Gut-brain axis: Role of lipids in the regulation of inflammation, pain and CNS diseases

Current Medicinal Chemistry

Volumn 25, Issue 32, 2018, Pages 3930-3952

  Russo, Roberto ^a   Cristiano, Claudia ^a   Avagliano, Carmen ^a   De Caro, Carmen ^a   Rana, Giovanna La ^a   Raso, Giuseppina Mattace ^a   Canani, Roberto Berni ^a   Meli, Rosaria ^a   Calignano, Antonio ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

AEA; Brain; Butyrate; Gut; IBS; Inflammation; Mood; Neurodegenerative disease; Pain; PEA

Indexed keywords

ANANDAMIDE; BUTYRIC ACID; CANNABINOID 1 RECEPTOR; ENDOCANNABINOID; LIPID; N ACYLETHANOLAMINE; OLEOILETHANOLAMIDE; PALMIDROL; UNCLASSIFIED DRUG; ETHANOLAMINE DERIVATIVE; N-ACYLETHANOLAMINES; VOLATILE FATTY ACID;

ABDOMINAL PAIN; ALZHEIMER DISEASE; AUTISM; BRAIN; CENTRAL NERVOUS SYSTEM DISEASE; CHRONIC PAIN; DYSBIOSIS; HUMAN; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; IRRITABLE COLON; MOOD DISORDER; MULTIPLE SCLEROSIS; NONHUMAN; OBESITY; PAIN; PARKINSON DISEASE; REVIEW; ANIMAL; DRUG EFFECT; ENTEROPATHY; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; CENTRAL NERVOUS SYSTEM DISEASES; DYSBIOSIS; ENDOCANNABINOIDS; ETHANOLAMINES; FATTY ACIDS, VOLATILE; GASTROINTESTINAL MICROBIOME; HUMANS; INFLAMMATION; INTESTINAL DISEASES; LIPIDS; PAIN;

EID: 85055604511     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867324666170216113756     Document Type: Review

References (278)

1. Schloissnig, S.; Arumugam, M.; Sunagawa, S.; Mitreva, M.; Tap, J.; Zhu, A.; Waller, A.; Mende, D.R.; Kultima, J.R.; Martin, J.; Kota, K.; Sunyaev, S.R.; Weinstock, G.M.; Bork, P. Genomic variation landscape of the human gut microbiome. Nature, 2013, 493(7430), 45-50.
2. Turnbaugh, P.J.; Ley, R.E.; Hamady, M.; Fraser-Liggett, C.M.; Knight, R.; Gordon, J.I. The human microbiome project. Nature, 2007, 449(7164), 804-810.
3. Palmer, C.; Bik, E.M.; DiGiulio, D.B.; Relman, D.A.; Brown, P.O. Development of the human infant intestinal microbiota. PLoS Biol., 2007, 5(7), e177.
4. Koren, O.; Knights, D.; Gonzalez, A.; Waldron, L.; Segata, N.; Knight, R.; Huttenhower, C.; Ley, R.E. A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets. PLOS Comput. Biol., 2013, 9(1), e1002863.
5. OHara, A.M.; Shanahan, F. The gut flora as a forgotten organ. EMBO Rep., 2006, 7(7), 688-693.
6. Sommer, F.; Bäckhed, F. The gut microbiotamasters of host development and physiology. Nat. Rev. Microbiol., 2013, 11(4), 227-238.
7. Collins, S.M.; Surette, M.; Bercik, P. The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol., 2012, 10(11), 735-742.
8. Montiel-Castro, A.J.; González-Cervantes, R.M.; Bravo-Ruiseco, G.; Pacheco-López, G. The microbiota-gut-brain axis: neurobehavioral correlates, health and sociality. Front. Integr. Nuerosci., 2013, 7, 70.
9. Berntson, G.G.; Sarter, M.; Cacioppo, J.T. Ascending visceral regulation of cortical affective information processing. Eur. J. Neurosci., 2003, 18(8), 2103-2109.
10. Li, J.; Butcher, J.; Mack, D.; Stintzi, A. Functional impacts of the intestinal microbiome in the pathogenesis of inflammatory bowel disease. Inflamm. Bowel Dis., 2015, 21(1), 139-153.
11. Lee, K.N.; Lee, O.Y. Intestinal microbiota in pathophysiology and management of irritable bowel syndrome. World J. Gastroenterol., 2014, 20(27), 8886-8897.
12. Czirr, E.; Wyss-Coray, T. The immunology of neurodegeneration. J. Clin. Invest., 2012, 122(4), 1156-1163.
13. Lampron, A.; Pimentel-Coelho, P.M.; Rivest, S. Migration of bone marrow-derived cells into the central nervous system in models of neurodegeneration. J. Comp. Neurol., 2013, 521(17), 3863-3876.
14. Caesar, R.; Tremaroli, V.; Kovatcheva-Datchary, P.; Cani, P.D.; Bäckhed, F. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metab., 2015, 22(4), 658-668.
15. Rousseaux, C.; Thuru, X.; Gelot, A.; Barnich, N.; Neut, C.; Dubuquoy, L.; Dubuquoy, C.; Merour, E.; Geboes, K.; Chamaillard, M.; Ouwehand, A.; Leyer, G.; Carcano, D.; Colombel, J.F.; Ardid, D.; Desreumaux, P. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat. Med., 2007, 13(1), 35-37.
16. Alhouayek, M.; Bottemanne, P.; Subramanian, K.V.; Lambert, D.M.; Makriyannis, A.; Cani, P.D.; Muccioli, G.G. N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis. FASEB J., 2015, 29(2), 650-661.
17. Kannampalli, P.; Shaker, R.; Sengupta, J.N. Colonic bu-tyrate-algesic or analgesic? Neurogastroenterol. Motil., 2011, 23(11), 975-979.
18. Cannon, W.B. Organization for physiological homeostasis. Physiol. Rev., 1929, 9, 399-431.
19. Foster, J.A.; McVey Neufeld, K.A. Gut-brain axis: How the microbiome influences anxiety and depression. Trends Neurosci., 2013, 36(5), 305-312.
20. Naseribafrouei, A.; Hestad, K.; Avershina, E.; Sekelja, M.; Linløkken, A.; Wilson, R.; Rudi, K. Correlation between the human fecal microbiota and depression. Neurogastroenterol. Motil., 2014, 26(8), 1155-1162.
21. Mangiola, F.; Ianiro, G.; Franceschi, F.; Fagiuoli, S.; Gasbarrini, G.; Gasbarrini, A. Gut microbiota in autism and mood disorders. World J. Gastroenterol., 2016, 22(1), 361-368.
22. Rhee, S.H.; Pothoulakis, C.; Mayer, E.A. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol., 2009, 6(5), 306-314.
23. Hughes, D.T.; Sperandio, V. Inter-kingdom signalling: communication between bacteria and their hosts. Nat. Rev. Microbiol., 2008, 6(2), 111-120.
24. Kunze, W.A.; Mao, Y.K.; Wang, B.; Huizinga, J.D.; Ma, X.; Forsythe, P.; Bienenstock, J. Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting cal-cium-dependent potassium channel opening. J. Cell. Mol. Med., 2009, 13(8B), 2261-2270.
25. Mao, Y.K.; Kasper, D.L.; Wang, B.; Forsythe, P.; Bienenstock, J.; Kunze, W.A. Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nat. Commun., 2013, 4, 1465.
26. Sudo, N; Chida, Y; Aiba, Y; Sonoda, J; Oyama, N; Yu, XN; Kubo, C; Koga, Y. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol., 2014, 558, 263-275.
27. Round, J.L.; Mazmanian, S.K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol., 2009, 9(5), 313-323.
28. Corthésy, B. Multi-faceted functions of secretory IgA at mucosal surfaces. Front. Immunol., 2013, 4, 185.
29. Cahenzli, J.; Balmer, M.L.; McCoy, K.D. Microbial-immune cross-talk and regulation of the immune system. Immunology, 2013, 138(1), 12-22.
30. Hooper, L.V.; Littman, D.R.; Macpherson, A.J. Interactions between the microbiota and the immune system. Science, 2012, 336(6086), 1268-1273.
31. Bercik, P; Denou, E; Collins, J; Jackson, W; Lu, J; Jury, J; Deng, Y; Blennerhassett, P; Macri, J; McCoy, KD; Verdu, EF; Collins, SM The intestinal microbiota affectcentral levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology, 2011, 141(2), 599-609, 609.e1-3.
32. Bravo, J.A.; Forsythe, P.; Chew, M.V.; Escaravage, E.; Savignac, H.M.; Dinan, T.G.; Bienenstock, J.; Cryan, J.F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA, 2011, 108(38), 16050-16055.
33. Cryan, J.F.; Dinan, T.G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci., 2012, 13(10), 701-712.
34. Bercik, P.; Park, A.J.; Sinclair, D.; Khoshdel, A.; Lu, J.; Huang, X.; Deng, Y.; Blennerhassett, P.A.; Fahnestock, M.; Moine, D.; Berger, B.; Huizinga, J.D.; Kunze, W.; McLean, P.G.; Bergonzelli, G.E.; Collins, S.M.; Verdu, E.F. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol. Motil., 2011, 23(12), 1132-1139.
