Original Research ARTICLE
The effect of gut microbiome composition on human immune responses: an exploration of interference by helminth infections
- 1Faculty of Information Technology and Science, Department of Mathematics, Parahyangan Catholic University, Indonesia
- 2Department of Biomedical Data Sciences, Leiden University Medical Center, Netherlands
- 3Faculty of Medicine, Department of Parasitology, University of Indonesia, Indonesia
- 4Faculty of Medicine, Department of Parasitology, Hasanuddin University, Indonesia
- 5Department of Parasitology, Leiden University Medical Center, Netherlands
- 6McDonnell Genome Institute, Washington University School of Medicine in St. Louis, United States
- 7Department of Medicine, Washington University School of Medicine in St. Louis, United States
- 8Department of Statistics, University of Leeds, United Kingdom
- 9Julius Center, Department of Biostatistics and Research Support, University Medical Center Utrecht, Netherlands
- 10Alan Turing Institute, United Kingdom
- 11Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Netherlands
Soil-transmitted helminths have been shown to have the immune regulatory capacity, which they use to enhance their long term survival within their host. As these parasites reside in the gastrointestinal tract, they might modulate the immune system through altering the gut bacterial composition. Although the relationships between helminth infections or the microbiome with the immune system have been studied separately, their combined interactions are largely unknown. In this study, we aim to analyze the relationship between bacterial communities with cytokine response in the presence or absence of helminth infections.
For 66 subjects from a randomized placebo-controlled trial, stool and blood samples were available at both baseline and 21 months after starting three-monthly albendazole treatment. The stool samples were used to identify the helminth infection status and fecal microbiota composition, while whole blood samples were cultured to obtain cytokine responses to innate and adaptive stimuli.
When subjects were free of helminth infection (helminth-negative), increasing proportions of Bacteroidetes was associated with lower levels of IL-10 response to LPS (estimate (95% confidence interval (CI)) -1.96 (-3.05, -0.87) ). This association was significantly diminished when subjects were helminth-infected (helminth positive) (p-value for the difference between helminth-negative versus helminth-positive was 0.002). Higher diversity was associated with greater IFN-γ responses to PHA in helminth-negative (0.95 (0.15, 1.75); versus helminth-positive -0.07 (-0.88, 0.73), p-value = 0.056) subjects. Albendazole treatment showed no direct effect in the association between bacterial proportion and cytokine responses, although the Bacteroidetes’ effect on IL-10 responses to LPS was lower in the albendazole-treated group (-1.74 (-4.08, 0.59) versus placebo (-0.11 (-0.84, 0.62); p-value = 0.193).
We observed differences in the relationship between gut microbiome composition and immune responses when comparing individuals infected or uninfected with geohelminths. Although these findings are part of a preliminary exploration, the data support the hypothesis that intestinal helminths may modulate immune responses, in unison with the gut microbiota.
Trial registration: ISRCTN, ISRCTN83830814. Registered 27 February 2008 - Retrospectively registered, http://www.isrctn.com/ISRCTN83830814
Keywords: helminth, gut microbiome, whole blood cytokine, Interleukin-10, Bacteroidetes, diversity, randomized controlled trial
Received: 12 Jun 2019;
Accepted: 25 Sep 2019.
Copyright: © 2019 Martin, Kaisar, Wiria, Hamid, Djuardi, Sartono, Rosa, Mitreva, Supali, Houwing-Duistermaat, Yazdanbakhsh and Wammes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mx. Ivonne Martin, Parahyangan Catholic University, Faculty of Information Technology and Science, Department of Mathematics, Bandung, 40141, West Java, Indonesia, I.Martin@lumc.nl