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A Small Intestinal Helminth Infection Alters Colonic Mucus and Shapes the Colonic Mucus Microbiome.

Thomas C Mules1,2, Francesco Vacca1, Alissa Cait1

  • 1Malaghan Institute of Medical Research, Kelburn, Wellington 6012, New Zealand.

International Journal of Molecular Sciences
|November 27, 2024
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Summary

Small intestinal helminths, like human hookworm, may treat ulcerative colitis by enhancing the colonic mucus barrier. This study shows helminths increase protective mucus proteins and alter the gut microbiome, suggesting a conserved therapeutic mechanism.

Keywords:
helminthhookwormintestinal barriermicrobiomemucustrefoil factor

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Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Ulcerative colitis is a chronic inflammatory disease of the colon.
  • Small intestinal helminths are being explored as a novel therapy for ulcerative colitis.
  • Strengthening the colonic mucus barrier is a potential therapeutic mechanism.

Purpose of the Study:

  • To investigate the effects of helminth infection on the colonic mucus barrier in mice and humans.
  • To identify the molecular and microbial changes associated with helminth-induced mucus modification.
  • To determine the role of IL-13 in mediating these changes.

Main Methods:

  • Comparison of mice infected with *Heligmosomoides polygyrus* and uninfected controls.
  • Histological, gene expression, and immunofluorescent analyses of colonic tissue.
  • Assessment of the colonic mucus microbiome and analysis of human cohort data.

Main Results:

  • *H. polygyrus* infection induced goblet cell hyperplasia and increased mucin sialylation in mouse colons.
  • Helminth infection upregulated resistin-like molecule-beta (RELM-β) and trefoil factors (TFFs), predominantly in an IL-13-dependent manner.
  • *H. polygyrus* increased *Ruminococcus gnavus* abundance, and human helminth infection correlated with elevated TFF blood levels.

Conclusions:

  • Small intestinal helminths significantly modify the colonic mucus barrier.
  • These modifications involve increased mucus production, altered protein expression, and changes in the mucus microbiome.
  • The findings support a conserved mucus-based mechanism for helminth therapy in ulcerative colitis.