Are the Effects of Malnutrition on the Gut Microbiota–Brain Axis the Core Pathologies of Anorexia Nervosa?

Abstract

Anorexia nervosa (AN) is a disabling, costly, and potentially deadly illness. Treatment failure and relapse after treatment are common. Several studies have indicated the involvement of the gut microbiota–brain (GMB) axis. This narrative review hypothesizes that AN is driven by malnutrition-induced alterations in the GMB axis in susceptible individuals. According to this hypothesis, initial weight loss can voluntarily occur through dieting or be caused by somatic or psychiatric diseases. Malnutrition-induced alterations in gut microbiota may increase the sensitivity to anxiety-inducing gastrointestinal hormones released during meals, one of which is cholecystokinin (CCK). The experimental injection of a high dose of its CCK-4 fragment in healthy individuals induces panic attacks, probably via the stimulation of CCK receptors in the brain. Such meal-related anxiety attacks may take part in developing the clinical picture of AN. Malnutrition may also cause increased effects from appetite-reducing hormones that also seem to have roles in AN development and maintenance. The scientific background, including clinical, microbiological, and biochemical factors, of AN is discussed. A novel model for AN development and maintenance in accordance with this hypothesis is presented. Suggestions for future research are also provided.

The Impact of Undernutrition Risk on Rehabilitation Outcomes in Ischemic Stroke Survivors: A Hospital-Based Study

“…Furthermore, UR may impact the composition of the gut microbiota, which has been implicated in neurological health. Changes in gut microbiota have been linked to inflammation, oxidative stress, and immune dysfunction, which may contribute to the development of severe neurological deficits in ISS at UR [ 23 ]. Therefore, early identification and management of UR in this population may be a critical intervention in improving neurological outcomes and overall health.…”

Current Discoveries and Future Implications of Eating Disorders

“…AN shows significant heritability as family studies have shown a substantial prevalence of AN in the first-degree relatives of a proband, who are about 11 times more likely to develop AN than controls [13]. Many concepts have been suggested by different scientists to explain and understand how AN is developed and maintained [14].…”

Anorexia nervosa and microbiota: systematic review and critical appraisal

“…These authors claim that a dysbiosis involving an increase in these bacteria would cause the segregation of ClpB affecting the aetiology of AN either by (a) a direct effect on the peripheral satiety routes -increasing PYY [ 25 , 26 ], or centrally through MC4R [ 27 ]; or (b) an indirect effect from the formation of anti-ClpB IgG antibodies cross-reactive with α-MSH that would form immune complexes, activating chronically the central MC4R receptor and inducing increased satiety and anxiety, or both. Recently, Frostad [ 28 ] has emphasized the role of CCK-4 as a complementary mechanism integrated into this model; malnutrition would cause disruption of the blood–brain barrier, increasing the sensitivity of CCK2 receptors to the CCK-4 peptide generated by enteroendocrine I cells during meals. Thus, anticipatory anxiety would occur that would favour psychological maintenance mechanisms such as the pursuit of thinness and weight overvaluation.…”