Neuropsychological Disorders

The intestines are very rich in nerves, have a two-way traffic with the brain and are therefore often referred to as the second brain (1,2). In addition, bowel diseases such as IBS and IBD are very often found in mental illness (3). Evidence that the microbiome can directly modulate the central nervous system, and vice versa, is accumulating (4). Indications for the relationship with the microbiome have been found at:

Depression
This is often associated with a dysregulated hypothalamic-pituitary-adrenal axis (HPA axis), increased serum cortisol status, and increased inflammatory factors found, and any of these factors can be modulated by the micobiome (3,5,6). In addition, abnormalities in the composition of the microbiome have been found in patients with severe depression (7). Another striking difference from healthy controls is an increased serum level of a specific short-chain fatty acid (valeric acid). This substance is produced by the microbiome, can cross the blood-brain barrier, and can have a direct influence on both the hypothalamus and the release of neurotransmitters (7). While meta-analyzes of probiotics are cautious due to the wide differences between various probiotic products and strains, a meta-analysis of probiotics for depression provides the first tentative evidence that probiotics may have a beneficial effect (8).

ADHD
An indication that the gut and / or metabolism play a role in this attention deficit hyperactivity disorder is that certain diets and nutritional supplements have been effective in reducing symptoms in several studies (9, 10). Multiple studies have also found increased inflammation in ADHD patients (11). The aforementioned influence of the microbiome on the immune system (and systemic low-grade inflammation) suggests a possible role of the microbiome in ADHD. Moreover, differences in the composition of the microbiome have also been found in ADHD (12,13). An RCT in which mothers were given probiotics or a placebo for the last four weeks of their pregnancy and then the children for the first six months, provides an initial cautious indication of a favorable effect, since after 13 years in the placebo group 5 of the 35 children had ADHD or had autism and zero in the probiotic group (14).

Autistic spectrum disorder
Autism is characterized as a developmental disorder and there is strong evidence that environmental factors during pregnancy (such as bacterial or viral infections in the mother) increase the risk of autism in the child (15). Neuroinflammation plays a role in this, which is, among other things, related to disturbances in the mother’s microbiome (15). In autistic children themselves, abnormalities in the composition of the microbiome have also been found, the most striking correlation being a tenfold increase in a specific bacterial genus (Clostridium) (4,5,15). In addition, there are indications that a large percentage of autistic persons have a history of antibiotic use and an increased level of an endotoxin of bacterial origin in the blood (LPS) has also been found in autistic individuals (5). Bowel problems such as chronic diarrhea are also common in autistic individuals and the microbiome differs from that of healthy children (4,10,16). Autistic children belong to the group of children most often referred to an MDL doctor (17). There is also evidence of an increased permeability of the gut wall, resulting in immune response (10). Finally, a study with an adapted form of poo transplantation shows that in 18 autistic children, not only did the intestinal complaints significantly reduce, but also the behavior score improved (18).

References
1. Gershon MD. The enteric nervous system: a second brain. Hosp Pract 1995,1999; 34: 31- 2,35-8,41-42 passim.
2. Ochoa-Repáraz J, Kasper LH. The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders? Curr Obes Rep. 2016; 5:51 – 64.
3. Dinan TG, Cryan JF. Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2013; 25: 713-9.
4. Kim N, Yun M, Oh YJ, Choi H-J. Mind-altering with the gut: Modulation of the gut-brain axis with probiotics. J Microbiol Seoul Korea. 2018; 56: 172-82.
5. Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A. Gut microbiota in autism and mood disorders. World J Gastroenterol. 2016; 22: 361-8.
Dash S, Clarke G, Berk M, Jacka FN. The gut microbiome and diet in psychiatry: focus on depression. Curr Opin Psychiatry. 2015; 28: 1-6.
7. Lv F, Chen S, Wang L, Jiang R, Tian H, Li J, Yao Y, Zhuo C. The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option. Oncotarget. 2017; 8: 100899–907.
8. Huang R, Wang K, Hu J. Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients [Internet]. 2016 [cited 2018 May 24]; 8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997396/
9. Pelsser LMJ. ADHD, a Food-Induced Hypersensitivity Syndrome: in Quest of a Cause The effects of a restricted elimination diet (RED) on ADHD, ODD and comorbid somatic complaints, and a preliminary survey of the mechanisms of an RED. [Nijmegen]: Radboud University; 2011.
10. Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC. Gut-microbiota-brain axis and effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther. 2015; 37: 984–95.
11. Cenit MC, Nuevo IC, Codoner-Franch P, Dinan TG, Sanz Y. Gut microbiota and attention deficit hyperactivity disorder: new perspectives for a challenging condition. Eur Child Adolesc Psychiatry. 2017; 26: 1081-92.
12. Aarts E, Ederveen THA, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, Smeekens SP, Netea MG, Buitelaar JK, Franke B, et al. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS ONE [Internet]. 2017 [cited 2018 May 26]; 12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581161/
13. Jiang H-Y, Zhou Y-Y, Zhou G-L, Li Y-C, Yuan J, Li X-H, Ruan B. Gut microbiota profiles in treatment-naïve children with attention deficit hyperactivity disorder. Behav Brain Res. 2018; 347: 408 – 13.
14. Partty A, Kalliomaki M, Wacklin P, Salminen S, Isolauri E. A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial. Pediatr Res. 2015; 77: 823-8.
15. Madore C, Leyrolle Q, Lacabanne C, Benmamar-Badel A, Joffre C, Nadjar A, Laye S. Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota. Neural Plast [Internet]. 2016 [cited 2018 May 26]; 2016. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093279/
16. Mayer EA, Padua D, Tillisch K. Altered brain-gut axis in autism: comorbidity or causative mechanisms? BioEssays News Rev Mol Cell Dev Biol. 2014; 36: 933-9.
17. Navarro F, Liu Y, Rhoads JM. Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol. 2016; 22: 10093–102.
18. Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open label study. Microbiome [Internet]. 2017 [cited 2018 May 26]; 5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264285/