Microbiota and Neurological Disorders: A Gut Feeling

BioResearch Open Access

Volumn 5, Issue 1, 2016, Pages 137-145

  Moos, Walter H ^a   Faller, Douglas V ^b   Harpp, David N ^c   Kanara, Iphigenia ^d,e   Pernokas, Julie ^f   Powers, Whitney R ^b,g   Steliou, Kosta ^b,h  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c MCGILL UNIVERSITY   (Canada)

^d HARVARD UNIVERSITY   (United States)

^e Consulate General of Greece in Boston ^*  (United States)

^f Advanced Dental Associates of New England   (United States)

^g BOSTON UNIVERSITY   (United States)

^h PhenoMatriX Inc   (United States)

Author keywords

autism; dementia; dysbiosis; epigenetic; exercise; fatty acids; histone deacetylase; immune system; microbiota; mitochondria; neurodegenerative; probiotics; schizophrenia; synthetic biology; lipoic acid

Indexed keywords

HISTONE DEACETYLASE INHIBITOR;

AGING; BRAIN DEVELOPMENT; DEMENTIA; DISEASE ASSOCIATION; DYSBIOSIS; EPIGENETICS; HOST PATHOGEN INTERACTION; HUMAN; INTESTINE FLORA; INTESTINE INNERVATION; NEOPLASM; NEUROLOGIC DISEASE; NONHUMAN; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SYNTHETIC BIOLOGY;

EID: 85008263188     PISSN: None     EISSN: 21647860     Source Type: Journal    
DOI: 10.1089/biores.2016.0010     Document Type: Review

References (193)

