Putative mechanisms for symptom generation by wheat components. CD, celiac disease; FODMAPs, fermentable oligo-, di-, and mono-saccharides and polyols; ATIs, α-amylase/trypsin inhibitors; IBS, irritable bowel syndrome; GI, gastrointestinal; TLR-4, toll-like-receptor-4; NCWS, non-celiac wheat sensitivity; NCGS, non-celiac gluten sensitivity.
Pharmacological targets of novel drugs for the management of visceral hypersensitivity (VH) in irritable bowel syndrome (IBS). TLRs, Toll-like receptors; PGE2, prostaglandin E2; IL-1β, interleukin-1β; H1-R, histamine-1 receptor; 5-HT, 5-hydrodytryptamine; TRPV1, transient receptor potential vanilloid type I; PKA, cAMP-dependent protein kinase; PKC, protein kinase C; ZO-1, Zona occludens protein-1; NK, neuro-kinin; NGF, nerve growth factor; Trk, tyrosine receptor kinase; VG-Cs, voltage-gated channels; KC, potassium channel; CaC, calcium channel; NaC, sodium channel; NERT, norepinephrine reuptake transporter; NMDA, N-methyl-D-aspartate; AMPA, α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; PAR, protease-activated receptors; R, receptor.
Flow chart documenting the results of search strategy.
Mechanisms of probiotic effects on the central nervous system. Probiotics influence central nervous system (CNS) function through direct and indirect mechanisms. Probiotics affect the hypothalamic-pituitary-adrenal (HPA) axis, by altering corticosteroid (CORT) and/or adrenocorticotropic hormone (ACTH) levels. The immune system is influenced by limited pro-inflammatory cytokine production and inflammation, and this, in turn, has effects on the CNS. Probiotics can also directly alter CNS biochemistry, such as by affecting brain-derived neurotrophic factor (BDNF), c-Fos, γ-aminobutyric acid (GABA), 5 hydroxytryptamine (5-HT), and dopamine (DA) levels, thus influencing mind and behavior. The vagus and enteric nerves are also involved in this gut-brain interaction and are affected by certain probiotics. Probiotics manipulate the gut microbiota (GM) by increasing microbiota diversity and beneficial bacteria composition. An “improved” GM changes metabolites, such as short-chain fatty acids (SCFAs) and tryptophan, and so improves CNS function indirectly. The GM also interacts with the endocrine, immune, and neural systems.