In 2017, alcohol use accounted for 2.84 million deaths, and it is estimated that nearly 1.5% of the population has alcohol use disorder (AUD) worldwide. Risk factors include binge drinking, adolescent alcohol use, family history of AUD, and psychiatric conditions including PTSD and ADHD. Treatment typically includes detoxification, counseling, and medical intervention. AUD is associated with significant changes in the gut microbiota which could alter the overall metabolic profile and impact the brain via the gut-brain axis.
A recent study published by Dr. Sophie Leclercq et al. in Translational Psychiatry investigated alterations in the levels of kynurenine pathway metabolites and investigated their correlation with gut microbiota and levels of microbe-derived fatty acids in AUD patients before and after hospitalization for alcohol detoxification. Patients had significantly lower levels of plasma 5-hydroxytryptophan, kynurenic acid (KYNA), anthranilic acid, 3-hydroxy-kynurenine, and xanthurenic acid compared to healthy matched controls. Additionally, there were significant elevations in plasma quinolinic acid (QUIN), picolinic acid, and kynurenine in patients, which were further elevated following the 3-week detox period. Furthermore, the KYNA to QUIN ratio was significantly lower in patients demonstrating an overall potential neurotoxic effect. However, it remains to be elucidated as to how much peripheral QUIN and KYNA effect the brain specifically. KYNA levels after detoxification were negatively correlated with alcohol cravings highlighting the potential therapeutic aspect for this NMDA receptor antagonist. In a previous study, Dr. Leclercq and colleagues demonstrated AUD patients had decreased abundance of several bacteria including Faecalibacterium (Leclercq et al, 2014). In the present study, they investigated the association of kynurenine metabolites with bacterial species. There were 22 identified bacterial taxa that associated with tryptophan and multiple kynurenine metabolites. Of these, QUIN was negatively associated with Faecalibacterium and positively associated with Akkermansia whereas KYNA was positively associated with Prevotella. Interestingly, Faecalibacterium prausnitzii has been demonstrated as one of the main bacterial species that is altered in gut dysbiosis (as discussed in detail by Lopez-Siles et al, 2017). This bacterium has anti-inflammatory properties and can metabolize tryptophan. Here, the authors demonstrated that F. prausnitzii was negatively correlated with KYN, QUIN, and importantly, there was a positive association with the neuroprotective ratio (KYNA/QUIN). Taken together this study demonstrates that F. prausnitzii might play a critical role in regulating the kynurenine pathway potentially via its anti-inflammatory properties.