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Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects.

Giacomin P, Zakrzewski M, Croese J, Su X, Sotillo J, McCann L, Navarro S, Mitreva M, Krause L, Loukas A, Cantacessi C - Sci Rep (2015)

Bottom Line: The intestinal microbiota plays a critical role in the development of the immune system.Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown.We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.

ABSTRACT
The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease. We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten. Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge. Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis.

No MeSH data available.


Related in: MedlinePlus

Hookworm infection and gluten challenge is associated with increased microbial richness.Pairwise comparisons depicting the overall taxonomic richness of the fecal microbiota of Trial subjects (A) prior to hookworm infection (T0) and following the administration of escalating doses of gluten (T52), and (B) post-hookworm infection (T8) and post-gluten challenge (T52), respectively.
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f5: Hookworm infection and gluten challenge is associated with increased microbial richness.Pairwise comparisons depicting the overall taxonomic richness of the fecal microbiota of Trial subjects (A) prior to hookworm infection (T0) and following the administration of escalating doses of gluten (T52), and (B) post-hookworm infection (T8) and post-gluten challenge (T52), respectively.

Mentions: Consistent with the results of our previous study28, a Principal Coordinates Analysis (PCoA) of the fecal microbial communities detected in the Trial subjects showed strong clustering of the samples by individual rather than infection status and/or exposure to escalating doses of gluten in the two main dimensions (Fig. 4), thus indicating that the community composition of each subject remained stable over the course of the trial. Similarly, both Anosim and Redundancy Analysis (RDA) indicated a clear clustering of samples by individual (p = 0.001 Anosim; p < 0.001 RDA). In the Trial subjects, hookworm infection and/or exposure to escalating doses of gluten did not impact community structure (p > 0.1 Anosim, p > 0.16 RDA), which is indicative of an inter-individual variability and intra-individual stability of the gut microbiota despite hookworm infection and gluten challenge. In line with this observation, there was no significant difference in relative abundance of any individual OTU identified in the study (97% sequence identity) across time points (FDR > 0.54 with both t-test and Wilcoxon test). While no significant difference in Shannon diversity was observed on the global microbial communities over the whole course of the study (p = 0.91, ANOVA), we detected a significant increase in bacterial species richness at T52 (following hookworm infection and exposure to 3 g/day of gluten) when compared to T0 (prior to hookworm infection) (p = 0.033, paired t-test) and at T36 (following hookworm infection and exposure to 350 mg/day gluten) when compared to T8 (following hookworm infection but prior to gluten challenge) (Fig. 5) (p = 0.007). Together, these data suggest that hookworm infection supports maintenance of the composition of the intestinal flora in the presence of escalating gluten challenges, with concomitant significant increases in microbial species richness.


Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects.

Giacomin P, Zakrzewski M, Croese J, Su X, Sotillo J, McCann L, Navarro S, Mitreva M, Krause L, Loukas A, Cantacessi C - Sci Rep (2015)

Hookworm infection and gluten challenge is associated with increased microbial richness.Pairwise comparisons depicting the overall taxonomic richness of the fecal microbiota of Trial subjects (A) prior to hookworm infection (T0) and following the administration of escalating doses of gluten (T52), and (B) post-hookworm infection (T8) and post-gluten challenge (T52), respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585380&req=5

f5: Hookworm infection and gluten challenge is associated with increased microbial richness.Pairwise comparisons depicting the overall taxonomic richness of the fecal microbiota of Trial subjects (A) prior to hookworm infection (T0) and following the administration of escalating doses of gluten (T52), and (B) post-hookworm infection (T8) and post-gluten challenge (T52), respectively.
Mentions: Consistent with the results of our previous study28, a Principal Coordinates Analysis (PCoA) of the fecal microbial communities detected in the Trial subjects showed strong clustering of the samples by individual rather than infection status and/or exposure to escalating doses of gluten in the two main dimensions (Fig. 4), thus indicating that the community composition of each subject remained stable over the course of the trial. Similarly, both Anosim and Redundancy Analysis (RDA) indicated a clear clustering of samples by individual (p = 0.001 Anosim; p < 0.001 RDA). In the Trial subjects, hookworm infection and/or exposure to escalating doses of gluten did not impact community structure (p > 0.1 Anosim, p > 0.16 RDA), which is indicative of an inter-individual variability and intra-individual stability of the gut microbiota despite hookworm infection and gluten challenge. In line with this observation, there was no significant difference in relative abundance of any individual OTU identified in the study (97% sequence identity) across time points (FDR > 0.54 with both t-test and Wilcoxon test). While no significant difference in Shannon diversity was observed on the global microbial communities over the whole course of the study (p = 0.91, ANOVA), we detected a significant increase in bacterial species richness at T52 (following hookworm infection and exposure to 3 g/day of gluten) when compared to T0 (prior to hookworm infection) (p = 0.033, paired t-test) and at T36 (following hookworm infection and exposure to 350 mg/day gluten) when compared to T8 (following hookworm infection but prior to gluten challenge) (Fig. 5) (p = 0.007). Together, these data suggest that hookworm infection supports maintenance of the composition of the intestinal flora in the presence of escalating gluten challenges, with concomitant significant increases in microbial species richness.

Bottom Line: The intestinal microbiota plays a critical role in the development of the immune system.Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown.We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.

ABSTRACT
The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease. We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten. Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge. Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis.

No MeSH data available.


Related in: MedlinePlus