35. Villeda, S.A.; Luo, J.; Mosher, K.I.; Zou, B.; Britschgi, M.; Bieri, G.; Stan, T.M.; Fainberg, N.; Ding, Z.; Eggel, A.; Lucin, K.M.; Czirr, E.; Park, J.S.; Couillard-Després, S.; Aigner, L.; Li, G.; Peskind, E.R.; Kaye, J.A.; Quinn, J.F.; Galasko, D.R.; Xie, X.S.; Rando, T.A.; Wyss-Coray, T. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 2011, 477(7362), 90-94.
36. Vicario, M.; Alonso, C.; Guilarte, M.; Serra, J.; Martínez, C.; González-Castro, A.M.; Lobo, B.; Antolín, M.; Andreu, A.L.; García-Arumí, E.; Casellas, M.; Saperas, E.; Mal-agelada, J.R.; Azpiroz, F.; Santos, J. Chronic psychosocial stress induces reversible mitochondrial damage and corticotropin-releasing factor receptor type-1 upregulation in the rat intestine and IBS-like gut dysfunction. Psychoneuroendocrinology, 2012, 37(1), 65-77.
37. Ewaschuk, J.B.; Diaz, H.; Meddings, L.; Diederichs, B.; Dmytrash, A.; Backer, J.; Looijer-van Langen, M.; Madsen, K.L. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am. J. Physiol. Gastrointest. Liver Physiol., 2008, 295(5), G1025-G1034.
38. OMahony, L.; McCarthy, J.; Kelly, P.; Hurley, G.; Luo, F.; Chen, K.; OSullivan, G.C.; Kiely, B.; Collins, J.K.; Shanahan, F.; Quigley, E.M. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology, 2005, 128(3), 541-551.
39. Ait-Belgnaoui, A.; Durand, H.; Cartier, C.; Chaumaz, G.; Eutamene, H.; Ferrier, L.; Houdeau, E.; Fioramonti, J.; Bueno, L.; Theodorou, V. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology, 2012, 37(11), 1885-1895.
40. OMahony, S.M.; Felice, V.D.; Nally, K.; Savignac, H.M.; Claesson, M.J.; Scully, P.; Woznicki, J.; Hyland, N.P.; Shanahan, F.; Quigley, E.M.; Marchesi, J.R.; OToole, P.W.; Dinan, T.G.; Cryan, J.F. Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience, 2014, 277, 885-901.
41. Bailey, M.T.; Dowd, S.E.; Galley, J.D.; Hufnagle, A.R.; Allen, R.G.; Lyte, M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stres-sor-induced immunomodulation. Brain Behav. Immun., 2011, 25(3), 397-407.
42. De Palma, G.; Collins, S.M.; Bercik, P.; Verdu, E.F. The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both? J. Physiol., 2014, 592(14), 2989-2997.
43. Powell, N.D.; Sloan, E.K.; Bailey, M.T.; Arevalo, J.M.; Miller, G.E.; Chen, E.; Kobor, M.S.; Reader, B.F.; Sheridan, J.F.; Cole, S.W. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc. Natl. Acad. Sci. USA, 2013, 110(41), 16574-16579.
44. Bailey, M.T.; Dowd, S.E.; Parry, N.M.; Galley, J.D.; Schauer, D.B.; Lyte, M. Stressor exposure disrupts commensal microbial populations in the intestines and leads to increased colonization by Citrobacter rodentium. Infect. Immun., 2010, 78(4), 1509-1519.
45. Campos-Rodríguez, R.; Godínez-Victoria, M.; Abarca-Rojano, E.; Pacheco-Yépez, J.; Reyna-Garfias, H.; Barbosa-Cabrera, R.E.; Drago-Serrano, M.E. Stress modulates intestinal secretory immunoglobulin A. Front. Integr. Nuerosci., 2013, 7, 86.
46. Rostène, W.; Kitabgi, P.; Parsadaniantz, S.M. Chemokines: a new class of neuromodulator? Nat. Rev. Neurosci., 2007, 8(11), 895-903.
47. Banks, W.A.; Kastin, A.J.; Broadwell, R.D. Passage of cytokines across the blood-brain barrier. Neuroimmuno-modulation, 1995, 2(4), 241-248.
48. Kelley, K.W.; Bluthé, R.M.; Dantzer, R.; Zhou, J.H.; Shen, W.H.; Johnson, R.W.; Broussard, S.R. Cytokine-induced sickness behavior. Brain Behav. Immun., 2003, 17(Suppl. 1), S112-S118.
49. Devane, W.A.; Hanus, L.; Breuer, A.; Pertwee, R.G.; Stevenson, L.A.; Griffin, G.; Gibson, D.; Mandelbaum, A.; Etinger, A.; Mechoulam, R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 1992, 258(5090), 1946-1949.
50. Mechoulam, R.; Ben-Shabat, S.; Hanus, L.; Ligumsky, M.; Kaminski, N.E.; Schatz, A.R.; Gopher, A.; Almog, S.; Martin, B.R.; Compton, D.R. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol., 1995, 50(1), 83-90.
51. Ryberg, E.; Larsson, N.; Sjögren, S.; Hjorth, S.; Hermansson, N.O.; Leonova, J.; Elebring, T.; Nilsson, K.; Drmota, T.; Greasley, P.J. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol., 2007, 152(7), 1092-1101.
52. Ross, R.A. Anandamide and vanilloid TRPV1 receptors. Br. J. Pharmacol., 2003, 140(5), 790-801.
53. Pertwee, R.G.; Howlett, A.C.; Abood, M.E.; Alexander, S.P.; Di Marzo, V.; Elphick, M.R.; Greasley, P.J.; Hansen, H.S.; Kunos, G.; Mackie, K.; Mechoulam, R.; Ross, R.A. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol. Rev., 2010, 62(4), 588-631.
54. Izzo, A.A.; Piscitelli, F.; Capasso, R.; Aviello, G.; Romano, B.; Borrelli, F.; Petrosino, S.; Di Marzo, V. Peripheral endocannabinoid dysregulation in obesity: relation to intestinal motility and energy processing induced by food deprivation and re-feeding. Br. J. Pharmacol., 2009, 158(2), 451-461.
55. DiPatrizio, N.V.; Piomelli, D. Intestinal lipid-derived signals that sense dietary fat. J. Clin. Invest., 2015, 125(3), 891-898.
56. Troy-Fioramonti, S.; Demizieux, L.; Gresti, J.; Muller, T.; Vergès, B.; Degrace, P. Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice. Diabetes, 2015, 64(3), 808-818.
57. Cota, D.; Marsicano, G.; Tschöp, M.; Grübler, Y.; Flach-skamm, C.; Schubert, M.; Auer, D.; Yassouridis, A.; Thöne-Reineke, C.; Ortmann, S.; Tomassoni, F.; Cervino, C.; Nisoli, E.; Linthorst, A.C.; Pasquali, R.; Lutz, B.; Stalla, G.K.; Pagotto, U. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J. Clin. Invest., 2003, 112(3), 423-431.
58. Hoareau, L.; Buyse, M.; Festy, F.; Ravanan, P.; Gonthier, M.P.; Matias, I.; Petrosino, S.; Tallet, F.; dHellencourt, C.L.; Cesari, M.; Di Marzo, V.; Roche, R. Anti-inflammatory effect of palmitoylethanolamide on human adipocytes. Obesity (Silver Spring), 2009, 17(3), 431-438.
59. Lam, Y.Y.; Ha, C.W.; Campbell, C.R.; Mitchell, A.J.; Dinudom, A.; Oscarsson, J.; Cook, D.I.; Hunt, N.H.; Caterson, I.D.; Holmes, A.J.; Storlien, L.H. Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS One, 2012, 7(3), e34233.
60. Muccioli, G.G.; Naslain, D.; Bäckhed, F.; Reigstad, C.S.; Lambert, D.M.; Delzenne, N.M.; Cani, P.D. The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol., 2010, 6, 392.
61. Zhu, C.; Solorzano, C.; Sahar, S.; Realini, N.; Fung, E.; Sassone-Corsi, P.; Piomelli, D. Proinflammatory stimuli control N-acylphosphatidylethanolamine-specific phospholipase D expression in macrophages. Mol. Pharmacol., 2011, 79(4), 786-792.
62. Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; Waget, A.; Delmée, E.; Cousin, B.; Sulpice, T.; Chamontin, B.; Ferrières, J.; Tanti, J.F.; Gibson, G.R.; Casteilla, L.; Delzenne, N.M.; Alessi, M.C.; Burcelin, R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 2007, 56(7), 1761-1772.
63. Silvestri, C.; Di Marzo, V. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab., 2013, 17(4), 475-490.
64. Geurts, L.; Muccioli, G.G.; Delzenne, N.M.; Cani, P.D. Chronic endocannabinoid system stimulation induces muscle macrophage and lipid accumulation in type 2 diabetic mice independently of metabolic endotoxaemia. PLoS One, 2013, 8(2), e55963.
65. Alhouayek, M.; Bottemanne, P.; Subramanian, K.V.; Lambert, D.M.; Makriyannis, A.; Cani, P.D.; Muccioli, G.G. N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis. FASEB J., 2015, 29(2), 650-661.
66. Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J.P.; Druart, C.; Bindels, L.B.; Guiot, Y.; Derrien, M.; Muccioli, G.G.; Delzenne, N.M.; de Vos, W.M.; Cani, P.D. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl. Acad. Sci. USA, 2013, 110(22), 9066-9071.
67. Alhouayek, M.; Lambert, D.M.; Delzenne, N.M.; Cani, P.D.; Muccioli, G.G. Increasing endogenous 2-arachidonoylglycerol levels counteracts colitis and related systemic inflammation. FASEB J., 2011, 25(8), 2711-2721.