1. Dietert J, Dietert R. The sum of our parts. Scientist. 2015;29:44-49.
2. Ghannoum M. The mycobiome. Scientist. 2016;30:32-37.
3. Fond G, Boukouaci W, Chevalier G, et al. The "psychomicrobiotic": targeting microbiota in major psychiatric disorders: a systematic review. Pathol Biol. 2015;63:35-42.
4. Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. BioRxiv. 2016 [Epub ahead of print]; DOI: http://dx.doi.org/10.1101/036103.
5. Blekhman R, Goodrich JK, Huang K, et al. Host genetic variation impacts microbiome composition across human body sites. Genome Biol. 2015;16:191.
6. Bohorquez DV, Liddle RA. The gut connectome: making sense of what you eat. J Clin Invest. 2015;125:888-890.
7. Koppel N, Balskus EP. Exploring and understanding the biochemical diversity of the human microbiota. Cell Chem Biol. 2016;23:18-30.
8. Forsythe P, Sudo N, Dinan T, et al. Mood and gut feelings. Brain Behav Immun. 2010;24:9-16.
9. Natarajan N, Pluznick JL. From microbe to man: the role of microbial short chain fatty acid metabolites in host cell biology. Am J Physiol Cell Physiol. 2014;307:C979-C985.
10. Dietert R, Dietert J. The microbiome and sustainable healthcare. Healthcare. 2015;3:100-129.
11. Caesar R, Tremaroli V, Kovatcheva-Datchary P, et al. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metabol. 2015;22:1-11.
12. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157:121-141.
13. Estes ML, McAllister AK. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat Rev Neurosci. 2015;16: 469-486.
14. Grogan D. The microbes within. Nature. 2015;518:S2.
15. Bäckhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015;17:690-703.
16. Debnath M, Venkatasubramanian G, Berk M. Fetal programming of schizophrenia: select mechanisms. Neurosci Biobehav Rev. 2015;49: 90-104.
17. Dominguez-Bello MG, Blaser MJ. Asthma: undoing millions of years of coevolution in early life? Sci Transl Med. 2015;7:307fs39.
18. van Opstal EJ, Bordenstein SR. Rethinking heritability of the microbiome. Science. 2015.;349:1172-1173.
19. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016;22:250-253.
20. Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, et al. The maternal microbiota drives early postnatal innate immune development. Science. 2016;351:1296-1302.
21. Al-Asmakh M, Hedin L. Microbiota and the control of blood-tissue barriers. Tissue Barriers. 2015;3:e10396.
22. McKenney PT, Pamer EG. 2015. From hype to hope: the gut microbiota in enteric infectious disease. Cell 163:1326-1332.
23. Scharschmidt TC, Vasquez KS, Truong H-A, et al. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity. 2015;43:1011-1021.
24. Wang Z, Roberts AB, Buffa JA, et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell. 2015;163:1585-1595.
25. Yang I, Corwin EJ, Brennan PA, et al. The infant microbiome. Implications for infant health and neurocognitive development. Nursing Res. 2016;65:76-88.
26. Moos WH, Maneta E, Pinkert CA, et al. Epigenetic treatment of neuropsychiatric disorders: autism and schizophrenia. Drug Dev Res. 2016;77:53-72.
27. Shakir R. Neurodegenerative noncommunicable diseases (neurology NCDs). Where are we now? J Neurol Sci. 2015;356:1-2.
28. Silberberg D, Anand NP, Michels K, et al. Brain and other nervous system disorders across the lifespan-global challenges and opportunities. Nature. 2015;527:S151-S154.
29. Borre YE, O'Keeffe GW, Clarke G, et al. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med. 2014;20:509-518.
30. de Theije CGM, Bavelaar BM, da Silva SL, et al. Food allergy and foodbased therapies in neurodevelopmental disorders. Pediatr Allergy Immunol. 2014;25:218-226.
31. Mayer EA, Knight R, Mazmanian SK, et al. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34:15490-15496.
32. Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain & behaviour- epigenetic regulation of the gut-brain axis. Genes Brain Behav. 2014;13:69-86.
33. Bienenstock J, Kunze W, Forsythe P. Microbiota and the gut-brain axis. Nutr Rev. 2015;73(S1):28-31.
34. Dash SR. The microbiome and brain health: what's the connection? Medscape, March 24, 2015. Accessed March 21, 2016, http://www.medscape.com/viewarticle/841748
35. Dinan TG, Stilling RM, Stanton C, et al. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015;63:1-9.
