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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

The fecal microbiota of Trial subjects differs from that of active CeD control subjects.Differences in the composition of the fecal microbiota of Trial subjects prior to hookworm infection (T0) and of active celiac disease Control subjects were determined at (A) phylum, (B) class and (C) genus level. *p < 0.05, **p < 0.01.
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f1: The fecal microbiota of Trial subjects differs from that of active CeD control subjects.Differences in the composition of the fecal microbiota of Trial subjects prior to hookworm infection (T0) and of active celiac disease Control subjects were determined at (A) phylum, (B) class and (C) genus level. *p < 0.05, **p < 0.01.

Mentions: Each of the eight Trial subjects had been on a strict GFD for at least 5 years prior to trial commencement, and recorded sub-clinical Marsh scores prior to entering the trial22. We first assessed the baseline pre-trial (T0) composition of the fecal microbiota of the Trial subjects and compared it with that of a cohort of individuals from the same metropolitan area with active Marsh 3 + grade CeD (Table S1). Trial subjects displayed a greater abundance of the phylum Bacteroidetes than Control subjects (t-test: p = 0.04; FDR = 0.12), while Firmicutes were more abundant in the Control subjects (p = 0.07; FDR = 0.12, Figs 1A and 2). In addition, Tenericutes RF39 were detected in the fecal microbiota of all Control subjects, but only in one Trial subject (ID12; Fig. 2). At the class level, Bacteroidia were more prevalent in the Trial subjects (p = 0.04; FDR = 0.17), whereas Erysipelotrichi were more abundant in the Control subjects (p = 0.02; FDR = 0.17), as were Clostridia, although the differences did not reach significance (p = 0.13; FDR = 0.2, Fig. 1B). Similarly, at genus level, Ruminococcus dominated the fecal microbiota of the Control subjects (p = 0.001; FDR = 0.02, Fig. 1C), while Lachnospira was more abundant in the Trial subjects (p = 0.027; FDR = 0.16) (Fig. 1C). Comparison of Kyoto Encyclopedia of Genes and Genomes (KEGG) functional profiles (predicted by PICRUSt) of Trial subjects pre-trial with those of the Control subjects displayed differential regulation of 8 biological pathways, with up-regulation of pathways linked to sugar uptake (i.e. “Multiple sugar transport system permease protein”, KO codes K02026 and K02025; p < 0.03; FDR = 0.2) in the Control subjects (Figure S1), associated with bacteria within the genus Ruminococcus (data not shown). Together, these data demonstrated that the microbiota of the healthy Trial subjects pre-hookworm and pre-gluten challenge was distinct from individuals with active CeD.


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)

The fecal microbiota of Trial subjects differs from that of active CeD control subjects.Differences in the composition of the fecal microbiota of Trial subjects prior to hookworm infection (T0) and of active celiac disease Control subjects were determined at (A) phylum, (B) class and (C) genus level. *p < 0.05, **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: The fecal microbiota of Trial subjects differs from that of active CeD control subjects.Differences in the composition of the fecal microbiota of Trial subjects prior to hookworm infection (T0) and of active celiac disease Control subjects were determined at (A) phylum, (B) class and (C) genus level. *p < 0.05, **p < 0.01.
Mentions: Each of the eight Trial subjects had been on a strict GFD for at least 5 years prior to trial commencement, and recorded sub-clinical Marsh scores prior to entering the trial22. We first assessed the baseline pre-trial (T0) composition of the fecal microbiota of the Trial subjects and compared it with that of a cohort of individuals from the same metropolitan area with active Marsh 3 + grade CeD (Table S1). Trial subjects displayed a greater abundance of the phylum Bacteroidetes than Control subjects (t-test: p = 0.04; FDR = 0.12), while Firmicutes were more abundant in the Control subjects (p = 0.07; FDR = 0.12, Figs 1A and 2). In addition, Tenericutes RF39 were detected in the fecal microbiota of all Control subjects, but only in one Trial subject (ID12; Fig. 2). At the class level, Bacteroidia were more prevalent in the Trial subjects (p = 0.04; FDR = 0.17), whereas Erysipelotrichi were more abundant in the Control subjects (p = 0.02; FDR = 0.17), as were Clostridia, although the differences did not reach significance (p = 0.13; FDR = 0.2, Fig. 1B). Similarly, at genus level, Ruminococcus dominated the fecal microbiota of the Control subjects (p = 0.001; FDR = 0.02, Fig. 1C), while Lachnospira was more abundant in the Trial subjects (p = 0.027; FDR = 0.16) (Fig. 1C). Comparison of Kyoto Encyclopedia of Genes and Genomes (KEGG) functional profiles (predicted by PICRUSt) of Trial subjects pre-trial with those of the Control subjects displayed differential regulation of 8 biological pathways, with up-regulation of pathways linked to sugar uptake (i.e. “Multiple sugar transport system permease protein”, KO codes K02026 and K02025; p < 0.03; FDR = 0.2) in the Control subjects (Figure S1), associated with bacteria within the genus Ruminococcus (data not shown). Together, these data demonstrated that the microbiota of the healthy Trial subjects pre-hookworm and pre-gluten challenge was distinct from individuals with active CeD.

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