In the current study, the effects of an expanded panel of Crohn’s disease risk alleles [6–10] that are associated with defects in innate immunity (NOD2, ATG16L1, IRGM, CARD9, XBP1, ORMDL3) on ileal microbial composition, were analyzed by combining the original patient cohort (referred to as “Batch 1 2005–2010”) with a second consecutive patient cohort collected between 2010 and 2012 (“Batch 2 2010–2012”, see Table 1”) Some of these genes are implicated in autophagy (e.g. ATG16L1, IRGM), or endoplasmic reticulum stress (e.g. XBP1, ORMDL3), and/or Paneth cell dysfunction (NOD2 ATG16L1, IRGM). This evidence concerns the gene ORMDL3 and Crohn disease.