Display options
Share it on

Front Neurosci. 2017 Mar 27;11:155. doi: 10.3389/fnins.2017.00155. eCollection 2017.

Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia?.

Frontiers in neuroscience

Jamie Joseph, Colin Depp, Pei-An B Shih, Kristen S Cadenhead, Geert Schmid-Schönbein

Affiliations

  1. Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
  2. Department of Psychiatry, University of CaliforniaSan Diego, La Jolla, CA, USA; Department of Psychology, VA San Diego Healthcare SystemSan Diego, CA, USA.
  3. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.

PMID: 28396623 PMCID: PMC5366345 DOI: 10.3389/fnins.2017.00155

Abstract

Growing interest in gut and digestive processes and their potential link to brain and peripheral based inflammation or biobehavioral phenotypes has led to an increasing number of basic and translational scientific reports focused on the role of gut microbiota within the context of neuropsychiatric disorders. However, the effect of dietary modification on specific gut metabolites, in association with immune, metabolic, and psychopathological functioning in schizophrenia spectrum disorders has not been well characterized. The short chain fatty acids (SCFA) acetate, butyrate, and propionate, major metabolites derived from fermentation of dietary fibers by gut microbes, interact with multiple immune and metabolic pathways. The specific pathways that SCFA are thought to target, are dysregulated in cardiovascular disease, type II diabetes, and systemic inflammation. Most notably, these disorders are consistently linked to an attenuated lifespan in schizophrenia. Although, unhealthy dietary intake patterns and increased prevalence of immune and metabolic dysfunction has been observed in people with schizophrenia; dietary interventions have not been well utilized to target immune or metabolic illness. Prior schizophrenia patient trials primarily focused on the effects of gluten free diets. Findings from these studies indicate that a diet avoiding gluten benefits a limited subset of patients, individuals with celiac disease or non-celiac gluten sensitivity. Therefore, alternative dietary and nutritional modifications such as high-fiber, Mediterranean style, diets that enrich the production of SCFA, while being associated with a minimal likelihood of adverse events, may improve immune and cardiovascular outcomes linked to premature mortality in schizophrenia. With a growing literature demonstrating that SCFA can cross the blood brain barrier and target key inflammatory and metabolic pathways, this article highlights enriching dietary intake for SCFA as a potential adjunctive therapy for people with schizophrenia.

Keywords: acetate; butyrate; cardiovascular disease; gastrointestinal; inflammation; propionate; psychosis; type II diabetes

