Střevní mikrobiota a poruchy autistického spektra

Stiahnuť PDF English version

Autori: P. Danhofer ¹; O. Horák ¹; L. Knedlíková ¹; S. Kolář ¹; A. M. Bittnerová ¹; P. Jabandžiev ²; H. Ošlejšková ¹
Pôsobisko autorov: Department of Pediatric Neurology, Masaryk University and University, Hospital, Brno, Czech Republic ¹; Department of Pediatrics, Masaryk, University and University Hospital, Brno, Czech Republic ²
Vyšlo v časopise: Cesk Slov Neurol N 2021; 84/117(2): 127-134
Kategória: Review Article
doi: https://doi.org/10.48095/cccsnn2021127

Súhrn

Poruchy autistického spektra (PAS) se řadí mezi neurovývojové a neuropsychiatrické poruchy s klinickou manifestací v dětském věku charakterizované obtížemi v sociální interakci a komunikaci, limitovanými zájmy a repetitivními prvky v chování. V posledních letech došlo k významnému nárůstu prevalence PAS, aktuálně postihuje 1–2 % dětí. V etiopatogenezi onemocnění se uplatňují genetické faktory, určitou roli hrají i faktory prostředí. U celé řady pacientů s PAS jsou přítomny rozmanité gastrointestinální obtíže, především zácpa nebo růjem, plynatost nebo nespecifické bolesti břicha. Spojitost mezi těmito obtížemi a symptomy PAS se dostává v posledních letech do popředí vědeckého zájmu, a to především z hlediska vývoje nových molekulárně-biologických metod, které zkoumají složení střevní mikrobioty. Komunikace mezi střevem a CNS (tzv. osa střevo-mozek) je umožněna vysoce komplexním obousměrným neurohumorálním komunikačním systémem. Tento systém umožňuje působení střevní mikrobioty na mozkové funkce a umožňuje, aby mozkové signály ovlivňovaly aktivitu střevní mikrobioty a funkce gastrointestinálního traktu. Autoři shrnují různé patofyziologické mechanizmy zapojené do těchto procesů a jsou detailně diskutovány i rozličné terapeutické modality, které zasahují do složení a funkce střevní mikrobioty, jako je užívání vankomycinu, oxytocinu, prebiotik a probiotik. Jsou shrnuty i dosavadní poznatky z oblasti indikace a účinnosti fekální transplantace u dětí s PAS.

Klíčová slova:

autismus – poruchy autistického spectra – střevní mikrobiota – probiotika – fekální transplantace

Zdroje

1. Arvidsson T, Danielsson B, Forsberg P et al. Autism in 3-6-year-old children in a suburb of Goteborg, Sweden. Autism 1997; 1(2): 163–173. doi: 10.1177/ 1362361397012004.

2. Baird G, Charman T, Baron-Cohen S et al. A screening instrument for autism in 18 months of age: a 6-year-follow-up study. J Am Acad Child Adolesc Psychiatry 2000; 39(6): 694–702. doi: 10.1097/ 00004583-200006000-00007.

3. Yin J, Schaaf CP. Autism genetics – an overview. Prenat Diagn 2017; 37(1): 14–30. doi: 10.1002/ pd.4942.

4. Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet 2014; 383(9920): 896–910. doi: 10.1016/ S0140-6736(13)61539-1.

5. Weintraub K. The prevalence puzzle: Autism counts. Nature 2011; 479(7371): 22–24. doi: 10.1038/ 479022a.

6. Danhofer P, Horák O, Aulická Š et al. Genetické a neurobiologické aspekty komorbidního výskytu poruch autistického spektra a epilepsie. Cesk Slov Neurol N 2019; 82/ 115(2): 148–154. doi: 10.14735/ amcsnn2019148.

7. Adams JB, Johansen LJ, Powell LD et al. Gastrointestinal flora and gastrointestinal status in children with autism – comparisons to typical children and correlation with autism severity. BMC Gastroenterol 2011; 11: 22. doi: 10.1186/ 1471-230X-11-22.

8. Bermon S, Petriz B, Kajeniene A et al. The microbiota: an exercise immunology perspective. Exerc Immunol Rev 2015; 21: 70–79.

9. Stilling RM, Dinan TG, Cryan JF. Microbial genes, brain and behavior – epigenetic regulation of the gut-brain axis. Genes Brain Behav 2014; 13(1): 69–86. doi: 10.1111/ gbb.12109.

10. Krejsek J. Roztroušená skleróza mozkomíšní, úloha střevní mikrobioty v poškozujícím zánětu. Cesk Slov Neurol N 2019; 82/ 115(2): 141–147. doi: 10.14735/ amcsnn2019141.

