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Influence of gut microbiota on xenobiotic toxicity in a Caenorhabditis elegans model with a focus on arsenic and PFAS
Örebro University, School of Science and Technology.ORCID iD: 0000-0003-1850-1412
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Exposure to environmental toxins presents a hazard to humans. Inorganic metalloid- arsenic (As), organic chemicals- per and poly-fluoroalkyl substances (PFAS) are frequently detected in the environment. Exposure to As and PFAS is associated with multiple adverse effects in humans and animals. However, little attention has been given to the interaction between host microbiota and pollutants. Gut microbiota interactions with the host and xenobiotics, is hy-pothesized to decrease xenobiotic toxicity. However, the role of microbiota on host responses during these exposure scenarios is poorly understood. Therefore, the aim was to study the influence of gut microbes on Caenorhabditis elegans responses using As and PFAS as environmental toxins. Specific objectives were to study the role of single microbes, and simple three microbe combinations with tractable diversity in nematode responses to As and PFAS. The study examined C. elegans physiological responses to As in the presence of single As resistant microbe Lysinibacillus sphaericus (Paper I) and simple 3-bacteria combinations (Paper IV). These studies showed that gut microbes decrease As toxicity and increase nematode survival through mediating host stress responses and fat metabolism. Combinations of microbes with toxins in microbiota also affect lifespan (Paper III). Furthermore, effects of PFAS mixtures were also analyzed on C. elegans and pathogen Staphylococcus aureus (Paper II); and role of gut microbe combinations during exposures to PFOS (Paper V). Exposure to PFAS/ PFOS increased virulence of pathogens and decreased host immunity, stress response and survival with opportunists; with non-pathogens C. elegans showed increased stress response and lived longer. These results emphasized that gut microbes contribute to alter xenobiotic toxicity in the host. Finally, this thesis presents novel insights into the role of gut microbes in modulating host physiological responses during As and PFAS exposures.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2023. , p. 86
Series
Örebro Studies in Life Science, ISSN 1653-3100 ; 19
Keywords [en]
C. elegans, physiological responses, gut microbe models, arse-nite, arsenate, PFAS, PFOS
National Category
Other Biological Topics
Identifiers
URN: urn:nbn:se:oru:diva-102436ISBN: 9789175294827 (print)OAI: oai:DiVA.org:oru-102436DiVA, id: diva2:1713946
Public defence
2023-01-19, Örebro universitet, Forumhuset, Hörsal F, Fakultetsgatan 1, Örebro, 13:15 (English)
Opponent
Supervisors
Available from: 2022-11-28 Created: 2022-11-28 Last updated: 2023-01-26Bibliographically approved
List of papers
1. Lysinibacillus sphaericus mediates stress responses and attenuates arsenic toxicity in Caenorhabditis elegans
Open this publication in new window or tab >>Lysinibacillus sphaericus mediates stress responses and attenuates arsenic toxicity in Caenorhabditis elegans
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2022 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 835, article id 155377Article in journal (Refereed) Published
Abstract [en]

