Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease - PubMed (original) (raw)

Martha Zakrzewski 2, Timothy P Jenkins 3, Xiaopei Su 3, Rafid Al-Hallaf 1, John Croese 4, Stefan de Vries 3, Andrew Grant 3, Makedonka Mitreva 5 6, Alex Loukas 1, Lutz Krause 7, Cinzia Cantacessi 1 3

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Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease

Paul Giacomin et al. Sci Rep. 2016.

Abstract

A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.

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Figures

Figure 1

Figure 1. Differences between the mucosally-associated microbiota of Trial and Control subjects, and of Trial subjects over the course of the experiment.

Differences in abundance of mucosally-associated bacteria (at the phylum- I, class – II, order - III and family – IV level) between Trial subjects prior to hookworm infection (T0) and of active coeliac disease Control subjects, based on LDA Effect Size (LEfSe) analysis (A) and paired t-test (B), with differences pre FDR indicated by the respective p-values. (C) Differences in overall taxonomic species richness (left panel) and diversity (right panel) between the mucosally-associated microbiota of Trial subjects prior to hookworm infection (T0) and that of Control subjects with active coeliac disease. Significant differences are indicated with asterisks (*p < 0.05).

Figure 2

Figure 2. Differences between the mucosally-associated microbiota of Trial subjects over the course of the experiment.

Differences in abundance of mucosally-associated bacteria, at the class (A), order (B), family (C) and genus (D) level, between the mucosally-associated microbiota of Trial subjects prior to hookworm infection (T0) and post-gluten challenge (T24 and T36).

Figure 3

Figure 3. Trends towards increased bacterial richness and diversity are observed in Trial subjects post-hookworm infection and gluten challenge.

Differences in overall taxonomic species richness and diversity between the mucosally-associated microbiota of Trial subjects prior to hookworm infection (T0) and post-gluten challenge (T24 and T36).

Figure 4

Figure 4. Unsupervised NMDS analysis.

Unsupervised NMDS analysis of the composition of the mucosally-associated microbiota of Trial subjects prior to hookworm infection (T0) and following exposure to escalating doses of dietary gluten (T24 and T36, respectively), as well as of Control subjects with active coeliac disease, ordered by time point (left panel), and subject ID (right panel), respectively.

Figure 5

Figure 5. Supervised RDA and CCA analyses reveal clustering according to time points.

Supervised RDA (A) and CCA (B) depicting the composition of the mucosally-associated microbiota of Trial subjects prior to hookworm infection (T0) and following exposure to escalating doses of dietary gluten (T24 and T36, respectively), as well as of Control subjects with active coeliac disease, ordered by time point (left panels), and subject ID (right panels), respectively.

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