Table 3.

Biologically active compounds produced by or stimulated by resident gut microbiota, their nerve function and associated conditions of chronic pain.

Type of Biologic	Active Biological	Nerve Function	Associated Conditions
Neurotransmitter	Serotonin	Major neurotransmitter of the CNS and is associated with cognitive abilities, mood, sleep and appetite [5], regulates nociception, motor activity and mood [54]	MDD, anxiety disorders, schizophrenia [55]
	Dopamine	Regulates motor control, reward and cognitive function [5]	PD, MDD, anxiety, RA, FM, CFS/ME, IBS [55]
	Acetylcholine	Neural cell signalling, plasticity and communication [56]	AD [56]
	GABA	Principal inhibitory neurotransmitter in CNS [54]	MDD, anxiety, RA, FM, CFS/ME, IBS [55]
	Glutamate	Principal excitatory neurotransmitter in the CNS [54]
Hormone	CRF	Regulates stress response [5]	MDD, anxiety disorders, IBS, FM, CFS [5]
Metabolites	Short chain fatty acids—acetate, propionate, and butyrate [21,27]	Regulate the expression of tryptophan 5-hydroxylase, stimulate mucosal release of endocrine agents, inhibit histone deacetylase activity, role in microbiota-gut-brain crosstalk [27]	Behavioural and neurologic pathologies, MDD, AD, PD, MS and autism [27,32] ALS [43,53]
Immune modulators	Interferons, cytokines, interleukins	Regulate neurodevelopment, neuroinflammation, and synaptic transmission	FM, RA, CFS, IBS, MDD, anxiety, and sleep disorders [5,50] neurodegenerative disease [57]