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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

Composition of the fecal microbial communities at phylotype level.Microbial composition of fecal samples from Trial subjects (ID*) prior to and following infection by Necator americanus (T0 and T8, respectively), as well as following administration of escalating doses of gluten (50 mg/day – T24; 350 mg/day – T36; 3 g/day – T52) as predicted in the analysis of the V1-V3 16S rRNA gene. Bubble sizes reveal the relative abundance (%) of phylotypes (based on 97% sequence identity) in each sample. The composition of the microbial communities detected in fecal samples from Control subjects with active celiac disease (C*) is also shown. OTUs listed were present in at least one sample at a relative abundance of ≥7%.
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f3: Composition of the fecal microbial communities at phylotype level.Microbial composition of fecal samples from Trial subjects (ID*) prior to and following infection by Necator americanus (T0 and T8, respectively), as well as following administration of escalating doses of gluten (50 mg/day – T24; 350 mg/day – T36; 3 g/day – T52) as predicted in the analysis of the V1-V3 16S rRNA gene. Bubble sizes reveal the relative abundance (%) of phylotypes (based on 97% sequence identity) in each sample. The composition of the microbial communities detected in fecal samples from Control subjects with active celiac disease (C*) is also shown. OTUs listed were present in at least one sample at a relative abundance of ≥7%.

Mentions: We next aimed to assess whether the nature of the commensal makeup was altered in the Trial subjects following experimental hookworm infection and subsequent escalating gluten challenges. All eight subjects were successfully infected with N. americanus, as evidenced by positive detection of hookworm eggs in the feces from weeks 8 to 52 post-infection22. Fecal samples were collected from each of these subjects 8 weeks after hookworm infection (T8), as well as at defined intervals following sequential challenges with 50 mg gluten/day for 12 weeks (T24), 350 mg gluten/day for 12 weeks (T36) and 3 g gluten/day for 2 weeks (T52). All samples were subjected to 454-based metagenomic sequencing; however, two Trial subjects did not provide fecal samples at either T52 (subject ID2) or T36 and T52 (ID12), hence sequence data was not available for these individuals at these time points. In addition, as the raw sequence data for Trial subject ID10 at T36 consisted of a total of 18 sequences only, this sample was excluded from subsequent analyses. A total of 346,669 useable reads were assigned to 7,262 Operational Taxonomic Units (OTUs) and 6 bacterial phyla, respectively (data available from the corresponding author upon request). Consistent with previous investigations, including our own28, the phyla Bacteroidetes and Firmicutes dominated the intestinal microbiota of all subjects included in the study at all time points investigated (Figs 2 and 3), with substantial inter-individual differences observed at all time points with regard to some of the less abundant phyla such as Proteobacteria, Tenericutes and Verrucomicrobia (Fig. 2). Further analysis of specific OTUs within the major phyla of Bacteroidetes and Firmicutes again revealed substantial inter-individual variation at all time points examined (Fig. 3).


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)

Composition of the fecal microbial communities at phylotype level.Microbial composition of fecal samples from Trial subjects (ID*) prior to and following infection by Necator americanus (T0 and T8, respectively), as well as following administration of escalating doses of gluten (50 mg/day – T24; 350 mg/day – T36; 3 g/day – T52) as predicted in the analysis of the V1-V3 16S rRNA gene. Bubble sizes reveal the relative abundance (%) of phylotypes (based on 97% sequence identity) in each sample. The composition of the microbial communities detected in fecal samples from Control subjects with active celiac disease (C*) is also shown. OTUs listed were present in at least one sample at a relative abundance of ≥7%.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Composition of the fecal microbial communities at phylotype level.Microbial composition of fecal samples from Trial subjects (ID*) prior to and following infection by Necator americanus (T0 and T8, respectively), as well as following administration of escalating doses of gluten (50 mg/day – T24; 350 mg/day – T36; 3 g/day – T52) as predicted in the analysis of the V1-V3 16S rRNA gene. Bubble sizes reveal the relative abundance (%) of phylotypes (based on 97% sequence identity) in each sample. The composition of the microbial communities detected in fecal samples from Control subjects with active celiac disease (C*) is also shown. OTUs listed were present in at least one sample at a relative abundance of ≥7%.
Mentions: We next aimed to assess whether the nature of the commensal makeup was altered in the Trial subjects following experimental hookworm infection and subsequent escalating gluten challenges. All eight subjects were successfully infected with N. americanus, as evidenced by positive detection of hookworm eggs in the feces from weeks 8 to 52 post-infection22. Fecal samples were collected from each of these subjects 8 weeks after hookworm infection (T8), as well as at defined intervals following sequential challenges with 50 mg gluten/day for 12 weeks (T24), 350 mg gluten/day for 12 weeks (T36) and 3 g gluten/day for 2 weeks (T52). All samples were subjected to 454-based metagenomic sequencing; however, two Trial subjects did not provide fecal samples at either T52 (subject ID2) or T36 and T52 (ID12), hence sequence data was not available for these individuals at these time points. In addition, as the raw sequence data for Trial subject ID10 at T36 consisted of a total of 18 sequences only, this sample was excluded from subsequent analyses. A total of 346,669 useable reads were assigned to 7,262 Operational Taxonomic Units (OTUs) and 6 bacterial phyla, respectively (data available from the corresponding author upon request). Consistent with previous investigations, including our own28, the phyla Bacteroidetes and Firmicutes dominated the intestinal microbiota of all subjects included in the study at all time points investigated (Figs 2 and 3), with substantial inter-individual differences observed at all time points with regard to some of the less abundant phyla such as Proteobacteria, Tenericutes and Verrucomicrobia (Fig. 2). Further analysis of specific OTUs within the major phyla of Bacteroidetes and Firmicutes again revealed substantial inter-individual variation at all time points examined (Fig. 3).

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