Anthranilic acid (AA), a downstream metabolite of the kynurenine pathway, has garnered significant research attention in recent years. It has been recognized as a derivative with immune-regulatory properties and therapeutic implications for autoimmune diseases and cancers, as seen with drugs like Tranilast. Subsequently, AA was identified as a risk factor for dementia, with higher plasma AA levels associated with an increased risk of dementia in the Framingham study. Notably, sex differences in AA levels have been observed; one study reported a correlation between AA and neocortical amyloid-β loading in females but not in males. More recently, AA has been implicated in the severity of viral infections, such as COVID-19 and dengue fever. In psychiatry, elevated baseline AA levels have been shown to predict the response to ketamine treatment in cases of treatment-resistant depression (see talk by Dr. Murata in our online webinar 6 – member access only). In this month’s highlight, we unveil a novel role for AA in regulating feeding behaviour and food addiction, offering potential therapeutic implications for obesity.
Castells-Nobau et al. demonstrated that Gokushovirus WZ-2015a, a bacteriophage belonging to the Microviridae family, is associated with food addiction as measured by the Yale Food Addiction Scale (YFAS) scores in a clinical cohort (IRONMET-CGM). Interestingly, this association was observed in females but not in males. These findings were corroborated in an animal study, where food addiction was induced by inoculating bacteriophages via faecal microbiota or viral transplantation.
Using an untargeted metabolomic approach in the clinical cohort, the researchers identified two key amino acid metabolic pathways – the tryptophan-kynurenine and phenylalanine-tyrosine pathways – suggesting that neurotransmitters play a role in food addiction caused by Gokushovirus. Furthermore, they showed that Gokushovirus in the gut can alter host tyrosine and tryptophan metabolism in the brains of mice. To gain deeper insights, a targeted analysis of tryptophan metabolism highlighted two key metabolites: indole-3-propionic acid (IPA) and anthranilic acid (AA), which were positively and negatively correlated with Gokushovirus, respectively. This finding suggests that lower AA levels are associated with food addiction. Indeed, AA supplementation was shown to reduce food addiction in both mice and Drosophila by regulating feeding behaviour through interactions with dopaminergic neurotransmission.
Collectively, this study provides clinical and preclinical evidence that AA acts as an endogenous factor capable of modulating feeding behaviour and potentially protecting against food addiction. These findings have significant implications for developing strategies to combat the obesity pandemic. The physiological role of AA in feeding behaviour and addiction is likely to generate substantial interest in the field, while its links to ageing (including dementia) and psychiatric disorders merit further investigation.