Host genotype and early life microbiota alterations have additive effects on disease susceptibility


Why do people develop chronic inflammatory illnesses, such as inflammatory bowel disease and auto-immunity, when they are adults? Is the trigger a recent exposure or may the seeds of the problem have formed much earlier in life? What is the role of genetic susceptibility in such processes?

In this issue of Mucosal Immunology, Goethel et al. (Mucosal Immunol. 1, 2019) developed an experimental system in mice to provide at least partial answers to these important questions, in a model relevant to inflammatory bowel disease (IBD). To examine the role of host genotype, they compared wild type C57BL/6 mice with their congenic NOD2 knockouts, focusing on an important innate immunity gene related to detection of bacterial derived ligands and regulation of inflammatory immune responses (Gut Microbes 4:222–231, 2013). To examine the role of the microbiota, mice were exposed, or not, to amoxicillin, an antibiotic with broad-spectrum activity against the normal constituents of the mammalian intestinal microbiome. Further, to examine developmental phenomena related to host age, mice were exposed either during early life or as adults.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1


  1. 1.

    Robertson, S. J. et al. Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis. Gut Microbes 4, 222–231 (2013).

  2. 2.

    Al Nabhani, Z. et al. Nod2 deficiency leads to a specific and transmissible mucosa-associated microbial dysbiosis which is independent of the mucosal barrier defect. J. Crohn’s Colitis 10, 1428–1436 (2016).

  3. 3.

    Goethel, A. et al. Nod2 influences microbial resilience and susceptibility to colitis following antibiotic exposure. Mucosal Immunol. 1, (2019).

  4. 4.

    Ubeda, C. et al. Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. J. Expo. Med. 209, 1445 (2012).

  5. 5.

    Arrieta, M. C. et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl. Med. 7, 307ra152–307ra152 (2015).

  6. 6.

    Honda, K. & Littman, D. R. J. The microbiota in adaptive immune homeostasis and disease. Nature 535, 75 (2016).

  7. 7.

    Ruiz, V. E. et al. A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity. Nat. Comm. 8, 518 (2017).

  8. 8.

    Zhang, X. S. et al. Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity. eLife 7, e37816 (2018).

  9. 9.

    Stappenbeck, T. S. & Virgin, H. W. Accounting for reciprocal host–microbiome interactions in experimental science. Nature 534, 191 (2016).

  10. 10.

    Nobel, Y. R. et al. Metabolic and metagenomic outcomes from early-life pulsed antibiotic treatment. Nat. Comm. 6, 7486 (2015).

  11. 11.

    Cox, L. M. et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705–721 (2014).

  12. 12.

    Rogawski, E. T. et al. Use of antibiotics in children younger than two years in eight countries: a prospective cohort study. Bull. Who. 95, 49 (2017).

Download references

Author information

T.C.B. and M.J.B. wrote the manuscript and conceptualized the figure.

Correspondence to Martin J. Blaser.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark