Table 1.

Summary of the mechanisms by which the gut microbiota may participate in the pathogenesis of celiac disease (CD).

Mechanisms	Study
Role of Environmental Factors
Bacterial expression of epitopes that mimic gliadin	Petersen [20]
Gram- negative bacterial lipopolysaccharide expression as a trigger for both the innate and adaptive immune systems	Kim [21]
Pseudomonas aeruginosa + gluten causes increased inflammation	Caminero [22]
Viral infections as a trigger for activation of the innate immune system	Araya [23]
Role of Microbiota Itself
-Production of immunogenic/tolerogenic gluten peptides -Release of zonulin -Promotion of epithelial mucosal maturation. -Modulation of the immune system through the production of pro-inflammatory/anti-inflammatory cytokines and peptides	Cristofori [24]
Role of Genetics
The genotype of infants at familial risk for CD influences the composition of the early gut microbiota	Olivares [25]
Infants genetically predisposed to CD show different gut microbiota composition (i.e., prevalence of Bacteroides)	Sanchez [26] De Palma [27]
Microbiome shifts observed in the first 6 months after birth in infants with a first-degree relative with CD can increase the risk for developing autoimmune diseases	Leonard [28]
Role of Perinatal Factors
Cesarian section Higher risk of CD due to an increased amount of Enterococcus faecalis vs. a decreased abundance of Bacteroides and Parabacteroides	Leonard [28]
Feeding type -Infant formula feeding might be a risk factor for developing CD, but inconsistent results. -Exclusively formula fed infants showed an increased abundance of Bifidobacteirum adolescentis, Ruminococcus gnavus and Lachnospiraceae, being the latter associated with allergic disease in infants and increased intestinal inflammation	Akobeng [29] Szajewska [30] Leonard [28]
Antibiotic use -No significant association between maternal antibiotic use during pregnancy and CD in offspring -Dose-dependent association	Marild [31] Myleus [32] Kemppainen [33] Marild [34] Dydensborg Sander [35] Canova [11]
Gastrointestinal (GI) infections -GI infections during the first 6–18 months of life is associated with an increased risk of CD by enhanced permeability of the intestine -Inconsistent results for the association between Rotaviruses and risk of CD -Association between Enteroviruses, Adenovirus type 12, Orthoreovirus, Candida albicans and risk of CD	Marild [34] Stene [36] Gatti [37] Lindfors [38] Lahdeaho [39] Bouziat [40] Corouge [41]