Exposure to toxic metals alters host response and that leads to disease development. Studies have revealed the effects of metals on microbial physiology, however, the role of metal resistant bacteria on host response to metals is unclear. The hypothesis that xenobiotic interactions between gut microbes and arsenic influence the host physiology and toxicity was assessed in a Caenorhabditis elegans model. The arsenic-resistant Lysinibacillus sphaericus B1CDA was fed to C. elegans to determine the host responses to arsenic in comparison to Escherichia coli OP50 food. L. sphaericus diet extended C. elegans lifespan compared to E. coli diet, with an increased expression of genes involved in lifespan, stress response and immunity (hif-1, hsp-16.2, mtl-2, abf-2, clec-60), as well as reduced fat accumulation. Arsenic-exposed worms fed L. sphaericus also had a longer lifespan than those fed E. coli and had an increased expression of genes involved in cytoprotection, stress resistance (mtl-1, mtl-2) and oxidative stress response (cyp-35A2, isp-1, ctl-2, sod-1), together with a decreased accumulation of reactive oxygen species (ROS). In comparison with E. coli, L. sphaericus B1CDA diet increased C. elegans fitness while detoxifying arsenic induced ROS and extending lifespan.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Arsenate, Arsenite, C. elegans, Lifespan, Lysinibacillus sphaericus, Reactive oxygen species
National Category
Biochemistry and Molecular Biology Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-98800 (URN)10.1016/j.scitotenv.2022.155377 (DOI)000797863000008 ()35460794 (PubMedID)2-s2.0-85129450732 (Scopus ID)
Funder
Knowledge Foundation, 20180027 20170118Örebro University
Available from: 2022-05-04 Created: 2022-05-04 Last updated: 2022-12-19Bibliographically approved
2. Per- and polyfluoroalkyl substances enhance Staphylococcus aureus pathogenicity and impair host immune response
Open this publication in new window or tab >>Per- and polyfluoroalkyl substances enhance Staphylococcus aureus pathogenicity and impair host immune response
2022 (English)In: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 314, article id 120294Article in journal (Refereed) Published
Abstract [en]

Per- and Poly-fluoroalkyl substances (PFAS) are one of the major persistent environmental contaminants. Epidemiological studies have linked PFAS exposures to altered immunity and increased occurrence of infections in children. However, the mechanisms leading to immune susceptibility to bacterial infections remains unclear. To elucidate the mechanism, transcriptional alteration in the Caenorhabditis elegans model caused by a PFAS contaminated environmental water and two reconstituted PFAS solutions were evaluated using RNA-sequencing. PFAS affected the expression of several genes involved in C. elegans immune surveillance to Gram-positive bacteria (cpr-2, tag-38, spp-1, spp-5, clec-7, clec-172). The combined exposure to PFAS and Staphylococcus aureus significantly reduced C. elegans survival and increased intestinal membrane permeability. Furthermore, the growth of S. aureus in the presence of PFAS increased the expression of virulence genes, specifically, the virulence gene regulator saeR and α-hemolysin, hla, which resulted in increased hemolytic activity. The present study demonstrated that PFAS exposure not only increased C. elegans susceptibility to pathogens by reducing host immunity and increasing intestinal membrane permeability, but also increased bacteria virulence. This presents a broader implication for humans and other animals, where environmental contaminants simultaneously reduce host resilience, while, increasing microbial pathogenicity.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
C. elegans, Hemolysin, Immune suppression, PFAS, S. aureus
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-101604 (URN)10.1016/j.envpol.2022.120294 (DOI)000882962000004 ()36181932 (PubMedID)2-s2.0-85139329946 (Scopus ID)
Funder
Knowledge Foundation, 20180027 20140180Örebro University
Available from: 2022-10-03 Created: 2022-10-03 Last updated: 2022-12-19Bibliographically approved
3. Gut microbiota composition affects fitness and lifespan in Caenorhabditis elegans
Open this publication in new window or tab >>Gut microbiota composition affects fitness and lifespan in Caenorhabditis elegans
(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-102776 (URN)
Available from: 2022-12-19 Created: 2022-12-19 Last updated: 2023-01-26Bibliographically approved
4. Gut microbes decrease arsenic toxicity through modulation of cytoprotective and antioxidative stress responses in Caenorhabditis elegans
Open this publication in new window or tab >>Gut microbes decrease arsenic toxicity through modulation of cytoprotective and antioxidative stress responses in Caenorhabditis elegans
(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-102777 (URN)
Available from: 2022-12-19 Created: 2022-12-19 Last updated: 2023-01-26Bibliographically approved
5. Gut microbial composition influences distinct outcomes to perfluorooctanesulfonicacid exposure in Caenorhabiditis elegans
Open this publication in new window or tab >>Gut microbial composition influences distinct outcomes to perfluorooctanesulfonicacid exposure in Caenorhabiditis elegans
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-102778 (URN)
Available from: 2022-12-19 Created: 2022-12-19 Last updated: 2022-12-19Bibliographically approved

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Mangu, Jagadish

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