Attenuation of immune activation in patients with multiple sclerosis on a wheat-reduced diet: a pilot crossover trial

Sinah Engel; Luisa Klotz; Timo Wirth; Ann-Katrin Fleck; Geethanjali Pickert; Melanie Eschborn; Samia Kreuzburg; Valentina Curella; Stefan Bittner; Frauke Zipp; Detlef Schuppan; Felix Luessi

doi:10.1177/17562864231170928

Attenuation of immune activation in patients with multiple sclerosis on a wheat-reduced diet: a pilot crossover trial

Ther Adv Neurol Disord. 2023 Jun 25:16:17562864231170928. doi: 10.1177/17562864231170928. eCollection 2023.

Authors

Affiliations

¹ Department of Neurology and Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
² Department of Neurology with Institute of Translational Neurology, University Hospital Münster, University of Münster, Münster, Germany.
³ Institute of Translational Immunology and Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
⁴ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁵ Department of Neurology and Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn²), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Abstract

Background: Western lifestyle has been associated with an increase in relapsing-remitting multiple sclerosis (RRMS). In mice, dietary wheat amylase-trypsin inhibitors (ATIs) activate intestinal myeloid cells and augment T cell-mediated systemic inflammation.

Objective: The aim of this study was to assess whether a wheat- and thus ATI-reduced diet might exert beneficial effects in RRMS patients with modest disease activity.

Methods: In this 6-month, crossover, open-label, bicentric proof-of-concept trial, 16 RRMS patients with stable disease course were randomized to either 3 months of a standard wheat-containing diet with consecutive switch to a > 90% wheat-reduced diet, or vice versa.

Results: The primary endpoint was negative, as the frequency of circulating pro-inflammatory T cells did not decrease during the ATI-reduced diet. We did, however, observe decreased frequencies of CD14⁺ CD16⁺⁺ monocytes and a concomitant increase in CD14⁺⁺ CD16^- monocytes during the wheat-reduced diet interval. This was accompanied by an improvement in pain-related quality of life in health-related quality of life assessed (SF-36).

Conclusion: Our results suggest that the wheat- and thus ATI-reduced diet was associated with changes in monocyte subsets and improved pain-related quality of life in RRMS patients. Thus, a wheat (ATI)-reduced diet might be a complementary approach accompanying immunotherapy for some patients.

Registration: German Clinical Trial Register (No. DRKS00027967).

Keywords: adaptive immune system; amylase–trypsin inhibitors; autoimmunity; gluten; inflammation; innate immune system; non-celiac wheat sensitivity; quality of life.