IL 17 elevations: Autism and recurrent Miscarriages

Posted By Braverman IVF & Reproductive Immunology || 2-August-2018



A recent study showed how maternal gut may trigger inflammation and disrupt fetal neurodevelopment thus leading to Autism

Microbiome are diverse and complex populations of microbes that are present at the interface between our body and the environment: skin, mouth, vagina, nasal cavity… Gut microbiota (gut flora) represent the largest human community of microbes and is directly involved in food absorption and homeostasis. Diet is a major component in gut microbiome regulation with an imbalance leading to an inflammatory response involved in the possible development of diseases (1). Gut microbiome can also be modulated by the intake of probiotics, good bacteria.

A recent study puts into light the role of the gut microbiome in modulating inflammation through IL-17 cytokine during pregnancy thus impacting neurodevelopment in the offspring.

1- We are pioneer in using an integrative approach to detect and manage maternal inflammation (including IL-17) and maternal microbiota to allow a healthy pregnancy

We, at Braverman Reproductive Immunology, have for years, been offering a complete immune screening panel before pregnancy and a tight monitoring during pregnancy to detect any immune dysregulation potentially dangerous to the pregnancy maintenance, including IL-17.

  • Besides disrupting fetal neurodevelopmental, IL-17 has many detrimental effects on women fertility, it may:
  • damage oocyte quality
  • be involved in miscarriage
  • be involved in obstetrical complications such as pre-eclampsia and pre-term labor
  • be implicated in fertility associated disorders such as PCOS and endometriosis

    You can learn more about IL-17 pleiotropic effects on fertility and the different strategies to help minimize its production in this blog.

  • We have developed a line of dietary supplements including our probiotic supplement “ENDO-Optimize probiotic” helping to keep control of your inflammation.

    With the right strain at the right dosage, our ENDO-Optimize probiotic could help reduce inflammation with the reduction of pro-inflammatory cytokines such as IL-17. ENDO-Optimize probiotic is available for sale and can be found online.

  • Although probiotics can help maintain your inflammation under control during pregnancy, IL-17 spikes require stronger therapies.

    When detected, our timely therapeutic interventions including Prednisone and Tacrolimus attempt to restore a tolerant immunologic state to likely reduce IL-17 spike and minimize the occurrence of obstetrical complications and potentially reduce the risk of neurodevelopmental damages to the growing fetus. It is important to note that Tacrolimus is also used in IL-17 mediated syndrome such as psoriasis for which we have a genetic test aiming to detect patients with a susceptibility to the disease.

    2- Maternal microbiome, inflammation and autism: what does the study show?

    A recent study published in the Journal of Immunology showed the complex

    communication between the maternal microbiome during pregnancy, inflammation and the risk of neurodevelopmental disorders including autism in the offspring. In this study where maternal inflammation is induced in pregnant mice (Maternal Immune Activation or MIA) and leads to autistic-like behaviors, the authors showed that maternal gut microbiota composition influences maternal inflammation and dictates the susceptibility to autism development in the offspring. Further, the study identifies IL-17, an inflammatory cytokine, as a key contributor to autism development. Indeed, blocking this molecule during pregnancy, prevents autistic-like behaviors in the offspring. Previous study in mice showed that the induction of inflammation during pregnancy, with a viral infection that triggers maternal immune activation (MIA), affects fetal brain development with dramatic consequences on pups that develop autism-like behavioral abnormalities (2-4).

    The central role of maternal IL-17 in autism development has been previously demonstrated and blocking IL17 pathway has also been shown to prevent autism-like behavior in the offspring (5) and was discussed in one of our previous blogs on our website http://www.preventautism.com/.

    This new study puts into light the role of the gut microbiome in modulating inflammation during pregnancy thus impacting neurodevelopment in the offspring. In the study, they used a same breed of pregnant mice, but their microbiota diversity was different (housed in two different laboratories), we will call the two groups A and B. As a result, they had a very different susceptibility to MIA-induced neurodevelopmental disorder in the offspring. More interestingly, when mice A are housed with bedding containing fecal samples from the mice B and inversely, the phenotype (development of autism traits) is switched between the two groups. Mice whose pups did not develop autism behaviors before are now developing hallmarks of autism in contact to the other microbiome and inversely.

    Altogether, these findings indicate the key role of the prenatal microbiome in shaping the development of autism-associated behaviors in these mice’ pups in the MIA model.

    At the forefront of research and innovation, we are, at Braverman Reproductive Immunology, developing a project with a major university to study the benefits of our immune therapies in decreasing the likelihood of autism in those that already have a child with ASD. Reccurent pregnancy losses and autism have some etiologies in common (inflammation). A better control of the uterine environment during pregnancy may help with both issues. Stay tune as we expect to announce this joint project shortly.

    For more information about our practice, please consult our website. Questions? Call 516.584.8710 
    We would be happy to help you take control of your fertility journey and answer any questions you may have. 


    References

    1- Schwartz S, et al. A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response. Genome biology. 2012; 13: r32.

    2- Girard S, Tremblay L, Lepage M, Sébire G. IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation. J Immunol. 2010 Apr 1; 184(7):3997-4005.

    3- Hsiao EY, Patterson PH. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behav Immun. 2011 May; 25(4):604-15.

    4- Khan D, Fernando P, Cicvaric A, Berger A, Pollak A, Monje FJ, Pollak DD. Long-term effects of maternal immune activation on depression-like behavior in the mouse. Transl Psychiatry. 2014 Feb 18; 4: e363.

    5- Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, Huh JR. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016 Feb 26;351(6276):933-9.

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