Written by Joyce Smith, BS. Treatment with the gut bacteria, B. fragilis, significantly improved behavioral problems and improved gut permeability in a mouse model of autism spectrum disorder.

Today research is telling us that the multiple colonies of bacteria inhabiting the gut can influence our health and disease. For example: TLR5 knockout mice develop obesity when altered gut bacteria increase their appetite; 1 mice with induced multiple sclerosis have gut bacteria that influence the demyelination of nerves; 2 gut bacteria can influence anxiety and behavior in mice; 3 and emotions can change in humans who drink fermented milk with probiotics. 4

Autism spectrum disorder (ASD) is a group of serious complex disorders of brain development, characterized by restricted repetitive behaviors and impaired social skills. ASD individuals often have altered GI motility, increased gut permeability 5 and increased prevalence of inflammatory bowel disease. 6

Based on the emerging “gut-microbiome-brain connection”, researchers Hsaio and team, using a mouse model, were able to link gut bacteria to autism spectrum disorder (ASD). By injecting pregnant mice with an immune stimulant, a process called maternal immune activation (MIA), they were able to affect the neurological development of the fetuses to produce offspring that had autism -like behaviors. These off-spring had “leaky gut” due to compromised intestinal barrier integrity, and an increased inflammatory response similar to what is observed in subsets of ASD. The offspring of these immune-activated female mice also had increased gut permeability due to the changes in the bacterial community that live there along with the metabolites that they produce.

When researchers fed these offspring mice Bacteroides fragilis, a gut bacteria that influences the immune system, the bacterial community was restored to its unaltered state, gut barrier integrity was restored, and behavioral abnormalities disappeared.

The results were as follows:

  • Before treatment with B. fragilis, the overall gut bacteria of the MIA adult offspring significantly differed from the gut bacteria of the controls (P=0.003). However, after treatment with B. fragilis, there were significant changes in the diversity of Clostridia and Bacteroidia compared to other bacteria. (P=0.007)
  • B. fragilis improved or eliminated many of the behavioral problems associated with ASD.
  • B. fragilis significantly altered 34% of the 322 metabolites that the researchers had identified. The metabolites, including N-acetylserine and serotonin were increased, which the authors felt might protect against some ASD symptoms.
  • B. fragilis improved gut barrier integrity in MIA offspring compared to controls.
  • B. fragilis also reduced levels of inflammatory protein which may have played a role in improved gut permeability.

This study lays the groundwork for future studies.

  • It provides evidence that MIA can cause gut permeability which can be reversed with a specific probiotic, in this case B. fragilis.
  • These results also “support a gut-microbiome-brain connection in ASD and identifies a potential probiotic therapy for GI and behavioral symptoms of autism”.
  • Future research using the same mouse model, along with profiling communities of gut bacteria and the metabolites that they produce, might provide the link to finding potential treatments for many health issues including cancers and mental illness.

Source: Hsiao, Elaine Y., et al. “Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.” Cell 155.7 (2013): 1451-1463.

© 2013 Elsevier Inc.

Click here to read the full text study.

References:

  1. Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328(5975):228-231.
  2. Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences. 2011;108(Supplement 1):4615-4622.
  3. Collins SM, Kassam Z, Bercik P. The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Current opinion in microbiology. 2013;16(3):240-245.
  4. Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013;144(7):1394-1401. e1394.
  5. de Magistris L, Familiari V, Pascotto A, et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. Journal of pediatric gastroenterology and nutrition. 2010;51(4):418-424.
  6. Kohane IS, McMurry A, Weber G, et al. The co-morbidity burden of children and young adults with autism spectrum disorders. PloS one. 2012;7(4):e33224.