68. Everard, A.; Geurts, L.; Caesar, R.; Van Hul, M.; Matamoros, S.; Duparc, T.; Denis, R.G.; Cochez, P.; Pierard, F.; Castel, J.; Bindels, L.B.; Plovier, H.; Robine, S.; Muccioli, G.G.; Renauld, J.C.; Dumoutier, L.; Delzenne, N.M.; Luquet, S.; Bäckhed, F.; Cani, P.D. Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status. Nat. Commun., 2014, 5, 5648.
69. Lo Verme, J.; Fu, J.; Astarita, G.; La Rana, G.; Russo, R.; Calignano, A.; Piomelli, D. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol. Pharmacol., 2005, 67(1), 15-19.
70. Borrelli, F.; Romano, B.; Petrosino, S.; Pagano, E.; Capasso, R.; Coppola, D.; Battista, G.; Orlando, P.; Di Marzo, V.; Izzo, A.A. Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent. Br. J. Pharmacol., 2015, 172(1), 142-158.
71. Esposito, G.; Capoccia, E.; Turco, F.; Palumbo, I.; Lu, J.; Steardo, A.; Cuomo, R.; Sarnelli, G.; Steardo, L. Palmitoylethanolamide improves colon inflammation through an enteric glia/toll like receptor 4-dependent PPAR-α activation. Gut, 2014, 63(8), 1300-1312.
72. Mattace Raso, G.; Russo, R.; Calignano, A.; Meli, R. Palmitoylethanolamide in CNS health and disease. Pharmacol. Res., 2014, 86, 32-41.
73. Mattace Raso, G.; Santoro, A.; Russo, R.; Simeoli, R.; Paciello, O.; Di Carlo, C.; Diano, S.; Calignano, A.; Meli, R. Palmitoylethanolamide prevents metabolic alterations and restores leptin sensitivity in ovariectomized rats. Endocrinology, 2014, 155(4), 1291-1301.
74. Piomelli, D. A fatty gut feeling. Trends Endocrinol. Metab., 2013, 24(7), 332-341.
75. Igarashi, M.; DiPatrizio, N.V.; Narayanaswami, V.; Piomelli, D. Feeding-induced oleoylethanolamide mobilization is disrupted in the gut of diet-induced obese rodents. Biochim. Biophys. Acta, 2015, 1851(9), 1218-1226.
76. Konturek, P.C.; Kania, J.; Kukharsky, V.; Raithel, M.; Ocker, M.; Rembiasz, K.; Hahn, E.G.; Konturek, S.J. Implication of peroxisome proliferator-activated receptor gamma and proinflammatory cytokines in gastric carcino-genesis: link to Helicobacter pylori-infection. J. Pharmacol. Sci., 2004, 96(2), 134-143.
77. Rajaram, M.V.; Brooks, M.N.; Morris, J.D.; Torrelles, J.B.; Azad, A.K.; Schlesinger, L.S. Mycobacterium tuberculosis activates human macrophage peroxisome proliferator-activated receptor gamma linking mannose receptor recognition to regulation of immune responses. J. Immunol., 2010, 185(2), 929-942.
78. Saubermann, L.J.; Nakajima, A.; Wada, K.; Zhao, S.; Terauchi, Y.; Kadowaki, T.; Aburatani, H.; Matsuhashi, N.; Nagai, R.; Blumberg, R.S. Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. Inflamm. Bowel Dis., 2002, 8(5), 330-339.
79. Desreumaux, P.; Dubuquoy, L.; Nutten, S.; Peuchmaur, M.; Englaro, W.; Schoonjans, K.; Derijard, B.; Desvergne, B.; Wahli, W.; Chambon, P.; Leibowitz, M.D.; Colombel, J.F.; Auwerx, J. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies. J. Exp. Med., 2001, 193(7), 827-838.
80. Adachi, M.; Kurotani, R.; Morimura, K.; Shah, Y.; Sanford, M.; Madison, B.B.; Gumucio, D.L.; Marin, H.E.; Peters, J.M.; Young, H.A.; Gonzalez, F.J. Peroxisome proliferator activated receptor gamma in colonic epithelial cells protects against experimental inflammatory bowel disease. Gut, 2006, 55(8), 1104-1113.
81. Dubuquoy, L.; Dharancy, S.; Nutten, S.; Pettersson, S.; Auwerx, J.; Desreumaux, P. Role of peroxisome prolifera-tor-activated receptor gamma and retinoid X receptor heterodimer in hepatogastroenterological diseases. Lancet, 2002, 360(9343), 1410-1418.
82. Mattace Raso, G.; Simeoli, R.; Russo, R.; Iacono, A.; Santoro, A.; Paciello, O.; Ferrante, M.C.; Canani, R.B.; Calignano, A.; Meli, R. Effects of sodium butyrate and its synthetic amide derivative on liver inflammation and glucose tolerance in an animal model of steatosis induced by high fat diet. PLoS One, 2013, 8(7), e68626.
83. Fleming, S.E.; Fitch, M.D.; DeVries, S.; Liu, M.L.; Kight, C. Nutrient utilization by cells isolated from rat jejunum, cecum and colon. J. Nutr., 1991, 121(6), 869-878.
84. Boren, J.; Lee, W.N.; Bassilian, S.; Centelles, J.J.; Lim, S.; Ahmed, S.; Boros, L.G.; Cascante, M. The stable isotope-based dynamic metabolic profile of butyrate-induced HT29 cell differentiation. J. Biol. Chem., 2003, 278(31), 28395-28402.
85. Canani, R.B.; Costanzo, M.D.; Leone, L.; Pedata, M.; Meli, R.; Calignano, A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J. Gastroenterol., 2011, 17(12), 1519-1528.
86. Cook, S.I.; Sellin, J.H. Review article: short chain fatty acids in health and disease. Aliment. Pharmacol. Ther., 1998, 12(6), 499-507.
87. De Preter, V.; Arijs, I.; Windey, K.; Vanhove, W.; Vermeire, S.; Schuit, F.; Rutgeerts, P.; Verbeke, K. Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway. Inflamm. Bowel Dis., 2012, 18(6), 1127-1136.
88. Thibault, R.; De Coppet, P.; Daly, K.; Bourreille, A.; Cuff, M.; Bonnet, C.; Mosnier, J.F.; Galmiche, J.P.; Shirazi-Beechey, S.; Segain, J.P. Down-regulation of the monocar-boxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology, 2007, 133(6), 1916-1927.
89. Lührs, H.; Gerke, T.; Müller, J.G.; Melcher, R.; Schauber, J.; Boxberge, F.; Scheppach, W.; Menzel, T. Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis. Scand. J. Gastroenterol., 2002, 37(4), 458-466.
90. Banasiewicz, T.; Krokowicz, Ł.; Stojcev, Z.; Kaczmarek, B.F.; Kaczmarek, E.; Maik, J.; Marciniak, R.; Krokowicz, P.; Walkowiak, J.; Drews, M. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis., 2013, 15(2), 204-209.
91. Vinolo, M.A.; Rodrigues, H.G.; Hatanaka, E.; Sato, F.T.; Sampaio, S.C.; Curi, R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J. Nutr. Biochem., 2011, 22(9), 849-855.
92. Berni Canani, R.; Di Costanzo, M.; Leone, L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin. Epigenetics, 2012, 4(1), 4.
93. Nøhr, M.K.; Pedersen, M.H.; Gille, A.; Egerod, K.L.; Engelstoft, M.S.; Husted, A.S.; Sichlau, R.M.; Grunddal, K.V.; Poulsen, S.S.; Han, S.; Jones, R.M.; Offermanns, S.; Schwartz, T.W. GPR41/FFAR3 and GPR43/FFAR2 as co-sensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology, 2013, 154(10), 3552-3564.
94. Russo, R.; De Caro, C.; Avagliano, C.; Cristiano, C.; La Rana, G.; Mattace Raso, G.; Berni Canani, R.; Meli, R.; Calignano, A. Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice. Pharmacol. Res., 2016, 103, 279-291.
95. Dubuquoy, L.; Rousseaux, C.; Thuru, X.; Peyrin-Biroulet, L.; Romano, O.; Chavatte, P.; Chamaillard, M.; Desreu-Desreu-maux, P. PPARgamma as a new therapeutic target in inflammatory bowel diseases. Gut, 2006, 55(9), 1341-1349. maux,
96. Eckmann, L. Animal models of inflammatory bowel disease: Lessons from enteric infections. Ann. N. Y. Acad. Sci., 2006, 1072, 28-38.
97. Yan, F.; Wang, L.; Shi, Y.; Cao, H.; Liu, L.; Washington, M.K.; Chaturvedi, R.; Israel, D.A.; Cao, H.; Wang, B.; Peek, R.M., Jr; Wilson, K.T.; Polk, D.B. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice. Am. J. Physiol. Gastrointest. Liver Physiol., 2012, 302(5), G504-G514.
98. Baumgart, D.C.; Sandborn, W.J. Crohns disease. Lancet, 2012, 380(9853), 1590-1605.
99. Ordás, I.; Eckmann, L.; Talamini, M.; Baumgart, D.C.; Sandborn, W.J. Ulcerative colitis. Lancet, 2012, 380(9853), 1606-1619.
100. Di Sabatino, A.; Battista, N.; Biancheri, P.; Rapino, C.; Rovedatti, L.; Astarita, G.; Vanoli, A.; Dainese, E.; Guerci, M.; Piomelli, D.; Pender, S.L.; MacDonald, T.T.; Maccarrone, M.; Corazza, G.R. The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease. Mucosal Immunol., 2011, 4(5), 574-583.