References

  1. Hypertension. 2002 Nov;40(5):612-8 - PubMed
  2. Schizophr Res. 2011 Feb;125(2-3):295-9 - PubMed
  3. Front Aging Neurosci. 2015 Apr 21;7:52 - PubMed
  4. Nutr Neurosci. 2004 Aug;7(4):247-9 - PubMed
  5. Gut Microbes. 2014 May-Jun;5(3):369-80 - PubMed
  6. Immune Netw. 2014 Dec;14(6):277-88 - PubMed
  7. J Am Coll Cardiol. 2011 Nov 8;58(20):2047-67 - PubMed
  8. Schizophr Res. 2004 Dec 15;72(1):29-39 - PubMed
  9. Schizophr Bull. 2013 May;39(3):575-82 - PubMed
  10. J Neuropsychiatry Clin Neurosci. 1994 Fall;6(4):348-57 - PubMed
  11. Curr Opin Clin Nutr Metab Care. 2010 Nov;13(6):715-21 - PubMed
  12. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Apr 5;42:20-34 - PubMed
  13. Br J Psychiatry. 1993 Jan;162:65-71 - PubMed
  14. Schizophr Res. 2016 Jan;170(1):177-83 - PubMed
  15. Biomed Pharmacother. 2002 Oct;56(8):365-79 - PubMed
  16. Am J Clin Nutr. 1999 Mar;69(3):354-65 - PubMed
  17. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jan 3;48:277-86 - PubMed
  18. Schizophr Res. 2012 May;137(1-3):190-5 - PubMed
  19. East Asian Arch Psychiatry. 2012 Jun;22(2):49-56 - PubMed
  20. Gut. 1987 Oct;28(10 ):1221-7 - PubMed
  21. Transl Psychiatry. 2016 May 03;6:e795 - PubMed
  22. Schizophr Res. 2012 May;137(1-3):147-50 - PubMed
  23. World J Biol Psychiatry. 2013 Sep;14(7):509-15 - PubMed
  24. Schizophr Res. 2015 Dec;169(1-3):494-5 - PubMed
  25. Schizophr Res. 2013 Jan;143(1):198-202 - PubMed
  26. N Engl J Med. 2013 Apr 4;368(14):1279-90 - PubMed
  27. Mol Psychiatry. 2016 Apr;21(4):554-64 - PubMed
  28. BMC Psychiatry. 2014 Jun 20;14 :184 - PubMed
  29. Nutr Rev. 2016 Jun;74(6):411-20 - PubMed
  30. Br J Psychiatry Suppl. 2007 Dec;51:s107-10 - PubMed
  31. J Nucl Med. 2009 Nov;50(11):1801-7 - PubMed
  32. Br J Psychiatry Suppl. 2004 Apr;47:S102-5 - PubMed
  33. Neurosci Biobehav Rev. 2011 Jan;35(3):573-88 - PubMed
  34. Biol Psychol. 2015 Apr;107:16-23 - PubMed
  35. Annu Rev Neurosci. 2002;25:409-32 - PubMed
  36. Arch Gen Psychiatry. 2003 Jun;60(6):585-94 - PubMed
  37. Neuroscience. 2015 Apr 2;290:126-37 - PubMed
  38. Neuropsychiatr Dis Treat. 2016 Feb 16;12:357-73 - PubMed
  39. Biol Psychiatry. 2001 Jul 15;50(2):71-83 - PubMed
  40. Neuropharmacology. 2015 Sep;96(Pt A):29-41 - PubMed
  41. Diabetes Obes Metab. 2010 Mar;12(3):204-9 - PubMed
  42. Neurobiol Dis. 2012 Dec;48(3):447-53 - PubMed
  43. Schizophr Res. 2014 Nov;159(2-3):395-403 - PubMed
  44. J Nutr. 2012 Jun;142(6):1019-25 - PubMed
  45. Int J Clin Exp Pathol. 2013 Jul 15;6(8):1574-84 - PubMed
  46. Schizophr Bull. 2003;29(2):393-7 - PubMed
  47. Brain. 2007 Sep;130(Pt 9):2387-400 - PubMed
  48. Int Rev Neurobiol. 2016;131:143-163 - PubMed
  49. Neuroimmunomodulation. 1995 Jul-Aug;2(4):241-8 - PubMed
  50. Clin Schizophr Relat Psychoses. 2016 Jul 25;:null - PubMed
  51. Mol Psychiatry. 2015 Jun;20(6):685-94 - PubMed
  52. Am J Psychiatry. 2003 Feb;160(2):284-9 - PubMed
  53. N Engl J Med. 2003 May 22;348(21):2082-90 - PubMed
  54. Lancet. 2004 Oct 9-15;364(9442):1312-3 - PubMed
  55. Am J Psychiatry. 2005 Jan;162(1):12-24 - PubMed
