Technical and Theoretic Limitations of the Experimental Evidence Supporting a Gut Bacterial Etiology in Mental Illness

• Mayer E.A.
• Tillisch K.
• Gupta A.

Gut/brain axis and the microbiota.

J Clin Invest. 2015; 125: 926-938

• Schloissnig S.
• Arumugam M.
• Sunagawa S.
• et al.

Genomic variation landscape of the human gut microbiome.

Nature. 2013; 493: 45-50

• Heintz-Buschart A.
• Wilmes P.

Human gut microbiome: function matters.

Trends Microbiology. 2018; 26: 563-574

• Sudo N.
• Chida Y.
• Aiba Y.
• et al.

Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice.

J Physiol. 2004; 558: 263-275

Psychobiotics: a new approach for treating mental illness?.

Crit Rev Food Sci Nutr. 2019; 59: 1230-1236

• Selhub E.M.
• Logan A.C.
• Bested A.C.

Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry.

J Physiol Anthropol. 2014; 33: 2https://doi.org/10.1186/1880-6805-33-2

• Kelly J.R.
• Borre Y.
• O’Brien C.
• et al.

Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat.

J Psychiatr Res. 2016; 82: 109-118

• Zheng P.
• Zeng B.
• Zhou C.
• et al.

Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism.

Mol Psychiatry. 2016; 21: 786-796

• Furness J.B.
• Callaghan B.P.
• Rivera L.R.
• Cho H.J.

The enteric nervous system and gastrointestinal innervation: integrated local and central control.

in: Microbial Endocrinology: The Microbiota-Gut-Brain axis in Health and Disease. Springer,
New York, NY2014: 39-71

The “biopsychosocial model”: 40 years of application in psychiatry.

Psychiatrike. 2017; 28: 107-110

• Yasuda K.
• Oh K.
• Ren B.
• et al.

Biogeography of the intestinal mucosal and luminal microbiome in the rhesus macaque.

Cell host & microbe. 2015; 17: 385-391

• Donaldson G.P.
• Lee S.M.
• Mazmanian S.K.

Gut biogeography of the bacterial microbiota.

Nat Rev Microbiol. 2016; 14: 20-32

• Sender R.
• Fuchs S.
• Milo R.

Revised estimates for the number of human and bacteria cells in the body.

PLoS Biol. 2016; 14e1002533

Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism.

Gut microbes. 2016; 7: 189-200

• Naseribafrouei A.
• Hestad K.
• Avershina E.
• et al.

Correlation between the human fecal microbiota and depression.

Neurogastroenterology Motil. 2014; 26: 1155-1162

Association between gut microbiota and autism spectrum disorder: a systematic review and meta-analysis.

Front Psychiatry. 2019; 10: 473https://doi.org/10.3389/fpsyt.2019.00473

• Nowakowski J.
• Chrobak A.A.
• Dudek D.

Psychiatric illnesses in inflammatory bowel diseases-psychiatric comorbidity and biological underpinnings.

Psychiatria polska. 2016; 50: 1157-1166

• Jalanka J.
• Hillamaa A.
• Satokari R.
• Mattila E.
• Anttila V.J.
• Arkkila P.

The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection.

Aliment Pharmacol Ther. 2018; 47: 371-379

• Wood N.C.
• Hamilton I.
• Axon A.T.R.
• et al.

Abnormal intestinal permeability: an aetiological factor in chronic psychiatric disorders?.

Br J Psychiatry. 1987; 150: 853-856

• Leclercq S.
• Matamoros S.
• Cani P.D.
• et al.

Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity.

Proc Natl Acad Sci. 2014; 111: E4485-E4493

• Braniste V.
• Al-Asmakh M.
• Kowal C.
• et al.

The gut microbiota influences blood-brain barrier permeability in mice.

Sci translational Med. 2014; 6 ()

• Karczewski J.
• Troost F.J.
• Konings I.
• et al.

Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier.

Am J physiology-gastrointestinal Liver Physiol. 2010; 298: G851-G859

• Maes M.
• Kubera M.
• Leunis J.C.
• Berk M.

Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut.

J affective Disord. 2012; 141: 55-62

• Bron P.A.
• Van Baarlen P.
• Kleerebezem M.

Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa.

