Letter: Dietary emulsifiers and intestinal health—The beginning of an evolving story: Authors’ reply

Abstract

We thank Dr Li for comments¹ on our study that described the first evaluation of diets high and low in emulsifiers added to the food supply on intestinal barrier function in healthy adults.² Dr Li introduced two aspects—the conduct of the study and its generalisability. The criticisms of conduct, specifically how dietary adherence was assessed, where nearly all food was supplied and food diaries kept, is unfounded. We agree that single blinding was a limitation, but not likely to be associated with much bias since end points were objective.

Dr Li's suggestion of examining the role of dietary emulsifiers among a larger and more diverse cohort for generalisability, which is important for making broad clinical practice recommendations, is premature and likely to dilute important data that can be gathered only from the highly controlled interventions provided to a targeted cohort. Our study was exploratory, attempting to provide proof-of-concept. Understanding a novel research question that had not been previously posed requires a stepwise programme. The pilot observations can indeed completely change the nature of that programme.

Preclinical findings led to the concept that emulsifiers added to our food supply are detrimental to intestinal health,³ but their effect has not been established in humans. We have developed a stepwise programme that aims to understand the true effect of emulsifiers in Crohn's disease. Step 1 was an analysis of the published literature.⁴ We discovered several key facts that were not well understood by researchers. For example, the term, ‘emulsifiers’, has been incorrectly applied to thickeners without surface-acting properties (such as carboxymethyl cellulose) and to polysaccharides that do neither (such as maltodextrin). In Step 2, we created a database of emulsifiers in the food supply in Australia and found that those studied in preclinical trials were not ubiquitous in the food supply as advertised and had been evaluated in huge doses with little relevance to exposure in the diet.⁵ From the database, we developed experimental diets that met heathy eating guidelines, but differed only in emulsifier content for use in clinical trials.⁵ These diets were palatable and tolerable.⁵ In Step 3, we studied effects in healthy humans.² The high, but not low, emulsifier diet was associated with improved barrier function when tested in a resting, unstressed, fasting state,² but enhanced the impairment of barrier function induced by corticotropin-releasing factor (CRH), a model of acute stress.⁶ In contrast, low emulsifier intake provided durable protection from this effect.² Such observations open issues of the association with emulsifier intake and innate immune cells, since CRH acts via mast cells.⁶ Step 4 is to test these diets in patients with active Crohn's disease (ACTRN12619000980134).

Hence, our pilot work, as correctly indicated by Dr Li,¹ has provided few answers, except to help direct avenues of future research, but has placed a big question mark over the scientific basis of demonising emulsifiers. It is still too early in this research pathway to embark on studies in multiple disease states and over the longer term, or to make dietary recommendations.

Jessica A. Fitzpatrick: Conceptualization; writing – review and editing. Peter R. Gibson: Conceptualization; writing – review and editing. Emma P. Halmos: Conceptualization; writing – review and editing.

None.

JAF: nil. PRG: served as a consultant or advisory board member for Anatara, Atmo Biosciences, Topas and Comvita; received research grants for investigator-driven studies from Atmo Biosciences and Mindset Health; received speaker honoraria from Dr Falk Pharma and Mindset Health Pty Ltd.; and was a shareholder in Atmo Biosciences. EPH: received research grants from Mindset Health Pty Ltd and the Gastroenterological Society of Australia IBD Clinical Project award. She has received honoraria or consulted for Ferring, Janssen, Abbvie, Takeda, Shire, Sandoz and Dr Falk Pharma.

This article is linked to Fitzpatrick et al papers. To view these articles, visit https://doi.org/10.1111/apt.18172 and https://doi.org/10.1111/apt.18226