  56. JAMA Psychiatry. 2015 Dec;72(12):1172-81 - PubMed
  57. Neurosci Lett. 1999 Aug 20;271(2):126-8 - PubMed
  58. Eur J Nutr. 2008 Mar;47(2):104-13 - PubMed
  59. Schizophr Res. 2001 Apr 30;49(3):243-51 - PubMed
  60. Schizophr Bull. 2014 Jan;40(1):181-91 - PubMed
  61. Br J Psychiatry. 1990 Mar;156:448 - PubMed
  62. Schizophr Res. 2008 Jan;98(1-3):111-7 - PubMed
  63. J Pharmacol Exp Ther. 1996 Mar;276(3):1189-200 - PubMed
  64. Schizophr Res. 2015 Dec;169(1-3):351-4 - PubMed
  65. J Intern Med. 1997 Nov;242(5):421-3 - PubMed
  66. Arch Gen Psychiatry. 1990 Feb;47(2):181-8 - PubMed
  67. Compr Psychiatry. 2014 Feb;55(2):233-47 - PubMed
  68. Clin Schizophr Relat Psychoses. 2014 Jan;7(4):223-30 - PubMed
  69. Am J Psychiatry. 2007 Dec;164(12):1842-9 - PubMed
  70. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Apr 5;42:115-21 - PubMed
  71. Am J Clin Nutr. 2006 Apr;83(4):760-6 - PubMed
  72. Arch Intern Med. 2010 Jan 25;170(2):126-35 - PubMed
  73. Circulation. 2003 Jul 15;108(2):161-5 - PubMed
  74. Am J Physiol. 1973 Jun;224(6):1450-3 - PubMed
  75. Br J Psychiatry. 2009 May;194(5):434-8 - PubMed
  76. Int Neurourol J. 2016 May;20(Suppl 1):S2-7 - PubMed
  77. Science. 1994 Oct 14;266(5183):294-8 - PubMed
  78. Schizophr Bull. 2013 Mar;39(2):306-18 - PubMed
  79. Epilepsia. 1992 Nov-Dec;33(6):1132-6 - PubMed
  80. Schizophr Res. 2005 Dec 1;80(1):45-53 - PubMed
  81. Obes Rev. 2016 May;17(5):442-54 - PubMed
  82. J Neurochem. 2009 Oct;111(2):510-21 - PubMed
  83. Cardiovasc Drug Rev. 2006 Spring;24(1):33-50 - PubMed
  84. Psychol Med. 1999 May;29(3):697-701 - PubMed
  85. Isr J Psychiatry Relat Sci. 2008;45(1):3-10 - PubMed
  86. Neurochem Res. 2015 May;40(5):906-14 - PubMed
  87. Nature. 2006 Dec 14;444(7121):860-7 - PubMed
  88. Eur Cytokine Netw. 2007 Sep;18(3):148-53 - PubMed
  89. Curr Pharm Des. 2011;17(12):1158-67 - PubMed
  90. Science. 1976 Jan 30;191(4225):401-2 - PubMed
  91. Diabetes Metab Res Rev. 2016 Jan;32(1):73-81 - PubMed
  92. Acta Psychiatr Scand. 2006 Feb;113(2):82-90 - PubMed
  93. Schizophr Bull. 2013 Jul;39(4):867-71 - PubMed
  94. Front Neurosci. 2015 Oct 21;9:372 - PubMed
  95. Am J Psychiatry. 2006 Mar;163(3):521-8 - PubMed
  96. Schizophr Res. 2012 Sep;140(1-3):169-74 - PubMed
  97. Biol Psychiatry. 2011 Mar 1;69(5):424-31 - PubMed
  98. Eur Psychiatry. 2016 Jan;31:8-12 - PubMed
  99. JAMA Psychiatry. 2014 Dec 1;71(12):1350-63 - PubMed
  100. Med Hypotheses. 2007;68(2):259-67 - PubMed
  101. Psychiatr Q. 2012 Mar;83(1):91-102 - PubMed
  102. Neuropsychol Rev. 2005 Jun;15(2):73-95 - PubMed
  103. Adv Neurobiol. 2016;13:307-326 - PubMed
  104. Can J Psychiatry. 2007 Jan;52(1):55-60 - PubMed
  105. N Engl J Med. 2008 Jul 17;359(3):229-41 - PubMed
  106. J Clin Psychiatry. 2016 Jan;77(1):131-2 - PubMed
  107. Schizophr Bull. 2007 Nov;33(6):1373-8 - PubMed
  108. Psychol Med. 1998 Mar;28(2):463-73 - PubMed
  109. Acta Psychiatr Scand. 2015 Oct;132(4):293-300 - PubMed
  110. Nature. 2016 Feb 11;530(7589):177-83 - PubMed
  111. Schizophr Res. 2012 Dec;142(1-3):171-6 - PubMed
  112. Neuroimage. 2006 Jan 15;29(2):409-16 - PubMed