36. Kaplan BJ, Rucklidge JJ, Romijn A, et al. The emerging field of nutritional mental health: inflammation, the microbiome, oxidative stress, and mitochondrial function. Clin Psychol Sci. 2015;3:964-980.
37. Sherman MP, Zaghouani H, Niklas V. Gut microbiota, the immune system, and diet influence the neonatal gut-brain axis. Pediatr Res. 2015;77:127-135.
38. Donaldson GP, Lee SM, Mazmanian SK. Gut biogeography of the bacterial microbiota. Nat Rev Microbiol. 2016;14:20-32.
39. Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451-1463.
40. Kraneveld AD, de Theije CGM, van Heesch F, et al. The neuro-immune axis: prospect for novel treatments for mental disorders. Basic Clin Pharmacol Toxicol. 2014;114:128-136.
41. Buie T. Potential etiologic factors of microbiome disruption in autism. Clin Ther. 2015;37:976-983.
42. Carding S, Verbeke K, Vipond DT, et al. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015;26:26191.
43. Frye RE, Rose S, Slattery J, et al. Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome. Microb Ecol Health Dis. 2015;26:27458.
44. Liu X, Cao S, Zhang X. Modulation of gut microbiota-brain axis by probiotics, prebiotics, and diet. J Agric Food Chem. 2015;63:7885-7895.
45. Reddy BL, Saier MH. Autism and our intestinal microbiota. J Mol Microbiol Biotechnol. 2015;25:51-55.
46. Mangiola F, Ianiro G, Franceschi F, et al. Gut microbiota in autism and mood disorders. World J Gastroenterol. 2016;22: 361-368.
47. Dinan TG, Borre YE, Cryan JF. Genomics of schizophrenia: time to consider the gut microbiome? Mol Psychiatry. 2014;19:1252-1257.
48. Nemani K, Ghomi RH, McCormick B, et al. Schizophrenia and the gut-brain axis. Prog Neuropsychopharmacol Biol Psychiatry. 2015;56:155-160.
49. Severance EG, Prandovszky E, Castiglione J, et al. Gastroenterology issues in schizophrenia: why the gut matters. Curr Psychiatry Rep. 2015;17:27.
50. Chadman KK. Making progress in autism drug discovery. Expert Opin Drug Discov. 2014;9:1389-1391.
51. Sekar A, Bialas AR, de Rivera H, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530:177-183.
52. Muir WJ, McKechanie AG. Can epigenetics help in the discovery of therapeutics for psychiatric disorders, especially schizophrenia? Expert Opin Drug Discov. 2009;4:621-627.
53. Bosia M, Pigoni A, Cavallaro R. Genomics and epigenomics in novel schizophrenia drug discovery: translating animal models to clinical research and back. Expert Opin Drug Discov. 2015;10:125-139.
54. Hinde K, Lewis ZT. Mother's littlest helpers. Breastmilk nourishes the microbes colonizing the neonatal intestinal tract. Science. 2015;348:1427-1428.
55. Meadow JF, Altrichter AE, Bateman AC, et al. Humans differ in their personal microbial cloud. PeerJ. 2015;3:e1258.
56. Zeevi D, Korem T, Zmora N, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163:1079-1094.
57. Zuker CS. Food for the brain. Cell. 2015;161:9-11.
58. Kabouridis PS, Pachnis V. Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system. J Clin Invest. 2015;125:956-964.
59. Goyal MS, Venkatesh S, Milbrandt J, et al. Feeding the brain and nurturing the mind: linking nutrition and the gut microbiota to brain development. Proc Natl Acad Sci U S A. 2015;112:14105-14112.
60. Janssen AWF, Kersten S. The role of the gut microbiota in metabolic health. FASEB J. 2015;29:3111-3123.
61. Ledford H. The genome unwrapped. Nature. 2015;528:S12-S13.
62. Takahashi K. Influence of bacteria on epigenetic gene control. Cell Mol Life Sci. 2014;71:1045-1054.
63. Stefano GB, Kream RM. Dysregulated mitochondrial and chloroplast bioenergetics from a translational medical perspective (Review). Int J Mol Med. 2016;37:547-555.
64. De Vadder F, Kovatcheva-Datchary P, Goncalves D, et al. Microbiotagenerated metabolites promote metabolic benefits via gut-brain neural circuits. Cell. 2014;156:84-96.
65. Jandhyala SM, Talukdar R, Subramanyam C, et al. Role of the normal gut microbiota. World J Gastroenterol. 2015;21:8787-8803.
66. Psichas A, Reimann F, Gribble FM. Gut chemosensing mechanisms. J Clin Invest. 2015;125:908-917.
67. Scheperjans F, Aho V, Pereira PAB, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord. 2015;30:350-358.
68. Saint-Georges-Chaumet Y, Edeas M. Microbiota-mitochondria inter-talk: consequence for microbiota-host interaction. FEMS Pathog Dis. 2016;74:ftv096.
69. Donohoe DR, Garge N, Zhang X, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13:517-526.