101. Franke, A.; McGovern, D.P.; Barrett, J.C.; Wang, K.; Rad-ford-Smith, G.L.; Ahmad, T.; Lees, C.W.; Balschun, T.; Lee, J.; Roberts, R.; Anderson, C.A.; Bis, J.C.; Bumpstead, S.; Ellinghaus, D.; Festen, E.M.; Georges, M.; Green, T.; Haritunians, T.; Jostins, L.; Latiano, A.; Mathew, C.G.; Montgomery, G.W.; Prescott, N.J.; Raychaudhuri, S.; Rotter, J.I.; Schumm, P.; Sharma, Y.; Simms, L.A.; Taylor, K.D.; Whiteman, D.; Wijmenga, C.; Baldassano, R.N.; Barclay, M.; Bayless, T.M.; Brand, S.; Büning, C.; Cohen, A.; Colombel, J.F.; Cottone, M.; Stronati, L.; Denson, T.; De Vos, M.; DInca, R.; Dubinsky, M.; Edwards, C.; Florin, T.; Franchimont, D.; Gearry, R.; Glas, J.; Van Gossum, A.; Guthery, S.L.; Halfvarson, J.; Verspaget, H.W.; Hugot, J.P.; Karban, A.; Laukens, D.; Lawrance, I.; Lemann, M.; Levine, A.; Libioulle, C.; Louis, E.; Mowat, C.; Newman, W.; Panés, J.; Phillips, A.; Proctor, D.D.; Regueiro, M.; Russell, R.; Rutgeerts, P.; Sanderson, J.; Sans, M.; Seibold, F.; Steinhart, A.H.; Stokkers, P.C.; Torkvist, L.; Kullak-Ublick, G.; Wilson, D.; Walters, T.; Targan, S.R.; Brant, S.R.; Rioux, J.D.; DAmato, M.; Weersma, R.K.; Kugathasan, S.; Griffiths, A.M.; Mansfield, J.C.; Vermeire, S.; Duerr, R.H.; Silverberg, M.S.; Satsangi, J.; Schreiber, S.; Cho, J.H.; Annese, V.; Hakonarson, H.; Daly, M.J.; Parkes, M. Genome-wide meta-analysis increases to 71 the number of confirmed Crohns disease susceptibility loci. Nat. Genet., 2010, 42(12), 1118-1125.
102. Cosnes, J.; Gower-Rousseau, C.; Seksik, P.; Cortot, A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology, 2011, 140(6), 1785-1794.
103. Chassaing, B.; Darfeuille-Michaud, A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology, 2011, 140(6), 1720-1728.
104. Macdonald, T.T. New cytokine targets in inflammatory bowel disease. Gastroenterol. Hepatol. (N. Y.), 2011, 7(7), 474-476.
105. Pandey, R.; Mousawy, K.; Nagarkatti, M.; Nagarkatti, P. Endocannabinoids and immune regulation. Pharmacol. Res., 2009, 60(2), 85-92.
106. Alhouayek, M.; Muccioli, G.G. The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends Mol. Med., 2012, 18(10), 615-625.
107. Sałaga, M.; Mokrowiecka, A.; Zakrzewski, P.K.; Cygankiewicz, A.; Leishman, E.; Sobczak, M.; Zatorski, H.; Małecka-Panas, E.; Kordek, R.; Storr, M.; Krajewska, W.M.; Bradshaw, H.B.; Fichna, J. Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH). J. Crohns Colitis, 2014, 8(9), 998-1009.
108. Storr, M.A.; Keenan, C.M.; Emmerdinger, D.; Zhang, H.; Yüce, B.; Sibaev, A.; Massa, F.; Buckley, N.E.; Lutz, B.; Göke, B.; Brand, S.; Patel, K.D.; Sharkey, K.A. Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors. J. Mol. Med., 2008, 86(8), 925-936.
109. Izzo, A.A.; Sharkey, K.A. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol. Ther., 2010, 126(1), 21-38.
110. Esposito, G.; Capoccia, E.; Turco, F.; Palumbo, I.; Lu, J.; Steardo, A.; Cuomo, R.; Sarnelli, G.; Steardo, L. Palmitoylethanolamide improves colon inflammation through an enteric glia/toll like receptor 4-dependent PPAR-α activation. Gut, 2014, 63(8), 1300-1312.
111. Butzner, J.D.; Parmar, R.; Bell, C.J.; Dalal, V. Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat. Gut, 1996, 38(4), 568-573.
112. Roediger, W.E. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet, 1980, 2(8197), 712-715.
113. Chapman, M.A.; Grahn, M.F.; Boyle, M.A.; Hutton, M.; Rogers, J.; Williams, N.S. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis. Gut, 1994, 35(1), 73-76.
114. Vernia, P.; Cittadini, M.; Caprilli, R.; Torsoli, A. Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate. Dig. Dis. Sci., 1995, 40(2), 305-307.
115. Vernia, P.; Monteleone, G.; Grandinetti, G.; Villotti, G.; Di Giulio, E.; Frieri, G.; Marcheggiano, A.; Pallone, F.; Caprilli, R.; Torsoli, A. Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: randomized, double-blind, placebo-controlled pilot study. Dig. Dis. Sci., 2000, 45(5), 976-981.
116. Guarner, F. What is the role of the enteric commensal flora in IBD? Inflamm. Bowel Dis., 2008, 14(14)(Suppl. 2), S83-S84.
117. Chassaing, B.; Darfeuille-Michaud, A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology, 2011, 140(6), 1720-1728.
118. Barcenilla, A.; Pryde, S.E.; Martin, J.C.; Duncan, S.H.; Stewart, C.S.; Henderson, C.; Flint, H.J. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Environ. Microbiol., 2000, 66(4), 1654-1661.
119. Lee, B.J.; Bak, Y.T. Irritable bowel syndrome, gut microbiota and probiotics. J. Neurogastroenterol. Motil., 2011, 17(3), 252-266.
120. Wouters, M.M.; Van Wanrooy, S.; Nguyen, A.; Dooley, J.; Aguilera-Lizarraga, J.; Van Brabant, W.; Garcia-Perez, J.E.; Van Oudenhove, L.; Van Ranst, M.; Verhaegen, J.; Liston, A.; Boeckxstaens, G. Psychological comorbidity increases the risk for postinfectious IBS partly by enhanced susceptibility to develop infectious gastroenteritis. Gut, 2016, 65(8), 1279-1288.
121. Camilleri, M. Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms. J. Physiol., 2014, 592(14), 2967-2980.
122. Ohman, L.; Simrén, M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat. Rev. Gastroenterol. Hepatol., 2010, 7(3), 163-173.
123. Muscatello, M.R.; Bruno, A.; Scimeca, G.; Pandolfo, G.; Zoccali, R.A. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome. World J. Gastroenterol., 2014, 20(24), 7570-7586.
124. Feng, C.C.; Yan, X.J.; Chen, X.; Wang, E.M.; Liu, Q.; Zhang, L.Y.; Chen, J.; Fang, J.Y.; Chen, S.L. Vagal anandamide signaling via cannabinoid receptor 1 contributes to luminal 5-HT modulation of visceral nociception in rats. Pain, 2014, 155(8), 1591-1604.
125. Klooker, TK; Leliefeld, KE; Van Den Wijngaard, RM; Boeckxstaens, GE The cannabinoid receptor agonist delta-9-tetrahydrocannabinol does not affect visceral sensitivity to rectal distension in healthy volunteers and IBS patients. Neurogastroenterol Motil., 2011, 23(1), 30-5. e2
126. Fichna, J.; Wood, J.T.; Papanastasiou, M.; Vadivel, S.K.; Oprocha, P.; Sałaga, M.; Sobczak, M.; Mokrowiecka, A.; Cygankiewicz, A.I.; Zakrzewski, P.K.; Małecka-Panas, E.; Krajewska, W.M.; Kościelniak, P.; Makriyannis, A.; Storr, M.A. Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study. PLoS One, 2013, 8(12), e85073.
127. Fichna, J.; Sałaga, M.; Stuart, J.; Saur, D.; Sobczak, M.; Zatorski, H.; Timmermans, J.P.; Bradshaw, H.B.; Ahn, K.; Storr, M.A. Selective inhibition of FAAH produces antidi-arrheal and antinociceptive effect mediated by endocannabinoids and cannabinoid-like fatty acid amides. Neurogastroenterol. Motil., 2014, 26(4), 470-481.
128. Sakin, Y.S.; Dogrul, A.; Ilkaya, F.; Seyrek, M.; Ulas, U.H.; Gulsen, M.; Bagci, S. The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents. Neurogastroenterol. Motil., 2015, 27(7), 936-944.
129. Finegold, S.M. State of the art; microbiology in health and disease. Intestinal bacterial flora in autism. Anaerobe, 2011, 17(6), 367-368.
130. Banasiewicz, T.; Kaczmarek, E.; Maik, J. Quality of life and the clinical symptoms at the patients with irritable bowel syndrome treated complementary with protected sodium butyrate. Gastroenterol Prakt., 2011, 5, 45-53.
131. Kern, JK; Geier, DA; Sykes, LK; Geier, MR. Relevance of neuroinflammation and encephalitis in autism. Front Cell Neurosci., 2016, 19(9), 519.
132. Horvath, K.; Papadimitriou, J.C.; Rabsztyn, A.; Drachen-berg, C.; Tildon, J.T. Gastrointestinal abnormalities in children with autistic disorder. J. Pediatr., 1999, 135(5), 559-563.
