# Interactions between helminth colonization and the gut microbiota

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $655,339

## Abstract

Abstract It is well established that helminth infections impact human immune responses, but the
mechanisms are incompletely understood. We hypothesize that the impact of helminths could be indirectly
mediated by alterations to the gut microbiota during infection. Both helminths and the gut microbiota can exert
powerful systemic immunoregulatory effects. Changes to the prevalence of helminth infections and the
microbiota may be environmental factors contributing towards the “hygiene hypothesis” and the rising
incidence of autoimmune diseases in developed nations. Dysbiosis (dysregulation of microbial communities) is
a common feature of many human diseases, especially those with an inflammatory component.
 We have studied the effects of helminth colonization on the microbiota of indigenous Malaysians, called the
“Orang Asli”. Our preliminary results have identified an antagonistic relationship between microbial
communities dominated by either Bacteroidales or Clostridiales communities. The expansion of Clostridiales
over Bacteroidales communities can be driven by type 2 cytokines (IL-4 and IL-13), which promote increased
mucus production by goblet cells. Mucus can directly promote the growth of human Clostridial strains. Using
mouse models, we could demonstrate that a cocktail of Clostridial strains could directly inhibit a Bacteroides
dominated community, even in the absence of helminth infections. We hypothesize that the expansion of
Clostridiales communities by helminth colonization promotes anti-inflammatory responses within the host; and
that Clostridiales strains from the Orang Asli are more potent at immune-regulation than existing strains.
 The effects of diet and nutrient intake and the interactions between helminth colonization and bacterial
networks need to be established. To test these ideas, we will assess alterations to the gut microbiota of Orang
Asli populations undergoing public health deworming programs. Along with dietary surveys, the proposed field
studies will provide longitudinal analyses of helminth-colonized individuals to establish cause and effect
relationships of helminths on the gut microbiota. Finally, we will isolate bacterial strains from the Orang Asli
and determine whether they replicate the anti-inflammatory effects of helminths in mice.
 Understanding physiological processes involved in the intersection of infection, nutrition, microbiota and
inflammation, could promote biomarker discovery and identify novel interventional strategies towards improving
global health. Our study builds upon existing collaborations between Dr. Loke (NYU), Dr. Lim (University of
Malaya), Dr. Cadwell (NYU) and Dr. Bonneau (NYU), with expertise in parasitology, microbiota studies,
microbiology and immunology, epidemiology and field studies, computational biology and biostatistics.
Accomplishment of the above goals will have important implications to individuals living in both developing
countries as well as developed countries.

## Key facts

- **NIH application ID:** 9839478
- **Project number:** 5R01AI130945-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ken Hashigiwa Cadwell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $655,339
- **Award type:** 5
- **Project period:** 2018-01-02 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839478

## Citation

> US National Institutes of Health, RePORTER application 9839478, Interactions between helminth colonization and the gut microbiota (5R01AI130945-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9839478. Licensed CC0.

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