11. Bilen M, Dufour JC, Lagier JC et al. The contribution of culturomics to the repertoire of isolated human bacterial archaeal species. Microbiome 2018; 6(1): 94. doi: 10.1186/ s40168-018-0485-5.

12. Rinninella E, Raoul P, Cintoni M et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 2019; 7(1): 14. doi: 10.3390/ microorganisms7010014.

13. Barrett E, Deshpandey AK, Ryan CA et al. The neonatal gut harbours distinct bifidobacterial strains. Arch Dis Child Fetal Neonatal Ed 2015; 100(5): F405–F410. doi: 10.1136/ archdischild-2014-306110.

14. Barrett E, Guinane CM, Ryan CA et al. Microbiota diversity and stability of the preterm neonatal ileum and colon of two infants. Microbiologyopen 2013; 2(2): 215–225. doi: 10.1002/ mbo3.64.

15. Virtanen S, Kalliala I, Nieminen P et al. Comparative analysis of vaginal microbiota sampling using 16S rRNA gene analysis. PLoS One 2017; 12(7): e0181477. doi: 10.1371/ journal.pone0181477.

16. He Y, Wu W, Zheng HM et al. Regional variations limits applications of healthy gut microbiome reference ranges and disease models. Nature 2018; 24(10): 1532–1535. doi: 10.1038/ s41591-018-0164-x.

17. Leach J. Gut microbiota: please pass the microbes. Nature 2013; 504(7478): 33. doi: 10.1038/ 504033c.

18. Sonnenburg ED, Smits SA, Tikhonov M et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature 2016; 529(7585): 212–215. doi: 10.1038/ nature16504.

19. Clemente JC, Pehrsson EC, Blaser MJ et al. The microbiome of uncontacted Amerindians. Sci Adv 2015; 1(3): e1500183. doi: 10.1126/ sciadv.1500183.

20. Al Omran Y, Aziz Q. The brain-gut axis in health and disease. Adv Exp Med Biol 2014; 817: 135–153. doi: 10.1007/ 978-1-4939-0897-4_6.

21. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 2012; 10(11): 735–742. doi: 10.1038/ nrmicro2876.

22. Sun Y, Zhang M, Chen CC et al. Stress-induced corticotropin releasing hormone-mediated NLRP6 inflammasome inhibition and transmissible enteritis in mice. Gastroenterology 2013; 144(7): 1478–1487. doi: 10.1053/ j.gastro.2013.02.038.

23. Dinan TG, Quigley EM, Ahmed SM et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology 2006; 130(2): 304–311. doi: 10.1053/ j.gastro.2005.11.033.

24. Li Q, Zhou JM. The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder. Neuroscience 2016; 324: 131–139. doi: 10.1016/ j.neuroscience.2016.03.013.

25. Vinolo MA, Rodrigues HG, Nachbar RT et al. Regulation of inflammation by short chain fatty acids. Nutrients 2011; 3(10): 858–876. doi: 10.3390/ nu3100858.

26. Galland L. The gut microbiome and the brain. J Med Food 2014; 17(12): 1261–1272. doi: 10.1089/ jmf.2014.7000.

27. Paul B, Barnes S, Demark-Wahnefried W et al. Influences of the diet and gut microbiome on epigenetic modulation in cancer and other diseases. Clin Epigenetics 2015; 7: 112. doi: 10.1186/ s13148-015-0144-7.

28. Dinan TG, Cryan JF. Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. J Physiol 2017; 595(2): 489–503. doi: 10.1113/ JP273106.

29. Yang J, Fu X, Liao X et al. Effects of gut microbial-based treatments on gut microbiota, behavioral symptoms, and gastrointestinal symptoms in children with autism spectrum disorder: a systematic review. Psychiatry Res 2020; 293: 113471. doi: 10.1016/ j.psychres.2020.113471.

30. Bernier R, Golzio C, Xiong B et al. Disruptive CHD8 mutations define a subtype of autism early in development. Cell 2014; 158(2): 263–276. doi: 10.1016/ j.cell.2014.06.017.

31. Finegold SM, Summanen PH, Downes J et al. Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children. Anaerobe 2017; 45: 133–137. doi: 10.1016/ j.anaerobe.2017.02.008.

32. Liu F, Li J, Wu F et al. Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review. Transl Psychiatry 2019; 9(1): 43. doi: 10.1038/ s41398-019-0389-6.

33. Strati F, Cavalieri D, Albanese D et al. New evidence on the altered gut microbiota in autism spectrum disorders. Microbiome 2017; 5(1): 24. doi: 10.1186/ s40168-017-0242-1.

34. Wang L, Christophersen CT, Sorich MJ et al. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder. Dig Dis Sci 2012; 57(8): 2096–20102. doi: 10.1007/ s10620-012-2167-7.

