Integrated Role of Microbial, Fungal, and Plant-Derived Interventions in the Management of Celiac Disease: A Narrative Review.

This narrative review examines complementary biological strategies for managing celiac disease (CeD) beyond a strict gluten-free diet (GFD). The authors synthesize evidence on several therapeutic approaches: (1) enzymatic degradation of immunogenic gluten peptides using bacterial and fungal prolyl endopeptidases (PEPs) and engineered enzyme combinations such as latiglutenase; (2) restoration of intestinal barrier integrity via the zonulin antagonist larazotide acetate; (3) gut microbiota modulation using probiotic strains including Lactobacillus and Bifidobacterium to reduce inflammation and support gliadin breakdown; and (4) plant-derived cysteine proteases from sprouting cereals as gluten detoxification agents. The review also considers enzymatic processing in food production to improve safety and accessibility of gluten-free products. The authors frame these strategies as a multidimensional complement to the GFD, particularly for patients with persistent symptoms or incomplete mucosal recovery following accidental gluten exposure. Limitations inherent to this study type include the absence of a systematic search protocol, potential selection bias in source inclusion, and the inability to draw causal conclusions. Primary clinical trial data across the reviewed interventions vary considerably in quality and scale.

Why this grade: This is a narrative review without a systematic search methodology, so it synthesizes existing literature but cannot itself generate new or graded clinical evidence.