  113. Mol Psychiatry. 2013 Jan;18(1):67-78 - PubMed
  114. Arch Gen Psychiatry. 2007 Oct;64(10):1123-31 - PubMed
  115. Br J Nutr. 2009 Oct;102(8):1154-60 - PubMed
  116. Int J Obes Relat Metab Disord. 1995 Nov;19(11):811-6 - PubMed
  117. Mol Psychiatry. 2005 Jul;10(7):637-50 - PubMed
  118. Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1779-92 - PubMed
  119. World J Gastroenterol. 2007 May 28;13(20):2826-32 - PubMed
  120. Biol Psychiatry. 2009 Mar 15;65(6):481-8 - PubMed
  121. Stroke. 2016 Apr;47(4):986-90 - PubMed
  122. Reprod Nutr Dev. 2004 May-Jun;44(3):273-82 - PubMed
  123. Eur Psychiatry. 2013 Mar;28(3):161-7 - PubMed
  124. N Engl J Med. 2001 Jan 4;344(1):3-10 - PubMed
  125. Br J Nutr. 2010 Aug;104 Suppl 2:S1-63 - PubMed
  126. Schizophr Res. 2015 Feb;161(2-3):283-90 - PubMed
  127. Schizophr Bull. 2011 Jan;37(1):94-100 - PubMed
  128. Schizophr Res. 2003 Apr 1;60(2-3):285-98 - PubMed
  129. Schizophr Bull. 2016 Nov;42(6):1504-1516 - PubMed
  130. Daru. 2014 Jul 10;22:55 - PubMed
  131. Schizophr Res. 2014 Nov;159(2-3):539-42 - PubMed
  132. Br J Pharmacol. 2004 Mar;141(5):874-80 - PubMed
  133. Glia. 2016 Feb;64(2):300-16 - PubMed
  134. Wiley Interdiscip Rev Syst Biol Med. 2010 Sep-Oct;2(5):577-93 - PubMed
  135. Ann Clin Psychiatry. 2015 Nov;27(4):289-96 - PubMed
  136. Acta Psychiatr Scand. 2016 Apr;133(4):289-97 - PubMed
  137. Biochem Biophys Res Commun. 2003 Apr 18;303(4):1047-52 - PubMed
  138. Schizophr Res. 2006 Sep;86(1-3):15-22 - PubMed
  139. Schizophr Res. 2015 Dec;169(1-3):491-3 - PubMed
  140. Psychiatry Res. 2010 Jan 30;175(1-2):47-53 - PubMed
  141. J Clin Exp Cardiolog. 2016 Apr;7(4):null - PubMed
  142. Atherosclerosis. 2008 Mar;197(1):12-24 - PubMed
  143. Arch Gen Psychiatry. 2012 Feb;69(2):129-38 - PubMed
  144. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):323-7 - PubMed
  145. Nutr Res. 2016 May;36(5):391-401 - PubMed
  146. J Psychiatr Res. 2005 Sep;39(5):499-508 - PubMed
  147. Vojnosanit Pregl. 2015 Dec;72(12):1085-92 - PubMed
  148. Schizophr Res. 2007 Mar;91(1-3):37-50 - PubMed
  149. Psychiatr Danub. 2016 Jun;28(2):104-10 - PubMed
  150. Circulation. 2001 Apr 3;103(13):1813-8 - PubMed
  151. Neurobiol Aging. 2007 Mar;28(3):424-39 - PubMed
  152. Ther Adv Psychopharmacol. 2014 Jun;4(3):110-6 - PubMed
  153. J Biol Chem. 2003 Mar 28;278(13):11312-9 - PubMed
  154. Food Funct. 2016 May 18;7(5):2347-56 - PubMed
  155. Mol Psychiatry. 2016 Jun;21(6):797-805 - PubMed
  156. Schizophr Bull. 2009 May;35(3):549-62 - PubMed
  157. JAMA Psychiatry. 2016 Sep 1;73(9):947-54 - PubMed
  158. Br J Psychiatry. 2006 Sep;189:204-12 - PubMed
  159. J Psychiatr Pract. 2015 May;21(3):190-7 - PubMed
  160. J Biol Chem. 2003 Jul 11;278(28):25481-9 - PubMed
  161. Arch Gen Psychiatry. 2004 Apr;61(4):354-60 - PubMed
  162. Schizophr Res. 2013 Aug;148(1-3):130-7 - PubMed
  163. Can J Psychiatry. 2003 Jun;48(5):345-7 - PubMed
  164. Schizophr Bull. 2016 Mar;42(2):309-17 - PubMed
  165. Iran J Public Health. 2015 May;44(5):639-45 - PubMed
  166. Curr Top Behav Neurosci. 2012;11:1-24 - PubMed
  167. J Clin Invest. 1985 Oct;76(4):1626-31 - PubMed