133. Buie, T.; Campbell, D.B.; Fuchs, G.J., III; Furuta, G.T.; Levy, J.; Vandewater, J.; Whitaker, A.H.; Atkins, D.; Bauman, M.L.; Beaudet, A.L.; Carr, E.G.; Gershon, M.D.; Hyman, S.L.; Jirapinyo, P.; Jyonouchi, H.; Kooros, K.; Kushak, R.; Levitt, P.; Levy, S.E.; Lewis, J.D.; Murray, K.F.; Natowicz, M.R.; Sabra, A.; Wershil, B.K.; Weston, S.C.; Zeltzer, L.; Winter, H. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics, 2010, 125(Suppl. 1), S1-S18.
134. Bolte, E.R. Autism and Clostridium tetani. Med. Hypotheses, 1998, 51(2), 133-144.
135. Williams, B.L.; Hornig, M.; Buie, T.; Bauman, M.L.; Cho Paik, M.; Wick, I.; Bennett, A.; Jabado, O.; Hirschberg, D.L.; Lipkin, W.I. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One, 2011, 6(9), e24585.
136. Kang, D.W.; Park, J.G.; Ilhan, Z.E.; Wallstrom, G.; Labaer, J.; Adams, J.B.; Krajmalnik-Brown, R. Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One, 2013, 8(7), e68322.
137. Wang, L.; Christophersen, C.T.; Sorich, M.J.; Gerber, J.P.; Angley, M.T.; Conlon, M.A. Increased abundance of Sut-terella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol. Autism, 2013, 4(1), 42.
138. Brigandi, S.A.; Shao, H.; Qian, S.Y.; Shen, Y.; Wu, B.L.; Kang, J.X. Autistic children exhibit decreased levels of essential Fatty acids in red blood cells. Int. J. Mol. Sci., 2015, 16(5), 10061-10076.
139. Siguel, E.N.; Lerman, R.H. Prevalence of essential fatty acid deficiency in patients with chronic gastrointestinal disorders. Metabolism, 1996, 45(1), 12-23.
140. Kim, J.; Carlson, M.E.; Kuchel, G.A.; Newman, J.W.; Watkins, B.A. Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression and epididymal fat mass while improving aspects of glucose use in muscle in C57BL/6J mice. Int. J. Obes., 2016, 40(1), 129-137.
141. Mostafa, G.A.; Al-Ayadhi, L.Y. Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: relation to gastrointestinal manifestations. Behav. Brain Funct., 2015, 11, 4.
142. Schultz, S.T. Can autism be triggered by acetaminophen activation of the endocannabinoid system? Acta Neurobiol. Exp. (Warsz.), 2010, 70(2), 227-231.
143. Trezza, V.; Vanderschuren, L.J. Bidirectional cannabinoid modulation of social behavior in adolescent rats. Psychopharmacology (Berl.), 2008, 197(2), 217-227.
144. Haller, J.; Varga, B.; Ledent, C.; Barna, I.; Freund, T.F. Context-dependent effects of CB1 cannabinoid gene disruption on anxiety-like and social behaviour in mice. Eur. J. Neurosci., 2004, 19(7), 1906-1912.
145. Tart, C.T. Marijuana intoxication common experiences. Nature, 1970, 226(5247), 701-704.
146. Chakrabarti, B.; Baron-Cohen, S. Variation in the human cannabinoid receptor CNR1 gene modulates gaze duration for happy faces. Mol. Autism, 2011, 2(1), 10.
147. Cassano, T.; Gaetani, S.; Macheda, T.; Laconca, L.; Romano, A.; Morgese, M.G.; Cimmino, C.S.; Chiarotti, F.; Bambico, F.R.; Gobbi, G.; Cuomo, V.; Piomelli, D. Evaluation of the emotional phenotype and serotonergic neurotransmission of fatty acid amide hydrolase-deficient mice. Psychopharmacology (Berl.), 2011, 214(2), 465-476.
148. DAgostino, G.; Cristiano, C.; Lyons, D.J.; Citraro, R.; Russo, E.; Avagliano, C.; Russo, R.; Raso, G.M.; Meli, R.; De Sarro, G.; Heisler, L.K.; Calignano, A. Peroxisome proliferator-activated receptor alpha plays a crucial role in behavioral repetition and cognitive flexibility in mice. Mol. Metab., 2015, 4(7), 528-536.
149. Kerr, D.M.; Downey, L.; Conboy, M.; Finn, D.P.; Roche, M. Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behav. Brain Res., 2013, 249, 124-132.
150. Macfabe, D.F. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microb. Ecol. Health Dis., 2012, 23.
151. MacFabe, D.F.; Cain, D.P.; Rodriguez-Capote, K.; Franklin, A.E.; Hoffman, J.E.; Boon, F.; Taylor, A.R.; Kavaliers, M.; Ossenkopp, K.P. Neurobiological effects of intraven-tricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav. Brain Res., 2007, 176(1), 149-169.
152. Pons, R.; Andreu, A.L.; Checcarelli, N.; Vilà, M.R.; Engel-stad, K.; Sue, C.M.; Shungu, D.; Haggerty, R.; de Vivo, D.C.; DiMauro, S. Mitochondrial DNA abnormalities and autistic spectrum disorders. J. Pediatr., 2004, 144(1), 81-85.
153. Kim, K.C.; Kim, P.; Go, H.S.; Choi, C.S.; Park, J.H.; Kim, H.J.; Jeon, S.J.; Dela Pena, I.C.; Han, S.H.; Cheong, J.H.; Ryu, J.H.; Shin, C.Y. Male-specific alteration in excitatory post-synaptic development and social interaction in pre-pre-natal valproic acid exposure model of autism spectrum disorder. J. Neurochem., 2013, 124(6), 832-843. natal
154. Kratsman, N.; Getselter, D.; Elliott, E. Sodium butyrate attenuates social behavior deficits and modifies the transcription of inhibitory/excitatory genes in the frontal cortex of an autism model. Neuropharmacology, 2016, 102, 136-145.
155. Dowlati, Y.; Herrmann, N.; Swardfager, W.; Liu, H.; Sham, L.; Reim, E.K.; Lanctôt, K.L. A meta-analysis of cytokines in major depression. Biol. Psychiatry, 2010, 67(5), 446-457.
156. Jokela, M.; Hamer, M.; Singh-Manoux, A.; Batty, G.D.; Kivimäki, M. Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies. Mol. Psychiatry, 2014, 19(8), 910-914.
157. Berton, O.; Nestler, E.J. New approaches to antidepressant drug discovery: beyond monoamines. Nat. Rev. Neurosci., 2006, 7(2), 137-151.
158. Fond, G.; Loundou, A.; Hamdani, N.; Boukouaci, W.; Dargel, A.; Oliveira, J.; Roger, M.; Tamouza, R.; Leboyer, M.; Boyer, L. Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis. Eur. Arch. Psychiatry Clin. Neurosci., 2014, 264(8), 651-660.
159. Dinan, T.G.; Cryan, J.F. Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology. Psychoneuroendocrinology, 2012, 37(9), 1369-1378.
160. Neufeld, K.A.; Kang, N.; Bienenstock, J.; Foster, J.A. Effects of intestinal microbiota on anxiety-like behavior. Commun. Integr. Biol., 2011, 4(4), 492-494.
161. Barden, N. Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression. J. Psychiatry Neurosci., 2004, 29(3), 185-193.
162. García-Ródenas, C.L.; Bergonzelli, G.E.; Nutten, S.; Schumann, A.; Cherbut, C.; Turini, M.; Ornstein, K.; Rochat, F.; Corthésy-Theulaz, I. Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats. J. Pediatr. Gastroenterol. Nutr., 2006, 43(1), 16-24.
163. Gareau, M.G.; Jury, J.; MacQueen, G.; Sherman, P.M.; Perdue, M.H. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut, 2007, 56(11), 1522-1528.
164. Diaz Heijtz, R.; Wang, S.; Anuar, F.; Qian, Y.; Björkholm, B.; Samuelsson, A.; Hibberd, M.L.; Forssberg, H.; Pettersson, S. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA, 2011, 108(7), 3047-3052.
165. Neufeld, K.M.; Kang, N.; Bienenstock, J.; Foster, J.A. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol. Motil., 2011, 23(3), 255-264, e119.
166. Phillips, J.G. The treatment of melancholia by the lactic acid bacillus. Br. J. Psychiatry, 1910, 56, 422-431.
167. Desbonnet, L.; Garrett, L.; Clarke, G.; Kiely, B.; Cryan, J.F.; Dinan, T.G. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience, 2010, 170(4), 1179-1188.
168. Bravo, J.A.; Forsythe, P.; Chew, M.V.; Escaravage, E.; Savignac, H.M.; Dinan, T.G.; Bienenstock, J.; Cryan, J.F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. USA, 2011, 108(38), 16050-16055.
169. Messaoudi, M.; Lalonde, R.; Violle, N.; Javelot, H.; Desor, D.; Nejdi, A.; Bisson, J.F.; Rougeot, C.; Pichelin, M.; Cazaubiel, M.; Cazaubiel, J.M. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr., 2011, 105(5), 755-764.
170. Bailey, M.T.; Dowd, S.E.; Galley, J.D.; Hufnagle, A.R.; Allen, R.G.; Lyte, M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stres-sor-induced immunomodulation. Brain Behav. Immun., 2011, 25(3), 397-407.
171. Lopresti, A.L.; Maker, G.L.; Hood, S.D.; Drummond, P.D. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2014, 48, 102-111.