Nat Rev Microbiol. 2012; 10: 66-78

• Hsiao E.Y.
• McBride S.W.
• Hsien S.
• et al.

Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

Cell. 2013; 155: 1451-1463

The high prevalence of poor physical health and unhealthy lifestyle behaviours in individuals with severe mental illness.

Issues Ment Health Nurs. 2011; 32: 589-597

• American Psychiatric Association

Diagnostic and Statistical Manual of Mental Disorders (DSM-5®).

American Psychiatric Pub,
2013

• David L.A.
• Maurice C.F.
• Carmody R.N.
• et al.

Diet rapidly and reproducibly alters the human gut microbiome.

Nature. 2014; 505: 559

• Monda V.
• Villano I.
• Messina A.
• et al.

Exercise modifies the gut microbiota with positive health effects.

Oxidative Med Cell longevity. 2017; : 3831972

Use of germ-free animal models in microbiota-related research.

J Microbiol Biotechnol. 2015; 25: 1583-1588

• Heijtz R.D.
• Wang S.
• Anuar F.
• et al.

Normal gut microbiota modulates brain development and behavior.

Proc Natl Acad Sci. 2011; 108: 3047-3052

Disruption of the gut ecosystem by antibiotics.

Yonsei Med J. 2018; 59: 4-12

• Lurie I.
• Yang Y.X.
• Haynes K.
• Mamtani R.
• Boursi B.

Antibiotic exposure and the risk for depression, anxiety, or psychosis: a nested case-control study.

J Clin Psychiatry. 2015; 76: 1522-1528

• Lambrichts S.
• Van Oudenhove L.
• Sienaert P.

Antibiotics and mania: a systematic review.

J affective Disord. 2017; 219: 149-156

FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions.

Clin Infect Dis. 2018; 67 ()

• Chaudhry I.B.
• Hallak J.
• Husain N.
• et al.

Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment.

J Psychopharmacol. 2012; 26: 1185-1193

• Liu F.
• Guo X.
• Wu R.
• et al.

Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: a double blind, randomized, controlled trial.

Schizophrenia Res. 2014; 153: 169-176

• Levkovitz Y.
• Mendlovich S.
• Riwkes S.
• et al.

A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia.

J Clin Psychiatry. 2010; 71: 138-149

• Deakin B.
• Suckling J.
• Barnes T.R.
• et al.

The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): a randomised, double-blind, placebo-controlled trial.

The lancet psychiatry. 2018; 5: 885-894

• Shibre T.
• Alem A.
• Abdulahi A.
• et al.

Trimethoprim as adjuvant treatment in schizophrenia: a double-blind, randomized, placebo-controlled clinical trial.

Schizophrenia Bull. 2009; 36: 846-851

• Zheng W.
• Zhu X.M.
• Zhang Q.E.
• et al.

Adjunctive minocycline for major mental disorders: a systematic review.

J Psychopharmacol. 2019; 33: 1215-1226

• Savitz J.B.
• Teague T.K.
• Misaki M.
• et al.

Treatment of bipolar depression with minocycline and/or aspirin: an adaptive, 2 × 2 double-blind, randomized, placebo-controlled, phase IIA clinical trial.

Translational psychiatry. 2018; 8: 1-11

• Bercik P.
• Denou E.
• Collins J.
• et al.

The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice.

Gastroenterology. 2011; 141: 599-609

• Brogden R.N.
• Speight T.M.
• Avery G.S.

Minocycline: a review of its antibacterial and pharmacokinetic properties and therapeutic use.

Drugs. 1975; 9: 251-291

• Delungahawatta T.
• Amin J.Y.
• Stanisz A.M.
• Bienenstock J.
• Forsythe P.
• Kunze W.A.

Antibiotic driven changes in gut motility suggest direct modulation of enteric nervous system.

Front Neurosci. 2017; 11: 588https://doi.org/10.3389/fnins.2017.00588

• Champagne-Jorgensen K.
• Kunze W.A.
• Forsythe P.
• Bienenstock J.
• Neufeld K.A.M.

Antibiotics and the nervous system: more than just the microbes?.

Brain Behav Immun. 2019; 77: 7-15

• McFarland L.V.
• Evans C.T.
• Goldstein E.J.

Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis.