  168. JAMA. 2003 Aug 20;290(7):912-20 - PubMed
  169. Lancet Psychiatry. 2016 Aug;3(8):717-29 - PubMed
  170. Arch Intern Med. 2007 Dec 10;167(22):2437-42 - PubMed
  171. J Clin Psychiatry. 2005 Feb;66(2):167-73 - PubMed
  172. Br J Psychiatry. 2003 Dec;183:534-9 - PubMed
  173. Neuropsychopharmacology. 2006 Oct;31(10 ):2091-120 - PubMed
  174. BMC Psychiatry. 2007 May 02;7:15 - PubMed
  175. BMC Gastroenterol. 2011 Mar 08;11:17 - PubMed
  176. N Engl J Med. 1990 Mar 22;322(12):789-94 - PubMed
  177. Am J Psychiatry. 1973 Jun;130(6):685-8 - PubMed
  178. Annu Rev Biomed Eng. 2006;8:93-131 - PubMed
  179. Biochim Biophys Acta. 2009 Sep;1790(9):869-77 - PubMed
  180. J Clin Gastroenterol. 2006 Mar;40(3):235-43 - PubMed
  181. Pharmacol Res. 2013 Jan;67(1):18-30 - PubMed
  182. Nutr Health. 2003;17(3):211-9 - PubMed
  183. Arch Gen Psychiatry. 1995 Oct;52(10 ):829-36 - PubMed
  184. Biol Psychiatry. 2011 Oct 1;70(7):663-71 - PubMed
  185. Brain Res. 2008 Oct 27;1237:35-43 - PubMed
  186. Ann Clin Psychiatry. 2006 Apr-Jun;18(2):99-105 - PubMed
  187. Nat Commun. 2014 May 21;5:3944 - PubMed
  188. Gut. 1998 Oct;43(4):506-11 - PubMed
  189. J Nutr. 2008 Dec;138(12):2293-6 - PubMed
  190. Schizophr Res. 2013 Jun;147(1):24-31 - PubMed
  191. Schizophr Bull. 2016 Jun 27;:null - PubMed
  192. Am J Psychiatry. 1965 May;121:1110-1 - PubMed
  193. Expert Rev Neurother. 2007 Jul;7(7):789-96 - PubMed
  194. Schizophr Res. 2005 Dec 1;80(1):19-32 - PubMed
  195. Arch Gen Psychiatry. 1985 Apr;42(4):329-34 - PubMed
  196. Am J Psychiatry. 2002 Jul;159(7):1080-92 - PubMed
  197. Schizophr Res. 2006 Mar;83(1):87-93 - PubMed
  198. Rev Psiquiatr Salud Ment. 2014 Apr-Jun;7(2):72-9 - PubMed
  199. Psychiatry Clin Neurosci. 2004 Aug;58(4):403-9 - PubMed
  200. NPJ Schizophr. 2016 May 04;2:16018 - PubMed
  201. Br J Nutr. 2016 Jun;115(11):1987-93 - PubMed
  202. Nature. 2003 Mar 13;422(6928):173-6 - PubMed
  203. BMJ. 1998 Sep 19;317(7161):784-5 - PubMed
  204. Nutr Metab (Lond). 2009 Feb 26;6:10 - PubMed
  205. J Nutr. 1996 Nov;126(11):2807-12 - PubMed
  206. Schizophr Bull. 2000;26(4):903-12 - PubMed
  207. Schizophr Res. 2015 Oct;168(1-2):456-60 - PubMed
  208. Nutrients. 2015 Jul 08;7(7):5532-9 - PubMed
  209. J Card Fail. 2015 Dec;21(12 ):963-7 - PubMed
  210. Arch Gen Psychiatry. 1963 Dec;9:548-51 - PubMed
  211. Clin Chim Acta. 1979 Mar 1;92(2):153-9 - PubMed
  212. Am J Psychiatry. 2002 Sep;159(9):1596-8 - PubMed
  213. Am J Psychiatry. 2013 Sep;170(9):1032-40 - PubMed
  214. JAMA Psychiatry. 2017 Mar 1;74(3):261-269 - PubMed
  215. Am J Psychiatry. 2003 Jan;160(1):13-23 - PubMed
  216. Am J Psychiatry. 2016 Jan;173(1):44-52 - PubMed
  217. Cell. 2010 Sep 3;142(5):687-98 - PubMed
  218. Am J Psychiatry. 2000 Jul;157(7):1141-9 - PubMed
  219. Am J Med. 1998 Mar 30;104(3A):2S-8S; discussion 21S-22S - PubMed
  220. Arch Gen Psychiatry. 1997 Feb;54(2):159-65 - PubMed
  221. Arch Psychiatr Nurs. 1995 Apr;9(2):68-76 - PubMed
  222. Trends Pharmacol Sci. 2013 Mar;34(3):167-77 - PubMed
  223. Am Heart J. 2005 Dec;150(6):1115-21 - PubMed

Publication Types

Grant support