A metagenome-wide association study of the gut microbiota in recurrent aphthous ulcer and regulation by thalidomide.

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.

Frequencies of abnormal humoral and cellular immune component levels in peripheral blood of patients with recurrent aphthous ulceration.

BACKGROUND/PURPOSE: Recurrent aphthous ulceration (RAU) has an incidence of approximately 20% in general population. However, its exact cause remains unknown. Increasing evidence suggests that immunologic mechanisms may play crucial roles in the etiology of this disease. MATERIALS AND METHODS: The peripheral blood samples were obtained from 85 patients with RAU during acute phase and 87 healthy controls. The serum levels of IgG, IgA, IgM, C3 and C4 were measured by immunoturbidimetry. In addition, the serum IgE levels were measured by electro-chemiluminescence immunoassay. Furthermore, the percentages of B, T, CD4+ T, CD8+ T lymphocytes and natural killer (NK) cells in peripheral blood were determined by flow cytometry. RESULTS: Our findings showed that the serum IgG, IgA, IgE, C3 and C4 levels of RAU patients were significantly higher than those of healthy controls. The percentages of CD4+ T cells and B cells in peripheral blood of RAU patients were significantly decreased, whereas the percentages of CD8+ T cells and NK cells of RAU patients were remarkably increased. Our results indicated that the IgG level was elevated in 18 patients (21.2%) and that the IgE level was increased in 21 patients (24.7%). Our results also showed that the frequency of abnormal IgG or IgE levels were significantly correlated with that of abnormal CD8+ T cell percentage in RAU patients. CONCLUSION: The levels of both humoral and cellular immune components could be altered in RAU. The relationship between humoral and cellular immune may be potentially important immunologic aspects involved in the pathogenesis of RAU.