70. Donohoe DR, Collins LB, Wali A, et al. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell. 2012;48:612-626.
71. Krishnan S, Alden N, Lee K. Pathways and functions of gut microbiota metabolism impacting host physiology. Curr Opin Biotechnol. 2015;36:137-145.
72. Velasquez-Manoff M. Gut microbiome: the peacekeepers. Nature. 2015;518:S3-S11.
73. Raman M, Ambalam P, Doble M. Short-chain fatty acids. In: Probiotics and Bioactive Carbohydrates in Colon Cancer Management. Springer: New Delhi, India; pp. 97-115; 2016.
74. Alenghat T, Artis D. Epigenomic regulation of host-microbiota interactions. Trends Immunol. 2014;35:518-525.
75. MacFabe DF. Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders. Microb Ecol Health Dis. 2015;26:28177.
76. Chuang D-M, Leng Y, Marinova Z, et al. Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci. 2009;32:591-601.
77. Steliou K, Boosalis MS, Perrine SP, et al. Butyrate histone deacetylase inhibitors. BioRes Open Access. 2012;1:192-198.
78. Thomas EA. Focal nature of neurological disorders necessitates isotypeselective histone deacetylase (HDAC) inhibitors. Mol Neurobiol. 2009;40:33-45.
79. Grayson DR, Kundakovic M, Sharma RP. Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders? Mol Pharmacol. 2010;77:126-135.
80. Canani RB, Di Costanzo M, Leone L. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenet. 2012;4:4.
81. Rosenstock TR. Lysine (K)-deacetylase inhibitors: the real next step to neuropsychiatric and neurodegenerative disorders? Cell Biol. 2013;2:a8.
82. Szyf M. Prospects for the development of epigenetic drugs for CNS conditions. Nat Rev Drug Discov. 2015;14:461-474.
83. Vizcarra JA, Wilson-Perez HE, Espay AJ. The power in numbers: gut microbiota in Parkinson's disease. Mov Disord. 2015;30:296-298.
84. Volmar C-H, Wahlestedt C. Histone deacetylases (HDACs) and brain function. Neuroepigenetics. 2015;1:20-27.
85. Bourassa MW, Alim I, Bultman SJ, et al. Butyrate, neuroepigenetics and the gut microbiome: can a high fiber diet improve brain health? Neurosci Lett. 2015 [Epub ahead of print]; DOI: 10.1016/j.neulet.2016.02.009.
86. van de Mark K, Chen JS, Steliou K, et al. α-Lipoic acid induces p27Kipdependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines. J Cell Physiol. 2003;194:325-340.
87. Bassett SA, Barnett MPG. The role of dietary histone deacetylases (HDACs) inhibitors in health and disease. Nutrients. 2014;6:4273-4301.
88. Rochette L, Ghibu S, Richard C, et al. Direct and indirect antioxidant properties of alpha-lipoic acid and therapeutic potential. Mol Nutr Food Res. 2013;57:114-125.
89. de Boer VCJ, Houten SM. A mitochondrial expatriate: nuclear pyruvate dehydrogenase. Cell. 2014;158:9-10.
90. Sutendra G, Kinnaird A, Dromparis P, et al. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell. 2014;158:84-97.
91. Mayr JA, Feichtinger RG, Tort F, et al. Lipoic acid biosynthesis defects. J Inherit Metab Dis. 2014. 37:553-563.
92. Ullah MW, Khattak WA, Ul-Islam M, et al. Metabolic engineering of synthetic cell-free systems: strategies and applications. Biochem Eng J. 2016;105:391-405.
93. Li S. Synthetic bioactive substances. In: Handbook of Food Chemistry. Cheung PCK, Mehta BM, (eds.) Springer-Verlag: Berlin, Germany; pp. 1-20; 2015 (ISBN: 978-3-642-41609-5).
94. Carlson DA, Smith AR, Fischer SJ, et al. The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate to healthy human subjects. Altern Med Rev. 2007;12:343-351.
95. Papanas N, Ziegler D. Efficacy of a-lipoic acid in diabetic retinopathy. Expert Opin Pharmacother. 2015;15:2721-2731.
96. Rochette L, Ghibu S, Muresan A, et al. Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. 2015;93:1021-1027.
97. Spalding MD, Sean T, Prigge ST. Lipoic acid metabolism in microbial pathogens. Microbiol Mol Biol Rev. 2010;74:200-228.
98. Zhang H, Luo Q, Gao H, et al. A new regulatory mechanism for bacterial lipoic acid synthesis. Microbiologyopen. 2015;4:282-300.
99. Pashaj A, Xia M, Moreau R. α-Lipoic acid as a triglyceride-lowering nutraceutical. Can J Physiol Pharmacol. 2015;93:1029-1041.
100. Dörsam B, Fahrer J. The disulfide compound α-lipoic acid and its derivatives: a novel class of anticancer agents targeting mitochondria. Cancer Lett. 2016;371:12-19.
101. Irwin MH, Moos WH, Faller DV, et al. Epigenetic treatment of neurodegenerative disorders: Alzheimer and Parkinson diseases. Drug Dev Res. 2016;77:109-123.