172. Ley, R.E.; Turnbaugh, P.J.; Klein, S.; Gordon, J.I. Microbial ecology: human gut microbes associated with obesity. Nature, 2006, 444(7122), 1022-1023.
173. Jeffery, I.B.; OToole, P.W.; Öhman, L.; Claesson, M.J.; Deane, J.; Quigley, E.M.; Simrén, M. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut, 2012, 61(7), 997-1006.
174. Naseribafrouei, A.; Hestad, K.; Avershina, E.; Sekelja, M.; Linløkken, A.; Wilson, R.; Rudi, K. Correlation between the human fecal microbiota and depression. Neurogastroenterol. Motil., 2014, 26(8), 1155-1162.
175. Jiang, H.; Ling, Z.; Zhang, Y.; Mao, H.; Ma, Z.; Yin, Y.; Wang, W.; Tang, W.; Tan, Z.; Shi, J.; Li, L.; Ruan, B. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav. Immun., 2015, 48, 186-194.
176. Sokol, H.; Pigneur, B.; Watterlot, L.; Lakhdari, O.; Ber-múdez-Humarán, L.G.; Gratadoux, J.J.; Blugeon, S.; Bri-donneau, C.; Furet, J.P.; Corthier, G.; Grangette, C.; Vasquez, N.; Pochart, P.; Trugnan, G.; Thomas, G.; Blot-tière, H.M.; Doré, J.; Marteau, P.; Seksik, P.; Langella, P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl. Acad. Sci. USA, 2008, 105(43), 16731-16736.
177. Maes, M.; Kubera, M.; Leunis, J.C.; Berk, M.; Geffard, M.; Bosmans, E. In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatr. Scand., 2013, 127(5), 344-354.
178. Löwe, B.; Andresen, V.; Fraedrich, K.; Gappmayer, K.; Wegscheider, K.; Treszl, A.; Riegel, B.; Rose, M.; Lohse, A.W.; Broicher, W. Psychological outcome, fatigue, and quality of life after infection with shiga toxin-producing Escherichia coli O104. Clin. Gastroenterol. Hepatol., 2014, 12(11), 1848-1855.
179. Goehler, L.E.; Park, S.M.; Opitz, N.; Lyte, M.; Gaykema, R.P. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav. Immun., 2008, 22(3), 354-366.
180. Lyte, M; Li, W; Opitz, N; Gaykema, RP; Goehler, LE Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyper-plasia Citrobacter rodentium. Physiol Behav., 2006, 30;89(3), 350-7.
181. Davey, K.J.; Cotter, P.D.; OSullivan, O.; Crispie, F.; Dinan, T.G.; Cryan, J.F.; OMahony, S.M. Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction is attenuated by antibiotic administration in the rat. Transl. Psychiatry, 2013, 3, e309.
182. Vince, A.J.; McNeil, N.I.; Wager, J.D.; Wrong, O.M. The effect of lactulose, pectin, arabinogalactan and cellulose on the production of organic acids and metabolism of ammonia by intestinal bacteria in a faecal incubation system. Br. J. Nutr., 1990, 63(1), 17-26.
183. Sun, J.; Wang, F.; Hong, G.; Pang, M.; Xu, H.; Li, H.; Tian, F.; Fang, R.; Yao, Y.; Liu, J. Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress. Neurosci. Lett., 2016, 618, 159-166.
184. Valvassori, S.S.; Varela, R.B.; Arent, C.O.; Dal-Pont, G.C.; Bobsin, T.S.; Budni, J.; Reus, G.Z.; Quevedo, J. Sodium butyrate functions as an antidepressant and improves cognition with enhanced neurotrophic expression in models of maternal deprivation and chronic mild stress. Curr. Neurovasc. Res., 2014, 11(4), 359-366.
185. Mamalakis, G.; Tornaritis, M.; Kafatos, A. Depression and adipose essential polyunsaturated fatty acids. Prostaglandins Leukot. Essent. Fatty Acids, 2002, 67(5), 311-318.
186. Carrié, I.; Clément, M.; de Javel, D.; Francès, H.; Bourre, J.M. Phospholipid supplementation reverses behavioral and biochemical alterations induced by n-3 polyunsaturated fatty acid deficiency in mice. J. Lipid Res., 2000, 41(3), 473-480.
187. Ross, B.M. Omega-3 polyunsaturated fatty acids and anxiety disorders. Prostaglandins Leukot. Essent. Fatty Acids, 2009, 81(5-6), 309-312.
188. Martins, J.G. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J. Am. Coll. Nutr., 2009, 28(5), 525-542.
189. Skouroliakou, M.; Konstantinou, D.; Koutri, K.; Kakavelaki, C.; Stathopoulou, M.; Antoniadi, M.; Xemelidis, N.; Kona, V.; Markantonis, S. A double-blind, randomized clinical trial of the effect of omega-3 fatty acids on the oxidative stress of preterm neonates fed through parenteral nutrition. Eur. J. Clin. Nutr., 2010, 64(9), 940-947.
190. Watkins, B.A.; Kim, J. The endocannabinoid system: directing eating behavior and macronutrient metabolism. Front. Psychol., 2015, 5, 1506.
191. Calder, P.C. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am. J. Clin. Nutr., 2006, 83(6)(Suppl.), 1505S-1519S.
192. Viveros, M.P.; Marco, E.M.; File, S.E. Endocannabinoid system and stress and anxiety responses. Pharmacol. Biochem. Behav., 2005, 81(2), 331-342.
193. Scherma, M.; Medalie, J.; Fratta, W.; Vadivel, S.K.; Makriyannis, A.; Piomelli, D.; Mikics, E.; Haller, J.; Yasar, S.; Tanda, G.; Goldberg, S.R. The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. Neuropharmacology, 2008, 54(1), 129-140.
194. Lafenêtre, P.; Chaouloff, F.; Marsicano, G. The endocannabinoid system in the processing of anxiety and fear and how CB1 receptors may modulate fear extinction. Pharmacol. Res., 2007, 56(5), 367-381.
195. Mato, S; Rodriguez-Puertas, R; González-Maeso, J; Meana, J; Sallés, J; Pazos, A Receptores centrales para cannabinoides en cerebro humano postmortem: estudio radiométrico en la depresión mayor. 1a Reunión nacional sobre investigación en cannabinoides Madrid 2000.
196. Witkin, J.M.; Tzavara, E.T.; Davis, R.J.; Li, X.; Nomikos, G.G. A therapeutic role for cannabinoid CB1 receptor antagonists in major depressive disorders. Trends Pharmacol. Sci., 2005, 26(12), 609-617.
197. Pistis, M.; Ferraro, L.; Pira, L.; Flore, G.; Tanganelli, S.; Gessa, G.L.; Devoto, P. Delta(9)-tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: an in vivo microdialysis study. Brain Res., 2002, 948(1-2), 155-158.
198. Hill, M.N.; Gorzalka, B.B. Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. Eur. Neuropsychopharmacol., 2005, 15(6), 593-599.
199. Kathuria, S.; Gaetani, S.; Fegley, D.; Valiño, F.; Duranti, A.; Tontini, A.; Mor, M.; Tarzia, G.; La Rana, G.; Calignano, A.; Giustino, A.; Tattoli, M.; Palmery, M.; Cuomo, V.; Piomelli, D. Modulation of anxiety through blockade of anandamide hydrolysis. Nat. Med., 2003, 9(1), 76-81.
200. Patel, S.; Hillard, C.J. Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J. Pharmacol. Exp. Ther., 2006, 318(1), 304-311.
201. Aso, E.; Ozaita, A.; Valdizán, E.M.; Ledent, C.; Pazos, A.; Maldonado, R.; Valverde, O. BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J. Neurochem., 2008, 105(2), 565-572.
202. Crupi, R.; Impellizzeri, D.; Bruschetta, G.; Cordaro, M.; Paterniti, I.; Siracusa, R.; Cuzzocrea, S.; Esposito, E. Co-Ultramicronized Palmitoylethanolamide/Luteolin Promotes Neuronal Regeneration after Spinal Cord Injury. Front. Pharmacol., 2016, 7, 47.
203. Braak, H.; de Vos, R.A.; Bohl, J.; Del Tredici, K. Gastric alpha-synuclein immunoreactive inclusions in Meissners and Auerbachs plexuses in cases staged for Parkinsons dis-ease-related brain pathology. Neurosci. Lett., 2006, 396(1), 67-72.
204. Holmqvist, S.; Chutna, O.; Bousset, L.; Aldrin-Kirk, P.; Li, W.; Björklund, T.; Wang, Z.Y.; Roybon, L.; Melki, R.; Li, J.Y. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol., 2014, 128(6), 805-820.
205. Devos, D.; Lebouvier, T.; Lardeux, B.; Biraud, M.; Rouaud, T.; Pouclet, H.; Coron, E.; Bruley des Varannes, S.; Naveil-han, P.; Nguyen, J.M.; Neunlist, M.; Derkinderen, P. Colonic inflammation in Parkinsons disease. Neurobiol. Dis., 2013, 50, 42-48.
206. Reijerkerk, A.; Kooij, G.; van der Pol, S.M.; Khazen, S.; Dijkstra, C.D.; de Vries, H.E. Diapedesis of monocytes is associated with MMP-mediated occludin disappearance in brain endothelial cells. FASEB J., 2006, 20(14), 2550-2552.