35. Hsiao EY, McBride SW, Hsien S et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013; 155(7): 1451–1463. doi: 10.1016/ j.cell.2013.11.024.

36. Ashwood P, Krakowiak P, Hertz-Picciotto I et al. Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol 2011; 232(1–2): 196–199. doi: 10.1016/ j.jneuroim.2010.10.025.

37. Sharon G, Cruz NJ, Kang DW et al. Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell 2019; 177(6): 1600–1618. doi: 10.1016/ j.cell.2019.05.004.

38. Tochitani S. Functions of maternally-derived taurine in fetal and neonatal brain development. Adv Exp Med Biol 2017; 975(1): 17–25. doi: 10.1007/ 978-94-024-1079-2_2.

39. Lee E, Lee J, Kim E. Excitation/ inhibition imbalance in animal models of autism spectrum disorders. Biol Psychiatry 2017; 81(10): 838–847. doi: 10.1016/ j.biopsych.2016.05.011.

40. Silverman JL, Smith DG, Rizzo SJ et al. Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med 2012; 4(131): 131ra51. doi: 10.1126/ scitranslmed.3003501.

41. Silverman JL, Oliver CF, Karras MN et al. AMPAKINE enhancement and social interaction in the BTBR mouse model of autism. Neuropharmacology 2013; 64(1): 268–282. doi: 10.1016/ j.neuropharm.2012.07.013.

42. Inoue K, Furukawa T, Kumada T et al. Taurine inhibits K+–Cl– cotransporter KCC2 to regulate embryonic Cl– homeostasis via with-no-lysine (WNK) protein kinase signaling pathway. J Biol Chem 2012; 287(25): 20839–20850. doi: 10.1074/ jbc.M111.319418.

43. Finegold SM, Molitoris D, Song Y et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 2002; 35 (Suppl 1): S6–S16. doi: 10.1086/ 341914.

44. Sandler RH, Finegold SM, Bolte ER et al. Short-term benefit from oral vancomycin treatment of regressive--onset autism. J Child Neurol 2000; 15(7): 429–435. doi: 10.1177/ 088307380001500701.

45. Chini B, Leonzino M, Braida D et al. Learning about oxytocin: pharmacologic and behavioral issues. Biol Psychiatry 2014; 76(5): 360–366. doi: 10.1016/ j.biopsych.2013.08.029.

46. Erdman SE, Poutahidis T. Probiotic „glow of health“: it is more than skin deep. Benef Microbes 2014; 5(2): 109–119. doi: 10.3920/ BM2013.0042.

47. Sanctuary MR, Kain JN, Chen SY et al. Pilot study of probiotic/ colostrum supplementation on gut function in children with autism and gastrointestinal symptoms. PLoS One 2019; 14(1): e0210064. doi: 10.1371/ journal.pone.0210064.

48. Grimaldi R, Gibson GR, Vulevic J et al. A prebiotic intervention study in children with autism spectrum disorders (ASDs). Microbiome 2018; 6(1): 133. doi: 10.1186/ s40168-018-0523-3.

49. Arnold LE, Luna RA, Williams K et al. Probiotics for gastrointestinal symptoms and quality of life in autism: a placebo-controlled pilot trial. J Child Adolesc Psychopharmacol 2019; 29(9): 659–669. doi: 10.1089/ cap.2018.0156.

50. Inoue R, Sakaue Y, Kawada Y et al. Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder. J Clin Biochem Nutr 2019; 64(3): 217–223. doi: 10.3164/ jcbn.18-105.

51. Liu J, Liu X, Xiong XQ et al. Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders – a pilot study. BMC Microbiol 2017; 17(1): 204. doi: 10.1186/ s12866-017-1096-1.

52. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA 2015; 313(4): 398–408. doi: 10.1001/ jama.2014.17103.

53. Moayyedi P, Surette MG, Kim PT et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 2015; 149(1): 102–109. doi: 10.1053/ j.gastro.2015.04.001.

54. Vrieze A, Van Nood E, Holleman F et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012; 143(4): 913–916. doi: 10.1053/ j.gastro.2012.06.031.

55. Kang DW, Adams JB, Gregory AC et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 2017; 5(1): 10. doi: 10.1186/ s40168-016-0225-7.

56. Kang DW, Adams J, Coleman D et al. Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota. Sci Rep 2019; 9(1): 5821. doi: 10.1038/ s41598-019-42183-0.

57. Zhao H, Gao X, Xi L et al. Mo1667 Fecal microbiota transplantation for children with autism spectrum disorder. Gastrointest Endosc 2019; 89(Suppl): AB512–AB513. doi: 10.1016/ j.gie.2019.03.857.