Neuropsychological disorders
Impression of the publications on the relevance of the microbiome
The intestines are very richly equipped with nerves, have a two-way traffic with the brain and are therefore often called the second brain (1,2). In addition, intestinal diseases such as IBS and IBD are very often found in mental illnesses (3). Evidence that the microbiome can bring about a direct modulation of the central nervous system, and vice versa, is accumulating (4). Evidence of its relationship with the microbiome has been found in:
Depression
This is often accompanied by a dysregulated hypothalamic-pituitary-adrenal axis (HPA axis), increased serum cortisol status, and increases in inflammatory factors, each of which can be modulated by the micomime (3,5,6). In addition, abnormalities in the composition of the microbiome have been found in patients with major depression (7). Another striking difference compared to healthy control subjects is an increased serum value 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). Although it is important to be careful with meta-analyses of probiotics because of the large differences between various probiotic products and strains, a meta-analysis on probiotics against depression provides the first tentative indications that probiotics may have a beneficial effect (8).
ADHD
An indication that the gut and/or metabolism plays a role in this attention deficit hyperactivity disorder is that certain diets and dietary supplements have been shown to effectively reduce symptoms in various studies (9, 10). Several studies have also found increased inflammation levels 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. In addition, 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 gives a first tentative indication of a beneficial effect, since after 13 years 5 of the 35 children in the placebo group had ADHD or autism and in the probiotic group zero (14).
Autistic spectrum disorder
Autism is characterized as a developmental disability, 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 associated with disturbances in the mother's microbiome (15). Abnormalities in the composition of the microbiome have also been found in autistic children themselves, with the most striking correlation being a tenfold increase in a certain bacterial genus (Clostridium) (4,5,15). In addition, there are indications that a large percentage of autistic people have a history of antibiotic use and an increased value of an endotoxin of bacterial origin (LPS) has also been found in the blood in autistic individuals (5). Intestinal problems such as chronic diarrhea are also common in autistic people and the microbiome differs from that of healthy children (4, 10, 16). Autistic children are among the most frequently referred children to an MDL doctor (17). There is also evidence of increased permeability of the intestinal wall, resulting in immune response (10). Finally, a study with a modified form of poo transplantation shows that in 18 autistic children, not only did the intestinal symptoms greatly decrease, but the behavioral score also 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.
6. 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, Codoñer-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. Pärtty A, Kalliomäki 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, Layé 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 D-W, 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/
Agenda
Knowledge & meetings
The Microbiome Center regularly organizes peer reviews, webinars and knowledge meetings for doctors and professionals. The sessions are aimed at both healthcare providers who are orienting themselves on microbiome therapy and experienced practitioners who want to deepen their knowledge.