Front Med. 2018; 5: 124https://doi.org/10.3389/fmed.2018.00124

• Hempel S.
• Newberry S.
• Ruelaz A.
• et al.

Safety of probiotics used to reduce risk and prevent or treat disease.

Evid report/technology Assess. 2011; : 1-645

• Ng Q.X.
• Loke W.
• Venkatanarayanan N.
• Lim D.Y.
• Soh A.Y.S.
• Yeo W.S.

A systematic review of the role of prebiotics and probiotics in autism spectrum disorders.

Medicina. 2019; 55: 129https://doi.org/10.3390/medicina55050129

• Parracho H.M.
• Gibson G.R.
• Knott F.
• Bosscher D.
• Kleerebezem M.
• McCartney A.L.

A double-blind, placebo-controlled, crossover-designed probiotic feeding study in children diagnosed with autistic spectrum disorders.

Int J probiotics prebiotics. 2010; 5: 69-74

• Slykerman R.F.
• Kang J.
• Van Zyl N.
• et al.

Effect of early probiotic supplementation on childhood cognition, behaviour and mood a randomised, placebo-controlled trial.

Acta Paediatr. 2018; 107: 2172-2178

• Ng Q.X.
• Peters C.
• Ho C.Y.X.
• Lim D.Y.
• Yeo W.S.

A meta-analysis of the use of probiotics to alleviate depressive symptoms.

J affective Disord. 2018; 228: 13-19

• Liu B.
• He Y.
• Wang M.
• et al.

Efficacy of probiotics on anxiety—a meta-analysis of randomized controlled trials.

Depress anxiety. 2018; 35: 935-945

• Huang R.
• Ning H.
• Yang L.
• et al.

Efficacy of probiotics on anxiety: a meta-analysis of randomized controlled trials.

Neuropsychiatry. 2017; 7: 862-871

• McKean J.
• Naug H.
• Nikbakht E.
• Amiet B.
• Colson N.

Probiotics and subclinical psychological symptoms in healthy participants: a systematic review and meta-analysis.

J Altern Complement Med. 2017; 23: 249-258

• Kristensen N.B.
• Bryrup T.
• Allin K.H.
• Nielsen T.
• Hansen T.H.
• Pedersen O.

Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials.

Genome Med. 2016; 8: 52https://doi.org/10.1186/s13073-016-0300-5

Ecological role of lactobacilli in the gastrointestinal tract: implications for fundamental and biomedical research.

Appl Environ Microbiol. 2008; 74: 4985-4996

• Li H.
• Limenitakis J.P.
• Fuhrer T.
• et al.

The outer mucus layer hosts a distinct intestinal microbial niche.

Nat Commun. 2015; 6: 1-13

• Smith N.W.
• Shorten P.R.
• Altermann E.
• Roy N.C.
• McNabb W.C.

The classification and evolution of bacterial cross-feeding.

Front Ecol Evol. 2019; 7: 153https://doi.org/10.3389/fevo.2019.00153

• Kuleshov V.
• Jiang C.
• Zhou W.
• Jahanbani F.
• Batzoglou S.
• Snyder M.

Synthetic long-read sequencing reveals intraspecies diversity in the human microbiome.

Nat Biotechnol. 2016; 34: 64-69

• Brandt L.J.
• Aroniadis O.C.
• Mellow M.
• et al.

Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection.

Am J Gastroenterol. 2012; 107: 1079-1087

• Gibbons R.J.
• Socransky S.S.
• Kapsimalis B.

Establishment of human indigenous bacteria in germ-free mice.

J Bacteriol. 1964; 88: 1316-1323

• Walker E.A.
• Katon W.J.
• Jemelka R.P.
• Roy-Byrne P.P.

Comorbidity of gastrointestinal complaints, depression, and anxiety in the Epidemiologic Catchment Area (ECA) study.

Am J Med. 1992; 92: S26-S30

• Hillilä M.T.
• Hämäläinen J.
• Heikkinen M.E.
• Färkkilä M.A.

Gastrointestinal complaints among subjects with depressive symptoms in the general population.

Aliment Pharmacol Ther. 2008; 28: 648-654

• Kang D.W.
• Adams J.B.
• Coleman D.M.
• et al.

Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota.

Scientific Rep. 2019; 9: 5821