A Role for the Microbiota-Gut-Brain Axis in Avoidant/Restrictive Food Intake Disorder: A New Conceptual Model

Abstract

Objective: Avoidant/restrictive food intake disorder (ARFID) is an eating disorder characterized by a severely restrictive diet leading to significant physical and/or psychosocial sequelae. Largely owing to the phenotypic heterogeneity, the underlying pathophysiological mechanisms are relatively unknown. Recently, the communication between microorganisms within the gastrointestinal tract and the brain-the so-called microbiota-gut-brain axis-has been implicated in the pathophysiology of eating disorders. This Spotlight review sought to investigate and conceptualize the possible ways that the microbiota-gut-brain axis is involved in ARFID to drive future research in this area.

Method: By relating core symptoms of ARFID to gut microbiota and its signaling pathways to the brain, we evaluated how the gut microbiota is potentially involved in the pathophysiology of ARFID.

Results: We hypothesized that the restricted type and amount of food intake characteristic of ARFID diminishes gut microbial diversity, including beneficial bacteria and their metabolites capable of signaling to the brain, to modulate biopsychological pathways relevant to ARFID: homeostatic signaling, food reward, interoception, sensory sensitivity, disgust, perseveration, fear-based learning, and mood. Candidate signaling mechanisms include microbial-induced effects on inflammation, cortisol, and neurotransmitters such as dopamine and serotonin.

Discussion: Through reviewing the extant evidence, we conceptualized a new theoretical framework of ARFID with an emphasis on microbiota-gut-brain axis signaling to inform future research. Although more research is necessary to evaluate this theoretical model, the tentative evidence suggests that therapeutics specifically targeting the gut microbiota for the treatment of ARFID symptomatology warrants more investigation.

Keywords: avoidant/restrictive food intake disorder; mechanisms; microbiota‐gut‐brain axis; model.

FIGURE 1

The pathophysiological microbiota‐gut‐brain‐axis model of avoidant/restrictive food intake disorder (ARFID). Evidence suggests that the microbiota‐gut‐brain‐axis plays a pathophysiological role in the onset and maintenance of symptoms of ARFID. A restricted diet in amount and variety of foods, including fiber and protein‐rich foods, promotes a specialized microbiota, thus depleting microbial diversity and their metabolites, including short‐chain fatty acids (SCFAs) and vitamins. High amounts of refined/processed sugar increase peripheral inflammation. Bidirectional biopsychological pathways through which these nutrition‐induced effects on the gut microbiota contribute to ARFID phenotypes include: homeostatic intake, food reward, interoception, sensory sensitivity, disgust, perseveration, fear‐based learning, and mood. Candidate biological mechanisms include vagal, inflammatory, and endocrinological signaling via microbial metabolites. GLP‐1: glucagon‐like peptide 1. HPA: hypothalamic–pituitary–adrenal. PYY: peptide YY.