alter the speciation and bioavailability of these contaminants. Chelation therapy is an important clinical treatment for managing metal(loid) toxicity in human. Chelating agents are organic or inorganic compounds capable of binding metal(loid) ions to form complex ring-like structure called ‘chelates’. Chelating agents can affect metal(loid) toxicity by mobilizing the toxic metal(loid)s and their subsequent excretion mainly through urine. This thesis provides a greater understanding of the interactions of selected gut microbes and heavy metal(loid)s in relation to metal(loid) toxicity to gut microbes, and gastrointestinal bioaccessibility and bioavailability of heavy metal(loid)s as impacted by gut microbes and chelating agents. The overall objective of the thesis is to examine the interactions between gut microbes and heavy metal(loid)s in relation to metal(loid) toxicity to gut microbes, and bioaccessibility and bioavailability of metal(loid)s. The specific objectives of the study include: (i) to demonstrate the effect of arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) on the growth of selected gut microbes; (ii) to examine the effect of selected gut microbes on the bioaccessibility of these heavy metal(loid)s; (iii) to examine the effect of selected chelating therapeutic agents on the bioaccessibility of heavy metal(loid)s; and (iv) to examine the effect of gut microbes and chelating therapeutic agents on the bioavailability of heavy metal(loid)s. Chapter 1 (Introduction) gives an overall outline of gut microbiome, environmental contaminants, the effect of heavy metal(loid)s on gut microbes, and bioaccessibility and bioavailability of heavy metal(loid)s as impacted by gut microbes. Chapter 2 (Literature review) covers the role of gut microbes in human health and the effects of environmental contaminants on gut microbes. Chapter 3 (Heavy metal(loid) toxicity to gut microbe) demonstrates the relationship between increasing concentration of selected heavy metal(loid)s and growth of gut microbes. The toxicity of four heavy metal(loid)s including As, Cd, Hg and Pb to three gut bacteria (Lactobacillus rhamnosus, Lactobacillus acidophilus and Escherichia coli) was examined. While the toxicity of all the cationic metal(loid)s (Cd, Pb and Hg) to gut bacteria decreased with pH, the anionic As species exhibited an opposite effect. The order of toxicity was Hg>Cd>Pb>As(III)>As(V) for E. coli; and Hg>Cd>As(III)>Pb>As(V) for the two Lactobacillus sp. Arsenite (AsIII) is more toxic than arsenate (AsV) to gut bacteria. The toxicity of these metal(loid)s to the bacteria depends on their speciation and bioavailability. Chapter 4 (Bioaccessibility of heavy metal(loid)s) investigated the gastrointestinal bioaccessibility of heavy metal(loid)s in selected orally ingested sources. The bioaccessibility of As (rice grain), Cd (offal pet food), Hg (fish feed) and Pb (complementary medicines) was examined by measuring gastrointestinal bioaccessibility test. The gastric bioaccessibility of As, Cd, Pb and Hg was less than that of intestinal bioaccessibility of these metals. Majority of the metal(loid)s extracted in gastric and intestinal extracts was present as metal(loid) complexes. The distribution of metal(loid)s in the gastric and intestinal extracts will have implications on their bioavailability. Chapter 5 (Bioaccessibility of heavy metal(loid)s as impacted by gut microbes) describes the influence of gut microbes on the bioaccessibility of heavy metal(loid)s. The bioaccessibility of As, Cd, Pb and Hg as impacted by three gut bacteria (L. rhamnosus, L. acidophilus and E. coli) was examined by measuring gastrointestinal bioaccessibility. This study demonstrated that gut microbes decreased bioaccessibility of metal(loid)s, which is likely to impact their bioavailability. The effect of gut microbes on bioaccessibility may be attributed to bioimmobilization of metal(loid)s through adsorption, precipitation, and complexation reactions. Chapter 6 (Gut microbes on bioaccessibility of heavy metal(loid)s as impacted by chelating agents) describes the impact of gut bacteria on chelate-induced bioaccessibility of heavy metal(loid)s. Firstly, the effect of three chelating agents (EDTA, DMSA and DMPS) on the solubility and bioaccessibility of As, Cd, Hg and Pb sources was examined. The results indicated that all the three chelating agents increased both gastric and intestinal bioaccessibility of As, Cd, Hg and Pb. The increase in chelate-induced bioaccessibility of heavy metal(loid)s is attributed to the complexation of metal(loid)s by the chelating agents. Secondly, the effect of two gut microbes (E. coli and L. acidophilus) on the bioaccessibility of As, Cd, Hg and Pb sources as impacted by two chelating agents (EDTA and DMPS) was examined. The results indicated that, in the presence of both gut microbes and chelating agents, there was a net increase in the bioaccessibility of heavy metal(loid)s indicating that chelate-mediated complexed metal(loid) species are not readily adsorbed by gut bacteria. Chapter 7 (Bioavailability of heavy metal(loid)s as measured by permeability test) compares the bioavailability of heavy metal(loid)s as measured by intestinal permeability. The intestinal permeability of As, Cd, Hg and Pb in the gastric and intestinal extracts as impacted by gut microbes (E. coli and L. rhamnosus) and chelating agents (EDTA and DMPS) was measured using Caco-2 test. The results demonstrated that the Papp (apparent permeability coefficient value), which measures the velocity with which a solute crosses the cell monolayer, was lower in the presence of chelating agents indicating low intestinal absorption. Similarly, the Papp value was markedly reduced in the presence of gut bacteria for all the metal(loid)s indicating low intestinal absorption in the presence of gut bacteria. The results may be attributed to a direct protection of the intestinal barrier against the metal(loid)s or indirect intestinal metal(loid) sequestration by the gut bacteria. Chapter 8 (Summary and conclusions) provides overall research conclusions and a summary of the major research findings. This chapter proposes possible future directions in research. This study demonstrated the toxicity of heavy metal(loid)s on the gut bacteria and also the effect of gut bacteria on the bioaccessibility and bioavailability of these heavy metal(loid)s. It is important to point out that the human gut hosts a large number of microbial species including bacteria, fungi, and archaea. In this study, the effect of only selected bacterial species on bioaccessibility and bioavailability of heavy metal(loid)s was examined. Future studies should focus on the effect of composite gut microbial consortia on bioaccessibility and subsequent bioavailability of toxic metal(loid)s.
- Subject
- gut microbes; gut microbiome; Caco-2; chelating agents; heavy metals; heavy metal(loid)s; bioaccessibility; bioavailability; lead; mercury; cadmium; arsenic
- Identifier
- http://hdl.handle.net/1959.13/1409420
- Identifier
- uon:36013
- Rights
- Copyright 2019 Shiv Shankar Bolan
- Language
- eng
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