Tryptophan Metabolites Along the Microbiota-Gut-Brain Axis: An Interkingdom Communication System Influencing the Gut in Health and Disease

Abstract

The ‘microbiota-gut-brain axis’ plays a fundamental role in maintaining host homeostasis, and different immune, hormonal, and neuronal signals participate to this interkingdom communication system between eukaryota and prokaryota. The essential aminoacid tryptophan, as a precursor of several molecules acting at the interface between the host and the microbiota, is fundamental in the modulation of this bidirectional communication axis. In the gut, tryptophan undergoes 3 major metabolic pathways, the 5-HT, kynurenine, and AhR ligand pathways, which may be directly or indirectly controlled by the saprophytic flora. The importance of tryptophan metabolites in the modulation of the gastrointestinal tract is suggested by several preclinical and clinical studies; however, a thorough revision of the available literature has not been accomplished yet. Thus, this review attempts to cover the major aspects on the role of tryptophan metabolites in host-microbiota cross-talk underlaying regulation of gut functions in health conditions and during disease states, with particular attention to 2 major gastrointestinal diseases, such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), both characterized by psychiatric disorders. Research in this area opens the possibility to target tryptophan metabolism to ameliorate the knowledge on the pathogenesis of both diseases, as well as to discover new therapeutic strategies based either on conventional pharmacological approaches or on the use of pre- and probiotics to manipulate the microbial flora.

Nutritional Support of Neurodevelopment and Cognitive Function in Infants and Young Children—An Update and Novel Insights

“…Recent studies suggest that essential amino acids like tyrosine and tryptophan could be important factors in neurodevelopment. Tryptophan is the substrate for 5-HT (serotonin), which has been implicated in the control of mucosal secretion and absorption of nutrients and acts as a vasodilator and regulator of motor and sensory functions, including perception of pain and nausea [ 109 , 110 ]. In the CNS, 5-HT is involved in the regulation of mood, behavior, and cognitive functions [ 111 , 112 ].…”

“…Anomalies in serotoninergic transmission have been linked to psychiatric disorders, such as major depression and schizophrenia [ 113 ]. Further metabolic reactions downstream of 5-HT yield melatonin [ 110 , 114 ], a hormone known to regulate circadian rhythms of behavior, physiology and sleep patterns [ 110 , 115 ]; all events essential for proper development of the brain. There is some limited evidence to suggest that feeding infant formula enriched with tryptophan improves sleep, which in turn may influence neurobehavioral development [ 109 , 116 ].…”

C-Type Lectins in Veterinary Species: Recent Advancements and Applications

“…Along with other PRRs, CTLs also are important constituents of the host–microbiome communication interface: symbiotic microbes interact with CTLs [ 129 ] and affect host cytokine production and CTL expression in trained innate immunity [ 130 ] and homeostasis [ 131 ] by epigenetic mechanisms. For the Dectin-1 targeting mushroom glucans lentinan [ 132 ] and proteo-β-glucan [ 133 ], a robust Dectin-1-mediated antidepressant-like effect was demonstrated in mouse models [ 133 , 134 ], illustrating the influence that CTLs may have upon animal and human cerebral functions via the microbiota–gut–brain signaling axis [ 135 ]. Many veterinary and human nutraceuticals, or pharmacologically active nutrition additives [ 136 , 137 ], are also likely to exhibit their respective immune stimulating and/or modulatory functions via CTL-mediated signalling.…”

Nutritional Support of Neurodevelopment and Cognitive Function in Healthy Children – An Update and Novel Insights

“…Recent studies suggest that essential amino acids like tyrosine and tryptophan could be important factors in neurodevelopment. Tryptophan is the substrate for 5-HT (serotonin) which has been implicated in the control of mucosal secretion and absorption of nutrients, and acts as a vasodilator and regulator of motor and sensory functions, including perception of pain and nausea [108,109]. In the CNS, 5-HT is involved in the regulation of mood, behavior, and cognitive functions [110,111].…”

“…Anomalies in serotoninergic transmission have been linked to psychiatric disorders, such as major depression and schizophrenia [112]. Further metabolic reactions downstream of 5-HT yield melatonin [109,113], a hormone known to regulate circadian rhythms of behavior, physiology and sleep patterns [109,114]; all events essential for proper development of the brain. There is some limited evidence to suggest that feeding infant formula enriched with tryptophan improves sleep, which in turn may influence neurobehavioral development [108,115].…”