207. Verslegers, M.; Lemmens, K.; Van Hove, I.; Moons, L. Matrix metalloproteinase-2 and-9 as promising benefactors in development, plasticity and repair of the nervous system. Prog. Neurobiol., 2013, 105, 60-78.
208. Svedin, P.; Hagberg, H.; Sävman, K.; Zhu, C.; Mallard, C. Matrix metalloproteinase-9 gene knock-out protects the immature brain after cerebral hypoxia-ischemia. J. Neurosci., 2007, 27(7), 1511-1518.
209. Keshavarzian, A; Green, SJ; Engen, PA; Voigt, RM; Naqib, A; Forsyth, CB; Mutlu, E.; Shannon, KM Colonic bacterial composition in Parkinson's disease. Mov. Disord., 2015, 1351e1360.
210. Unger, M.M.; Spiegel, J.; Dillmann, K.U.; Grundmann, D.; Philippeit, H.; Bürmann, J.; Faßbender, K.; Schwiertz, A.; Schäfer, K.H. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord., 2016, 32, 66-72.
211. Quigley, E.M. Microflora modulation of motility. J. Neurogastroenterol. Motil., 2011, 17(2), 140-147.
212. Cassani, E.; Privitera, G.; Pezzoli, G.; Pusani, C.; Madio, C.; Iorio, L.; Barichella, M. Use of probiotics for the treatment of constipation in Parkinsons disease patients. Minerva Gastroenterol. Dietol., 2011, 57(2), 117-121.
213. Heetun, Z.S.; Quigley, E.M. Gastroparesis and Parkinsons disease: a systematic review. Parkinsonism Relat. Disord., 2012, 18(5), 433-440.
214. Hyland, N.P.; Quigley, E.M.; Brint, E. Microbiota-host interactions in irritable bowel syndrome: epithelial barrier, immune regulation and brain-gut interactions. World J. Gastroenterol., 2014, 20(27), 8859-8866.
215. Ankri, S.; Mirelman, D. Antimicrobial properties of allicin from garlic. Microbes Infect., 1999, 1(2), 125-129.
216. Brenes, M.; Medina, E.; Romero, C.; De Castro, A. Antimicrobial activity of olive oil. Agro Food Ind. Hi-Tech, 2007, 18, 6-8.
217. Lebouvier, T.; Neunlist, M.; Bruley des Varannes, S.; Coron, E.; Drouard, A.; NGuyen, J.M.; Chaumette, T.; Tas-selli, M.; Paillusson, S.; Flamand, M.; Galmiche, J.P.; Damier, P.; Derkinderen, P. Colonic biopsies to assess the neuropathology of Parkinsons disease and its relationship with symptoms. PLoS One, 2010, 5(9), e12728.
218. Pouclet, H.; Lebouvier, T.; Coron, E.; des Varannes, S.B.; Rouaud, T.; Roy, M.; Neunlist, M.; Derkinderen, P. A comparison between rectal and colonic biopsies to detect Lewy pathology in Parkinsons disease. Neurobiol. Dis., 2012, 45(1), 305-309.
219. Singh, R.K.; Rai, D.; Yadav, D.; Bhargava, A.; Balzarini, J.; De Clercq, E. Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid. Eur. J. Med. Chem., 2010, 45(3), 1078-1086.
220. Lai, S.W.; Liao, K.F.; Lin, C.L.; Sung, F.C. Irritable bowel syndrome correlates with increased risk of Parkinsons disease in Taiwan. Eur. J. Epidemiol., 2014, 29(1), 57-62.
221. Marques, S.C.; Oliveira, C.R.; Pereira, C.M.; Outeiro, T.F. Epigenetics in neurodegeneration: a new layer of complexity. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2011, 35(2), 348-355.
222. Abel, T.; Zukin, R.S. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr. Opin. Pharmacol., 2008, 8(1), 57-64.
223. Konsoula, Z.; Barile, F.A. Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders. J. Pharmacol. Toxicol. Methods, 2012, 66(3), 215-220.
224. St Laurent, R.; OBrien, L.M.; Ahmad, S.T. Sodium butyrate improves locomotor impairment and early mortality in a ro-tenone-induced Drosophila model of Parkinsons disease. Neuroscience, 2013, 246, 382-390.
225. Rao, J.S.; Ertley, R.N.; Lee, H.J.; DeMar, J.C., Jr; Arnold, J.T.; Rapoport, S.I.; Bazinet, R.P. n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Mol. Psychiatry, 2007, 12(1), 36-46.
226. Bousquet, M.; Gibrat, C.; Saint-Pierre, M.; Julien, C.; Calon, F.; Cicchetti, F. Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33(8), 1401-1408.
227. Mahmoudi, S.; Samadi, P.; Gilbert, F.; Ouattara, B.; Moris-sette, M.; Grégoire, L.; Rouillard, C.; Di Paolo, T.; Lévesque, D. Nur77 mRNA levels and L-Dopa-induced dy-skinesias in MPTP monkeys treated with docosahexaenoic acid. Neurobiol. Dis., 2009, 36(1), 213-222.
228. More, S.V.; Choi, D.K. Promising cannabinoid-based therapies for Parkinsons disease: motor symptoms to neuro-protection. Mol. Neurodegener., 2015, 10, 17.
229. Esposito, E.; Impellizzeri, D.; Mazzon, E.; Paterniti, I.; Cuzzocrea, S. Neuroprotective activities of palmitoyletha-nolamide in an animal model of Parkinsons disease. PLoS One, 2012, 7(8), e41880.
230. Avagliano, C; Russo, R; De Caro, C; Cristiano, C; La Rana, G; Piegari, G; Paciello, O; Citraro, R; Russo, E; De Sarro, G; Meli, R; Mattace Raso, G; Calignano, A. Palmitoylethanolamide protects mice against 6-OHDA-induced neurotoxicity and endoplasmic reticulum stress: In vivo and in vitro evidence. Pharmacol Res., 2016, 113(Pt A), 276-289.
231. Gu, Y.; Luchsinger, J.A.; Stern, Y.; Scarmeas, N. Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimers disease. J. Alzheimers Dis., 2010, 22(2), 483-492.
232. Aziz, Q.; Doré, J.; Emmanuel, A.; Guarner, F.; Quigley, E.M. Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol. Motil., 2013, 25(1), 4-15.
233. Hornig, M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr. Opin. Rheumatol., 2013, 25(4), 488-795.
234. Mandal, M.D.; Mandal, S. Honey: its medicinal property and antibacterial activity. Asian Pac. J. Trop. Biomed., 2011, 1(2), 154-160.
235. Mitew, S.; Kirkcaldie, M.T.; Dickson, T.C.; Vickers, J.C. Altered synapses and gliotransmission in Alzheimers disease and AD model mice. Neurobiol. Aging, 2013, 34(10), 2341-2351.
236. Paula-Lima, A.C.; Brito-Moreira, J.; Ferreira, S.T. Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimers disease. J. Neurochem., 2013, 126(2), 191-202.
237. Carlino, D.; De Vanna, M.; Tongiorgi, E. Is altered BDNF biosynthesis a general feature in patients with cognitive dysfunctions? Neuroscientist, 2013, 19(4), 345-353.
238. Lakhan, S.E.; Caro, M.; Hadzimichalis, N. NMDA receptor activity in neuropsychiatric disorders. Front. Psychiatry, 2013, 4, 52-55.
239. Brenner, S.R. Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimers disease and Parkinson-Dementia-Complex in humans and Equine Motor Neuron Disease in horses. Med. Hypotheses, 2013, 80(1), 103-108.
240. He, F.; Balling, R. The role of regulatory T cells in neurodegenerative diseases. Wiley Interdiscip. Rev. Syst. Biol. Med., 2013, 5(2), 153-180.
241. Schwartz, K.; Boles, B.R. Microbial amyloidsfunctions and interactions within the host. Curr. Opin. Microbiol., 2013, 16(1), 93-99.
242. Tran, L.; Greenwood-Van Meerveld, B. Age-associated remodeling of the intestinal epithelial barrier. J. Gerontol. A Biol. Sci. Med. Sci., 2013, 68(9), 1045-1056.
243. Ball, M.J.; Lukiw, W.J.; Kammerman, E.M.; Hill, J.M. Intracerebral propagation of Alzheimers disease: strengthening evidence of a herpes simplex virus etiology. Alzheimers Dement., 2013, 9(2), 169-175.
244. Douglas-Escobar, M.; Elliott, E.; Neu, J. Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr., 2013, 167(4), 374-379.
245. Ochoa-Repáraz, J.; Mielcarz, D.W.; Begum-Haque, S.; Kasper, L.H. Gut, bugs, and brain: role of commensal bacteria in the control of central nervous system disease. Ann. Neurol., 2011, 69(2), 240-247.
246. Berer, K.; Mues, M.; Koutrolos, M.; Rasbi, Z.A.; Boziki, M.; Johner, C.; Wekerle, H.; Krishnamoorthy, G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature, 2011, 479(7374), 538-541.
247. van der Stelt, M.; Mazzola, C.; Esposito, G.; Matias, I.; Petrosino, S.; De Filippis, D.; Micale, V.; Steardo, L.; Drago, F.; Iuvone, T.; Di Marzo, V. Endocannabinoids and beta-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels. Cell. Mol. Life Sci., 2006, 63(12), 1410-1424.
248. Fidaleo, M.; Fanelli, F.; Ceru, M.P.; Moreno, S. Neuroprotective properties of peroxisome proliferator-activated receptor alpha (PPARα) and its lipid ligands. Curr. Med. Chem., 2014, 21(24), 2803-2821.