102. Prasad KN. Simultaneous activation of Nrf2 and elevation of dietary and endogenous antioxidant chemicals for cancer prevention in humans. J Am Coll Nutr. 2016;35:175-184.
103. Lombard JH. Depression, psychological stress, vascular dysfunction, and cardiovascular disease: thinking outside the barrel. J Appl Physiol. 2010;108:1025-1026.
104. Silva MCC, de Sousa CNS, Gomes PXL, et al. Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:142-148.
105. Vasconcelos GS, Ximenes NC, de Sousa CNS, et al. Alpha-lipoic acid alone and combined with clozapine reverses schizophrenia-like symptoms induced by ketamine in mice: participation of antioxidant, nitrergic and neurotrophic mechanisms. Schizophr Res. 2015;165:163-170.
106. Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Arch Gen Psychiatry. 1994;51:199-214.
107. Lafioniatis A, Orfanidou MA, Papadopoulou ES, et al. Effects of the inducible nitric oxide synthase inhibitor aminoguanidine in two different rat models of schizophrenia. Behav Brain Res. 2016;309:14-21.
108. Ying Z, Kampfrath T, Sun Q, et al. Evidence that alpha-lipoic acid inhibits NF-kappaB activation independent of its antioxidant function. Inflamm Res. 2011;60:219-225.
109. Buendia I, Michalska P, Navarro E, et al. Nrf2-ARE pathway: an emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases. Pharmacol Ther. 2016;157:84-104.
110. Beauloye C, Horman S, Bertrand L. Even is better than odd: one fat may conceal another. Am J Physiol Heart Circ Physiol. 2015;309:H1112-H1114.
111. Shenderov BA, Midtvedt T. Epigenomic programing: a future way to health? Microb Ecol Health Dis. 2014;25:24145.
112. Hill GE. Mitonuclear ecology. Mol Biol Evol. 2015;32:1917-1927.
113. Johnston IG, Williams BP. Evolutionary inference across eukaryotes identifies specific pressures favoring mitochondrial gene retention. Cell Systems. 2016;2:101-111.
114. Wilkins JF, Ubeda F, Van Cleve J. The evolving landscape of imprinted genes in humans and mice: conflict among alleles, genes, tissues, and kin. Bioessays. 2016;38:482-489.
115. Atladottir HO, Thorsen P, Østergaard L, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord. 2010;40:1423-1430.
116. Choi GB, Yim YS, Wong H, et al. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016;351:933-939.
117. Marangoni C, Hernandez M, Faedda GL. The role of environmental exposures as risk factors for bipolar disorder: a systematic review of longitudinal studies. J Affect Disord. 2016;193:165-174.
118. Brasil P, Pereira Jr. JP, Gabaglia CR, et al. Zika virus infection in pregnant women in Rio de Janeiro-preliminary report. N Engl J Med. 2016 [Epub ahead of print]; DOI: 10.1056/NEJMoa1602412.
119. Broutet N, Krauer F, Riesen M, et al. Zika virus as a cause of neurologic disorders. N Engl J Med. 2016;374:1506-1509.
120. Estes ML, McAllister AK. Maternal TH17 cells take a toll on baby's brain. Science. 2016;351:919-920.
121. Victora CG, Schuler-Faccini L, Matijasevich A, et al. Microcephaly in Brazil: how to interpret reported numbers? Lancet. 2016;387:621-623.
122. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behavior. Nat Rev Neurosci. 2012;13: 701-712.
123. Zmora N, Zeevi D, Korem T, et al. Taking it personally: personalized utilization of the human microbiome in health and disease. Cell Host Microbe. 2016;19:12-20.
124. Katsiardanis K, Diamantaras A-A, Dessypris N, et al. Cognitive Impairment and dietary habits among elders: the Velestino study. J Med Food. 2013;16:343-350.
125. Babio N, Becerra-Tomás N, Martínez-González MA, et al. Consumption of yogurt, low-fat milk, and other low-fat dairy products is associated with lower risk of metabolic syndrome incidence in an elderly Mediterranean population. J Nutr. 2015;145:2308-2316.
126. Petra AI, Panagiotidou S, Hatziagelaki E, et al. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther. 2015;37:984-995.
127. Klein N, Kemper KJ. Integrative approaches to caring for children with autism. Curr Probl Pediatr Adolesc Health Care. 2016 [Epub ahead of print]; DOI: 10.1016/j.cppeds.2015.12.004.
128. Eisenstein M. Living factories of the future. Nature. 2016;531:401-403.
129. Bel S, Hooper LV. A bacterial nudge to T-cell function. Nature. 2015;526:328-330.
130. Leslie M. Microbes aid cancer drugs. Science. 2015;350:614-615.
131. Pinero-Lambea C, Ruano-Gallego D, Fernández LA. Engineered bacteria as therapeutic agents. Curr Opin Biotechnol. 2015;35:94-102.
