Microbial-Derived Tryptophan Metabolites and Their Role in Neurological Disease: Anthranilic Acid and Anthranilic Acid Derivatives

Abstract

The gut microbiome provides the host access to otherwise indigestible nutrients, which are often further metabolized by the microbiome into bioactive components. The gut microbiome can also shift the balance of host-produced compounds, which may alter host health. One precursor to bioactive metabolites is the essential aromatic amino acid tryptophan. Tryptophan is mostly shunted into the kynurenine pathway but is also the primary metabolite for serotonin production and the bacterial indole pathway. Balance between tryptophan-derived bioactive metabolites is crucial for neurological homeostasis and metabolic imbalance can trigger or exacerbate neurological diseases. Alzheimer’s, depression, and schizophrenia have been linked to diverging levels of tryptophan-derived anthranilic, kynurenic, and quinolinic acid. Anthranilic acid from collective microbiome metabolism plays a complex but important role in systemic host health. Although anthranilic acid and its metabolic products are of great importance for host–microbe interaction in neurological health, literature examining the mechanistic relationships between microbial production, host regulation, and neurological diseases is scarce and at times conflicting. This narrative review provides an overview of the current understanding of anthranilic acid’s role in neurological health and disease, with particular focus on the contribution of the gut microbiome, the gut–brain axis, and the involvement of the three major tryptophan pathways.

Anthranilic Acid, a GPR109A Agonist, and Schizophrenia

“…Deficiency of kynurenine 3-monooxygenase ( KMO ), that catalyzes 3HK formation from Kyn in brains of individuals with schizophrenia, shifts downstream Kyn metabolism from production of 3HK toward formation of KYNA, an endogenous antagonist to N-methyl-D-aspartate receptors (NMDAR). 10 - 12 Pharmacological elevation of endogenous KYNA levels activates nigral dopamine neurons. 13 The KYNA hypothesis causatively links up-regulated formation of KYNA with positive, negative, and cognitive symptoms of schizophrenia.…”

A New Direction for the Green, Environmentally Friendly and Sustainable Bioproduction of Aminobenzoic Acid and Its Derivatives

“…OABA has various functions, including anti-inflammatory, analgesic [35], antibacterial [36], and mood-improving effects [37]. Therefore, it is commonly used in the treatment of psychiatric disorders, inflammation, and other related diseases [38,39]. In addition, OABA can also be used as a compound precursor in the chemical and food industries, such as food additives, dyes, perfumes, crop protection compounds, plastics, and so on [40].…”

Anthranilic Acid: A Versatile Monomer for the Design of Functional Conducting Polymer Composites

“…Anthranilic acid is a key metabolite in a number of biochemical pathways [82][83][84][85] and has also been exploited in numerous therapeutic applications. In many cases, these have helped to inform the subsequent translation of this molecule to engineering contexts-whether for advanced materials or sensor applications.…”

“…It has since been found to be non-essential for human health, but, nevertheless, it remains a key intermediate in human biochemistry. It has been implicated as both a diagnostic and prognostic marker for conditions including chronic brain injury, Huntington's disease, stroke, depression, coronary heart disease, intrathoracic disease, and osteoporosis [82][83][84][85]. Anthranilic acid arises through the catabolism of tryptophan via the Kynurenine pathway and is normally a momentary intermediate that undergoes further conversion (summarized in Figure 3), eventually resulting in the production of nicotinamide (NAD+).…”

“…Upon the generation of the radical cation (II), the unpaired electron can be delocalized The in vivo conversion of anthranilic acid is enzymatic and otherwise chemically stable such that dysregulation of the kynurenine pathway can lead to its accumulation. Another key source of anthranilic acid is the gut microbiome, where microbes within the gastrointestinal tract share similar Kynurenine enzymatic machinery to the mammalian host [83,84]. It is noteworthy that there is considerable clinical interest in monitoring changes in systemic anthranilic acid concentrations, but it could also be a critical fecal marker for gut health.…”