249. Zhang, H.; Gao, Y.; Qiao, P.F.; Zhao, F.L.; Yan, Y. Fenofi-brate reduces amyloidogenic processing of APP in APP/PS1 transgenic mice via PPAR-α/PI3-K pathway. Int. J. Dev. Neurosci., 2014, 38, 223-231.
250. DAgostino, G.; Russo, R.; Avagliano, C.; Cristiano, C.; Meli, R.; Calignano, A. Palmitoylethanolamide protects against the amyloid-β2535-induced learning and memory impairment in mice, an experimental model of Alzheimer disease. Neuropsychopharmacology, 2012, 37(7), 1784-1792.
251. Root-Bernstein, R.S.; Westall, F.C. Serotonin binding sites. II. Muramyl dipeptide binds to serotonin binding sites on myelin basic protein, LHRH, and MSH-ACTH 410. Brain Res. Bull., 1990, 25(6), 827-841.
252. Westall, F.C. Molecular mimicry revisited: gut bacteria and multiple sclerosis. J. Clin. Microbiol., 2006, 44(6), 2099-2104.
253. Ivanov, I.I.; Atarashi, K.; Manel, N.; Brodie, E.L.; Shima, T.; Karaoz, U.; Wei, D.; Goldfarb, K.C.; Santee, C.A.; Lynch, S.V.; Tanoue, T.; Imaoka, A.; Itoh, K.; Takeda, K.; Umesaki, Y.; Honda, K.; Littman, D.R. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 2009, 139(3), 485-498.
254. Winer, S.; Paltser, G.; Chan, Y.; Tsui, H.; Engleman, E.; Winer, D.; Dosch, H.M. Obesity predisposes to Th17 bias. Eur. J. Immunol., 2009, 39(9), 2629-2635.
255. Lord, G.M.; Matarese, G.; Howard, J.K.; Baker, R.J.; Bloom, S.R.; Lechler, R.I. Leptin modulates the T-cell immune response and reverses starvation-induced immuno-suppression. Nature, 1998, 394(6696), 897-901.
256. La Cava, A.; Matarese, G. The weight of leptin in immunity. Nat. Rev. Immunol., 2004, 4(5), 371-379.
257. Frisullo, G.; Mirabella, M.; Angelucci, F.; Caggiula, M.; Morosetti, R.; Sancricca, C.; Patanella, A.K.; Nociti, V.; Iorio, R.; Bianco, A.; Tomassini, V.; Pozzilli, C.; Tonali, P.A.; Matarese, G.; Batocchi, A.P. The effect of disease activity on leptin, leptin receptor and suppressor of cytokine signalling-3 expression in relapsing-remitting multiple sclerosis. J. Neuroimmunol., 2007, 192(1-2), 174-183.
258. Lock, C.; Hermans, G.; Pedotti, R.; Brendolan, A.; Schadt, E.; Garren, H.; Langer-Gould, A.; Strober, S.; Cannella, B.; Allard, J.; Klonowski, P.; Austin, A.; Lad, N.; Kaminski, N.; Galli, S.J.; Oksenberg, J.R.; Raine, C.S.; Heller, R.; Steinman, L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med., 2002, 8(5), 500-508.
259. Miyake, S.; Kim, S.; Suda, W.; Oshima, K.; Nakamura, M.; Matsuoka, T.; Chihara, N.; Tomita, A.; Sato, W.; Kim, S.W.; Morita, H.; Hattori, M.; Yamamura, T. Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. PLoS One, 2015, 10(9), e0137429.
260. Atarashi, K.; Tanoue, T.; Oshima, K.; Suda, W.; Nagano, Y.; Nishikawa, H.; Fukuda, S.; Saito, T.; Narushima, S.; Hase, K.; Kim, S.; Fritz, J.V.; Wilmes, P.; Ueha, S.; Matsushima, K.; Ohno, H.; Olle, B.; Sakaguchi, S.; Taniguchi, T.; Morita, H.; Hattori, M.; Honda, K. Treg induction by a ra-tionally selected mixture of Clostridia strains from the human microbiota. Nature, 2013, 500(7461), 232-236.
261. Tao, R.; de Zoeten, E.F.; Ozkaynak, E.; Chen, C.; Wang, L.; Porrett, P.M.; Li, B.; Turka, L.A.; Olson, E.N.; Greene, M.I.; Wells, A.D.; Hancock, W.W. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med., 2007, 13(11), 1299-1307.
262. Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J.R.; Pfeffer, K.; Coffer, P.J.; Rudensky, A.Y. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 2013, 504(7480), 451-455.
263. Haghikia, A.; Jörg, S.; Duscha, A.; Berg, J.; Manzel, A.; Waschbisch, A.; Hammer, A.; Lee, D.H.; May, C.; Wilck, N.; Balogh, A.; Ostermann, A.I.; Schebb, N.H.; Akkad, D.A.; Grohme, D.A.; Kleinewietfeld, M.; Kempa, S.; Thöne, J.; Demir, S.; Müller, D.N.; Gold, R.; Linker, R.A. Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity, 2015, 43(4), 817-829.
264. Furusawa, Y.; Obata, Y.; Fukuda, S.; Endo, T.A.; Nakato, G.; Takahashi, D.; Nakanishi, Y.; Uetake, C.; Kato, K.; Kato, T.; Takahashi, M.; Fukuda, N.N.; Murakami, S.; Mi-yauchi, E.; Hino, S.; Atarashi, K.; Onawa, S.; Fujimura, Y.; Lockett, T.; Clarke, J.M.; Topping, D.L.; Tomita, M.; Hori, S.; Ohara, O.; Morita, T.; Koseki, H.; Kikuchi, J.; Honda, K.; Hase, K.; Ohno, H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 2013, 504(7480), 446-450.
265. Wang, L.; de Zoeten, E.F.; Greene, M.I.; Hancock, W.W. Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP3+ regulatory T cells. Nat. Rev. Drug Discov., 2009, 8(12), 969-981.
266. Cummings, J.H.; Pomare, E.W.; Branch, W.J.; Naylor, C.P.; Macfarlane, G.T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut, 1987, 28(10), 1221-1227.
267. Banati, M.; Csecsei, P.; Koszegi, E.; Nielsen, H.H.; Suto, G.; Bors, L.; Trauninger, A.; Csepany, T.; Rozsa, C.; Jakab, G.; Molnar, T.; Berthele, A.; Kalluri, S.R.; Berki, T.; Illes, Z. Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system. Eur. J. Neurol., 2013, 20(11), 1492-1495.
268. Ezendam, J; de Klerk, A; Gremmer, ER; van Loveren, H Effects of Bifidobacterium animalisadministered during lactation on allergic and autoimmune responses in rodents. Clin. Exp. Immunol., 2008, 154, 424-431.
269. Ezendam, J.; van Loveren, H. Lactobacillus casei Shirota administered during lactation increases the duration of auto-immunity in rats and enhances lung inflammation in mice. Br. J. Nutr., 2008, 99(1), 83-90.
270. Maassen, C.B.; Claassen, E. Strain-dependent effects of probiotic lactobacilli on EAE autoimmunity. Vaccine, 2008, 26(17), 2056-2057.
271. Kobayashi, T.; Kato, I.; Nanno, M.; Shida, K.; Shibuya, K.; Matsuoka, Y.; Onoue, M. Oral administration of probiotic bacteria, Lactobacillus casei and Bifidobacterium breve, does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis. Immunopharmacol. Immu-notoxicol., 2010, 32(1), 116-124.
272. Kobayashi, T.; Suzuki, T.; Kaji, R.; Serata, M.; Nagata, T.; Ando, M.; Iizuka, R.; Tsujibe, S.; Murakami, J.; Kiyo-shima-Shibata, J.; Kato, I.; Nanno, M.; Shida, K. Probiotic upregulation of peripheral IL-17 responses does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis mouse models. Immunopharmacol. Im-munotoxicol., 2012, 34(3), 423-433.
273. Kwon, H.K.; Kim, G.C.; Kim, Y.; Hwang, W.; Jash, A.; Sahoo, A.; Kim, J.E.; Nam, J.H.; Im, S.H. Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin. Immunol., 2013, 146(3), 217-227.
274. Takata, K.; Kinoshita, M.; Okuno, T.; Moriya, M.; Kohda, T.; Honorat, J.A.; Sugimoto, T.; Kumanogoh, A.; Kayama, H.; Takeda, K.; Sakoda, S.; Nakatsuji, Y. The lactic acid bacterium Pediococcus acidilactici suppresses autoimmune encephalomyelitis by inducing IL-10-producing regulatory T cells. PLoS One, 2011, 6(11), e27644.
275. Rezende, R.M.; Oliveira, R.P.; Medeiros, S.R.; Gomes-Santos, A.C.; Alves, A.C.; Loli, F.G.; Guimarães, M.A.; Amaral, S.S.; da Cunha, A.P.; Weiner, H.L.; Azevedo, V.; Miyoshi, A.; Faria, A.M. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells. J. Autoimmun., 2013, 40, 45-57.
276. Piccio, L.; Stark, J.L.; Cross, A.H. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J. Leukoc. Biol., 2008, 84(4), 940-948.
277. Kleinewietfeld, M.; Manzel, A.; Titze, J.; Kvakan, H.; Yo-sef, N.; Linker, R.A.; Muller, D.N.; Hafler, D.A. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature, 2013, 496(7446), 518-522.
278. Baker, D.; Pryce, G. The endocannabinoid system and multiple sclerosis. Curr. Pharm. Des., 2008, 14(23), 2326-2336.