132. Vetizou M, Pitt JM, Daillere R, et al. Anticancer immunotherapy by CTLA- 4 blockade relies on the gut microbiota. Science. 2015;350:1079-1084.
133. Garber K. Drugging the gutmicrobiome. Nat Biotechnol. 2015;33:228-231.
134. Kali A. Human microbiome engineering: the future and beyond. J Clin Diagn Res. 2015;9:DEO1-DEO4.
135. Zhou L, Foster JA. Psychobiotics and the gut-brain axis: in the pursuit of happiness. Neuropsychiatr Dis Treat. 2015;11:715-723.
136. Escoll P, Mondino S, Rolando M, et al. Targeting of host organelles by pathogenic bacteria: a sophisticated subversion strategy. Nat Rev Microbiol. 2016;14:5-19.
137. Hayden EC. Tech investors bet on synthetic biology. Nature. 2015;527:19.
138. Jarvis LM. Harnessing the hordes in the microbiome. Chem Eng News. 2015;93(38):12-19.
139. Khanna S, Pardi DS, Kelly CR, et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile Infection. J Infect Dis. 2016 [Epub ahead of print]; DOI: 10.1093/ infdis/jiv766.
140. Byrd AL, Segre JA. Adapting Koch's postulates. Criteria for disease causation must take microbial interactions into account. Science. 2016;351:224-226.
141. Madhusoodanan J. Viral soldiers. Scientist. 2016;30:27-33.
142. Pfeiffer JK, Virgin HW. Transkingdom control of viral infection and immunity in the mammalian intestine. Science. 2016;351:aad5872.
143. Devkota S. Prescription drugs obscure microbiome analyses. Patient populations should be stratified for medications when looking for gut microbial signatures of disease. Science. 2016;351:452-453.
144. Wilson JW, Ott CM, Quick L, et al. Media ion composition controls regulatory and virulence response of Salmonella in spaceflight. PLoS One. 2008;3:e3923.
145. Li P, Shi J, Zhang P, et al. Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility. FASEB J. 2015;29:3263-3273.
146. Ritchie LE, Taddeo SS, Weeks BR, et al. Space environmental factor impacts upon murine colon microbiota and mucosal homeostasis. PLoS One. 2015;10:e0125792.
147. Schierholz S, Huot D. NASA astronaut Scott Kelly returns safely to Earth after one-year mission. March 2, Release 16-023. Accessed March 20, 2016, http://www.nasa.gov/press-release/nasa-astronaut-scott-kellyreturns- safely-to-earth-after-one-year-mission
148. Snyder C, Kream RM, Ptacek R, et al. Mitochondria, microbiome and their potential psychiatric modulation. Autism Open Access. 2015;5:2.
149. Parashar A, Udayabanu M. Gut microbiota regulates key modulators of social behavior. Eur Neuropsychopharmacol. 2016;26:78-91.
150. Taylor RW. Impact of space flight on bacterial virulence and antibiotic susceptibility. Infect Drug Resist. 2015;8:249-262.
151. Hutchison III CA, Chuang R-Y, Noskov VN, et al. Science. 2016;351:aad6253.
152. Menezes AA, Montague MG, Cumbers J, et al. Grand challenges in space synthetic biology. JRS Interface. 2015;12: 20150803.
153. Ciechonska M, Grob A, Isalan M. From noise to synthetic nucleoli: can synthetic biology achieve new insights? Integr Biol. 2016;8:383-393.
154. Prince M, Bryce R, Albanese E, et al. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimer's Dement. 2013;9:63-75.
155. Lin M, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787-795.
156. Currais A. Ageing and inflammation-A central role for mitochondria in brain health and disease. Ageing Res Rev. 2015;21:30-42.
157. Mattson MP. Late-onset dementia: a mosaic of prototypical pathologies modifiable by diet and lifestyle. Nat Aging Mech Dis. 2015;1:15003.
158. Quaglio G, Brand H, Dario C. Fighting dementia in Europe: the time to act is now. Lancet Neurol. 2016;15:452-454.
159. Satizabal CL, Beiser AS, Chouraki V, et al. Incidence of dementia over three decades in the Framingham Heart Study. N Engl J Med. 2016;374:523-532.
160. Wu Y-T, Fratiglioni L, Matthews FE, et al. Dementia in western Europe: epidemiological evidence and implications for policy making. Lancet Neurol. 2016;15:116-124.
161. Winblad B, Amouyel P, Andrieu S, et al. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol. 2016;15:455-532.
162. Subramanian S, Blanton LV, Frese SA, et al. Cultivating healthy growth and nutrition through the gut microbiota. Cell. 2015;161:36-48.
163. Koufaris C, Sismani C. Modulation of the genome and epigenome of individuals susceptible to autism by environmental risk factors. Int J Mol Sci. 2015;16:8699-8718.
164. Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe. 2015;17:565-576.
165. Schmidt C. Mental health: thinking from the gut. Nature. 2015;518: S12-S15.
166. Millan MJ, Andrieux A, Bartzokis G, et al. Altering the course of schizophrenia: progress and perspectives. Nat Rev Drug Discov. 2016 [Epub ahead of print]; DOI: 10.1038/nrd.2016.28.
167. Oriach CS, Robertson RC, Stanton C, et al. Food for thought: the role of nutrition in the microbiota-gut-brain axis. Clin Nutr Exp. 2016;6:25-38.
168. Maslowski KM, Mackay CR. Diet, gut microbiota and immune responses. Nat Immunol. 2011;12:5-9.
169. Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528:262-266.
170. Lee SH, de La Serre CB. Gut microbiome-brain communications regulate host physiology and behavior. J Nutr Health Food Sci. 2015;3:1-12.
171. Marette A, Jobin C. SCFAs take a toll en route to metabolic syndrome. Cell Metab. 2015;22:954-956.
172. MacFabe DF, Cain DP, Rodriguez-Capote K, et al. Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res. 2007;176:149-169.
173. MacFabe DF Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microb Ecol Health Dis. 2012;23:19260.
174. MacFabe D. Autism: metabolism, mitochondria, and the microbiome. Global Adv Health Med. 2013;2:52-66.
175. Galland L. The gut microbiome and the brain. J Med Food, 2014;17:1261-1272.
176. Goldani AAS, Downs SR, Widjaja F, et al. Biomarkers in autism. Front Psychiatry. 2014;5:100.
177. Foley KA, MacFabe DF, Kavaliers M, et al. Sexually dimorphic effects of prenatal exposure to lipopolysaccharide, and prenatal and postnatal exposure to propionic acid, on acoustic startle response and prepulse inhibition in adolescent rats: relevance to autism spectrum disorders. Behav Brain Res. 2015;278:244-256.
178. Frye RE, Slattery J, MacFabe DF, et al. Approaches to studying and manipulating the enteric microbiome to improve autism symptoms. Microb Ecol Health Dis. 2015;26:26878.
179. Mezzelani A, Landini M, Facchiano F, et al. Environment, dysbiosis, immunity and sex-specific susceptibility: a translational hypothesis for regressive autism pathogenesis. Nutr Neurosci. 2015;18:145-161.
180. Shultz SR, Aziz NAB, Yang L, et al. Intracerebroventricular injection of propionic acid, an enteric metabolite implicated in autism, induces social abnormalities that do not differ between seizure-prone (FAST) and seizure-resistant (SLOW) rats. Behav Brain Res. 2015;278:542-548.
181. Oyarzabal A, Bravo-Alonso I, Sánchez-Arago M, et al. Mitochondrial response to the BCKDK-deficiency: some clues to understand the positive dietary response in this form of autism. BBA-Mol Basis Dis. 2016;1862:592-600.
182. da Silva PGC, Domingues DD, de Carvalho LA, et al. Neurotrophic factors in Parkinson's disease are regulated by exercise: evidence-based practice. J Neurol Sci. 2016;363:5-15.
183. Gwynette MF, Warren NJ, Warthen J, et al. Yoga as an intervention for patients with autism spectrum disorder: a review of the evidence and future directions. Autism Open Access. 2015;5:3.
184. Duzel E, van Praag H, Sendtner M. Can physical exercise in old age improve memory and hippocampal function? Brain. 2016;139:662-673.
185. Luu K, Hall PA. Hatha yoga and executive function: a systematic review. J Altern Complement Med. 2016;22:125-133.
186. O'Mahony SM, Clarke G, Dinan TG, et al. Early-life adversity and brain development: is the microbiome a missing piece of the puzzle? Neuroscience. 2015;322. [Epub ahead of print]; DOI: 10.1016/j.neuroscience. 2015.09.068.
187. Charbonneau MR, O'Donnell D, Blanton LV, et al. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell. 2016;164:859-871.
188. Cowan CSM, Callaghan BL, Kan JM, et al. The lasting impact of early-life adversity on individuals and their descendants: potential mechanisms and hope for intervention. Genes Brain Behav. 2016;15:155-168.
189. Pennisi E. The right gut microbes help infants grow. Science. 2016;351:582.
190. Blanton LV, Charbonneau MR, Salih T, et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016;351:aad3311.
191. Schwarzer M, Makki K, Storelli G, et al. Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition. Science. 2016;351:854-857.
192. Thaiss CA, Elinav E. Exploring new horizons in microbiome research. Cell Host Microbe. 2014;15:662-667.
193. Ash C, Mueller K. Manipulating the microbiota. Science. 2016;352:531.